Whole Brain Teaching...?

Oh dear. The Kansas City Star asks: Teachers learn ways to keep students' attention, but are brain claims valid?

Probably not. Unless you're buying a brain scanner or a plush brain, product 'brain claims' are generally just marketing patter. But let's see.

When Chris Biffle called out the word "Class!" Wednesday morning at Walsh University, 450 teachers and administrators yelled back, "Yes!"

"Class class?" he said. "Yes! Yes!" they replied.

"Classity classity," he said.
"Yessity yessity," they chanted back.

Biffle, one of the co-founders of Southern California-based Whole Brain Teaching LLC, is leading a two-day conference about his method. He calls the technique "Class-Yes." Whole Brain Teaching's website says "Class Yes" activates the prefrontal cortex of the brain and "readies students for instruction"...

Whole Brain Teaching reminds me of Brain Gym, a notorious bit of British neuro-nonsense from a few years ago. According to the WBT research page, they have over 50,000 registered teachers and 2 million views of their videos. This also informs us that:

Class-Yes: Our primary attention-getter activates the prefrontal cortex, often called the CEO of the brain... Little if any learning can take place if the prefrontal cortex is not engaged.

while even "mirror neurons" have a role to play:

Mirror: Many brain scientists believe that we learn by mirroring the gestures and activities of others. They have identified mirror neurons scattered throughout the brain that are activated by mimicking the behavior we observe. Our own experience in WBT classroom indicates that when a class mirrors our gestures and, when appropriate, repeats our words, a powerful learning bond is created between students and teachers.

There are lots of problems here, but here's the most fundamental: the theory behind the system seems to be that activating particular parts of students' brains, through a special task, will help them to use that part of their brain when it comes to the actual lesson a few minutes later. But I know of no evidence that bits of the brain "warm up" like that; if anything they're more likely to "wear out" through lack of energy and nutrients although I don't think that's likely either.

If such warm-ups did work, your best bet for activating your primary visual cortex, for example, would be to stare at a rapidly-changing pattern of random colors for a few minutes. That wouldn't improve your vision. It would just give you a headache.

In fact, why not just activate your entire noggin, pharmacologically? Just grab some pentylenetetrazol - a drug that blocks inhibitory signals between brain cells. Snort a few lines of that and if you survive the resulting seizure, go and learn something and see if you're really good at it.

I'm not saying Whole Brain Teaching is useless, I'm not saying anything about the method itself, but the "brain" claims are misleading. Many of the things they recommend are teaching aids and classroom exercises, and no doubt those are helpful. Plus, psychological factors like teacher motivation, student engagement, and a positive atmosphere are vital in learning, and it doesn't matter if you achieve them through neurosciencey gimmicks, they're still going to help... well, except in terms of educating people to spot neurosciencey gimmicks.

But that's teaching. It's nothing to do with the brain.

The Racist Brain?

Is the human brain... a racist?

There are some worrying indications that it could be. After all, the cerebrum is largely composed of so-called "white" matter, and the only black area is a little 'ghetto' at the bottom called, shockingly, the substantia nigra...!

Seriously though. There's a paper just out in Nature Neuroscience from Kubota et al that looks at The Neuroscience Of Race. It's a fine review as far as it goes, but to me at least, it really shows up the limits of contemporary neuroscience.

We are told that

A network of interacting brain regions is important in the unintentional, implicit expression of racial attitudes and its control. On the basis of the overlap in the neural circuitry of race, emotion and decision-making, we speculate as to how this emerging research might inform how we recognize and respond to variations in race and its influence on unintended race-based attitudes and decisions.

So there have been studies investigating which bits of American's brains activate in response to looking at photos of black people vs. white people. It emerges that "a network of interacting brain regions" light up. But so what?

Sure, the brain reacts differently to seeing people of different races. Of course it does - it reacts differently to everything, so long as we can perceive a difference; that's how we perceive a difference. And of course race, a deeply emotive issue in American politics and culture, activates 'emotional' parts of the brain - that's how it's emotive.

The included studies all scanned Americans and (presumably) mostly college students. Now most American college students are not active racists, and indeed I'd imagine that their emotional brains are more likely to be worrying self-referentially about racism than about the actual race of the stimuli. No-one seems to have scanned card-carrying members of the KKK. Furthermore, "race" in these studies almost always means "blackness". What about Latinos, Asians?

So what have we learned?

I don't think we've learned much about race. "Race" after all is a confused mixture of emotions, attitudes and beliefs. These differ greatly from person to person, and even the same individual may experience conflicting feelings in different contexts. Kubota et al note this and say that it may explain the mixed findings (black faces activate the amygdala more than white in some studies, not in others) but I'd have said that in this case, only inconsistent results are credible.

What does it tell us about the brain? I'd say not much. The authors weave a neat little narrative - in response to seeing black faces, the amygdala and other emotional areas activate as a negative emotional response; the ACC then detects this racist response and sees that it's unacceptable, and the DLPFC then suppresses it like a parent hurriedly interrupting a young child who's making a faux pas.

But all the elements of this story - the automatic, emotional amygdala, the supervisory DLPFC - are borrowed from other neuroscience studies so at best the race literature confirms these theories but it doesn't even really do that, because there are many other possible interpretations.

I'd say that we need to know much more in terms of the 'basic' neuroscience of emotion, attitudes and beliefs because we can tackle the hornet's nest of race in the brain.

Kubota JT, Banaji MR, and Phelps EA (2012). The neuroscience of race. Nature neuroscience, 15 (7), 940-8 PMID: 22735516

This Is Your Brain On Ethics - Really

A new study published in Social Cognitive and Affective Neuroscience offers a look at the neural correlates of ethical decision making: Differential Neural Circuitry and Self-Interest in Real versus Hypothetical Moral Decisions

There have been quite a few studies using neuroimaging to measure activations associated with tackling hypothetical moral dilemmas but what makes the new paper interesting is that the participants were faced with a real moral choice. Well, mostly real.

The task was called "Your Pain, My Gain". The participants were put in the MRI scanner and given £20 at the start of the experiment. Then they could spend some of the money to help save another person from getting electric shocks. The more they spent, the less severe the pain administered to the victim. Video footage of the victim receiving the shocks was then played to the decider, and the process repeated.

Selfish people could choose to keep more of the cash, if they could handle the guilt of knowing that they were shocking their poor victim. At the end of the study, the remaining sum was multiplied by a random factor of between 1 and 10, meaning that there was, potentially, £200 at stake - a serious amount of money.

Actually, the task was a sham - as these experiments usually are. All of the 'shock' videos were pre-recorded, there was no victim, so the decision to keep the money had no effect. But the experimenters tried to make it as believable as possible (out of 18 volunteers, 4 were skeptical, and they were excluded).

There was also a comparison task, which was the same idea, but the participants were told it was purely hypothetical, and would have no real consequences.

The fMRI data showed (although note, some of these did not use multiple comparisons correction) that both the 'real' and hypothetical tasks activated a 'shared moral network':

Although both the hypothetical and the real tasks also led to different patterns of individual activation as well - the authors write:

hypothetical moral decisions mapped closely onto the imagination network, while real moral decisions elicited activity in the bilateral amygdala and anterior cingulate—areas essential for social and affective processes.

Hmm. To be honest the results are a bit messy but the method is extremely interesting. I've written before about the need to keep it real when it comes to stimuli in fMRI experiments so this is important: hypothetical moral dilemmas are no substitute for the real thing. Personally I'm holding out for someone to replicate the Milgram experiment in the MRI scanner although I'm not sure anyone would get ethical approval for that nowadays...

Feldmanhall O, Dalgleish T, Thompson R, Evans D, Schweizer S, and Mobbs D (2012). Differential Neural Circuitry and Self-Interest in Real versus Hypothetical Moral Decisions. Social cognitive and affective neuroscience PMID: 22711879

Neuroplasticity Revisited

A fascinating case report details a remarkable recovery from serious brain injury: Characterization of recovery and neuropsychological consequences of orbitofrontal lesion.

The patient "M. S." was a previously healthy 29 year old Israeli graduate student who suffered injuries in a terrorist attack. As the MRI scans above show, she lost large parts of her orbitofrontal cortex and ventromedial prefrontal cortex, although the left side was only partially affected. She also lost her right eye.

These areas are known to be involved in emotion and decision making. Her lesions are somewhat similar to those suffered by the famous Phineas Gage, and as we'll see, her symptoms were too - but only temporarily.

One year after the injury...

M.S.’s complaints included a sense of general fatigue, loss of taste and smell, difficulty concentrating and emotional changes including irritability, lability, depression and social isolation. She reported failing to make new social contacts, having lost most of her old friends, and a diminished need for social relationships.

M.S. reported that family and friends commented on her change from a quiet and pleasant person to a rude, annoying, uninhibited, and unstoppable talkative person following the injury... M.S. had become apathetic, without a sense of time, and with no plans for the future.

On examination, M.S. was fully cooperative. She had difficulty concentrating and required frequent breaks. She appeared euphoric, laughed frequently and inappropriately, talked too much,made inappropriate remarks and jokes, yawned loudly... M.S. found it difficult to sit still and showed utilization behavior, continuously fidgeting and touching objects on the table. She had a tendency to continue performing tasks after completion was stated.

These personality and mood changes are reminisicent of those Phineas Gage suffered. Strangely, she scored 33 on the self-report depression scale the BDI, which corresponds to "severe depression", but from the description she doesn't sound depressed in the normal sense. These scales were not designed for people with brain lesions. Her cognitive function and memory was mostly normal but with clear impairments on some tests.

Anyway, that was after 1 year, and if that were the end it would be a rather sad story, but there's a happy ending. After this she got psychotherapy and rehabilitation treatment. 7 years later she had a follow-up assessment and she was much improved.

Her mood, attention-span and so forth were reported as normal. She struggled with her graduate studies, finding them more difficult than before the injury, and had eventually quit them, but she'd got a new job. She had recently got married.

Her performance on neuropsychological tests designed to measure prefrontal cortex damage was mostly normal, and she did much better on the ones that she used to be impaired on. She still did poorly on the Iowa Gambling Task, which is very sensitive vmPFC damage.

Overall, though, she had made a "magnificent" recovery despite losing a large chunk of her brain. I've previously been skeptical of some of the stronger claims of neuroplasticity or "brain remodelling", but some parts of the brain are more plastic than others and the prefrontal cortex seems to be one of the most flexible.

Fisher T, Shamay-Tsoory SG, Eran A, & Aharon-Peretz J (2011). Characterization of recovery and neuropsychological consequences of orbitofrontal lesion: A case study. Neurocase, 17 (3), 285-93 PMID: 21667397

The Brain's Sarcasm Centre? Wow, That's Really Useful

A team of Japanese scientists have found the most sarcastic part of the brain known to date. They also found the metaphor centre of the brain and, well, it's kind of like a pair of glasses.

The paper is Distinction between the literal and intended meanings of sentences and it's brought to you by Uchiyama et al. They took 20 people and used fMRI to record neural activity while the volunteers read 4 kinds of statements:

• Literally true
• Nonsensical
• Sarcastic
• Metaphorical

The neat thing was that the statements themselves were the same in each case. The preceding context determined how they were to be interpreted. So for example, the statement "It was bone-breaking" was literally true when it formed part of a story about someone in hospital describing an accident; it was metaphorical in the context of someone describing how hard it was to do something difficult; and it was nonsensical if the context was completely unrelated ("He went to the bar and ordered:...").

Here's what they found. Compared to the literally-true and the nonsensical statements, which were a control condition, metaphorical statements activated the head of the caudate nucleus, the thalamus, and an area of the medial PFC they dub the "arMPFC" but which other people might call the pgACC or something even more exotic; names get a bit vague in the frontal lobe.


The caudate nucleus, as I said, looks like a pair of glasses. Except without the nose bit. The area activated by metaphors was the "lenses". Kind of.

Sarcasm however activated the same mPFC region, but not the caudate:

Sarcasm also activated the amygdala.

*

So what? This is a very nice fMRI study. 20 people is a lot, the task was well-designed and the overlap of the mPFC blobs in the sarcasm-vs-control and the metaphor-vs-control tasks was impressive. There's clearly something going on there in both cases, relative to just reading literal statements. Something's going on in the caudate and thalamus with metaphor but not sarcasm, too.

But what can this kind of study tell us about the brain? They've localized something-about-metaphor to the caudate nucleus, but what is it, and what does the caudate actually do to make that thing happen?

The authors offer a suggestion - the caudate is involved in "searching for the meaning" of the metaphorical statement in order to link it to the context, and work out what the metaphor is getting at. This isn't required for sarcasm because there's only one, literal, meaning - it's just reversed, the speaker actually thinks the exact opposite. Whereas with both sarcasm and metaphor you need to attribute intentions (mentalizing or "Theory of Mind").

That's as plausible an account as any but the problem is that we have no way of knowing, at least not from imaging studies, if it's true or not. As I said this is not the fault of this study but rather an inherent challenge for the whole enterprise. The problem is - switch on your caudate, metaphor coming up - a lot like the challenge facing biology in the aftermath of the Human Genome Project.

The HGP mapped the human genome, and like any map it told us where stuff is, in this case where genes are on chromosomes. You can browse it here. But by itself this didn't tell us anything about biology. We still have to work out what most of these genes actually do; and then we have to work out how they interact; and they we have to work out how those interactions interact with other genes and the environment...

Genomics people call this, broadly speaking, "annotating" the genome, although this is not perhaps an ideal term because it's not merely scribbling notes in the margins, it's the key to understanding. Without annotation, the genome's just a big list.

fMRI is building up a kind of human localization map, a blobome if you will, but by itself this doesn't really tell us much; other tools are required.

Uchiyama HT, Saito DN, Tanabe HC, Harada T, Seki A, Ohno K, Koeda T, & Sadato N (2011). Distinction between the literal and intended meanings of sentences: A functional magnetic resonance imaging study of metaphor and sarcasm. Cortex; a journal devoted to the study of the nervous system and behavior PMID: 21333979

Absolutely Confabulous

Confabulation is a striking symptom of some kinds of brain damage. Patients tell often fantastic stories about things that have happened to them, or that are going on now. It's a classic sign of Korsakoff's syndrome, a disorder caused by vitamin B1 deficiency due to chronic alcoholism.

Korsakoff's was memorably illustrated on House (Season 1 Episode 10, to be exact). Here's a clip; unfortunately, it's overdubbed in Russian, but you can hear the original if you pay attention.

Why does confabulation happen? An influential theory is that confabulation is caused by a failure to filter out irrelevant memories. Suppose I ask you to tell me what happened yesterday. As you reply, yesterday's memories will probably trigger all kinds of associations with other memories, but you'll able to recognize those as irrelevant: that wasn't yesterday, that was last week.

A confabulating patient can't do that, this theory says, so they end up with a huge jumble of memories; the confabulated stories are an attempt to make some sense of this mess. See above for my attempt to confabulate a story linking the three random concepts of a cat, a fire engine and a chair.

Now British neuroscientists Turner, Cipolotti and Shallice argue that this is only part of the truth: Spontaneous confabulation, temporal context confusion and reality monitoring. They discuss three patients, all of whom began to confabulate after suffering ruptured aneurysms of the anterior communicating artery, which destroyed parts of their ventromedial prefrontal cortex.

The patient's stories are tragic, although we can take solace in the fact that they presumably don't know that. The confabulations ranged from the mildly odd:

Patient HS was a 59-year-old man admitted after being found disoriented in the street. [he] had undergone clipping of an ACoA aneurysm 25 years previously. He had been left with a profound confusional state, memory impairment, and confabulation. As a result, HS had been unable to return to work and had spent at least part of the intervening period homeless...

He... continued to produce spontaneous confabulations involving temporal distortions (believing that he had undergone surgery only 18 months previously) and other source memory distortions (confusing memories of interactions with the examiner with interactions with other patients).

To the surreal:

GN was disoriented to place, situation, and time and produced consistent confabulations, for example, believing that the year was 1972 and that he was in a hospital in America after being shot. He regularly produced markedly bizarre confabulations, for example, reporting that he had attended a party the night before and met a woman with a bee’s head. He frequently attempted
to act upon his mistaken beliefs, for example, attempting to leave the hospital to attend meetings.

Anyway, in order to try to discover the mechanism of confabulation, they gave the patients some memory tests. The results were clear: the confabulating patients had no problems remembering stuff, but were unable to tell where they remembered it from.

For example, in one task, the subjects were shown a series of pictures, some of which appeared only once, and some of which were repeated. They had to say which ones were repeats.

The patients did normally the first time they did this task, but when they did the test again, this time with a different subset of pictures repeated, they ran into problems, saying pictures that appeared only once during the session were repeats. They were unable to tell the difference between repeats within the session and repeats from previous sessions. This replicates an earlier study of other confabulators.

But Turner et al found that this lack of awareness for the source of information, wasn't just limited to when things happened. The confabulating patients were also unable to tell the difference between things they'd actually heard, and things they'd only imagined.

Subjects were read a list of 15 words, and also told to silently imagine 15 other words (e.g. "imagine a fruit beginning with A" - apple). They were later asked to remember the words and to say whether they were heard or just imagined. Patients did well on the task except that they wrongly said that they'd actually heard many of the imagined words.

The authors conclude that confabulation is caused by a failure to recognize the source of memories, not just in terms of time, but in terms of whether they were real or fantasy. For a confabulator, all memories are of equal importance. Why this happens as a result of damage to certain parts of the brain remains, however, a mystery.

Turner MS, Cipolotti L, & Shallice T (2010). Spontaneous confabulation, temporal context confusion and reality monitoring: A study of three patients with anterior communicating artery aneurysms. Journal of the International Neuropsychological Society : JINS, 1-11 PMID: 20961471

The Prefrontal Cortex Is Holistic

The question of whether the brain is "modular" - whether different parts do different things - has been a neuroscientific talking point since the days of the phrenologists.

They were the guys who believed that, not only were there modules, but that you could tell how big they were by measuring the shape of someone's skull, and so learn about their personality.

Phrenology made modules unfashionable for a while, but today they're back, and most of fMRI consists in trying to find areas of the brain that do different stuff, but in a new paper Wilson et al argue against taking modularism too far: Functional localization within the prefrontal cortex: missing the forest for the trees?

Their focus is the prefrontal cortex (PFC), a large chunk of the front of the brain which is bigger in humans than in any other species. The PFC is routinely subdivided into segments, each with (presumably) a different function. So we have the "emotional" vmPFC, the "memory" dlPFC, the "pleasure" OFC, etc.

Wilson et al don't dispute that there are some variations in function between different bits of the PFC, but they say that in all the excitement over localization, we may have overlooked the role of the PFC as a whole.

They discuss evidence from monkeys with PFC damage (or lesions which disconnect it from the rest of the brain). Damage to the entire PFC, they say, leaves monkeys completely unable to perform tasks which require storing concepts over time. For example, they can't learn that whenever they see, say, a red button, they ought to press it to get food. But if part of the PFC is intact, and it doesn't matter which part, monkeys can do this with only minor problems.

However, the PFC isn't required for all tasks. If the task only involves information which is all presented at once, the lesioned monkeys are OK. So they could learn, given a big panel covered in red buttons, to push the buttons to get food, because the buttons are all there simultaneously.

Hence the data from these tasks are congruent with the notion that [the PFC] is only crucial in memory during tasks requiring the processing of temporally complex events. This can be defined as an event to be learned about, in which information that is crucial to that learning is presented at more than one point in time, or that can only be interpreted with respect to a preceding event.

They say that evidence from human neuroimaging studies supports this view.

A meta-analysis has shown consistent recruitment of the same network of regions in the PFC across a range of cognitive demands. The authors argue that this supports specialization of function within the PFC, but of an unexpected nature, namely ‘a specific frontal-lobe network that is consistently recruited for solution of diverse cognitive problems’. The idea that large and different regions of the PFC are recruited by any task at hand supports our argument that the function of the PFC as a whole exceeds the sum of the functions of its subcomponents.

This all has echoes of Karl Lashley, an early neuroscientist (died 1958) who proposed the theory of "mass action" - that the whole cortex contributes to behaviour, rather than each part doing different things ("modularism").

Jerry Fodor, whose classic book The Modularity of Mind (1983) helped to rehabilitate modularism from its reputation as "phrenological", was also an advocate of this view - within limits.

Fodor argued that some brain systems, like vision, hearing and language, were cortical modules, but that above this, there was a non-modular system which was the basis for thought, intelligence and decision making. If I remember correctly, he didn't explicitly say that the prefrontal cortex was this system, but I'm sure he'd have no objections to Wilson et al's account.

Wilson CR, Gaffan D, Browning PG, & Baxter MG (2010). Functional localization within the prefrontal cortex: missing the forest for the trees? Trends in neurosciences PMID: 20864190

Sociopathic Dementia

Frontotemporal dementia (FTD) is a tragic, but scientifically fascinating, disease.


FTD only accounts for a small fraction of dementias in total (estimates range from 2% to 10%), but it typically strikes people aged in their 50s or 60s, i.e. much earlier than the average for Alzheimer's disease, the most common cause of dementia. As a result, FTD accounts for a large proportion of early-onset cases.

The symptoms are different to those of Alzheimer's, at least in the early stages. Memory problems and confusion are not prominent. Nor are hallucinations and delusions, which are seen in 20% of Alzheimer's, but only 2% of FTD.

Instead, patients often present with language problems - either forgetting what words mean, starting with uncommon words and progressing to easy ones ("semantic dementia"), or losing the ability to articulate speech ("nonfluent aphasia").

But the most disturbing effects are behavioural and personality changes. These are not seen in all cases, but in some people (the "behavioural variant"), they are the main symptom. Patients may begin to act entirely out of character, including criminal acts.

Aggressive behaviour is also sometimes seen in Alzheimer's, but it's usually associated with confusion or hallucinations: people "don't know what they're doing". In FTD, patients can commit serious crimes even though their cognitive function is pretty much intact: they do know what they're doing.

Mario F. Mendez discusses this in a new paper, The Unique Predisposition to Criminal Violations in Frontotemporal Dementia, and asks whether people who commit crimes while suffering from FTD should be considered legally responsible for their apparantly "sociopathic" actions. He presents 4 case histories.

Patient 1: A left-handed male in his sixties began stalking and attempting to molest children for the first time in his life. He followed children home from school and tried to touch them... On another occasion, he stood at the foot of a pool and stared at the children for a prolonged time.

When he exposed himself to his neighbor’s children, he was arrested. The patient did not deny his actions, could describe them in detail, and endorsed them as wrong and harmful. Despite this, he stated that he did not feel that he was causing harm at the time of his acts.

The patient’s personality had deteriorated over the prior four years, with decreased concern for others, disinhibition, and compulsive hoarding. He had caused disturbances at work, such as intruding into others’ conversations and walking into others’ offices... constantly pilfering... hiding money.... In addition, he ate indiscriminately, even going through waste containers and eating garbage. He stopped showering and wore the same clothes every day.

Neuropsychological testing and brain scans suggested early FTD, and his mother had reportedly suffered unspecified dementia; FTD is often genetic. He was not prosecuted. This case has a lot in common with the man who became a pedophile after surgery for a brain tumour: not just the pedophilia, but other symptoms like compulsive hoarding, over-eating, etc.

Patient 4: A right-handed man in his early fifties had a hit-and-run accident and left the scene without concern. He had struck a van with passengers but kept driving. The police stopped him a short distance away from the scene, and he did not deny his action.

Leaving the scene of an accident was not characteristic of his premorbid personality, yet he had had several recent traffic violations... He could recall and describe the accident, knew that it was wrong to leave the scene, but did not feel the need to stop at the time.

Over the prior two years, the patient’s pervasive behavior had significantly changed. He had become disengaged and emotionally detached; for example, he did not react to the death of his mother...

He was no longer embarrassed over passing gas or belching in public or appearing partially clothed in front of others. The patient had a tendency toward hyperorality, especially for peanuts, and had a decline in personal hygiene. Other aspects of the history included dysarthria and a recent tendency to choke on liquids.

This patient showed clear signs of motor neuron disease, which occurs in up to 15% of FTD cases. He died, as a result of the progression of the motor neuron disease, one year later, after developing other symptoms of FTD. His death meant he could not be tried for the hit-and-run.

Mendez notes that legally, these patients would probably not qualify for the "insanity defence". Under the British M'Naghten Rules, also adopted by the USA, the defendant is only eligible if they were

labouring under such a defect of reason, from disease of the mind, as not to know the nature and quality of the act he was doing; or, if he did know it, that he did not know he was doing what was wrong.

These patients do not fit that bill.

Finally, why does FTD cause sociopathic behaviour? Mendez says that it is because it involves degeneration of the vmPFC, linking FTD patients to the classic case of Phineas Gage whose vmPFC was destroyed by a flying iron rod. But Gage, while he did show personality changes, actually managed to function fairly well in society.

So temporal lobe degeneration probably also contributes to the FTD behavioural syndrome, especially since many of the symptoms (like compulsive eating) are seen in monkeys with temporal lobe lesions.

Mendez MF (2010). The unique predisposition to criminal violations in frontotemporal dementia. The journal of the American Academy of Psychiatry and the Law, 38 (3), 318-23 PMID: 20852216

Is Your Brain A Communist?

Capitalists beware. No less a journal than Nature has just published a paper proving conclusively that the human brain is a Communist, and that it's plotting the overthrow of the bourgeois order and its replacement by the revolutionary Dictatorship of the Proletariat even as we speak.

Kind of. The article, Neural evidence for inequality-averse social preferences, doesn't mention the C word, but it does claim to have found evidence that people's brains display more egalitarianism than people themselves admit to.

Tricomi et al took 20 pairs of men. At the start of the study, both men got a $30 payment, but one member of each pair was then randomly chosen to get a $50 bonus. Thus, one guy was "rich", while the other was "poor". Both men then had fMRI scans, during which they were offered various sums of money and saw their partner being offered money too. They rated how "appealing" these money transfers were on a 10 point scale.

What happened? Unsurprisingly both "rich" and "poor" said that they were pleased at the prospect of getting more cash for themselves, the poor somewhat more so, but people also had opinions about payments to the other guy:

the low-pay group disliked falling farther behind the high-pay group (‘disadvantageous inequality aversion’), because they rated positive transfers to the high-pay participants negatively, even though these transfers had no effect on their own earnings. Conversely, the high-pay group seemed to value transfers [to the poor person] that closed the gap between their earnings and those of the low-pay group (‘advantageous inequality aversion’)

What about the brain? When people received money for themselves, activity in the ventromedial prefrontal cortex (vmPFC) and the ventral striatum correlated with the size of their gain.

However, when presented with a payment to the other person, these areas seemed to be rather egalitarian. Activity rose in rich people when their poor colleagues got money. In fact, it was greater in that case than when they got money themselves, which means the "rich" people's neural activity was more egalitarian than their subjective ratings were. Whereas in "poor" people, the vmPFC and the ventral striatum only responded to getting money, not to seeing the rich getting even richer.


The authors conclude that this

indicates that basic reward structures in the brain may reflect even stronger equity considerations than is necessarily expressed or acted on at the behavioural level... Our results provide direct neurobiological evidence in support of the existence of inequality-averse social preferences in the human brain.

Notice that this is essentially a claim about psychology, not neuroscience, even though the authors used neuroimaging in this study. They started out by assuming some neuroscience - in this case, that activity in the vmPFC and the ventral striatum indicates reward i.e. pleasure or liking - and then used this to investigate psychology, in this case, the idea that people value equality per se, as opposed to the alternative idea, that "dislike for unequal outcomes could also be explained by concerns for social image or reciprocity, which do not require a direct aversion towards inequality."

This is known as reverse inference, i.e. inference from data about the brain to theories about the mind. It's very common in neuroimaging papers - we've all done it - but it is problematic. In this case, the problem is that the argument relies on the idea that activity in the vmPFC and ventral striatum is evidence for liking.

But while there's certainly plenty of evidence that these areas are activated by reward, and the authors confirmed that activity here correlated with monetary gain, that doesn't mean that they only respond to reward. They could also respond to other things. For example, there's evidence that the vmPFC is also activated by looking at angry and sad faces.

Or to put it another way: seeing someone you find attractive makes your pupils dilate. If you were to be confronted by a lion, your pupils would dilate. Fortunately, that doesn't mean you find lions attractive - because fear also causes pupil dilation.

So while Tricomi et al argue that people, or brains, like equality, on the basis of these results, I remain to be fully convinced. As Russell Poldrack noted in 2006

caution should be exercised in the use of reverse inference... In my opinion, reverse inference should be viewed as another tool (albeit an imperfect one) with which to advance our understanding of the mind and brain. In particular, reverse inferences can suggest novel hypotheses that can then be tested in subsequent experiments.

Tricomi E, Rangel A, Camerer CF, & O'Doherty JP (2010). Neural evidence for inequality-averse social preferences. Nature, 463 (7284), 1089-91 PMID: 20182511

Deep Brain Stimulation for Depressed Rats

Deep-brain stimulation (DBS) is probably the most exciting emerging treatment in psychiatry. DBS is the use of high-frequency electrical current to alter the function of specific areas of the brain. Originally developed for Parkinson's disease, over the past five years DBS has been used experimentally in severe clinical depression, OCD, Tourette's syndrome, alcoholism, and more.

Reports of the effects have frequently been remarkable, but there have been few scientifically rigorous studies, and the number of psychiatric patients treated to date is just dozens. So the true usefulness of the technique is unclear. How DBS works is also a mystery. Even the most basic questions - such as whether high-frequency stimulation switches the brain "on" or "off" - are still being debated.

Recent data from rodents sheds some important light on the issue: Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats. The authors took rats, and implanted DBS electrodes in the infralimbic cortex. This area is part of the vmPFC. It's believed to be the rat equivalent of the human region BA25, the subgenual cingulate cortex, which is the most common target for DBS in depression. The current settings (100 microA, 130 Hz, 90 microsec) were chosen to be similar to the ones used in humans.

In a standard rat model of depression, the forced-swim test, infralimbic DBS exerted antidepressant-like effects. DBS was equally as effective as imipramine, a potent antidepressant, in terms of reducing "depression-like" behaviours, namely immobility.

This is not all that surprising. Almost everything which treats depression in humans also reduces immobility in this test (along with few things which don't treat it). Much more interesting is what did and did not block the effects of DBS in these rats.

First off, DBS worked even when the rat's infralimbic cortex had been destroyed by the toxin ibotenic acid. This strongly suggests that DBS does not work simply by activating the infralimbic cortex, even though this is where the electrodes were implanted.

Crucially, infralimbic lesions did not have an antidepressant effect per se, which also rules out the theory that DBS works by inactivating this region. (Infralimbic lesions produced by other methods did have a mild antidepressant effect, but it was smaller than the effect of DBS. This may still be important, however.)

What did block the effects of DBS was the depletion of serotonin (5HT). Serotonin is known to its friends as the brain's "happy chemical", although it's a bit more complicated than that. Most antidepressants target serotonin. And rats whose serotonin systems had been lesioned got no benefit from DBS in this study.

So this suggests that DBS might work by affecting serotonin, and indeed, DBS turned out to greatly increase serotonin release, even in a distant part of the brain (the hippocampus). Interestingly this lasted for nearly two hours after the electrodes were switched off.

Depletion of another neurotransmitter, noradrenaline, did not alter the effects of DBS.

Overall, it seems that infralimbic DBS works by increasing serotonin release, but that this is not because it activates or inactivates the infralimbic cortex itself. Rather, nearby structures must be involved. The most likely explanation is that DBS affects nearby white-matter tracts carrying signals between other areas of the brain; the infralimbic cortex might just happen to be "by the roadside". Many researchers believe that this is how DBS works in humans, but this is the first hard evidence for this.

Of course, evidence from rats is never all that hard when it comes to human mental illness. We need to know whether the same thing is true in people. As luck would have it, you can temporarily reduce human serotonin levels with a technique called acute tryptophan depletion This reverses the effects of antidepressants in many people. If this rat data is right, it should also temporarily reverse the benefits of DBS. Someone should do this experiment as soon as possible - I'd like to do it myself, but I'm British, and all the DBS research happens in America. Bah, humbug, old bean.

There's a couple of others things to note here. In other behavioural tests, infralimbic DBS also had antidepressant-like effects: it seemed to reduce anxiety, and it made rats more resistant to the stress of having electrical shocks (although only slightly.) Finally, DBS in another region, the striatum, had no antidepressant effect at all. That's a bit odd because DBS of the striatum does seem to treat depression in humans - but the part of the striatum targeted here, the caudate-putamen, is quite separate to the one targeted in human depression, the nucleus accumbens.

Hamani, C., Diwan, M., Macedo, C., Brandão, M., Shumake, J., Gonzalez-Lima, F., Raymond, R., Lozano, A., Fletcher, P., & Nobrega, J. (2009). Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats Biological Psychiatry DOI: 10.1016/j.biopsych.2009.08.025

The Man With Half A Brain

A lovely new paper reports in fascinating detail on a man who lost a uniquely large portion of his brain: Bilateral limbic system destruction in man.

The authors, Feinstein et al from Iowa City, have studied the patient, "Roger", for 14 years. Roger was born in 1952, and lived a fairly uneventful life until he contracted herpes simplex encephalitis (HSE) at the age of 28.

HSE is an extremely rare condition in which the herpes virus infects the central nervous system. Untreated, it is fatal in 70% of people. Survivors suffer varying degrees of neurological damage. Roger suffered more than most - his is the worst case of herpes encephalitis damage among patients currently alive, and there are only three recorded cases of similarly extensive lesions. Roger lost almost his entire "limbic system":

The amount of destroyed neural tissue is extensive and includes bilateral damage to core limbic and paralimbic regions, including the hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right hemisphere is more extensively affected than the left, although the lesions are largely bilateral.

"Limbic system" is an old, vague, but still popular term for a collection of brain structures located deep in the centre of the brain (but not to be confused with the basal ganglia). It's often thought of as the "primitive", "emotional" part of the brain, and there is some truth to this. Roger's limbic system was profoundly damaged on both sides; on the right side, the lesion included the whole temporal lobe and most of the ventral prefrontal cortex as well.

What happened to Roger's mind when his brain suffered such injury? In many ways, remarkably little. His only major impairment is profound anterograde amnesia: he is unable to remember anything that has happened since the infection, which was 28 years ago.

For Roger, not much has changed over the past 28 years. He has virtually no episodic memories for any events that have transpired over the past three decades. For example, he has no recollection of 9/11, and when shown pictures of the planes crashing into the World Trade Center he often responds with bewilderment, speculating that Russia must be attacking America.

This is, obviously, a disabling deficit: Roger cannot lead a normal life. But in other areas of mental functioning, he is quite normal. His IQ is above average; his speech and language abilities are excellent; his vision and hearing are normal, although he has no sense of taste or smell. His short term (working) memory, attention, and reasoning abilities are unimpaired. His motor abilities are fine - he is reportedly an excellent bowler - and he is able to improve motor skills through practice. And his recall of things which happened before the infection is largely preserved, although the few years just before the infection are partially lost.

Fascinatingly, Roger's personality and emotional life seems to have been changed by the infection as well, but in a rather fortunate way -

Roger appears remarkably unconcerned by his condition. He hardly ever complains and, in general, shows little worry for anything in life. Both of his parents and his sister fervently claim that “Roger is always happy,” an observation that is consistent with our own impression. Moreover, based on his family’s report, Roger is paradoxically happier now than he was before his brain damage. ... His premorbid disposition of being somewhat reserved and introverted has shifted to being outgoing and extroverted...

Most conversations with Roger involve animated speech that is replete with prosody, gesture, and, often times, laughing. He readily displays signs of positive emotion including happiness, amusement, interest, and excitement. As previously noted, Roger’s positive mood has remained essentially unchanged over nearly three decades.

His only other reported quirks are an insatiable appetite, and a habit of collecting and holding onto everyday items.

What does all this mean? Neuroscientists will find little about the case surprising. No textbooks are going to have to be rewritten. Roger's inability to form new memories, combined with preserved memory of events up to the few years before the damage, is similar to that seen in other cases of bilateral hippocampus damage. The most famous being the sadly recently deceased patient "H. M.", but there have been plenty of others. The hippocampus seems to be necessarily for forming new long term memories, but the memories themselves are stored elsewhere.

Roger's happy-go-lucky disposition is also not too unexpected, given that he suffered bilateral damage to the ventromedial prefrontal cortex (vmPFC). Last year I wrote about a study from the same Iowa team finding that damage to this area seems to protect against depression. And this is the same region which was targeted by the infamous prefrontal lobotomies of the 40s and 50s - which, for all their ethical shortcomings, sometimes did seem to relieve people of mental anguish.

For me, Roger provides two main lessons, both rather satisfying ones. Firstly, even after losing large parts of the brain, life goes on. The brain is modular, and we can live without many of the modules. And secondly, if our emotional circuitry is damaged, we generally feel better, rather than worse. To put it another way, perhaps, happiness is our default state, and emotions just have a habit of getting in the way.

Feinstein, J., Rudrauf, D., Khalsa, S., Cassell, M., Bruss, J., Grabowski, T., & Tranel, D. (2009). Bilateral limbic system destruction in man Journal of Clinical and Experimental Neuropsychology, 1-19 DOI: 10.1080/13803390903066873

No ventral prefrontal cortex? No problem!

Brain damage - it's not much fun when it's your brain, but for science, it's often good news. While neuroimaging can find the neural correlates of mental processes - areas of the brain which become active during the experience of an emotion, say - lesion studies are often necessary to establish the direction of causality. Just because somewhere in the brain is activated during the experience of fear, for example, doesn't mean that this area is responsible for our feelings of fright; it might just happen to be lighting up as a side effect. Neuroimaging can't tell the difference, but if someone suffers damage to some part of the brain and then becomes fearless, it becomes possible to establish which parts do what. Localizing a function to a certain region of the brain is not the same as understanding it, of course, but it's a start.

The main problem with lesion studies is that there aren't enough of them. Because of those pesky ethical considerations, you can't just go around poking holes in people's brains - you have to wait until damage occurs naturally. In many interesting parts of the brain, localized damage is frustratingly uncommon.

Yet good things come to those who wait. The Journal of Neuroscience have just published a landmark lesion study by Koenigs et. al.(*) who studied two separate, large groups of people who had suffered brain damage to a range of areas - Vietnam veterans with combat head injuries, and Iowa citizens who had suffered tumors, strokes, and other medical conditions. In both samples they measured symptoms of depression and attempted to correlate them with the location of the lesions.

They succeeded. In both samples, patients who had suffered damage to the ventro-medial prefrontal cortex (vmPFC), which sits a few inches behind the center of the forehead, seemed to be protected against depression. Compared to people who had suffered lesions to all of the other parts of the brain, people with vmPFC damage on both sides of the brain were rated as having fewer depressive symptoms, both according to their own report and the observations of the experimenters. In particular, they reported being almost completely free of emotional or subjective symptoms such as feelings of guilt, sadness, or self-dislike. For illustration, they describe the incredible (and ironic) case of a woman with a self-inflicted vmPFC lesion:

We identified one patient in the Iowa registry who represents an intriguing case of an apparent alleviation of severe depression after a bilateral vmPFC lesion. ... per secondary report the patient was being treated for depression when she attempted suicide 11 years ago by means of a gunshot to the head. The gunshot destroyed most of ventral PFC, including vmPFC bilaterally, but left intact most of dorsal PFC. The patient’s neuropsychologist, neurosurgeon, and long-term boyfriend all remarked that her depression was markedly diminished after the brain injury (boyfriend, speaking 16 months after the injury: “no sign of depression whatsoever since the accident”; neuropsychologist: “she never shows distress, worry, or anger”).

Overall, these results are exciting, but unsurprising - the vmPFC is commonly thought of as being involved in emotion and emotional decision making; Antonio Damasio famously inferred this from the case of Phineas Gage, who after losing his medial prefrontal cortex to an iron rod, became impulsive, reckless, and unconcerned for himself or others. It's not difficult to see that someone with such characteristics might be resistant to such emotional difficulties as depression, or, say, post-traumatic stress - and indeed Koenigs et. al. previously reported that such lesions also protect against PTSD in combat veterans.

Fascinatingly, old-fashioned psychosurgery frequently ended up destroying much the same areas of the brain; the desired result, sometimes achieved, was a patient who no longer cared or worried about anything - which was thought preferable to someone paralyzed by despair or anxiety. The point is that the vmPFC is not specifically a "depression area of the brain" - although these results suggest that it is necessary for the experience of depression, it is probably also responsible for a broad range of other emotions, and patients lacking a vmPFC clearly lack more than just sadness. (If there is a "depression area", which is possible, my money's on the subgenual cingulate cortex.)

The paper also reported that damage to another part of the brain, the dorsal prefrontal cortex (bilateral), seemed to cause depression - however, there were only 5 patients with this kind of damage, of whom 2 were clinically depressed, so it's harder to interpret this result:

The proportion of individuals meeting DSM-IV criteria for "current" MDD was significantly greater for the dorsal PFC lesion group (2 of 5) than for the non-PFC lesion group (1 of 101; p = 0.005) or non-brain-damaged group (0 of 54; p = 0.006). Thus, bilateral dorsal PFC lesions were associated with a relatively high prevalence of subsequent major depression.

A few things to note: Case histories are anecdotes, not data - and the brain of the woman described above is extensively abnormal; CT scans, not for the squeamish. The total number of vmPFC patients here was just twenty. This is the largest group of these patients studied so far, because this kind of injury is very rare, but this is still a smallish sample. Most importantly, levels of depression in the control groups in this study were fairly low. The vmPFC group showed essentially zero depressive symptoms, but even the control patients only showed mild symptoms on average, and only a couple of them were diagnosed with actual clinical depression. So the between-group differences were, while statistically significant, modest.

(*) Annoyingly, pretty much every paper from Mike Koenigs is a landmark lesion study. It's always the same lesion patients. Not that this is a major problem, I'm just annoyed that he gets to study them and not me.

M. Koenigs, E. D. Huey, M. Calamia, V. Raymont, D. Tranel, J. Grafman (2008). Distinct Regions of Prefrontal Cortex Mediate Resistance and Vulnerability to Depression Journal of Neuroscience, 28 (47), 12341-12348 DOI: 10.1523/JNEUROSCI.2324-08.2008