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An Earnest Appeal to You, the Mankind

in SciWorld by

Dear Human,

Do you know that the fitness tracker you are wearing, or the smartphone app monitoring your daily physical activity, or the electronic health record (EHR) from your clinical visits are a few of the major sources of my training? What is this training for? Who is my employer? The answer to the latter question is the healthcare industry. And, I am training to fulfill my job responsibilities, which are plenty: correctly diagnose diseases, predict novel disease patterns, identify the invisible population who are at risk, predict the success of clinical drug trials, so on and so forth. But, aren’t clinicians and researchers worldwide already doing this? Yes! But, the manual labor, time and the costs are too high as compared to the results, which often have errors or missing values. Hence, they have put me to task. To meet these demands, my training needs to be robust. And boy, it is (or at least the opportunity is)! I am currently floating in a vast ocean of information from biomedical research, patient records, and wearable devices. The more information I get to train over, the better will be my efficiency. All this sounds hunky-dory till I get to the glaring stumbling blocks in my learning/training.

First, this vast ocean of information is extremely noisy and miscellaneous. Often, I don’t know what to do with a piece of information that I have picked up because it doesn’t have a label or notes attached to it. In other cases, I find conflicting labels on the same piece of information. This, typically, happens when two different parties have labeled the concerned piece of data after referring to two different medical ontologies. So, the problem is more with inconsistencies/conflicts amongst the ontologies and not so much with the labelling itself. But, I am at the receiving end of this, and indirectly is the healthcare industry. Second, despite its size, this ocean is not representative of the entire world population as we have a huge chunk of people without access to primary health care. So, in a word, the ocean that I am floating in is ‘biased’. Third, disease progression over time is often unsynchronized or discontinuous among patients. A major limitation in me is that I lack the ability to handle time-course analysis. Fourth, the causes and patterns of progression for most of the diseases are not completely known. Adding to this is the limited number of patients recorded for each disease type. Thus, to classify these medical conditions into domains for my improved training appears difficult right now. Finally, although I have been created by man, for man, interpreting me is like reading a black box – a complex system whose internal mechanisms are not clearly understood. Interpreting my workings is crucial and has far-reaching consequences as clinicians these days are increasingly relying on data-driven solutions for decision-making and patient monitoring.

With the stumbling blocks in place, let me now give you a quick overview of what you can do to make me work better for you. First, since patient numbers for capturing information are limited, collect as many features as possible for each available candidate. They could be electronic health records, wearable devices, information from social media, environments, surveys, online communities, genome profiles, and beyond. Try working on an approach that could let you throw all these data together and integrate them to help me generate actionable insights. Protecting me, and sensitive patient data would be another priority that you’d need to work on. Add more expert knowledge that is curated from medical journals, research papers, and professionals into the existing information ocean. This would help me train in the right direction. Moreover, considering that time is an important factor in every health care-related problem, another dimension to work on is to make me time-sensitive. And finally, of course, make me more interpretable for the clinicians. The more they will understand me, and my results, the finer I can work for them.

And while I end this letter, I realize that I forgot to introduce myself. Anyway, the subject is way deeper than my name, so in a way, it matters less (?). Some of you might already know me. For others who don’t, I am Deep Learning (DL), a subset of machine learning in AI.

My way of functioning and decision-making mimics your brain. I am currently used in a lot of other application domains, but today I wanted to have a word with you on my role in health care. Because if you survive, I survive. And, vice-versa. Get the drift?

Thanks for your time.

Yours faithfully,

DL

 

Reference: Deep learning for healthcare: review, opportunities and challenges

Photo courtesy: Nvidia blog

Cover image courtesy: http://startupheretoronto.com/partners/cvca/vc-investing-convergence-ai-healthcare/

 

Author: Saikata Sengupta

Saikata Sengupta is currently pursuing her Ph.D. from Department of Neurology at Friedrich Schiller University, Germany. You can follow her on Linkedin or Twitter

 

 

Editor: Arunima Singh, PhD

Arunima obtained her PhD in Computational chemistry from the University of Georgia, USA, and is currently a postdoctoral researcher at New York University. She enjoys traveling, reading, and the process of mastering a new cuisine. Her motivation to move to New York was to be a part of this rich scientific, cultural, and social hub.

Second editor: Manoja Eswara, PhD

Manoja Eswara did her Ph. D. from University of Guelph, Canada and is currently doing her postdoctoral fellowship in Cancer Epigenetics at Lunenfeld Tanenbaum Research Institute, Toronto, Canada.

 

The contents of Club SciWri are the copyright of PhD Career Support Group for STEM PhDs (A US Non-Profit 501(c)3, PhDCSG is an initiative of the alumni of the Indian Institute of Science, Bangalore. The primary aim of this group is to build a NETWORK among scientists, engineers and entrepreneurs).

This work by Club SciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

 

Bosch on LSD

in SciWorld by

Hofmann’s bad trip

 

Inadvertent of its consequences, Albert Hofmann, a chemist working for the Sandoz Laboratories (now Novartis), meticulously wrote these lines in his journal:

4/19/43 16:20: 0.5 cc of 1/2 pro mil aqueous solution of diethylamide tartrate orally = 0.25 mg tartrate. Taken diluted with about ten cc water. Tasteless.

17:00: Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.

Supplement of 4/21: Home by bicycle. From 18:00- ca.20:00 most severe crisis. (See special report)

Here the notes on his laboratory book abruptly stop. The detached tone of his writing, so typical in scientific reports where the first person is usually self-effaced, would soon morph into prophetic. His inner self would also dissolve in the process, but this time not in the wake of fighting vanity or pursuing objectivity. In fact, he had been able to write the last words only with great effort.

What followed was a relentless sensory assault, a parade of kaleidoscopic images in constant flux that unfolded from a central point in the visual scene. These colorful visions eroded all borders, assuming the shape of Gothic buttresses and vaults, countless repetitions of pillars, ferocious flowers, masts and ropes of vessels and iterated church choirs.

 

The doors of perception

 

In 1929, Hofmann had joined the Sandoz chemistry department in Basel, attracted by their ongoing research on the medicinal properties of natural compounds. His boss was Professor Arthur Stoll, who had amassed a wealth of experience in this field, after his stint with Professor Richard Willstätter, a recipient of the Nobel Prize for his work on chlorophyll and CO2 assimilation. His job was to isolate the active principles of known medicinal plants, producing more stable versions of them by chemical synthesis.

The transmission of scientific knowledge often obeys dynastic rules; being the last shoot in a noble lineage of distinguished plant chemists certainly emboldened Hofmann, who got down to work vigorously. After all, he had championed the enzymatic digestion of chitin, the component of insect shells and crustacean claws, ultimately proving that this molecule is an analog of cellulose, the structural backbone of plants. Both kingdoms surrendered to him, and the faculty board hastily followed: his Ph.D. was rated with distinction.

Albert Hofmann (1906-2008), the Swiss chemist that synthesized LSD.

His first target molecule was ergotamine, isolated in 1918 by Stoll himself. Ergotamine was the first ergot alkaloid obtained in pure form and was used in obstetrics and to fight migraines. Ergot is produced by a fungus (Claviceps purpurea) that grows parasitically on rye wheat. The first mention of the medicinal use of ergot to precipitate childbirth appears already in the herbal of Adam Lonitzer and dates from 1582.

When Hofmann resumed work on ergot alkaloids in Basel, research on these substances had lost momentum; competitors on the other side of the Atlantic had taken an edge over the Basel team. In the early 1930s, W.A. Jacobs and L.C. Craig of the Rockefeller Institute had identified the chemical core common to all ergot compounds. They named it lysergic acid.

Feeling that he was on the right track, Hofmann trusted Louis Pasteur’s words: ” In the realm of scientific observation, luck is granted only to those who are prepared.” In chemistry, those were days of never ending fractional extractions followed by cycles of precipitation and recrystallization. One day in 1938, Hofmann was combining lysergic acid with amines, a reaction that yielded a family of compounds with structural similarities. He singled out one of these substances, the 25th derivative in the synthetic series, for pharmacological testing. LSD-25, as he named it, caused powerful uterine contractions perfectly in tune with the normal effects of ergot alkaloids. But there was something else to it: the research report indicated, in passing, that animals became particularly restless. Physicians and pharmacologists did not consider the new substance interesting enough to pursue further tests, and investigations on LSD-25 stopped.

In spite of this, Hofmann had a strange presentiment about it and kept a sample safely in his drawer. The feeling that this substance could have unusual properties haunted him for a long time. Five years later, he decided to revisit the relatively uninteresting LSD-25. While he was repeating one of the steps leading to its synthesis, the vapors emanating from the mixture inebriated him, causing him to interrupt his work right away. The exposure to the compound conjured strange visions that felt incredibly palpable. Once the effects receded, Hofmann realized that he had struck gold.

Three days later, on April 19, 1943, he self-administered LSD-25 and unveiled a whole new world.

 

Bosch & St. Anthony’s Triptych

 

In the Middle Ages people sometimes used contaminated rye grains to bake bread, without even suspecting that ergot mold, when heated, transforms into a form of lysergic acid diethylamide, widely known today as LSD. Medieval chronicles tell us of horrifying cases of victims suffering from burning pain, and convulsions in most cases accompanied by vivid hallucinations. This condition could easily aggravate and develop into a gangrenous form, which usually led to the detachment of limbs. This disease caused ravages amidst impoverished and famine-stricken rural communities in medieval Europe, affecting in particular France and the Netherlands. Its various names record the geographical scope of the outbreak: ignis sacer, mal des ardents, holy fire, heiliges Feuer. In Paris alone, during the year 1418, fifty thousand people were presumably killed by ergotism. For many it was another sign of divine wrath, a godly punishment inflicted upon those who deviated from the righteous path.

On her excellent book on Bosch, Laurinda Dixon tackles the difficult job of analyzing the intriguing iconography of his paintings. In 1495, Hieronymus Bosch painted The St. Anthony Triptych, currently owned by the Museu Nacional de Arte Antiga, in Lisbon. On these oil panels, we follow the saint through different episodes of his life, as Satan and his acolytes systematically test his proverbial endurance to temptations. He is far from being alone on this perilous journey, for Bosch has seeded around him a myriad of figures drawn out of his bestiary. With a stunning calligraphic precision that makes us think of French illuminated manuscripts, demonic creatures of all sorts tease the saint and fittingly punish lustful lovers and gluttons reminding the viewer what sinners are to expect in the next life. Were these images comparable to the visions experienced by consumers of contaminated bread? Bosch bookends the central panel with his trademark infernal scene but also masters the sweet dissolution of the landscape into a horizon made of gradations of blue, an approach that would later reach the climax in the hands of Joachim Patinir.

 

Hieronymus Bosch, St. Anthony’s Triptych, Museu Nacional de Arte Antiga, Lisbon.

Given his long fight with demons and his renewed strength based on the unshakeable faith in Christ, St. Anthony, who was also the father of monasticism, seemed an ideal inspirational figure for those suffering from ergotism. Not surprisingly, his cult resurged during these bleak years, and the Antonite order of monks specialized in giving medical care to the ailing. Hospitals run by the order were labeled: a passerby affected by ergotism would immediately recognize the amputated limbs of former patients hanging above the entrance portals, as a welcoming sign. These were the designated places for treatment and boasted high levels of hygiene, a peaceful atmosphere and a healthy diet of pork sourced from the pigs kept at the monastery. This animal was sacred to St Anthony; a small pet pig is one of his symbols.

But Antonite monasteries were also chemistry laboratories, fully equipped with distilleries ready to produce the cooling elixirs and surgical anesthetics necessary for their mission. Monks would pour one of these healing potions over St. Anthony’s relics, spread among different monasteries of the order, and collect the precious balm to treat the victims of ergotism.

Based on a thorough study of extant contemporary books and engravings, Dixon makes a convincing case that the fantastic domes in the picture are nothing less than laboratory apparatus, dispelling esoteric connotations usually associated with Bosch work. Chemistry and pharmacology were inseparable in those days, and the art of distillation was widely available in manuals that proposed homemade recipes to produce medicines. In them, we find funnels and flasks, not unlike the one used by the strange character at the bottom of the left panel.

On the left, detail of the right panel (top). On the right, furnace, folio 106v from MS Harley 2407, fifteenth century, British Library, London. Taken from the book “Bosch”, written by Laurinda Dixon, Copyright Phaidon Press, 2003. 

To alleviate the burning pain, monks preconized the use of mandrake root (Mandragora) to induce numbness. Interestingly, mandrake root’s forked appearance served as a pretext for its anthropomorphic representation in contemporary books. By drying this root, monks produced talismans against the holy fire, which strongly resembled the man-tree hybrid in the painting. The oversized cherry tomato in the central panel might also be an allusion to mandrakes’ fruit.

From left to right. Mandrake, Mandrake from Pier Andrea Mattioli (Commentarii, Venice, 1565) & detail of St. Anthony’s Triptych (central panel). Images were taken and adapted from the book “Bosch”, written by Laurinda Dixon, Copyright Phaidon Press, 2003. 

Interestingly, mandrake’s root has in itself powerful hallucinogenic and narcotic effects, which added to the visions induced by lysergic acid. The flying fish that crosses the skies might be a visual correlate of a feeling often reported by LSD consumers: Hofmann himself felt he was “floating outside of my own body” during his 1943 trip.

We do not know if the Antonite order commissioned this painting, but Bosch’s work probably provided a devotional image in support of those affected by this terrible disease.

 

Matthias Grünewald and the Isenheim Altarpiece

 

Between 1512 and 1516, Matthias Grünewald worked on an altarpiece commissioned by the Superior of the St. Anthony’s Order for its hospital at Isenheim, in Alsace.

Grünewald created a poignant narrative with an expressionistic accent on the representation of suffering, which becomes tangible when viewing the altarpiece in its closed state. The visitor to the Musée d’Unterlinden discovers a triptych, whose central panel is a deeply moving representation of Christ in the Cross. The atmosphere is lugubrious: under a black sky, we see the lacerated body of Christ, pierced by uncountable wounds. With bluish lips, his hands are still crisped, transmitting the drama of a person who just passed away: we can almost feel his last breath.

The Isenheim Altarpiece, closed panels view. Painted by Matthias Grünewald between 1512-1516. Musée d’Unterlinden, Colmar.

The outer wings reveal a diverse scene. Using a bright palette of colors, Grünewald vitally tells us the story of the Annunciation of the Archangel St. Gabriel to the Virgin, the birth of Christ and the Resurrection. This last panel is boldly chromatic: Christ emerges from the tomb in a halo of blinding light that dissolves his face, with further rays of light pouring out of his wounds. One can easily imagine the ecstatic impression left in the viewers that suffered from the Fire of St. Anthony.

Detail of the Resurrection, from the Isenheim Altarpiece, Musée d’Unterlinden, Colmar.

The inner wings introduce us to the episodes in the life of St. Anthony. We learn of his trip to visit St. Paul when both were hermits living in the desert. However, there is nothing in this landscape that would remind us of Egypt, the original setting of the story. The meeting point is a dense wood covered by lichens, more reminiscent of Northern Europe. The pendant of this scene, the right wing, focuses on the temptations suffered by St. Anthony. Grotesque demons pull the saint by the hair, but suddenly, amidst this virulent assault, God appears above them surrounded by an army of angels. One of them even trespasses a demon with a lance, arriving at the rescue of the saint who famously asked: “Oh, Lord, where were you, good Jesus, why didn’t you come to heal my wounds?”

Detail from the inner wings of the Isenheim Altarpiece showing “St. Anthony is attacked by the demons”, Musée d’Unterlinden, Colmar.

 

Otto Dix & Der Krieg

 

To conclude, we will mention another German painter who was seduced by the story of St. Anthony. Otto Dix, who had fought in the First World War, denounced the corrupt postwar society of the 1920s and 1930s in a series of corrosive paintings that satirized militarism and its consequences. When the Nazis came to power, they expelled Dix from the Art Academy in Dresden and banned him from publicly exhibiting his work. Soon afterward, he joined the lists of Degenerate Art. 260 of his works were removed from the German public collections: many of them were sold to galleries outside Germany or simply burnt. The atmosphere turned dangerously threatening for Dix and his family. Ostracized by the regime, he followed the saint’s fate and transformed into a modern hermit, retiring himself to the Lake Constance.

                                                                        Otto Dix, The temptation of St. Anthony, 1937.

His Temptation of St. Anthony is imbued with the vibrant colors of the Isenheim Altarpiece, a work he particularly appreciated. The Saint crawls under the weight of a sinful blond woman who pushes him down with her foot. This character is reminiscent of the prostitutes he painted in the early 1920s. Adopting the paroxysmal realism of his predecessor, he condemned the war in his triptych from the years 1929-1932, laying the ground for contemporary artists like Anselm Kiefer, who reflect on the consequences of totalitarianism.

 

Otto Dix, Der Krieg, 1929-1932. Dresden , Staatliche Kunstsammlungen, Gemäldegalerie Neue Meister.

 

References

Hofman A. LSD-My problem child:  Reflections on sacred drugs, mysticism, and science. Published by J.P. Tarcher Inc., 1983.

Dixon L, Bosch (Art & Ideas), Phaidon Press Ltd., 2003.

Karcher E, Dix, Published by Taschen, 2010.

De Paepe P, Le retable d’Issenheim, Musée d’Unterlinden, Editions Artlys, Paris, 2015.

 

Featured image: Pixabay

About the Author:

My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

The Gentleman’s Hesitation….& The Invention of Stethoscope

in Medness/SciWorld by

René Laennec (1781 – 1826) was a thorough gentleman. In retrospect, he’d turn out to be a knight in shining white apron.

In 1816, the young French doctor was worried that he could be getting ”inappropriately close’ to a young patient who had been suffering from chest infection. He would recall later, ”…. I was consulted by a young woman laboring under general symptoms of diseased heart, and in whose case percussion and the application of the hand were of little avail on account of the great degree of fatness.The… method of direct auscultation [was] being rendered inadmissible by the age and sex of the patient…”

Laennec resolved the problem of medical diagnostics and social decency in one shot. He ”rolled a quire of paper into a kind of cylinder and applied one end of it to the region of the heart and the other to my ear ”
Within a few months, he had invented that universal symbol of medical science – the STETHOSCOPE

Reference:

  1. https://www.medisave.co.uk/blog/the-invention-of-the-stethoscope/
  2. https://thechirurgeonsapprentice.com/2015/04/21/laennecs-baton-a-short-history-of-the-stethoscope/
  3. https://commons.wikimedia.org/wiki/File%3ARene-Theophile-Hyacinthe_Laennec_(1781-1826)_with_stethoscope.jpg

 

Author Profile:

for sciwri

Anirban Mitra, Ph.D.

Anirban Mitra did his PhD from the Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru and is now a teacher of biology, based in Kolkata. His interests range from biological evolution to history of science and facets of India’s past.

Blog Design and infographics: Abhinav Dey

Featured Image: Ipsa Jain

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This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Time perception in the brain

in SciWorld by
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In our previous two entries, we discussed how painters and writers reflected on the passage of time, and we also learned what philosophers and physicists had to say about this issue. Now it’s the time of neurobiology! How does our brain perceive time? What are the neural bases and possible mechanisms underlying time perception? Is there any internal clock or pacemaker? Is timekeeping distributed among different brain areas?

via GIPHY

Temporal processing is a daunting task. A rich gamut of behaviors depends on our capacity to calibrate and align incoming signals timely. We sample these inputs at various channels, in distant brain areas, and with different processing speeds. However, our brain does an excellent job in generating a coherent picture of the world around us, updating this report to match the fluctuation of external signals.

From prestissimo to largo

We have the ability to compute timing differences that span 10 orders of magnitude, from microseconds to a day (Fig. 1). Separate channels deal with this wealth of information. It seems that we have distinct neural systems that process different timescales. On the high-end of this spectrum, we encounter the neurons of the cochlear nuclei that are responsible for sound localization. They achieve an astonishing feat: they can detect time differences of microseconds in the arrival of sound to both ears. Entrained by the light/dark cycle and other signals, the suprachiasmatic nucleus of the hypothalamus is the mammalian master clock that regulates aspects of metabolism and the daily sleep/wakefulness cycle. In between these two extremes of performance, a network of regions associated with the thalamus, cortex, and striatum operate in the range of seconds to minutes, working as coincident detectors (Buhusi & Meck, 2005). Recent research has also implicated the hippocampus in keeping track of how much time elapsed and in discriminating between similar intervals in the scale of minutes (Jacobs et al., 2013).

Figure 1. Time-scale of temporal processing (taken from Buonomano & Karmarkar, 2002).

Given the scope of this subject, in this article we will concentrate on events taking place in tens or hundreds of milliseconds: speech perception, motion processing in the visual and somatosensory systems and some cues in music perception occur in this time scale.

Time matters for neural circuits

In “The organization of behavior” (1949), Donald Hebb recognized the importance of time in sculpting network properties when he introduced the groundbreaking concept of concurring excitation as a way of strengthening synaptic connections. The Hebbian synapse model suggested that if a neuron is repeatedly involved in the excitation of another neuron, the connection between them will be more efficient as a result of changes taking place in one or both cells. Basically, if two neurons fire together, they wire together. Another plasticity rule appeared later: spike-timing dependent plasticity (STDP). STDP goes one step further, proposing that the strength of a synapse depends on the relative timing of presynaptic and postsynaptic action potentials (Fig. 2). The spike order can make a dramatic difference, potentiating or depressing the synapse.

Figure 2. Scheme of spike-timing dependent plasticity (STDP). In the canonical form of STDP shown here, a presynaptic action potential closely precedes a spike in the postsynapse (red and black bars on top), leading to long-term potentiation (LTP, positive change in synaptic strength). On the contrary, the reversal of this sequence results in long-term depression (LTD, negative change in synaptic strength). In some systems, the temporal requirements for LTP and LTD are exactly the opposite, compared with the canonical STDP. The time window (about 50 ms) can also change depending on the brain region (for details, see Sjöström et al., 2008).

In silico, neural network models incorporating time-dependent realistic features were able to extract temporal information (see Buonomano & Merzenich, 1995). One of these implementations was paired-pulse facilitation (PPF); a known plasticity mechanism in which an impulse evokes a larger postsynaptic potential if it was closely preceded by another impulse. A dynamic neural profile essentially means that a train of action potentials will change the state of the network, inducing activity-dependent transformations in the circuits. When new inputs arrive later, even if they have the same duration and amplitude, they may still evoke a different pattern of activity simply due to the altered state of the circuit. We will come back later to state-dependent networks and their relevance for time-keeping mechanisms.

Central clocks or distributed mechanisms?

In the literature, there are two models that account for the locus of temporal processing in the millisecond time scale. Some authors maintain that an internal clock in our brain sets the pace, pretty much like a computer’s clock. Others think that various regions of the brain share the job of encoding timedifferences (Eagleman et al., 2005; Buonomano & Karmarkar, 2002). In the latter model, the dynamic state of the networks could per se, encode durations, as seen above (Buonomano & Merzenich, 1995). One of the building blocks of this temporal code might be short-term synaptic plasticity, which could instruct circuits with their recent history of activity, keeping track of what happened on the network a few hundred milliseconds ago.

The centralized and diffuse models can, in turn, be subdivided into two classes: in one of them, the same group of neurons encodes time irrespective of the sensory modality. In the second class, the group of neurons that sets the pace, change depending on the type of sensory input (visual cues, tones, touch stimuli, etc.).

Psychophysics can help us discriminate between these scenarios. This discipline quantitatively addresses the complex relations between incoming physical stimuli and our responses to them. In time perception experiments, the participant is confronted with two stimuli (a tone for instance) separated by a variable interval of time. Paired-stimuli are randomized, and the subject has to indicate whether the longer segment was the first one or the second one (Fig. 3).

Figure 3.  An experimental paradigm in psychophysics. Two tones flank time intervals of varying duration; the participant is asked to tell which stimulus presentation was longer. Taken from Buonomano & Karmarkar, 2002.

If there is a centralized time-sensing area in the brain, individuals that are good at discriminating visual cues might be equally good at discriminating sound stimuli. The psychophysical data so far show that for some tasks there seems to be a central time-sensing mechanism. This clock is tuned to particular time intervals and can be generalized to different modalities, as long as the tested duration remains the same (Buonomano & Karmarkar, 2002). According to some authors, there could be labeled lines, where groups of neurons would be tuned to specific intervals. If this is true, then it would be possible to selectively abolish timing for an interval of time while leaving others untouched, but this idea awaits experimental backup. It is also not clear how these experiments can dissect between a pacemaker and a timekeeper for millisecond durations. For stimuli lasting seconds to minutes, pharmacological manipulations could discriminate between the clock stage and memory storage, based on their sensitivity to dopamine and acetylcholine, respectively (see Buhusi & Meck, 2005).

Neural basis of time perception

The cerebellum works as an internal clock operating in the millisecond range, particularly in motor processing tasks like the eyeblink conditioning. In this protocol, the training of an animal includes paired presentations of a tone and an air-puff delivered to the eye. Trained animals learn to blink their eyes in response to the sound cue alone. Interestingly, they do so after a particular interval of time that matches the gap between tone and puff presentation during training sessions. Lesions in the cerebellum abolish the timing of the response (Buonomano & Karmarkar, 2002).

Time distortion by causality

Our internal register of time can be expanded or compressed depending on factors such as causality and sensory feedback. Haggard and collaborators showed how voluntary actions contract the perceived duration of time between two stimuli, as a mechanism of conscious binding of actions and their effects. Involuntary actions, on the contrary, perceptually expanded the time interval between stimuli, indicating a prominent role of agency in the internal representation of temporal information (Haggard et al., 2002).

As a baseline assessment, subjects had to watch the clock and judge the onset of four different stimuli, which were initially presented all alone. In the voluntary condition, they had to press a key at a time of their choice. In the involuntary condition, trans-cranial magnetic stimulation (TMS) was used to induce a muscle twitch by stimulation of the motor cortex. There was a sham TMS condition, in which they had to indicate the timing of a click produced by TMS, with no muscle twitch following afterward. Finally, in the auditory condition, they had to signal the occurrence of a tone (Fig. 4).

Figure 4. The pattern of perceptual shifts is the evidence of a binding effect mediated by voluntary movement, as opposed to involuntary actions. Negative perceptual shifts (in ms) indicate that an event is perceived earlier in an operant environment compared to its presentation alone in the baseline condition. Binding of the first event toward the subsequent tone is shown as an anticipatory perception of the tone and delayed perception of the key press. Taken from Haggard et al., 2002.

In the operant condition, voluntary action, sham TMS, and the TMS click were followed 250 ms later by the sound. Interestingly, perceptual shifts between single event presentations (baseline test) and their operant context, indicated a strong attraction for voluntary actions and the tone. The involuntary action (muscle twitch triggered by TMS stimulation, without the intention of the subject) and its subsequent sound showed the opposite behavior. In other words, conscious, intentional aspects of motor control perceptually anticipated the perceived occurrence of the tone and delayed the key press action.

 

Did you know this?

Source: YouTube

 

References

Buhusi C V & Meck W H. What makes us tick? Functional and neuronal mechanisms of interval timing. Nature Reviews in Neuroscience, vol. 6, pp. 755-765 (2005). doi:10.1038/nrn1764

Haggard P, Clark S & Kalogeras J. Voluntary action and conscious awareness. Nature Neuroscience, vol. 5, nr. 4, pp. 382-385 (2002). doi: 10.1038/nn827

Sjöström J, Rancz E, Roth A & Häusser M. Dendritic excitability and synaptic plasticity. Physiological Reviews, vol. 88, pp. 769-840 (2008). doi:10.1152/physrev.00016.2007.

Buonomano D V & Karmarkar U R. How do we tell time? Neuroscientist, vol. 8, nr. 1, pp. 42-51 (2002).

Jacobs N S, Allen T A, Nguyen N & Fortin N J. Critical role of the hippocampus in memory for elapsed time. The Journal of Neuroscience, vol. 33, nr. 34, pp. 13888-13893 (2013). doi:10.1523/JNEUROSCI.1733-13.2013

Eagleman D M, Tse P U, Buonomano D, Janssen P, Nobre A C & Holcombe A O. Time and the brain: How subjective time relates to neural time. The Journal of Neuroscience, vol. 25, nr. 45, pp. 10369-10371 (2005). doi:10.1523/JNEUROSCI.3487-05.2005

Buonomano D V & Merzenich M M. Temporal information transformed into a spatial code by a neural network with realistic properties. Science, vol. 267, pp. 1028-1030 (1995). doi: 10.1126/science.7863330

 

Featured Video source: Youtube

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Curiously Robert

in Face à Face/SciWorld/Theory of Creativity by

“A great storyteller dances up the ladder of understanding, from information to knowledge to wisdom. Through symbol, metaphor, and association, the storyteller helps us interpret information, integrate it with our existing knowledge, and transmute that into wisdom”, said Maria Papova. Going by that, it is only fair to say that Robert Krulwich is a good storyteller -one curious soul who learns and talks and writes about the wonders of science.

Starting his career as a journalist to cover politics and economics, he had his first brush with science while covering the story of identifying Huntington’s Chorea disease. It was then he met Milton Wexler, a psychoanalyst popular among Hollywood stars, who wanted to understand if his daughter and wife suffer from the same disease. It was in his pursuit that he invited young science stalwarts for parties in Los Angeles, among his usual Hollywood clients. Amidst those fun-filled activities in the unusual teaming of scientists and movie actors in LA, they went on to find the first ever genetic marker for Huntington’s Chorea back in 1983 when there was no PCR or fancy sequencing machines. Covering this story had Robert thinking that, unlike finance analysts and politicians (who he had reported about regularly until then), scientists were having the time of their lives being ‘curiously alive and busy.’  The excitement of learning the unknown was so contagious that Robert decided to be the ‘reporter of very little things’ for ABC News, so he could cover bacteria, genes, atoms and other little things which cannot be seen with the naked eyes. While his boss was not too keen on the whole idea, he did manage to do it. The desire to explore and learn about this completely different world had got into him. While he did not train in science (he studied law), he has learned science as a part of his job.

With his new found passion, he did a television show on string theory – something that he admits might have been the most difficult thing to show on television. His show went on after an hour long show that had cocktail waitresses and extra terrestrials (E.T.) having sex. And to his joy, he could keep the audience (3.5 million people) glued to the television screen, listening to him talking about a ‘squiggly wave’ that some scientists believed to be the fundamental particle of the universe. His boss was surprised that the audience that enjoyed the show about cocktail waitresses and E.T. would watch a show about Physics.  He believes that people can have seemingly contradictory ideas in a span of two hours. And that people will listen, if you have a good story to tell.

He makes stories that are ‘beautiful’.  While beauty is a subjective meditation, a musician knows she got it right when she listens to the notes. Likewise, he ‘just knows’ when he achieves the right balance and knows when a story will hook you and stay in your mind long after it has been told. He calls it ‘renting the brain space’.  This is what Robert and Jad Abumrad do at Radiolab. He and Jad use a system to arrive at a delicate balance of ‘beauty’ which is a combination of fun, learning, and the simplicity of storytelling. The method involves what Robert calls, ‘smarty and dummy edits.’ After working on a piece, researching it, writing, and recording; he turns to replaying it. During this exercise, one part of him knows the story and one does not. While one questions the choice of words, the other thinks about whether concept is understandable as a whole. After that, the story goes to someone who is an expert on the subject to make sure that the content is scientifically correct. Then the story is conveyed to a lay person who does not know about the subject, to specifically identify the parts that are not clear. Speaking of a lack of formal science training, he conceded that not understanding science could be a disadvantage, “because of all the things that you don’t know, you don’t know.”  The advantage, he thinks, is that he is closer to the audience, who is as naïve as him. It is through this process of multiple edits and re-edits, filtering the script multiple times by both the informed and uninformed that a right balance (the beauty?) is arrived. This process of learning brings surprises, wonder and joy for him and those elements are then successfully conveyed to the audience. From his experience at Radiolab, he knows if you describe something joyously, ‘it is hard to resist’.

Jad and Robert, hosts of Radiolab. (Photo Courtesy: WNYC)

He mentioned that it is easy to appeal to basic curiosity. He shared the experience of talking to the slightly disagreeable bunch of politicians in Virginia who believed that science is a conspiracy against their God. He questioned them how the cloud stays in the air, or why is the sky blue. How the big white puffy cloud that is so huge- so moist- and hence so heavy, staying up in the air with nothing holding it beneath. And then he prompted them to use their God-given mind to answer the puzzle. He observed, if you ask a question, people always want to know the answer.

Sun and clouds. Drawing by Robert Krulwich.

He pointed out that much of the hostility to science comes from the fact that science language is inaccessible to the masses. People assume that they are not going to be able to understand it; they feel left out of the conversation and, hence, threatened by science. He revealed his tricks for sharing science with people who are suspicious of science. He mentioned that simple visualizations of science are particularly useful in these kinds of scenarios since not everyone can read scientific data. Like to an anti-vaxxer, you would present the data may be like this:

A representational graph that depicts the drop in disease prevalence after introduction of vaccine at Year 3

And then, adopt the other person’s view, conspire with them. Ask them why they think the government or the doctors would want to make so many people sick. And often such people are not able to come up with good arguments and then you can gently show the data again while generating doubts about their arguments. This, in his experience, opens up people’s minds to the idea of science, and educates them about the rational underpinnings of how nature works.

I wondered if religion could be the reason of hostility towards science, as religion and science are often perceived as exclusive of each other. Carl Sagan wrote in ‘The demon-haunted world, “the very act of understanding is a celebration of joining, merging even if on a very modest scale, with the magnificence of the cosmos…. Science is not only compatible with spirituality; it is a profound source of spirituality.” I asked Robert’s opinion about these two seemingly contrasting ideas. He made a poignant observation, pointing out that faith is about seeking a closer relationship with the universe and seeking ‘enlightenment’. While faith and religion give you the feeling that you know certain things about the universe, science gives you a sense of being stupid. A scientist is often excited while standing next to a mystery, trying to understand it, devising tests of the universe, discovering some of the answers, which in turn opens up more questions. Hence, the practice of science, while trying to understand the universe, always keeps one feeling stupid and sometimes even wrong in light of the newly revealed data. Scientists are, he noted, like excited people watching the climax of a cricket match when it’s still not clear who will win. Religion is more about seeking peace and comfort and staying away from trouble. While they are different, he says, it is possible to practice the two together.

Creature in the woods. Drawing by Robert Krulwich.

He opines that by provoking fundamental curiosity of the human mind, one can get people interested in science, irrespective of religious affiliations. He asserted that his job is not to convince anyone of anything. This is reminiscent of what Isaac Asimov said once, “Now, they may say that I believe evolution is true and I want everyone to believe that evolution is true. But I don’t want everyone to believe that evolution is true; I want them to study what we say about evolution and to decide for themselves.” This is exactly what Radiolab does!

During the discussion on hostility towards science, he also mentioned that science fiction, poetry, and literature prepare humans for newer ways of appreciating science. It is kind of interesting, he pointed out, that time travel is not mentioned in any ancient text in eastern or western culture, but H.G. Wells and his peers thought of it way back in 1850’s all of a sudden. They not only took us to the future but also got us back from the future.  Fast forward 150 years and now a seven-year-old dreams of traveling back in time and meeting dinosaurs. Time travel, now a part of human imagination, was not the case a few centuries ago! It (Science fiction) often operates within the confines of known boundaries of science, and trespasses from there to explore new ideas. The contribution of science fiction to the progress of science is celebrated well.  It is known that space travel, the internet, online learning, wasting time on the web (yes, I know you are reading this online) were predicted much before they happened by the likes of H.G. Wells, Jules Verne, Arthur C Clarke and Issac Asimov. Isaac Asimov said, “Science fiction is important because it fights the natural notion that there’s something permanent about things the way they are right now.”  Such literary artwork allows science to remain in public imagination. And Robert has clearly done his part by bringing science to everyone via his art of storytelling.

A portrait of Robert by the author

During my discussion with Robert, I could observe in action what Maria Papova said about storytelling. Through his experiences of storytelling, his observations have transcended knowledge and into wisdom. Stephen Hawking wondered, “Why does the universe go to all the bother of existing?” As thinkers, let us take an infinitely small step closer to the answer, perhaps the ultimate wisdom.

Cover image: Curiosity. Drawing by Robert Krulwich.

About the Author

Ipsa Jain is a Ph.D. student at IISc. She wants to gather and spread interestingness. She prefers painting and drawing over writing. She posts on Facebook and Instagram as Ipsawonders.

Dr. Ananda Ghosh, Dr. Somdatta Karak and Anand Varma edited the article.

Coomassie Blues- A Colonial Legacy(?) in Molecular Biology

in SciWorld by

Editor’s note: Ask any biochemist and they will tell you about the joy of seeing a single blue band after painstaking hours/days of protein purification. After all, the one sermon from Kornberg that every biochemist will take to their graves is to “Never waste pure thoughts on an impure protein”. Yes we have been through those blues of seeing more blue bands in a gel than expected. But, did you know the stain that we use to paint our gels and lab coats was named before it was synthesized? Either ways, take a trip down the memory lane and know more about Coomassie sans the Blues in #ClubSciWri’s latest post from Anirban Mitra. –Abhinav Dey

 

By the late 19th century, the British Empire was the largest political entity in human history. Queen Victoria’s government ruled over 1/4th of the planet’s land mass and 1/4th of its population. However, one region that was still unconquered was Western and Southern Africa.

The wars that the British launched to subdue the Zulu tribes of South Africa are well-known (thanks to several dramatic movies from Hollywood). But the African monarchy that arguably gave the British their toughest competition was the ASHANTI.

At its height, the Ashanti Kingdom covered a significant part of Western Africa, in the region that is today’s Ghana and neighboring lands. Their expanse had been built largely by a successful military which had come up, independent of ‘civilized’ Europe, along with several modern innovations including improved tactics for jungle warfare and even a medical corps. It is, thus, no surprise that 4 wars had to be fought before the British subdued them totally. Finally in 1896, the 4th Anglo-Ashanti war ended Ashanti dominance. Newspapers across the world reported that the British army had finally captured the Ashanti capital of Coomassie .

Few months later, Levinstein Ltd, a British dye-manufacturing company, introduced a new acid wool dye to the markets of Europe. And, as a marketing strategy, they used the name of a recently-conquered city for their new product. It was kind-of natural. Thanks to the colonial victory, Coomassie had become a well-known name.

Thus, was born the name ‘Coomassie Brilliant Blue’.

Decades later, as the modern discipline of ‘molecular biology’ kicked off in the far-away universities of Europe and the USA, 2 Australian scientists found the same dye could be very reliably used to tag a variety of protein molecules. They published their findings in the well-known journal Biochemica Biophysica Acta.

Today Coomassie staining of proteins after electrophoresis is one of the routine techniques for any biochemical laboratory. It’d not be an exaggeration to say that almost everyone uses it everyday. Of course, the dye’s oblique connection with the subjugation of Africa is all but forgotten. And, the city is now known by its non-anglicized name – Kumasi.
Something like ‘Calcutta’ and ‘Kolkata’ 😉

 

Infographic by: Abhinav Dey

 

Meanwhile, at a bench near you

Comic Source

About the Featured Image from Ipsa jain: The image shows the daily life of person from Kumasi on one side. The right side depicts how a dye for wool yarn is used to stain proteins (secondary structures come from wool ball, then unwound for electrophoresis of proteins). The right hand corner shows the shapes of three places where this story took place, Kumasi (Now in Ghana), Britain and Australia. The two seemingly disconnected stories on left and right are connected by the story of origin of the name for Coomassie blue dye.

 

 

Author Profile:

for sciwri

Anirban Mitra, Ph.D.

Anirban Mitra did his PhD from the Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru and is now a teacher of biology, based in Kolkata. His interests range from biological evolution to history of science and facets of India’s past.

Blog Design: Abhinav Dey

Creative Commons License
This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

The time of philosophers

in SciWorld by

Editor’s Note: With our cameras, we ‘try’ to capture time, well preserved in our sequential snapshots on a daily basis. But have you ever wondered how our consciousness perceives the sense of time and the temporal sequences? Is it a mere birth of our illusionist memories enabling us to differentiate the past, present and thereafter the future? Or maybe time is real and not a product of our mind- well quantified and qualified in the metric sense.

If these questions ever flooded your mind while wrapping up your To Do List, you are at the right place. Do not miss the Sunday Blog at ClubSciWri where Gaston revisits the controversies on the physical nature of time and sheds light on what neuroscientists/philosophers have to say on the enigma of time. – Rituparna Chakrabarti


In the novel A l’ombre des jeunes filles en fleurs (Within a budding grove), written by Marcel Proust in 1919, Madame Swann says: ¨The soldier is convinced that a certain interval of time, capable of being indefinitely prolonged, will be allowed him before the bullet finds him, the thief before he is taken, men in general before they have to die.¨ Such a high hope also pervades Jorge Luis Borges’ tale El Milagro secreto (The secret miracle), included in the collection Ficciones (Fictions).

Jorge Luis Borges

In this narration, we learn that a writer is going to be executed at 9 am. As he stands in front of the firing squad, thanks to an unexpected intercession, his death is momentarily suspended. First surprised, then grateful, he realizes that the world around him came to a timely pause. The bullets froze halfway during their trip, and the curls of smoke from his last cigar have not yet dissipated. In his mind, however, that fraction of an instant will take a full year. Enough time to revise his entire literary output. Immobile, fixed like a pinned butterfly, he goes through Virgil’s poems. He takes the opportunity to mentally finish a sluggish play that had been waiting for a proper end, but just when he found it, he was fatally shot. It was 9.02 am. Two precious minutes were magnanimously granted, not a second more.

Borges argued that time could not have possibly stopped because the writer’s thoughts were still flowing: in short, it is our mind that dictates the tempo. Inasmuch as we are consciously aware of ourselves and what surrounds us, time persists. But what time was he talking about? The internal time of the unfinished play, the writer’s life, the external time of the firing squad and the story itself all converge on a multiple epilogue, leaving us to the idea that Death correctly realigns all timelines, closing all books in synchrony. This tale points to a singularity: an apparent divorce might exist between the metric sense of time and its tensed counterpart.

Proust’s novel inaugurated a new direction in storytelling, featuring a low-pace parade of subjective states, where we often find vignettes, psychological studies of characters and reminiscences. These two examples help to illustrate an intriguing idea: do we use our consciousness to sense time? We appear to perceive events unfurling over that canvas which is our conscious experience. Interestingly, we also grasp their temporal sequence. In this essay and its follow-up, we will succinctly revisit two significant controversies on the nature of time and learn what neuroscientists and philosophers have to say on this elusive subject.

La plage de Cabourg (The beach at Cabourg), painted by René Xavier François Prinet (1910).
Most of Within a budding grove takes place on a seaside resort called Balbec, probably inspired by
Cabourg. © RMN (Musée d’Orsay)/ Hervé Lewandowski.

Time recaptured

One of the first attributes that come to mind when we talk about time is the duration of events. In the Vth century, Saint Augustine reasoned that whatever is measured and computed as duration cannot be in the past, because whatever happened, ceased to be and therefore cannot be perceived any longer, nor it can be in the present since the present lacks any duration. To solve this insurmountable problem he invoked memory as the necessary bridge between the two.

In The experience and perception of time (Le Poidevin, 2015) we learn that E.R. Clay and William James coined the term “specious moment”. This interval of time goes from a few seconds to about a minute, and represents a duration of time that is perceived both as present and as temporally extended. However, the concept of presentness is more complicated than it may appear: we can perceive something that is happening right now, but we can also momentarily hold something in our short-term memory and still recognize it as belonging to the past. But then what is pastness, if such a word exists? Pastness could also be encoded in our memory because it is our memory that forms past-tensed beliefs. According to this view, by merely having a memory of something, we could know that that something already happened, lying further away from our “specious moment.” This approach to characterize past events is troublesome because we can also have false memories: we can recall events that never occurred.

Der Entdecker (The discoverer), painted by Siegfried Zademack (2012).

The “specious moment” could, therefore, define a sliding window over which we integrate what goes on in our conscious experience. The contents of this time interval could be safely labeled as our present experience at any given moment and then moved for storage to vacate space for new incoming experiences. Failure in updating this register could probably compromise our common functioning mode. Many authors believed in the “strength of the memory trace” as a way of explaining how the past is engraved: the older the event, the stronger its persistence. But again, here we encounter a problem because recent events can fade more quickly than older ones.

How do we establish a time order of events? In his article, Le Poidevin discusses two alternative explanations. According to D.H. Mellor, the time at which we formed experiences specifies the temporal order of events, following a protocol that would be insensitive to the contents of those memories. Daniel Dennett’s view is exactly the opposite: the brain might establish the right causal order of events, taking account of the content of the experiences and inferring the correct temporal order.

Newton, Leibniz, and Kant

In the early XVIIIth century Isaac Newton and Gottfried Leibniz held a controversy over the fatherhood of infinitesimal calculus. But this was not the only point of divergence: the nature of time would prove to be another intellectual battlefield. In his article Kant’s views on space and time (Janiak, 2016), Andrew Janiak digests Kant’s contributions under the light of the XVIIth century metaphysics and the Newton-Leibniz debate. In this context, if time was real and not a product of our mind, then it had to be a substance in its right or a property of a substance.

Newton believed that time was an actual entity that could be objectively measured, a substance that could persist on its own. Leibniz, on the contrary, thought that time was inherent to objects and emanated from their relations.According to Leibniz, time does not exist independently of objects and is merely a property of them. What was Kant’s take on these two conflicting views? He rejected the absolutist transcendental realism supported by Newton, arguing that time is not a substance because it is causally inert and inaccessible (it cannot be affected by interactions with things) and also imperceptible. He also attacked Leibniz’s version of transcendental realism, claiming that time does not depend on substances for its existence.

Top view: Leibniz’s manuscript sketching the first calculating machine. Bottom: Leibniz’s calculating machine from 1694.

To escape from this gridlock, Kant introduced a groundbreaking concept: time is an a priori intuition. In Kant’s terminology, intuition is an objective, singular and immediate conscious representation that becomes apprehensible right away. For instance, I have a direct conscious intuition of “my laptop” right in front of me, e.g. I can represent it without invoking any accessory bit of information. A concept, however, is something different. Concepts are also objective but general and mediate. To clarify the representation of “my laptop” as a concept, I would need to refer to other concepts like “computing portable device”, “battery operated”, “operator of symbols”, etc. Now for Kant, time is not something objective and real, neither a substance nor the property of a substance; instead it is something ideal, a product of our mind.But is it a concept? He argues that it cannot be a concept because we cannot grasp it by making reference to other concepts that define it; in short, we cannot place it within other classes. Time pertains to a class of its own.

After discussing concepts and intuitions as different types of objective conscious representations, Kant went one step further and reflected on how we get to those representations. He distinguished between an a priori way of representing things, which does not require previous experience, and an empirical way. He concluded that time is an a priori intuition because it is an innate product of our mind and we can represent it without any prior experience of it. This idea was the stepping stone to the development of his philosophical system, known as transcendental idealism.

Einstein and Bergson: Relative time vs. absolute time

In her book The physicist and the philosopher (Canales, 2015), Jimena Canales offers a gripping account of the famous debate on the nature of time held in 1922 between Henri Bergson and Albert Einstein at the Societé Française de Philosophie in Paris. This clash and its ramifications sent ripples through the international community of physicists and philosophers and ultimately led to their alignment on either side of an intellectual rift that would oppose two fundamentally different views on this subject. Canales makes the point that this controversy, that ended with the setback of Bergson’s influence, ushered in a period of expansion of science as a dominant framework to understand our world.

For Bergson, time included aspects that we cannot entirely capture by a materialistic approach such as the one preconized by science. He wanted to overcome Descartes’ mechanical view of the universe and claimed that our subjective experience of time is a necessary part of its study. The mystery of time, which was the fabric of the universe and our lives, transcended any attempt to quantify it; arid science, with its emphasis on clocks and measuring devices, could only grasp it partially. He believed that time was absolute, making itself evident through the constant change of the universe, like an unstoppable vital impulse (élan vital) that traversed all processes. Bergson was not so much interested in clocks: he wanted to know, first of all, why we are obsessed with time and why we created watches in the first instance.

Albert Einstein on a picnic day. Albert Einstein Archives / Princeton University Press

Einstein was awarded the Nobel Prize in Physics in 1921, but he would only receive the prize one year later and not for relativity. An internal memorandum of the Nobel Institute later revealed that Bergson’s critique had been central to this decision. Although in 1919 Sir Arthur Eddington had provided experimental evidence supporting Einstein’s predictions that light bends in gravitational fields, relativity was far from being widely accepted. Even the people whose work had been seminal for the development of this theory were skeptical about its implications.

Henri Poincaré, for instance, did not believe that it was revolutionary and indeed took sides with Bergson against materialism and mechanistic philosophies. He was a supporter of conventionalism, a current of thought that maintained that scientists choose one theory in particular just because it is convenient.Einstein’s view was exactly the opposite; he believed that theories were meant to be a model of the Universe and not just a suitable formulation. Likewise, Hendrik Lorentz, who developed the relativity equations together with Einstein, believed that there was a difference between time and space and continued to look for an absolute concept of time.

An important consequence of relativity implied that the time-space frame of a moving object slows down and contracts when measured in the observer’s frame. If we would place a clock in a space rocket and another one on Earth, which clock would give the correct time? Einstein would reply both because time depends on the system of reference and is not absolute, as Bergson maintained. Einstein accepted that we could have a psychological understanding of time, (for instance when we are too anxious or bored), but this was not objective, and therefore irrelevant to its study. Einstein accused Bergson of objectifying psychological aspects of time that are purely mental constructs. Bergson, in turn, stated that by considering a time-space continuum and denying an absolute time, Einstein “was grafting a dangerous metaphysics into his science.”

Other efforts tried to reconcile these two opposing views. Heidegger sketched a possible third way that could overcome this duality. He argued that human life does not happen in time, but rather is time itself. Heidegger incorporated the dimension of “everydayness”, where the time measured by clocks, the time of the Universe would be interwoven with the psychological time, the time of our lives.

Perhaps it would be fitting to end this article in the same way that we started it.Bergson’s vitalism and its emphasis on the psychological intuition of time were a significant influence in Marcel Proust’s writing. Indeed both men shared more than philosophical interests: Bergson married Proust’s cousin.

“The time which we have at our disposal every day is elastic; the passions that we feel expand it, those that we inspire contract it; and habit fills up what remains.” (Madame Swann in Within a budding grove).

References

  1. Marcel Proust, A l’ombre des jeunes filles en fleurs, Editions Gallimard, 1954.
  2. Jorge Luis Borges, El milagro secreto (en Ficciones), Emecé, 2004.
  3. Le Poidevin, Robin, “The Experience and Perception of Time”, The Stanford Encyclopedia of Philosophy (Summer 2015 Edition), Edward N. Zalta (ed.), URL = <https://plato.stanford.edu/archives/sum2015/entries/time-experience/>.
  4. Janiak, Andrew, “Kant’s Views on Space and Time”, The Stanford Encyclopedia of Philosophy(Winter 2016 Edition), Edward N. Zalta (ed.), URL = <https://plato.stanford.edu/archives/win2016/entries/kant-spacetime/>.
  5. Jimena Canales. “The Physicist and the Philosopher: Einstein, Bergson and the debate that changed our understanding of time”. Princeton University Press, 2015.

 

Feature image: Pixabay

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Seeing the movement: our visual brain at work

in SciWorld by

Editor’s note: When on Facebook, whether you choose to ignore your frenemy’s vacation pics or hit ‘like’, your brain is consistently driving under influence of visual stimuli. Life never lets your brain take a moment of pause from decision making. If you ever wondered how your brain is wired to decide, you cannot miss the Sunday Blog from #ClubSciWri. Gaston traces the history of neurological research in perception and decision-making.  We might soon be headed towards an AI-based world, but it is undeniable that in the race to replace, human intelligence will always be the yardstick and the checkered flag.- Abhinav Dey

 

Having discussed the ways in which painters tackled the problem of representing motion in art, we can, therefore, ask ourselves the following question: how is this type of information processed in our brain? On a different occasion, we will describe the stream of visual information from the retina via the lateral geniculate nucleus (LGN) to the posterior pole of the occipital lobe, which contains the primary visual cortex (V1).

From V1, information flows along two channels: a ventral pathway extending towards the temporal lobe and a more dorsal pathway, that projects towards the parietal lobe (see figure below). The ventral stream of information is mainly concerned with establishing identities and building categories of visual objects. Running in an anterior direction from the occipital lobe, neurons lying along this pathway are selectively activated by increasingly more complex visual stimuli. Disruption of this network leads to a deficit in object recognition, called agnosia.


Neurons with complex response profiles in the inferotemporal lobe are capable of responding not only to different pictures of a person (celebrities like Scarlett Johansson and unfortunately, your mother in law as well) but also to that person’s written or spoken name. This feature suggests an ability to encode concepts beyond the boundaries of sensory modalities. But this will be the subject of another entry in the blog.

Motion perception in blindness?

Here we will focus on the dorsal pathway which contains the middle temporal region (MT) also called V5. The discovery of this area is an attractive story in itself. One century ago, WW1 was ravaging Europe, and severely injured military personnel flooded hospitals like the Empire Hospital for Officers, where the first character of our story was working as a promising neurologist. In 1917 George Riddoch performed a series of visual tests on soldiers that suffered from shell shock wounds affecting the occipital pole. Below I show the visual fields of Lieut. Col. T.

His right occipital pole was damaged, resulting in left hemianopsia (blindness of a half-field of view). Interestingly, he would perceive moving objects lying on his left-field but not stationary ones. He would typically miss pieces of meat on the left side of his plate, but he could detect moving objects on that side, although he reported blurry shapes and grayish colors. Riddoch quickly realized that there was a complete dissociation of both visual attributes: objects presented in the blind hemifield were invisible when kept stationary but were soon detectable when they moved. These results suggested the existence of separate pathways dealing with static and kinetic visual information.

V5 & The rise of the modular visual brain

Another piece of the puzzle was added in 1969 when Semir Zeki identified a prominent tract of thick fibers connecting V1 with a clear zone in the temporal lobe, a region he called V5. Were the neurons in this area responsible for detecting motion?

In 1974, Zeki recorded in monkeys the electrical activity of these neurons in response to presentations of visual stimuli on a screen. Below I show a representative experiment.

The visual stimulus is on the left, which in this case was a bar that moved in two directions, as indicated by the arrows. The dashed line square shows the borders of the receptive field for that particular neuron. The receptive field of a visual neuron is the area of the visual field in which a presentation of a visual stimulus evokes an electrical response from that neuron. The right panel shows the action potentials (stereotyped all or none electrical signals) fired by the neuron as a readout of its electrical activity during the processing of visual information. All cells within V5 were motion sensitive, and interestingly, a subset of them was directionally selective.

This discovery served as the basis for a modular theory of how the visual brain works in primates, arguing that functionally specialized regions handle specific attributes of a visual scene. Several lines of evidence indicate that color, shape, and motion are processed in parallel by separate areas of our brain, populated by neurons that are selectively excited by those features and following a ¨division of the labour¨ scheme. However, since we normally have a unique and integrated perceptual impression of the world that surrounds us, how does the brain succeed in merging back the scattered information bits to yield a coherent view? We do not have a definitive answer to that yet, but we will sketch it in a different article on this blog.

Neuronal correlates of decision-making

Another interesting question is the following: what is the relation between perceptual judgment and the electrical activity of neurons? When sitting a behavioral test in which we are asked to discriminate between two visual stimuli by their features, is the activity of one or a few neurons driving the perceptual decision? Is this decision based on any complex function of the firing rate of one or a few neurons? Or is it rather a pooled signal coming from a larger circuit, what counts here?

In 1989, Bill Newsome addressed this question by doing an elegant experiment. Monkeys were trained to report the direction of motion of a random dot display (basically a cloud of points moving stochastically in all directions of the screen), in which some dots moved coherently while the rest did it in a haphazard fashion. They changed the strength of the signal by varying the percentage of coherent dots: the higher the percentage of coherence, the more obvious was the general direction of the movement emerging from the pattern of dots. At the same time they recorded the activity of single neurons in area MT (V5). For any given neuron, they placed the dots cloud in the receptive field and adjusted the motion direction to match the neuron’s preference.

They alternated tests in which they presented the optimal stimulus and a ¨null¨ one (an 180°-rotated version of the best stimulus, which evokes no response from that neuron). At the end of each trial, the monkey had to indicate his judgment and report whether the stimulus corresponded to the ¨null¨ or preferred direction. The authors computed a psychometric function from the animal’s behavioral responses and a neurometric function that characterized the neuron’s sensitivity to the motion’s signal. The results are shown below for the neuron’s electrical activity (full black circles) and the psychophysical values (white circles), recorded simultaneously for each trial.

First, we observe that already at 12% of coherence (meaning that 12% of points move in one direction, 88% are stochastic) both curves saturate: the monkey gets it right 100% of the time. On the Y-axis, the curves start at a correctness value of 0.5 because the performance would be 50% correct by chance.

The result is surprising: both curves are similar, but the neuronal data lies to the left of the behavioral data, meaning that the neurons were somewhat more sensitive than the monkey. In other words, had the monkey strictly used his MT neurons as predictors to guide his choice, he would have probably outperformed himself. These results show that we can construct quite an accurate description of the monkey’s performance from the signals of a small number of neurons whose selectivities match the demands of the perceptual task.

A new route?

And now, to finish this article we go back to Riddoch because we still need to complete the puzzle! As I said before, his patients reported the perception of movement in the blind field of view. Loss of V1 due to gunshot wounds affecting the occipital pole has a devastating effect on eyesight, because it cuts off retinal inputs (sent to V1 via the lateral geniculate nucleus), to cortical visual areas that process particular features of a stimulus, like V5 (MT).

But then, if they were blind, how could they possibly detect movement? In 2004, Sincich and coworkers provided a possible explanation. Using retrograde tracers, they revealed the existence of a direct anatomical connection between the lateral geniculate nucleus (LGN), which receives input from the retina, and motion-sensitive area MT. The funny part is that this tract bypasses V1, and therefore Riddoch’s patients might have still preserved some residual perception-notably for moving stimuli- despite having suffered substantial damages to V1.

This example illustrates the modular organization of the visual brain, with functionally specialized areas that treat specific attributes of a visual scene. When one of them does not do the job, our brain puts together the pieces…but the puzzle remains incomplete.

References

  1. From Neuron to Brain. Nicholls, JG; Martin AR; Fuchs PA; Brown DA; Diamond ME & Weisblat DA. , pp. 476-496, 5th Edition, Sinauer Press (2012).
  2. Functional organization of a visual area in the posterior bank of the superior temporal sulcus of the rhesus monkey. Zeki S. The Journal of Physiology, 236, pp. 549-573 (1974).
  3. Dissociation of visual perceptions due to occipital injuries, with especial reference to the appreciation of movement. Riddoch G. Brain 40, 15–57 (1917).
  4. Neuronal correlates of a perceptual decision. Newsome WT; Britten KH & Movshon JA. Nature 341, 52–54. (1989).
  5. Bypassing V1: a direct geniculate input to area MT. Sincich LC; Park KF; Wohlgemuth MJ & Horton JC. Nature Neuroscience 7, pp. 1123-1128 (2004).

 

This blog was originally published here by Gaston Sendin.

Featured image source: Pixabay

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Motion seen through a painter’s palette

in SciWorld by

Editor’s note: The science of motion continues to fascinate us. For Kepler it was the planetary, for Ansel Adams it was the optical, and for Heisenberg it remained uncertain. But have you ever wondered how captivating it was for the pioneers of art and sculpture to capture the different forms of motion? In the Sunday Blog from #ClubSciWri, Gaston Sendin walks us through this intriguing journey from static to kinetic art of representing motion.Abhinav Dey

This blog was originally posted by Gaston Sendin (February 17, 2017) on neurokunst.com

The illusion of movement

Motion has always fascinated humanity. In pre-Socratic Greece, Zeno of Elea distrusted its credentials, arguing that “it is impossible to move because what moves must reach the half-way point earlier than the end.” Since the number of half-points between two end-points of a journey is infinite, he concluded that it is impossible to traverse an infinite number of states in a limited time. He was inadvertently sowing the seeds of calculus, which would remain dormant for a while.

At the beginning of XXth century, poets and painters were adamant in proclaiming the virtues of motion and speed. In his Manifesto del Futurismo (1909), Marinetti wrote: Up to now, literature has glorified contemplation, ecstasy and reverie. We want to exalt the aggressive movement, feverish insomnia, the racing step, the deadly jump, the slap and the punch. We declare that the world’s magnificence has been enriched by a new beauty: the beauty of speed1. They defied the current artistic canon and sought a new creative vigor in burgeoning cities with their tingling mixture of urban life traits: multitudes rushing through the streets on their way to the theaters, cars moving in a frenzy and virulent outdoor political meetings. They woke up to a new sensitivity and celebrated the polyphony of modern industrial societies.

The Italian Futurism

In this context, Giacomo Balla painted ¨The hand of the violinist¨. Both hands and musical instrument are far from being portrayed as stationary objects; in fact, quite the opposite is true. Balla’s use of force lines to accentuate the feeling of motion visually disintegrates matter into a finely powdered cloud of vibrating lines, describing an arc that extends from the lower right corner to the upper left one. Reminiscent of the discovery of atoms and sub-atomic particles, which was occurring almost simultaneously, it enthroned a new pulsating life. Suddenly, Zeno’s infinite halfway-points reappear, and this time we can almost grasp them. The original V-shaped framing, unfurling like a fan, further stresses the kinetic energy trapped in this scene.

Giacomo Balla- The hand of the violinist, 1912

The Russian avant-garde

Almost at the same time, in Soviet Russia, Vladimir Tatlin, was infusing the geometric abstraction of Suprematism, with a new vigorous architectural scope. Suprematists regarded the geometric forms in primary colors as intermediate snapshots (Zeno’s halfway points) taken during their evolution against a white background (representing the infinite space in El-Lissitzky’s cosmovision). Tatlin went one step further, reaching a new level of complexity.

He intended to more explicitly represent all those fractional states of movement, at the same time. He aimed at organically embodying time-space (El-Lissitzky’s fourth dimension) in a new entity that defied the painting’s two dimensions. This approach necessarily required new forms of expression that hybridize architecture and sculpture. His vision gained considerable momentum when he was commissioned with the construction of a kinetic tower to commemorate the 3rd International Socialist.

The Monument was supposed to be a third higher than the Eiffel Tower. Tatlin conceived this colossal structure as a shrine for governmental institutions. The iron and glass structure would contain three building blocks which would house the executive, administrative and propaganda offices of the Comintern. They would rotate at different speeds (the first one, a cube, once a year; the second one, a pyramid, once a month; the third one, a cylinder, once a day). This kinetic project, which was born out of an obsession for the transforming power of machines (and therefore, a hopeful and celebratory role for the industry), propelled by the speed of historical changes, was never completed but it opened the eyes of other artists. His interest in movement and machines would eventually lead him to study bird-flight and design gliders.

In a convoluted way, his spiraling lines paid tribute to another artist who was also concerned with faithfully conveying the illusion of motion. In his Assunzione della Vergine (1515-1518, Santa Maria Gloriosa Dei Frari, Venezia), Tiziano confronts us with a scene of dramatic power which would immediately put him at the forefront of the Venetian school. The view represents the heavenly ascension of the Virgin. At the bottom, the disciples extend their arms upwards, directing their gaze to follow the supernatural event and this vertical upheaval is further echoed by the angels that surround the Virgin, who in turn reinforces the general direction of the movement. Bottom-up zigzagging lines organize this turmoil, acting like a whirlwind and drawing the agitated masses of characters to it. The viewer too is compelled to follow them. The kinetic force of this painting is evident from its helical construction and deviates from the serene and dignified template set before by Giovanni Bellini.

Orphic painters and kinetic art

After the Italian futurists and the Russian constructivists like Tatlin, other artists would take over the illusory representation of movement. Already in the 1910s, the Orphic painters (Sonia and Robert Delaunay) would create circular patterns where the illusion of rotation, like blades of a spinning windmill, was based on the interaction of light and color. Delaunay would write: ¨Vision is our highest sense, the one that most intimately communicates with our brain, with consciousness. Our understanding is in correlation with our perception¨ 2

Robert Delaunay, Formes circulaires. Soleil n°2, 1912-1913. Centre Pompidou, Mnam.

However, so far all these different attempts to represent motion in painting were static; they subtly hinted at the movement, but they did not explicitly address it. The breakthrough would come with the work of artists like Alexander Calder, Julio Le Parc, Jesús Soto and Jean Tinguely, among others. As preconized by the Bauhaus school, they would integrate technology and the use of industrial production methods into their work (not surprisingly, one of their mentors was Laszlo Moholy-Nagy, who also combined light and movement into luminokinetic works). Within the so-called kinetic art movement, different approaches lived together. In many of Soto’s works, for instance, the illusion of movement is recreated when the spectator walks around an otherwise static geometric pattern. Tinguely added a good pinch of irony: his purposeless automata, built around unlikely combinations of discarded industrial elements, seem to incarnate the old idea of perpetuum mobile while satirizing the teleology behind modern means of production, questioning their role in modern societies.

Jean Tinguely, Gismo, 1960, coll. Stedelijk Museum Amsterdam. Foto Gert Jan van Rooij.

QUOTES

1 La letteratura esaltò fino ad oggi l’immobilità pensosa, l’estasi ed il sonno. Noi vogliamo esaltare il movimento aggressivo, l’insonnia febbrile, il passo di corsa, il salto mortale, lo schiaffo ed il pugno. Noi affermiamo che la magnificenza del mondo si è arricchita di una bellezza nuova; la bellezza della velocità. From Le Figaro, February 20th, 1909.

Translation: “The exalted literature up to now thoughtful immobility, ecstasy and sleep. We intend to exalt aggressive action, a feverish insomnia, the running pace, the mortal leap, the punch and the slap. We affirm that the world’s magnificence has been enriched by a new beauty; the beauty of speed.”

 2 L’œil est notre sens le plus élevé, celui qui communique le plus étroitement avec notre cerveau, la conscience. […] Notre compréhension est corrélative de notre perception. Robert Delaunay. De l’impressionnisme à l’abstraction, 1906-1914, éditions du Centre Pompidou, 1999, p.167.

Translation: “The eye is our highest meaning, the one that communicates most closely with our brain, consciousness. […] Our understanding is correlative of our perception. Robert Delaunay. From Impressionism to Abstraction, 1906-1914, editions of the Center Pompidou, 1999, p.167.”

References

https://plato.stanford.edu/entries/paradox-zeno/

https://monoskop.org/Monoskop

Peter Humfrey, ¨La Peinture de la Renaissance à Venise¨, Societé nouvelle Adam Biro, Paris, 1996.

Semir Zeki, ¨Visión interior¨, Antonio Machado Libros, Madrid, 2005.

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Featured Image source: Pixabay

Light Music for the Masses: A Story of LEDs

in SciWorld by

This blog was originally posted by Gaston Sendin (January 28, 2017) on neurokunst.com

Optics: fast and furious imaging

With optics coming of age and its widespread use in biomedical sciences, scientists invest substantial efforts in new imaging technologies. The aim is to reconcile versatility, performance and cost issues. Developments take place in the design of new molecules with expanded capabilities (e.g., increased resistance to photodamage, exquisite sensitivity to excitation frequency, chemical stability). But they also pursue the engineering of more flexible sensors and stimulators with improved performance (e.g. higher quantum efficiency detectors, higher signal-to-noise ratios and the choice of selectable wavelengths of excitation with narrower bandwidths).

Being able to quickly switch across different stimulation wavelengths while keeping them as narrow as possible is of great value for the experimenter. The optical properties of most materials largely depend on the wavelength that is used to study them. Working with “pure” light, as monochromatic as possible, is, therefore, a highly coveted aspiration that guides current efforts in optics.

The most popular type of optical setup in cellular neurobiology consists of a light source (usually a xenon lamp) coupled to a monochromator, a device that allows selecting a particular wavelength from the many available at the input. The output of the monochromator is coupled to the microscope and can, therefore, excite the biological sample lying under its objective. Although this design has been widely successful, to achieve a multi-band output and faster changes, some optical elements need to be brought on board, having an impact on the overall price. In a recent paper published in Nature Scientific Reports, Belušič and co-workers (1) found an elegant and inexpensive solution to circumvent this drawback and obtain multi-band stimulation at an extremely attractive price tag of 700€!

The LED synthesizer & how it works

The light source of this multi-spectral synthesizer, as they call it, is comprised of 20 LEDs of different colors, which are aligned in a row and forming an intrinsic multi-band light stimulator. The light coming from these LEDs is focused on a planar reflective diffraction grating. A grating is a flat optical component containing ridges at very precise intervals along its surface.According to the principle of diffraction established by Fresnel and Huygens, light hitting such a periodic structure is decomposed into several beams traveling in different directions. The wavelength of each light source and the spacing of the ridges on the grating set these trajectories. Diffraction of longer wavelengths (red) will be larger than shorter ones (violet). Therefore, using the grating, one can combine beams of different wavelengths.

LED synthesizer
                             The LED synthesizer in action!

The resulting composite beam then travels through a light guide equipped with a single aspheric lens. This lens minifies the diffracted “rainbow-type” pattern of colors produced by the grating and brings it into focus at its center. The combination of grating and light-guide fiber also had an unexpectedly beneficial consequence. The emerging light had significantly narrower spectral bands; the planar refractive grating not only combines several wavelengths into a single output beam but also cleans their spectra, narrowing their bandwidth.

What can we do with LEDs?

How about testing this gadget in a biological preparation? The authors used sharp electrodes to measure changes in the membrane voltage evoked by short pulses of monochromatic light, in photoreceptor cells from the blowfly’s eye. Stimuli were given with the LED synthesizer or with a classic photo stimulator. To map the photoreceptor’s response to light of different colors, they swept across a series of wavelengths, from 355 nm (ultraviolet) to 625 nm (red light) and were able to obtain a full spectral sensitivity curve in less than 2 seconds. These curves, constructed from the electrical responses to each wavelength presentation, were the same for both stimulation strategies.

As a proof of concept of its potential in biomedical imaging, they moved on to determine the absorption spectrum of oxyhemoglobin and deoxyhemoglobin species in a blood lysate. They presented a series of monochromatic light pulses spanning from 393 nm to 625 nm using either the LED synthesizer or a conventional spectrophotometer. A comparison of experimental results with tabulated data from the literature revealed that for measurements above 440 nm, both absorbance curves were nicely matching, indicating a similar performance for both optical devices.

Their next goal was to find out whether the LED synthesizer could as well discern between oxygenated and deoxygenated hemoglobin in a living tissue and therefore imaged blood vessels of the frog’s abdominal skin. Here the advantage is that oxyhemoglobin is enriched in the veins whereas arteries contain its deoxygenated counterpart. The results were very promising: they could identify spectral components containing enough optical information to discriminate between arteries and veins in the visual field, purely based on their absorption values.

Applications of the LED synthesizer

The LED synthesizer, therefore, represents a robust imaging device offering fast switchable control of the wavelength’s output and equalling to a large extent the performance of a monochromator-based setup, but at a considerably lower price. It can be assembled using inexpensive off-the-shelf equipment, namely cheaply available LEDs, a light guide, an aspheric lens and a planar reflective grating. The amount of undesired light (stray light) in the optical system is significantly reduced. LEDs also have a long operational life, a stable output and one can easily manipulate them and replace them if necessary, unlike the more cumbersome xenon lamps. When coupled to an ophthalmoscope, this imaging device is useful in clinical vision physiology (fundus examination, for instance) and more sophisticated applications in biomedical science (optogenetics, fluorescence microscopy).

Photodamage: Fluorescent molecules do not last forever. Upon repeated excitation, they undergo irreversible chemical changes after which they are no longer fluorescent. Photobleaching, as this process is also known, depends on the illumination level. Photobleaching is used in an optical imaging strategy called FRAP (fluorescence recovery after photobleaching), which is used to track the mobility of fluorescently labeled cellular proteins of interest. With this technique, we can selectively wipe out the fluorescence within a cell region and subsequently monitor its recovery as non-bleached fluorescently labeled proteins in the vicinity gradually start to repopulate the bleached area.

Quantum efficiency of a detector: the percent of incident photons that generate a signal. Not to be mixed with the quantum yield of a fluorescent molecule, which is a measure of its fluorescence efficiency, given by the fraction of all excited molecules that relax by fluorescence emission.

Signal-to-noise ratio: Electronic detectors are often compared by their signal-to-noise ratio, which is a measure of the variation of a signal that indicates the confidence in the measurement of its magnitude.

LED: Light emitting diodes. Resistors, capacitors, and inductors are linear circuit elements, meaning that a doubling of an applied signal (for instance, voltage) will lead to a doubling of the response (current). Diodes, on the contrary, are non-linear and let current flow in one direction, behaving as rectifiers. LEDs contain a semiconductor crystal coated with impurities that generate two regions: a negative n-region (charged with electrons), and a p-region (with positive charge carriers). If sufficient voltage is applied, electrons flow across the junction between both regions, releasing energy in the form of photons.

References

1) A fast multi-spectral light synthesizer based on LEDs and a diffraction grating.
Belušič G, Ilič M, Meglič A & Pirih P
Scientific Reports 6, Article number: 32012 (2016).
doi:10.1038/srep32012

2) Methods in Cellular Imaging, edited by Ammasi Periasamy, Oxford University Press, UK, 2001.

3) Imaging: A Laboratory Manual, edited by Rafael Yuste, Cold Spring Harbor Laboratory Press, US, 2011.

About the Author: My name is Gaston Sendin, and I am a neurobiologist who is passionate about science communication and the history of art. The sensory systems are particularly attractive to me, because they can be exquisitely tuned to specific features of our world. I have so far used electrophysiological and optical methods to study sensory processing in the zebrafish and in mice, focusing on vision and hearing.

After finishing my studies in Biology at the University of Buenos Aires (Argentina), I went on to pursue a Ph.D. in Neuroscience at the International Max-Planck Research School & the University of Göttingen (Germany). Doing research in sensory neurobiology, I was a post-doctoral fellow at the MRC-Laboratory of Molecular Biology in Cambridge (UK), the Department of Artificial Intelligence at the University of Groningen (Netherlands) and the Inserm-Institute for Neuroscience of Montpellier (France).

Featured image source: Pixabay

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