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Picture 1Here is a heads up for a recent study demonstrating – again – that the amygdala is not merely a “fear centre” in the brain. I have previously blogged about the amygdala, first not being a single structure, and that it is not only involved in fear.

In 2007, a team of French researchers demonstrated that direct stimulation of the amygdala did evoke emotional responses, but that there was a difference between which hemisphere was stimulated. Right amygdala stimulations induced aversive responses, in particular fear and sadness. In contrast, left hemisphere stimulation induced either positive (happiness) or negative emotions (fear, anxiety, sadness). As the abstract reads:

Very few studies in humans have quantified the effect obtained after direct electrical stimulation of the amygdala, in terms of both emotional and physiological responses. We tested patients with drug-resistant partial epilepsies who were explored with intracerebral electrodes in the setting of presurgical evaluation. We assessed the effects of direct electric stimulations in either the right or the left amygdala on verbally self-reported emotions (Izard scale) and on psychophysiological markers of emotions by recording skin conductance responses (SCRs) and by measuring the electromyographic responses of the corrugator supercilii (EMGc). According to responses on Izard scales, electrical stimulations of the right amygdala induced negative emotions, especially fear and sadness. In contrast, stimulations of the left amygdala were able to induce either pleasant (happiness) or unpleasant (fear, anxiety, sadness) emotions. Unpleasant states induced by electrical stimulations were accompanied by an increase in EMGc activity. In addition, when emotional changes were reported after electrical stimulation, SCR amplitude for the positively valenced emotions was larger than for the negative ones. These findings provide direct in vivo evidence that the human amygdala is involved in emotional experiences and strengthen the hypothesis of a functional asymmetry of the amygdala for valence and arousal processing.

Interestingly, there is more to say about this study. First, it may be that there is a systematic bias introduced by the way the researchers did the study. By using high-frequency (50 Hz) stimulation in 1 second, they might have induced one characteristic response of the amygdala. This structure is often seen as having quick “on-off” responses. Thus, one second pulse trains is actually a long duration for the amygdala. So a pulse of 20 milliseconds could be hypothesised to produce different responses. Also, the researchers found that GSR responses were actually larger for positive emotions, when they were reported. As the amygdala has often been implicated in unconscious emotional responses (mostly aversive responses) one may speculate that the left-hemisphere amygdala involvement in positive emotions may be related to conscious emotions.

As always, new findings leads to numerous novel questions, ideas and hypotheses. Which is why science is so much fun. But it is important to note the change we see today the role of the amygdala in emotional responses. We are moving away from the LeDouxian paradigmatic focus on fear (and some aversion)as the sole emotion of the brain, and more towards a balanced view towards a similar focus on positive emotions and (hopefully) more complex human emotions. Through this development, we can see that novel findings are breaking down the old ideas of neo-phrenology, breaking single structures into smaller parts, and into parts of a larger network of convergence and divergence structures. Keep your eyes open, more is on the way.

-Thomas

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I just found this through mindhacks, and thought it was nice how well this illustrates the amazement one can get from witnessing neurological injury and disease. Through my early clinical practices, I’ve seen several kinds of unilateral neglect, blindsight, amnesias, aphasias, weird dementias (Wernicke-Korsakoff, fronto-polar, Parkinson Plus), and youtube may be the place to find good illustrations of this to the general public.

-Thomas

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-Thomas

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I’m having the pleasure of reading The brain that changes itself by Norman Doidge, as a reviewer for a potential translation here in Denmark. Brain plasticity, or neuroplasticity, has always been a hot topic, from it’s (re)birth in modern neuroscience, and all the way up until today, where researchers are still fiercely debating how plastic the brain is and how functions relate to brain structures – aka the debate of modularism. In its early days, the neuroscientific community strongly believed that the modularity of the brain was established during childhood, and that little, if any, change could occur later on. Researchers suggesting otherwise were eschewed, heavily criticized on the ground that their data/ideas did not fit into the existing model. The land did not fit onto the map, so to say. This book is dedicated to the idea of neuroplasticity.

The book introduces brain plasticity in a very vivid and close-up manner, as Doidge tells the story from the inside, through some of the biggest names in this research, including the late Paul Bach-y-Rita, Michael Merzenich, and Gerald Edelman. Not only is the book very interesting to read as a historical background, but it also takes a look behind the scenes in two ways. Doidge has talked the researchers himself, and bring their experience of how plasticity came to go from a ignored (and carreer risky business) field, to a scientifically acceptable and highly influential topic. Even today, one may claim that we do not fully comprehend or apply the insights from this research.

Doidge also does a great job in describing patient cases of brain plasticity, including:

(…) a woman born with half a brain that rewired itself to work as a whole, a woman labeled retarded who cured her deficits with brain exercises and now cures those of others, blind people learning to see, learning disorders cured, IQs raised, aging brains rejuvenated, painful phantom limbs erased, stroke patients recovering their faculties, children with cerebral palsy learning to move more gracefully, entrenched depression and anxiety disappearing, and lifelong character traits altered.

(from the book cover)

The stories from both researchers and patients are written in a most vivid and entertaining way, and the first 100 pages alone makes the book a page-turner. The book as a whole is filled with these fantastic descriptions and stories that equal great writers such as Oliver Sacks.

So how about the sex part? Yes, this is where I got a little puzzled, too. Going from the insights of neuroplasticity, Doidge turns his attention to sexual disorders and abberations. This is, of course, both a very interesting, challenging and risky choice, but it is also a topic that Doidge is intimately close to through his clinical work. In much the same manner as the description of neuroplasticity cases, we are presented to patients of Doidge (or his peers) that suffer from psychological illnesses, in particular sex related problems. Interestingly, it seems that the insights from plasticity can be applied to these disorders and problems, and Doidge does a great job in presenting and discussing these issues.

My quarrel, however, is with Doidge’s theoretical position — psychoanalysis. Is it not itself strange to combine the insights from the edgy yet stringent scientific approaches of neuroplasticity with the unscientific theoretical (armchair) century old approach? Doidge does use the suggestions from Freud to interpret the psychological cases he presents. This includes the interpretation of dreams, a business receiving a lot of criticism, too. At best, I think this part of the book becomes an anachronism. The problem lies in why, at all, Doidge needs to invoke a theoretical position like psychoanalysis at all in order to understand what is going on. This is where science becomes fiction, and where the book breaks down. But not totally. If one is aware of the problems associated with psychoanalysis and science, the book is still a wonderful read.

-Thomas

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amygdalaoid.jpegThat almond-shaped structure we call amygdala is typically thought of as solely (or mainly) involved in negative affect. However, some studies have suggested that the amygdala is also involved in other processes, such as novelty (of faces). It should come as a big surprise, however, to many researchers that this structure is also involved in positive emotions. It runs counter to many ideas and interpretations of amygdala activation in, e.g., fMRI studies.

Even more so, in a recent paper in TICS, Elisabeth Murray from the NIH put forth three distinct claims regarding amygdala function (and structure):

  1. amygdala plays a role in positive affect, and therefore not exclusively — or even mainly — in negative affect
  2. contrary to an influential model, recent evidence points to a distinction between emotion and reward and contradicts previous conclusions about the role of the amygdala in reward processing
  3. the amygdala is not a single “thing” but a conglomerate of structures playing different roles in emotional and non-emotional processes

The research reviewed is, as always in the case of Murray, well supported and yet controversial. To anyone studying emotions and reward, it’s a must-read. But even to people studying other functions and regions, it’s a principal discussion and a well-needed lesson in the still-present oversimplified neo-phrenology seen in cognitive neuroscience.

So next time you see the amygdala light up during a brain scan, resort from interpreting it as a sign of anxiety or fear.

-Thomas

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kandel150.jpgThis year’s annual question at Edge was, “What are you optimistic about?”. Now, Brockman has asked Eric Kandel to outline the four neuroscience breakthroughs made in 2006 that makes him optimistic about our future possibility of understanding the brain. The first breakthrough is research into the role of microRNAs in the formation of synapses. The second is research into the encoding of external space in the hippocampus and the entorhinal cortex. Kandel’s third choice is research into social interaction, including Rebecca Saxe’s imaging studies of Theory of Mind, and Barry Dickson’s discovery that if the male form of the protein fruitless is expressed in female Drosophila, the females will display male courship behaviour. And his fourth is the possibility, through neuroimaging and other new techniques, of understanding the effects of psychotherapy on psychiatric diseases.

All four advances are clearly great causes for optimism. But maybe there are other breakthroughs worth mentioning? What about research into decision-making, or comparative genetic studies casting light on the evolution of the hominid brain? I bet that you readers have your own suggestions. Please share them with us in the comments section.

-Martin

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figure1.jpgIs binding the single most important concept in neuroscience? I think it is, even without making the concept too general or vague. On the contrary, binding seems to be a general concept to understand the workings of the brain. No more need for modules of perception, cognition, memory and action. Binding is the solution.

More specifically, what is binding? Or, to reframe the question 100%: what happens when the brain works? To many, the brain binds information together at all levels throughout the brain. If you perceive an object, that particular object is a mixture between colour, form, position, movement etc., that is bound together. Because of you look at the early sensory processes in the brain, we know that the features of an object are treated by separate processes in the brain. Accordingly, they can be lesioned separately, leading to e.g. acquired colour blindless but with intact movement perception.

(more…)

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mysticfigure.jpgA new report in Nature demonstrates that electrical stimulation of the temporoparietal junction in the brain induces a sensation of the presence of an illusory “shadowy person”. One of the hallmarks of certain forms of schizophrenia is just this phenomenon: the eery feeling of someone’s presence. Now, it has been demonstrated in a study using electrical brain activation in a person without a history of psychiatric problems.

Basically, the study was performed on a subject that was at the preoperative stage of surgery for epilepsy. A normal procedure is to anaesthesize the patient before opening the skull, and then wake the patient up before stimulating the brain. The aim of such stimulation is to find the location of epilepsy onset, as well as to stimulate the areas surrounding this region, in order to map functionally important regions (e.g. language that are important in language). Such preoperative procedures are known to lead to a better surgical sensitivity, i.e. the ability to remove all of the abnormal tissue, and a higher surgical selectivity, i.e. avoding removal of normal tissue. In this way, neurosurgeons often evoke a number of sensations and behaviours in patients, including the disruption of speech, visual phosphenes, and memory deficits.

In the present case, the neurosurgeons found that electrical stimulation lead to a feeling of the presence of another person. Moreover, the patient reported that this figure was taking the same posture as herself, and even sometimes interfering with a task she was performing:

When stimulated (…) the patient had the impression that somebody was behind her. Further stimulation induced the same experience, with the patient describing the “person” as young and of indeterminate sex, a “shadow” who did not speak or move, and whose position beneath her back was identical to her own (“He is behind me, almost at my body, but I do not feel it”). (…) Further stimulations [other location] were applied while the seated patient performed a naming (language-testing) task using a card held in her right hand: she again reported the presence of the sitting “person”, this time displaced behind her to her right and attempting to interfere with the execution of her task (“He wants to take the card”; “He doesn’t want me to read”).

Stimulation of the temporoparietal junction (shown with an arrow in the image above) thus seems to distort some kind of body image, or maybe even efference copy (PDF) of self-actions. Both functions that are dramatically affected in abnormal brain states following certain kinds of delusional schizoprenia and brain injury.

The finding also nicely relates to the Swiss group’s earlier study combining EEG, TMS and the study of an epilepsy patient, where it was found that disruption of the temporoparietal junction function led to an “impaired mental transformation of one’s own body”. Here, the researchers concluded that:

the [temporoparietal junction, TPJ] is a crucial structure for the conscious experience of the normal self, mediating spatial unity of self and body, and also suggest that impaired processing at the TPJ may lead to pathological selves such as [out-of-body experience].

Here is the full story:

Induction of an illusory shadow person
By Arzy et al
Nature 443, 287

Stimulation of a site on the brain’s left hemisphere prompts the creepy feeling that somebody is close by.

The strange sensation that somebody is nearby when no one is actually present has been described by psychiatric and neurological patients, as well as by healthy subjects, but it is not understood how the illusion is triggered by the brain1, 2. Here we describe the repeated induction of this sensation in a patient who was undergoing presurgical evaluation for epilepsy treatment, as a result of focal electrical stimulation of the left temporoparietal junction: the illusory person closely ‘shadowed’ changes in the patient’s body position and posture. These perceptions may have been due to a disturbance in the multisensory processing of body and self at the temporoparietal junction.
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1. Laboratory of Cognitive Neuroscience, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
2. Presurgical Epilepsy Evaluation Unit, University Hospital, Geneva 1211, Switzerland
3. Department of Neurology, University Hospital, Geneva 1211, Switzerland
4. Center for Cognitive Neuroscience, Dartmouth College, Dartmouth, New Hampshire 03755, USA

-Thomas

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einstein.jpgWhat characterizes Albert Einstein‘s brain? Why did he become a genius? Can we trace it down to brain-related factors? A growing literature on the relationship between intelligence and brain structure and function has demonstrated several relationships. Those studies, however, are typically based on comparison of brains of high versus mean IQ groups. Studying individual geniuses and what is special about their brains are rare in the scientific literature. However, there are a few exceptions.

In a study by Colombo et al in Brain Research Reviews, the brain of Albert Einstein is studied and compared to four age-matched individuals without any known neurological or psychiatric symptoms. The researchers found that

Einstein’s astrocytic processes showed larger sizes and higher numbers of interlaminar terminal masses, reaching sizes of 15 μm in diameter.

And they further notice that

These bulbous endings are of unknown significance and they have been described occurring in Alzheimer’s disease

…which would mean that, if anything, the size and number of interlaminal terminal masses in Einstein’s brain would make it more like an Alzheimer-patient than like a genius.

Colombo and colleagues are indeed sceptic about the findings and interpretations in the literature on Einstein’s brain. But why do this study in the first place? I’m baffled — to put it mildly — that this kind of study is published in a well-esteemed (well, any) scientific journal. This due to especially three factors relating to the validity of the study:

  1. There are only four control subjects. This provides no information about what the population as a whole looks like for the given brain measurement. IOW, we cannot know anything about the natural variance in the population of our measures, let alone know much about the mean value. Given this, the up-to-15-μm-diameter interlaminal terminal masses means nothing, since we cannot know anything about whether Einstein’s brain is special
  2. One is studying an old and degenerated brain. The fact that the study is of Einstein’s brain at a high age (76 years) seems irrelevant to discover what made his brain so special during the age at which he formulated and developed his theoretical ideas, i.e. decades earlier. This period not only includes the time at which he wrote about relativity, but also an earlier and less known period when he wrote the Annus Mirabilis Papers. This latter series of articles are concerned with the photoelectric effect, also recognized as papers that alone deserve a Nobel prize. And those papers were even written by Einstein during his spare time!
  3. Why not study a group of geniuses? Indeed, why only rely on one data point? Why not include a larger sample of geniuses, not only from physics, but from other sciences? Einstein was not the only genius around. Living in Denmark and passing through the Copenhagen University physics buildings regularly, I am immediately reminded of Niels Bohr, a contemporary to Einstein that matches Einstein’s genius in every respect. It would thus be much more interesting to see a group study of geniuses. It might be hard to do a genius post-morten study for both practical and ethical reasons, but one can do in vivo studies of today’s geniuses, right? One data point, even if it’s Einstein, is really not enough. Doing a group study we could also ask questions such as whether there are differences between male and female geniuses, or whether the develop and age different from the general population.

Einstein’s brain is indeed an interesting topic, but in order to make valid inferences from a study of his brain, we should consider including his brain among a number of related geniuses. Doing any kind of study of one genius’ brain is unlikely to produce any valid finding at all.

-Thomas

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In an interesting paper in the latest version of Progress in Neurobiology, Yuri I. Arshavsky from UCSD writes about the epistemological dualism that exists in modern neuroscience. basically, Arshavsky claims that there is a covert dualism in the way that neuroscientists are treating mind-related topics, especially the study of “consciousness”. Indeed, as he claims:

This covert dualism seems to be rooted in the main paradigm of neuroscience that suggests that cognitive functions, such as language production and comprehension, face recognition, declarative memory, emotions, etc., are performed by neural networks consisting of simple elements.

This might initially sound a bit strange. Is not cognitive functions such as face perception due to operational simple elements? Face perception as such is a combination of many simple processes that operate in unison. So what is Arshavsky proposing? Indeed he suggests the existence of a certain kind of brain cells:

(The) performance of cognitive functions is based on complex cooperative activity of “complex” neurons that are carriers of “elementary cognition.” The uniqueness of human cognitive functions, which has a genetic basis, is determined by the specificity of genes expressed by these “complex” neurons. The main goal of the review is to show that the identification of the genes implicated in cognitive functions and the understanding of a functional role of their products is a possible way to overcome covert dualism in neuroscience.

So there should exist a subset of neurons that integrate information from a variety of input. This sounds strange, since all neurons integrate inputs from thousands of inputs, many from a large variety of inputs. So what are complex neurons? Here, we are told that:

(…) neural networks involved in performing cognitive functions are formed not by simple neurons whose function is limited to the generation of electrical potentials and transmission of signals to other neurons, but by complex neurons that can be regarded as carriers of “elementary” cognition. The performance of cognitive functions is based on the cooperative activity of this type of complex neurons.

In this way, complex neurons seem to be integrative neurons, i.e. cells that integrate information from a variety of processes. This could include the multi-modal neurons found in the functional sub-structures of the medial temporal lobe, such as the hippocampus, perirhinal, entorhinal and temporopolar cortex. But would it not mean the colour processing nodes in the visual cortex? Which IMO leads us back to a basic question: what is a functional unit in the brain. yes, the neuron is a basic building block of information processing in the brain. But what is special about language, memory and so forth in the brain?

It is possible that Arshavsky is not radical enough: what we should seek out is to avoid using generalistic and folk-psychological concepts in the first place. We should possibly not study “language”, “memory” or “consciousness”, since these concepts will always allude to fundamental assumptions of “language-ness”, “memory-ness” and “consciousness-ness”, IOW that there is something more to explain after we have found out how the brain produces what we recognize and label a cognitive function.

Maybe neuroscientists are not using a poor strategy after all? Maybe ignoring the past history of philosophy of mind is the best solution. I’m not sure (nor am I sure that I represent Arshavsky’s view properly). But how we choose to label a cognitive function depend on our past historical influence and learning, as well as our current approach.

-Thomas

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