Encephalon #63

Of Two Minds has just put up the 63rd edition of Encephalon. A nice round-up as usual, with congratulations of course going to Omnibrain on his good fortune... :-p My three highlights as usual:

- Brain Blogger brings us a short piece on serotonin: specifically, how the genetic basis of the serotonin system, and the natural variation in the system as a result of individual genetic differences, results in different susceptibilities to anxiety, depression etc. Possibly also responsible for certain differences in personalities (seems sensible to me, but then I imagine that there are many drivers for ones personality). The interesting question then arises though of whether medicine should be used to make up for some of these individual differences. A fascinating question, whose answer has wide ranging consequences.

- Are birth defects the result of traumas that the mother has been subject to? This question with a seemingly obvious negatory answer is tackled by Vaughan over at Mind Hacks. The theory known as 'maternal impression' was well known in the 19th century, but passed out of use in the late 19th century. However, in the second half of the 20th century, a number of studies showed that severe maternal stress did have an effect on the children's brain development. Vaughans article is well worth the read.

- And finally, the question of Free-Will! PsyBlog reviews three fascinating studies on how manipulating people's views on free-will (by getting them to read statements either for or against the concept of free-will) led to their behaviours being modified. A decreased belief in free will led to people being less helpful towards others, and even increased agression! Which leads to a view that a belief in free will is beneficial to society. The concepts free-will and determinism (as promoted by science) must however be reconciled since our society is fundamentally based on the former, and increasingl on the latter.

Encephalon #59 @ Ionian Enchantment

Recently put up is the latest edition of Encephalon, at Ionian Enchantment. I'll get around to posting something other than links to the Encephalon editions sooner or later, but I'm afraid my blog is less of a priority than getting work done for my PhD... :-) Anyways, my three posts of particular interest in this fortnight's compilation:

- From Mind Hacks is a short piece on the Ganzfeld procedure: a method often used to induce hallucinations. Is it just me, or is the last hallucination that Vaughan mentions slightly disturbing...

- Physical exercise and 'brain health' from Sharp Brains

- Something that I found of particular interest is a review of a paper by Clark and Wheeler on Embodied cognition and cultural evolution, at Neuroanthropology. It's a long (but very good) review of the paper and the concepts involved, but helpfully some of the more important points are highlighted. Essentially, the problem is as follows (copied from article):

Whereas embodied cognition models the brain as a product of dynamic
interplay among processes at different time-scales — evolutionary,
developmental, and immediate –, evolutionary psychologists tend to assume the
existence of underlying, enduring structures in the brain, shaped by natural
selection and encoded (even where we cannot find evidence) in genetic
structures.

As far as I'm concerned a fascinating review of a paper which I will now endeavor to get my grubby little hands on...

Encephalon #58 at Highlight Health

Didn't get around to it yesterday, but the latest Encephalon has been put up at Highlight Health. With the special theme of Decision Making, I particularly like the organisation of this one, with submissions put into one of four categories: needs, preferences, values and emotions. The contributions aren't half bad either! :-)

- A look at peoples ability to perform multiple tasks at once - or rather a lack of it... from SharpBrains

- On confabulation, brain damage and the lack of a role for memory? From the BPS Research Digest blog

- Something I've sort of mentioned before: a brief review of definitions of intelligence from Brain Blogger

Fetal Pain?

The issue of abortion is obviously a contentious one, from a moral, medical and emotional point of view. Of central importance to this debate is the question of whether a fetus can feel pain during surgery or during other operative procedures. Necessary for this is an objective assessment of when a fetus can feel pain, or rather, when during development do the mechanisms underlying pain reception and processing emerge to form a functioning system.

In this paper by Vanhatalo and Niewenhuizen (2000), a review of the development of the pain systems of the fetus is given, followed by the discussion of a particularly pertinent and scientific (i.e. not emotionally laden) question: what is the effect of noxious (read: painful) stimuli on the subsequent development of the fetus?

Given that a formal definition of pain (as stated by the aptly named International Association for the Study of Pain) is given as "a unpleasant sensory and emotional experience associated with actual or potential tissue damage", it may be seen that pain is an inherently subjective phenomenon. Indeed, all of the standard measures of pain rely on subjective scales and the verbal reports of the patients - which are clearly not suitable for neonate use. Indirect measures such as behavioural reactions and autonomic responses to noxious stimuli must therefore be used.

In addition to these indirect indicators of pain, an understanding of the development of the development of the pain mechanisms themselves. Three levels are described in the following paragraphs: the somatosensory functions, the physiological reflexes and the pain behaviours.
The somatosensory pain system involves the pain receptors and associated neural pathways. The development of these takes place relatively early on in development: by the 7th week receptors appear around the mouth, and by the20th week they are present all over the body. This is followed by synapse connection to the spinal cord. These lower levels have been relatively well characterised. At higher levels (sub-cortical and cortical regions), the picture is less clear. Thalamo-cortical connections occur at approximately week 25, but it is not until week 29 that evoked potentials can be measured from the cortex, indicating the formation of meaningful functional pathways at this time. Despite this, there are likely to be other connections formed between the sensory periphery and "deeper brain areas" when the spine and thalamic connections are formed at week 20, allowing the potential for sub-cortical processing of pain at this time. There are naturally many other relevant developmental milestones, but it is important to note that the initial pain related pathways which form in the fetus may be very different from those in the mature individual - giving an indication of the importance of individual development both pre- and post-natally.

The second element of fetal pain characterisation is the behavioural reflexes displayed, including withdrawal reflexes, other body movements and even vocalisations. These reflexes are, however, known to be mediated entirely by the spinal cord, and therefore do not involve "higher perception of pain". Additionally, there is no clear correlation between intensity of the stimulus, and strength of the reflex - meaning that the reflex cannot be used as a reliable indicator of 'painfulness'. However, there is some evidence that facial expressions, for fetus's as young as 26 weeks, may more accurately give an indication of pain level.

The third level in characterising pain is the development of the autonomic and endocrine systems. In mature humans for example, changes in autonomic responses (e.g. increased heart rates, and production of various hormones such as cortisol) may be used as indicators for pain - similar mechanisms may also apply to the developing fetus. However, as yet (or at least at the time of the paper), there appears to be no reliable correlation upon which to base a measurement scale.

Finally, the question of how prenatal pain affects the subsequent development of the fetus is examined. It is noted that subcortical pain processing may occur a number of weeks prior to any noxious stimuli processing in the cortex. Also noted is the plasticity of the nervous system throughout this period, meaning that development is strongly shaped by external input - a number of studies have provided evidence for ...correlations of the early pain experiences to later behavioural variables or to later developmental outcomes..." - particularly the effects on stress responses. In summary: the presence of pain during development can have profound long-term effects on both neurological and psychological development.

In conclusion, the authors note that while the fist sensory experiences (read: conscious experience?) of pain are theoretically possible around the 26th week of gestation (corresponding to the growth of the thalamocortical connections), noxious stimuli could have a damaging effect on fetal development irrespective of processing in the brain. This is because pain also results in activation of stress responses which do not rely on cortical processing. Hence, the authors point to week 10 (development of spinal cord afferents) as being of significance in terms of effect of pain on development – and finish with the question: “which sensory experiences are potentially harmful for the development of a fetus?”.

Note: this paper is from 2000 - those mentions of mechanisms as not being well characterised may now be well understood. If anyone knows of any such advancements, I'd be happy to hear about them – I'm by no means an expert on this topic :-)

Sampsa Vanhatalo, Onno van Niewenhuizen (2000). Fetal Pain? Brain and Development, 22, 145-150

Encephalon #56

Welcome to the 56th edition of Encephalon, here at Combining Cognits. After the emerald anniversary a fortnight ago, I felt I had to find some significance for this issue number – and so I turned to the infinite wisdom of Wikipedia and found the answer (wait for it...):

56 (fifty-six) is the natural number following 55 and preceding 57.

So there we have it. Who said Wikipedia was useless* :-) Anyways, moving swiftly on, we have in this edition we have a nice range of submissions, though dual themes seemed to emerge: Anti-social behaviour, and the somewhat predictable Brains (code for 'I can't quite find a category to cover the rest, even though they're each interesting')**.

o~~~~~~o

Anti-Social Behaviour

With anti-social behaviour being of growing concern in the U.K. at least, with multiple thousands of complaints to the authorities every day, a recently published paper in Biological Psychiatry on cortisol and aggressive behaviour has received a lot of media attention. This paper has been taken up by two of our submitting authors. The Neurocritic provides us with an overview of the paper, highlighting the differing levels of cortisol in subjects with a “Conduct Disorder” with control subjects when performing a frustrating game. Daniel at Neuroanthropology also looks at this paper, but he takes a much more critical line, and broadens his discussion to much wider issues: from criticising the methodology of the study itself, to the media hyping almost beyond recognition (a pet hate for most people methinks), and a commentary on general societal attitudes towards misbehaving youths. A nice discussion piece I feel.

One factor which has pointed to as being a major contributor to anti-social behaviour is alcohol. Besides the social effects, the personal and physiological effects are very pronounced. Jared at Brain Blogger takes us through some of these effects – what it does to cells and tissues, and the potential effects (albeit on a longer time-scale) on the bodily organs and brain, specifically mentioning Korsakoffs syndrome (which has in past been the subject of my personal interest).

One property of alcohol which can make its effects far worse (and which is in common with narcotic substances) is that it can be very addictive, which may lead to the personal and social problems previously mentioned. Dr. Shock brings us an overview of addiction, and raises the possible use of deep-brain stimulation methods to counteract it. (In a pertinent post, Vaughan at Mind Hacks recently posted a list of DBS-related applications)

Going back to our theme of anti-social behaviour: let's say the police pick you up and charge you for some transgression of the law. However, the media (here at least) seems to delight in telling the occasional story of how some obviously guilty (and non mentally impaired) crook has got off free (or lightly at least) with a tale of mental problems. Now clearly, each case must be taken on its individual merits (and I wish to make no general statement regarding the validity of any such claims of mental impairment), but Joshua at Science Blog takes us through a problem with such a legal defence. Given that cognitive science holds that all human behaviour comes from the 'brain' (or more generally the CNS), to say that your brain 'made you do the deed' is a perfectly accurate statement in all cases. In Joshua's words: “...most people prefer that the legal system only punish those who are responsible for wrongdoing. If we exclude from responsibility everybody whose actions are caused by their brains, we must exclude everybody.” There's a bit more to it than that though: what if someone has a genuine problem which has not yet been characterised?

o~~~~~~o

Brains, and everything else...

Jared of Brain Blogger brings us a summary of a paper on the impairments in empathy that many people suffer after undergoing a traumatic brain injury. However, it is not as simple as it may first appear: there didn't appear to be a relationship between severity of the brain trauma and the empathy deficiency, nor could the low empathy scores be predicted by measures of emotion.

Next comes a subject very close to my own interests: Chris Hallquist of Biology of Mind discusses consciousness and qualia, though particularly pointing out the shortcomings of introspection.

Dan of “Sports are 80% Mental” brings us a review of a paper on the six elements of a momentum chain: elements of a sporting event which, when they occur, have an effect on the performance of the athletes, and the outcome of the game, and which typically result from a “precipitating event”. An interesting perspective on the effect of affect and cognition on sport, and things can change very quickly.

Walter of Highlight Health reviews a study of the molecular characterisation of brain tumours, which is based on the Cancer Genome Atlas (TCGA). In the words of Walter, the TCGA “...is an integrated network of clinical sites, core resources and specialized genome characterization and genome sequencing centers that work together to accelerate our understanding of the molecular basis of cancer”. This study in particular identified a number of pathways central to brain tumours, and importantly used a “...statistically robust number of samples...”. The post provides the details, so best not to rely on my paraphrasing.

With two late entries, we have a review of a book by James Zull on teaching methods based on the neurobiology of learning, and a review of recent developments in cognitive health and brain fitness, both from SharpBrains.

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And finally, if you're short of reading, we have from Neuroanthropology a compilation of links on various subjects – particularly the section on “The Brain”.

That's it from me and this edition, I hope it has approached the level of interest and quality I have come to expect from Encephalon. In a fortnight's time, the 57th edition will be brought to us by the ever stimulating Mind Hacks. Submissions in the usual fashion: send a title, URL and summary to encephalon.host ~at~ gmail ~dot~ com.

o~~~~~~o

* Incidentally, I don't – I'm just being facetious. As a first stop (followed by many other more academically reputable stops), it can be a very useful resource for general indicative definitions and pointers to more information.
** Although I have to admit, I have performed some very unsubtle shoe-horning to fit the entries to these themes – for which I apologise.

Encephalon #55

The 55th edition of Encephalon (the 'emerald aniversary' edition) is now up at Neuroscientifically Challenged. My three picks as usual:

- Five points on why, even though absolutely important and fascinating, neuroplasticity has been overstated (or mis-stated at least), from Neuroanthropology. I particularly agree with point four, which states that "...much of the story of neuroplasticity is in developmental settings, in the normal interactions and activities that occur during childhood..." - an aspect very much understated, though I'd say implicitly assumed.

- From the ever thorough Mo at Neurophilosophy comes a review of Developmental topographagnosia - a disorder that essentially leads to a difficulty in producing cognitive maps, as Mo says: "It therefore seems plausible that a reluctance to form cognitive maps, starting from an early age and continuing throughout life, could result in a reduced capacity for the hippocampus to perform this particular function." For me, this seems to lead on nicely from the neuroplasticity post - development of the individual as being of central importance.

- Finally, from Neuronism comes a nice little article on computational neuroscience - building general models and theories in order to make predictions.

The next edition of Encephalon will be held here at Combining Cognits on October the 13th, so get your posts written and readied, and send them to encephalon {dot} host {at} gmail {dot} com as usual. Until then!

Special Issue on Arousal, Alertness and Attention

I recently came across a special issue of the Annals of the New York Academy of Sciences on Molecular and Biophysical Mechanisms of Arousal, Alertness, and Attention. It is May's issue, but for some reason, my alerting mechanism only told me about it on Monday. It's split into four main sections: (1) Elementary Central Nervous System Arousal; (2) The Emotion-Cognition Interface (which I think look particularly interesting); (3) Alertness and Attention; and (4) Circadian Rhythms in the Activation of Behavior (with a main emphasis on sleep). Anyways, some details in case of interest:

Issue 1129 - Table of Contents
Molecular and Biophysical Mechanisms of Arousal, Alertness, and Attention
DOI: 10.1196/annals.1417.034

Excerpt from preface:

"The volume starts with the most primitive function, generalized arousal, and then considers disorders of this function that cause comatose or vegetative states. After a series of chapters on emotion, alertness and attention, we finish with chapters on one of the most dynamic areas in neuroscience: sleep and circadian rhythms. "

The Inseparability of Emotion and Cognition

A paper on how emotion and cognition should not really be considered as separate entities, but as integrated - a move away from functional specialisations in the brain, and towards widespread interaction and integration for the production of behaviour. Abstract:

The current view of brain organisation supports the notion that there is a considerable degree of functional specialisation and that many regions can be conceptualised as either 'affective' or 'cognitive'. Popular examples are the amygdala in the domain of emotion and the lateral prefrontal cortex in the case of cognition. This prevalent view is problematic for a number of reasons. Here, I will argue that complex cognitive-emotional behaviours have their basis in dynamic coalitions of networks of brain areas, none of which should be conceptualised as specifically affective or cognitive. Central to cognitive-emotional interactions are brain areas with a high degree of connectivity, called hubs, which are critical for regulating the flow and integration of information between regions.

Reference: Pessoa L (2008) On the relationship between emotion and cognition. Nat Rev Neurosci 9:148-158 - full text (may require subscription)

The Animat project at Reading University

As reported on the BBC news website (and now many other news channels), and as subsequently nicely summarised by Mo at Neurophilosophy, the Animat project at the University of Reading aims to use a biological neuron culture to not just control a mobile robot, but also to receive sensory signals (in this case from 4 sonar sensors) from the robot - thus a closed loop system. The work is being done by CIRG (of which I am a part), in collaboration with the Pharmacy department, and hopes to allow the the biological neuronal culture to learn control of the mobile robot through the feedback mechanism in order to produce meaningful real-world behaviours - such as obstacle avoidance for example.

The official press release is here, and further information can be found here.

On Grandmother Cells

Grandmother cells were proposed as single neurons which encoded for a single concept - in this case one's Grandmother. The concept was used as a straw-man to criticise sensory hierarchy-based brain organisation theories, but the ideas underlying it are becoming increasingly accepted (not the single neuron per concept I hasten to add). In a paper by Charles Gross (2002 - full ref below), a history of the term is given, with origins and influences.

These cells were originally proposed at the opposite end of the spectrum to ensemble or population coding - where it is the pattern of activity across a group of neurons which codes for a sensory percept. Although the term was coined by Jerry Lettvin in the late 1960's, after which its use quickly proliferated, it was actually proposed as a scientific theory a number of years earlier by the Polish neurophysiologist Jerzy Konorski.

Proposed in his work "Integrative Activity of the Brain" (1967), Konorski predicted the existence of individual neurons sensitive to sensory stimuli such as faces, hands, emotional expressions, etc - and named them "Gnostic" neurons. These were proposed to be located in specific areas of the cortex (in "gnostic fields"), such as the ventral temporal cortex (for the face field), and the posterior parietal cortex (for space fields). These predictions have proven reasonably similar to current proposals for the extra-striate visual cortex in monkeys.

Naturally however, Konorski's work was influenced by that of others. Firstly, in the early 1960's, Hubel and Wiesel demonstrated the hierarchical processing of sensory information in the geniculo-striate system: from simple receptive fields up to the ability to selectively generalise across the retina. Secondly was research on what was then known as the Association Cortex by Pribram and Mishkin: lesions of the inferior temporal cortex produced specific visual cognition impairments in monkeys.

These two bodies of evidence, along with his own familiarity with various agnosias which follow human cortical lesions, led to Konorski's proposal of gnostic cells as a means of accounting for these cognitive impairment effects. Despite the publication of these ideas, and the subsequent coining of the term 'grandmother cells', for at least a decade afterwards, gnostic cells were only taken up in the learning literature, not the perception literature. The term has now, however, had greater use in general textbooks and the pattern recognition literature.

Two features of the gnostic cells have long histories in neuroscience research. Firstly, they are examples of labeled line coding. Labeled line coding refers to a neuron property that allows it to code a particular stimulus property, such as line orientation in the visual field. Secondly, gnostic cells were held to be at the top of a 'hierarchy of increasing convergence'. This concept of convergence hierarchies had, for example, been proposed by William James (the pontifical cell), C.S. Sherrington (in "Man on His Nature", 1940), and Barlow (with the slightly modified concept of cardinal cells, 1972).

In conclusion, the paper notes that the idea of convergence of neural input onto one cell seems to have arisen independently a number of times - and that contemporary human brain imaging have revealed cortical regions (e.g. inferior temporal cortex) which resemble the gnostic fields proposed by Konorski.

As an example of more recent research efforts in exploring this converging hierarchy proposal, Quiroga et al ("Sparse but not 'grandmother-cell' coding in the medial temporal lobe", TICS, 12(3), 2008) - which also involved the somewhat infamous experiments which identified the 'Jennifer Aniston cells' - identified very sparse coding of visual percepts in the medial temporal lobe. In this paper though, a number of arguments were presented for why these cannot be considered to be grandmother cells - a view which I think may be widespread: sparse encoding but not convergence onto a single cell.

Gross, C. (2002). Genealogy of the "Grandmother Cell". The Neuroscientist, 8(5), 512-518.

Encephalon #51

The 51st issue of Encephalon is now up at The Mouse Trap - an ode to the brain, which nicely intertwines the submitted subjects. Two which I found particularly interesting:

- From Effortless Incitement, a summary of a paper on the encoding of concepts in the mouse brain.

- On the exaggerated claims surrounding mirror neurons, from Neuroscientifically Challenged, particularly concerning an essay by Damasio and Meyer in Nature on Convergence/Divergence Zones.

Encephalon #41

The 41st issue of Encephalon is now up at Pure Pedantry (ok, so I'm a few days late...). An excellent round-up as usual, with the following posts being particularly interesting to me:

- From Neuroanthropology comes a piece on dissociation strategies, particularly in regard to sporting activities. Dissociation in this context refers to the ability to (or rather the effect of) perform some conscious task completely independantly of the actions you are making, the actions themselves thus no longer being consciously considered: for example, focussing on repeatedly counting to 100 whilst running. Indeed, attempting to concentrate on the physical activity, rather than dissociating from it, may actually impair performance.

- From Providentia comes the story of Solomon Shereshevsky, a man with an extraordinary memory - although he is better known as 'S' in Alexander Luria's writings. After much testing, Luria concluded that Solomon had an extreme case of synesthesia, where all stimuli were converted to (or rather strongly associated with) visual images. A nice reminder that many of the subjects of the classic (and most well-known) psychology case studies were just people trying to on with their lives in spite of their 'impairments'.

- Finally, from The Neurocritic, comes a review of an earth-shattering neuroimaging study press release which shows that hungry people are more attracted to pictures of food (specifically donuts in this case) than full people are :-) Despite the ridicule, there is also a review of the actual published paper, which revealed activation in the locus coeruleus during the hungry state, a hitherto generally overlooked region.

Encephalon returns

I haven't posted for a while now due to other commitments, but for now a link to the new incarnation of Encephalon, the first issue of which is now up at Sharp Brains. It has more posts than usual (24 in all), with a wide range of subjects: from God to stress, and free will to depression, via a healthy sprinkling of other neuroscience-related matters...

I guess it could be the 39th edition of Encephalon? (Unless I've missed one somewhere...)

Link to new Encephalon Home

New low-power MRI machine

As reported in January's issue of the IEEE Spectrum, what is essentially a very low power MRI (magnetic resonance imaging) machine has produced its first images of a human brain. Whereas a standard MRI machine produces magnetic fields of around 1.5 tesla, this new version produces only around 46 microtesla - an over thirty thousand-fold reduction, and a field apparently comparable in strength to the earths' magnetic field. This reduction in power results in a slightly different method for producing the images.

In a standard MRI machine, a strong magnetic field is used to align the proton in each of the hydrogen atoms before using an RF pulse to knock them out of alignment. As they snap back into alignment with the magnetic field, they emit a signal which can be detected and used to create a 3D image. In the new version, the very small magnetic field isn't enough to align the protons, so a short duration (1 second) magnetic pulse of slightly higher magnitude (30 millitesla). The resulting signals are very small, so an array of highly sensitive magnetometers are used (so-called superconducting quantum interference devices, or SQUIDS). A hugely important additional advantage of using these SQUIDS is that they are also used in the MEG (magnetoencephalography) imaging technique. This potential for MRI and MEG using the same machine raises the intriguing possibility of producing simultaneous structural images (using the MRI) and brain activation maps (using the MEG).

One other major advantage of using this low-power MRI technique is its potential to image tumors. Due to the subtle differences between cancerous and non-cancerous tissue, the differences are not readily captured by standard MRI pictures - whereas the low-power version can. Furthermore, the possibility arises of using this type of imaging during operations themselves, as the very low magnetic fields used would not interfere with the use of metal surgical implements. As with any newly developed technology though, it will be a fair few years before it will be in full use - although this situation will be helped due to comparatively low cost of the new device: due to the absent need for high magnetic fields, the new machines may cost as little as one tenth of its high-powered counterpart.

UPDATE 29/01: Vaughan at MindHacks has pointed out the downsides of using SQUIDs, which I didn't mention.

Encephalon #38

The 38th edition of Encephalon was put at Not Exactly Rocket Science on Monday/Tuesday. Another excellent instalment of the brain sciences blog carnival, with the following contributions being (for me) particularly interesting:

- Firstly, two posts on Mirror Neurons, and how they're not all they're cracked up to be: at Brians on Purpose comes a post on how the role of mirror neurons in every aspect of human cognition has been blown out of all proportion, and from The Neurocritic is a post questioning the 'specialness' of mirror neurons, and the difference between primary motor cortex activation, and action.

- Secondly, Cgnitive Daily reviews a study on attention and intention which concludes that our conscious intentions have a greater effect on perception (and the memory thereof) than priming.

The function of the Hippocampus

In a 2004 Neuron paper, Howard Eichenbaum describes the function of the hippocampus in terms of three cognitive processes:

"The hippocampus is envisioned as critically involved in the rapid encoding of events as associations among stimulus elements and context, in the encoding of episodes as sequences of events, and in linking episodes by common features into relational networks that support flexible inferential memory expression."

There is mounting evidence for the first of these cognitive functions that the hippocampus performs which is associative representation: the encoding of "...associations among stimuli, actions, and places that compose discreet events." Functional neuroimaging studies have provided some evidence for this, however, they have also shown activation of the surrounding cortical regions - indicating that the cortex is also involved in this process of associating stimuli, albeit (perhaps) in a different manner. There has also been increasing evidence for the role of the hippocampus in learning the context of events. For example, in fear conditioning, it has been found that damage to the hippocampus results in a lack of contextual fear conditioning, without affecting the conditioned response.

The second cognitive function proposed to be mediated by the hippocampus is sequential organisation, which is "...the organisation of an episode as a sequence of events that unfolds over time." This is evidenced by the fact that damage to the hippocampus impairs order memory, bu not recognition memory. Similarly, it has been shown that it is not the relative memory trace strengths which are use to determine temporal order - and it is suggested that sequence learning is "...mediated by declarative and non-declarative strategies involving distinct memory systems, and these forms of representation are independant."

The third cognitive function is the linking of common features of disparate memory episode to create flexible representations. This is the consolidation (abstraction) of common features of different episodes into representations in their own right - the creation of semantic information from episodic memory. Further functional neuroimaging studies have shown that extensive cortical networks are activated in addition to the hippocampus when factual information is acquired. There is however a proposed difference in processing method for the two regions which facilitate this linking process: "...the hippocampus rapidly learns about individual experiences and prevents interference by separating representations of those experiences, whereas the cortex gradually extracts regularities over many experiences." This suggests a uniform underlying representation - although there would be differences based on the manner in which the memories are formed. Furthermore, it has been found that the learning of hierarchical relationships in rats is impaired by hippocampal damage. In summary, the findings suggest that while the cortex can perform complex associations, the hippocampus is required to create linkages between related memories which support inferences.

In addition to the funtional neuroimaging and behavioural evidence in support of the proposal of these three cognitive functions, the paper also reviews neural firing pattern support for these proposals, which are presented below by means of quotes of the summarising sentences.

For associative representations:

"...a prevalent property of hippocampal firing patterns involves the representation of unique associations of stimuli, their significance, specific behaviours, and the places where these events occur."

For sequential organisation:

"...the hippocampal network encodes routes through space as a meaningful sequence of events that characterise a particular spatially extended experience."

For relational networking:

"...compelling evidence for the notion that some hippocampal cells represent common features among the various episodes that could serve to link memories obtained in separate experiences."

This paper has reviewed the evidence for the proposal that the hippocampus supports three major cognitive functions. However, with this comes the acknowledgement that numerous cortical regions are also involved in these processes. Perhaps these proposals, taken with a complementary theory of cortical cognitive functioning, may be able to address some more global cognitive issues.

Eichenbaum, H. (2004). Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron, 44(-), 109-120.

"Modelling natural action selection"

Introduction to the Special Issue "Modelling natural action selection"
Philosophical Transactions of the Royal Society London B
September 2007

A special issue containing fourteen papers on various aspects of modelling action selection in animals and humans. There are multiple methods in the study of biological action selection ("of deciding 'what to do next'"), each approaching the problem from different points of view: be it ethology or psychology studying the biological systems, or artificial intelligence or artificial life attempting to build artefacts based on the biological principles. These differing approaches may be characterised by distinguishing between the analytical and synthetic methods in the behavioural and brain sciences, as proposed by Braitenberg.

The analytical method seeks to describe transitions in behaviour (and to explain why they occur in any given context), either functionally through reference to some concept of utility, or mechanistically through reference to underlying neural systems. It is at the overlap between these two approaches that modelling (the "synthetic" approach - the creation of artificial systems which behave as natural ones) has an increasing influence: "what would it take to build a system that acts in this way?" It is not only formal mathematical models which are of interest, but also, and in cooperation, simulations for which mathematical solutions are intractable or unknown. This usually consists of extracting desired properties to be reproduced through observation, and their characterisation using tools from more traditional experimental sciences. In this way, novel hypotheses may be developed, and empirical data may be analysed from the perspective of the simulation model.

In creating models of action selection (and of other models of biological functioning), there are four important questions which need to be addressed and which should also be bourne in mind during development (quote from paper): "...is the model sufficiently constrained by biological data that its functioning can capture interesting properties of the natural system of interest? Do manipulations of the model, intended to mirror scientific procedures or observed natural processes, result in similar outcomes to those seen in real life? Does the model make predictions? Is the model more complex than it needs to be in order to describe a phenomenon, or is it too simple to engage with empirical data?" Concerning this last question, there is then a trade-off between simplicity for the purposes of analysis and adequate complexity for a sufficient model of the process(es) in question, neither extreme of which is suitable.

The introductory paper (by Prescott, Bryson and Seth) summarises the eight main areas covered by the special issue contributors (optimality of action selection, cortical-basal ganglia substrates, behavioural sequencing, subcortical substrates, disorders, perceptual selection, units of selection, and action selection in social contexts) and provides a discussion of modelling strategies and techniques in general. I hope to summarise a few of these papers in the coming weeks (particularly Botvinicks paper on a model of Fusters 'hierarchies').

Contents of special issue, here. Unfortunately, all of the papers are available by subscription only.

- Introduction. Modelling natural action selection TJ Prescott, JJ Bryson and AK Seth
- Do we expect natural selection to produce rational behaviour? AI Houston, JM McNamara and MD Steer
- The ecology of action selection: insights from artificial life AK Seth
- Compromise strategies for action selection FL Crabbe
- Action selection and refinement in subcortical loops through basal ganglia and cerebellum JC Houk, C Bastianen, D Fansler, A Fishbach, D Fraser, PJ Reber, SA Roy and LS Simo
- Cortical mechanisms of action selection: the affordance competition hypothesis P Cisek
- Towards an executive without a homunculus: computational models of the prefrontal cortex/basal ganglia system TE Hazy, MJ Frank and RC O'Reilly
- Multilevel structure in behaviour and in the brain: a model of Fuster's hierarchy MM Botvinick
- Is there a brainstem substrate for action selection? MD Humphries, K Gurney, and TJ Prescott
- Understanding decision-making deficits in neurological conditions: insights from models of natural action selection MJ Frank, A Scheres and SJ Sherman
- Extending a biologically inspired model of choice: multi-alternatives, nonlinearity and value-based multidimensional choice R Bogacz, M Usher, J Zhang and JL McClelland
- Biologically constrained action selection improves cognitive control in a model of the Stroop task T Stafford and KN Gurney
- Agent-based modelling as scientific method: a case study analysing primate social behaviour JJ Bryson, Y Ando and H Lehmann
- An agent-based model of group decision making in baboons WI Sellers, RA Hill and BS Logan
- Spatial models of political competition with endogenous political parties M Laver and M Schilperoord

Encephalon #35

I've been slacking recently when it comes to updating the blog... Anyways...

The 35th edition of Encephalon is now up at The Primate Diaries, with 17 of the best neuroscience (and related) posts from the last fortnight. I particularly liked the post from Pure Pedantry with some videos of synapse activation by insertion of AMPA-R into neurons (if I understand correctly, you're much better off reading it for yourself). Fascinating!

Part 3 - Areal specificity in the PFC and temporal integration

In this third and final part of my review of this paper by Fuster (reference at the end of this post), the paper turns to look a little more closely at what neural mechanisms are at play in the performance of the central function it is proposed to carry out: temporal integration of information, and more generally, the temporal organisation of behaviour.

The paper then turns to the question of the supposed area specialisations in the cortex: the Network Memory theory predicts that functional subdivisions do not exist, but multiple lesion studies have suggested the opposite, to the extent that some cortical regions are generally accepted to be tied to a particular function. The PreFrontal Cortex (PFC) in particular has been subject to many proposed functional subdivisions, according to functions such as attention, working memory (visual, spatial and verbal), and involvement in episodic and semantic memory. The two points of views thus need to be reconciled.

Fuster addresses this problem by proposing that there is a common underlying process to all of the previously mentioned functions. As has been mentioned, this common process is proposed to be temporal integration. An example of this process in the PFC is given by cells which respond specifically to two temporally separate stimuli which have been associated through experience. These neurons have been demonstrated in monkey studies where the presented stimuli consisted of colours and sounds, so that for a given behavioural goal (which for the monkeys was learning and remembering associations between a colour and a sound, for some reward) cells "...seemed to belong to executive networks that, ..., integrated sounds with colours over time." This example demonstrates a principle with important implications for the concept of working memory, particularly the view of executive functions. Instead of dedicated neural circuitry for executive processes as has been proposed by most psychologically based working memory theories, this example (and other converging evidence) indicates that "...executive working memory seems to be essentially based on the ad hoc activation of executive networks of long-term memory."

From this proposal, it becomes necessary to answer two questions: (1) how are these executive networks activated in a timely fashion for the task at hand; and (2) how is this network (or networks) maintained active for the temporal bridging of separate components?

In order to process perceptual information, some form of modulation is required from the PFC – this being necessary for the context dependant retrieval of information from the posterior cortex (i.e. The perceptual hierarchy of the Network Memory theory). Feedback from these regions would then activate executive representations in the PFC. Together with the influences from sub-cortical regions, and the obvious effect of the external environment on the activation of perceptual and motor memories, this loop may be held responsible for the so called 'monitoring' function of the PFC, where relevant information is activated and made available as and when required. It also addresses the question of 'implementation' of working memory: this mechanism strongly indicates that "[it] is as widely distributed as the long-term memory that supports it." Furthermore, the cooling (known to inhibit brain function in a relatively tightly specified region) of any of these implicated regions in monkeys when performing a behavioural task produces deficits in performance indicative of working memory deficit. This may be explained by viewing such an inhibition as interrupting the 'loops' of recurring activity just mentioned, and thus impairing the monitoring function. In summary then: "Working memory is emerging as a mechanism of temporal integration essentially based on the concurrent and recurrent activation of cell assemblies in long-term memory networks of frontal and posterior cortex."

In the paper conclusion, we are reminded of the evidence from a wide range of disciplines in support of the proposed cardinal function of the PFC being the temporal organisation of behaviour, and temporal integration: anatomical interconnections, and developmental evidence (both in the individual and in evolutionary history). The PFC operates as part of the perception-action cycle, which links the actions of the animal with the environment and its internal neural dynamics.

REF: Fuster (2001), "The Prefrontal Cortex – An update: Time is of the essence", Neuron, vol. 30, pp319-333

Part 2 - The PFC: a temporal organiser

There have been a number of studies in the past (including Endel Tulving, who proposed the view of separate semantic and episodic memory, and the associated HERA model), particularly neuroimaging based, which have observed two things in particular: firstly that the encoding of new memories activates the left PFC more than the right PFC, and secondly that the reverse activation profile is seen when memory is retrieved. This indicates the sort of specialisation that Fuster moves away from. An argument is thus provided to counter this: "...it is not altogether clear that the asymmetric activations of the two prefrontal cortices in encoding and retrieval are attributable to their differential involvement in these two cognitive operations. The apparent functional dissociation of right and left PFC may be a product of the subtractive method if the material utilized to test the two operations carries a different semantic load... in both encoding and retrieval tasks, the executive memory networks of lateral PFC may be activated inasmuch as the tasks consist of temporally integrative acts based on internal or external contingencies." In summary, the lateral PFC's most important function is the temporal organisation of behaviour.

Whereas routine behaviours sequences may be made up of chained behaviours, where one action leads to the next, there is no temporal contingency required - i.e. no planning. However, when ambiguity or uncertainty is introduced, such temporal planning ("cross-temporal contingencies") is required. Hence the role of the PFC (in delay tasks, for example, where there is at least one ambiguity that needs to be resolved) in temporal integration. The figure below, taken directly from the paper (figure 4 in paper), gives examples of these two events: in the top case, a routine sequence of behaviours occurs, and in the bottom, a complex or novel sequence. In this latter case, any given act is contingent on the goal, the plan, and other acts - this is the hypothesised role of the lateral PFC: the temporal organisation of behaviour.


Given this role for the lateral PFC, working memory is proposed as the first "temporal integrative function" of the PFC which has been verified in primates using electrophysiology. These experiments, which used delayed response tasks (and occurred in the early '70s), have identified four properties of neural firing related to spatial memory (thus also working memory):
(1) it was absent after stimuli that did not call for prospective action;
(2) it was absent in the mere expectation of reward;
(3) it was correlated with the accuracy of the animal's performance; and
(4) it could be diminished or aborted by distracting stimuli occurring in the delay period.

These properties strongly indicate "retention of the memorandum" (that which is to be remembered), which is dependant on the future need for action. "In sum, considerable evidence from several methodologies supports a prospective role of the PFC, in addition to its retrospective role of working memory. Ingvar (1985) dubbed that prospective role the 'memory of the future'". The retention of the memorandum could then allow the activation of the necessary motor functions (so called motor attention or preparatory set), thus priming the system as a whole for the execution of the required actions: “A temporally symmetric and complementary function of preparatory set, or 'motor attention' would activate the network's motor components and thus prime executive systems for the anticipated action.”

The final part of this paper review will be posted tomorrow, on more specific cortical mechanisms involved in this proposed function of the PFC...

REF: Fuster (2001), “The Prefrontal Cortex – An update: Time is of the essence”, Neuron, vol. 30, pp319-333