prefrontal cortex

is the area of the brain at the very front of the frontal lobes. It is involved in "executive functions", such as working memory, decision-making, planning and judgment. Prefrontal regions appear to be particularly sensitive to the effects of aging. It is thought that the reduced ability to recall the context of memories that occurs with advancing age, is evidence that the prefrontal cortex is also critical for context processing - a process involved in many cognitive functions. A recent study has also revealed that emotional stimuli and attentional functions are integrated in a specific part of the prefrontal cortex - the anterior cingulate (located between the right and left halves).

Common health complaints increase Alzheimer's risk

October, 2011

Two large studies respectively find that common health complaints and irregular heartbeat are associated with an increased risk of developing Alzheimer’s, while a rat study adds to evidence that stress is also a risk factor.

A ten-year study involving 7,239 older adults (65+) has found that each common health complaint increased dementia risk by an average of about 3%, and that these individual risks compounded. Thus, while a healthy older adult had about an 18% chance of developing dementia after 10 years, those with a dozen of these health complaints had, on average, closer to a 40% chance.

It’s important to note that these complaints were not for serious disorders that have been implicated in Alzheimer’s. The researchers constructed a ‘frailty’ index, involving 19 different health and wellbeing factors: overall health, eyesight, hearing, denture fit, arthritis/rheumatism, eye trouble, ear trouble, stomach trouble, kidney trouble, bladder control, bowel control, feet/ankle trouble, stuffy nose/sneezing, bone fractures, chest problems, cough, skin problems, dental problems, other problems.

Not all complaints are created equal. The most common complaint — arthritis/rheumatism —was only slightly higher among those with dementia. Two of the largest differences were poor eyesight (3% of the non-demented group vs 9% of those with dementia) and poor hearing (3% and 6%).

At the end of the study, 4,324 (60%) were still alive, and of these, 416 (9.6%) had Alzheimer's disease, 191 (4.4%) had another sort of dementia and 677 (15.7%) had other cognitive problems (but note that 1,023 were of uncertain cognitive ability).

While these results need to be confirmed in other research — the study used data from broader health surveys that weren’t specifically designed for this purpose, and many of those who died during the study will have probably had dementia — they do suggest the importance of maintaining good general health.

Common irregular heartbeat raises risk of dementia

In another study, which ran from 1994 to 2008 and followed 3,045 older adults (mean age 74 at study start), those with atrial fibrillation were found to have a significantly greater risk of developing Alzheimer’s.

At the beginning of the study, 4.3% of the participants had atrial fibrillation (the most common kind of chronically irregular heartbeat); a further 12.2% developed it during the study. Participants were followed for an average of seven years. Over this time, those with atrial fibrillation had a 40-50% higher risk of developing dementia of any type, including probable Alzheimer's disease. Overall, 18.8% of the participants developed some type of dementia during the course of the study.

While atrial fibrillation is associated with other cardiovascular risk factors and disease, this study shows that atrial fibrillation increases dementia risk more than just through this association. Possible mechanisms for this increased risk include:

  • weakening the heart's pumping ability, leading to less oxygen going to the brain;
  • increasing the chance of tiny blood clots going to the brain, causing small, clinically undetected strokes;
  • a combination of these plus other factors that contribute to dementia such as inflammation.

The next step is to see whether any treatments for atrial fibrillation reduce the risk of developing dementia.

Stress may increase risk for Alzheimer's disease

And a rat study has shown that increased release of stress hormones leads to cognitive impairment and that characteristic of Alzheimer’s disease, tau tangles. The rats were subjected to stress for an hour every day for a month, by such means as overcrowding or being placed on a vibrating platform. These rats developed increased hyperphosphorylation of tau protein in the hippocampus and prefrontal cortex, and these changes were associated with memory deficits and impaired behavioral flexibility.

Previous research has shown that stress leads to that other characteristic of Alzheimer’s disease: the formation of beta-amyloid.

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When age helps decision making

October, 2011

New study modifies findings that younger adults are better decision-makers by showing older adults are better when the scenarios involve multiple considerations.

Research has shown that younger adults are better decision makers than older adults — a curious result. A new study tried to capture more ‘real-world’ decision-making, by requiring participants to evaluate each result in order to strategize the next choice.

This time (whew!), the older adults did better.

In the first experiment, groups of older (60-early 80s) and younger (college-age) adults received points each time they chose from one of four options and tried to maximize the points they earned.  For this task, the younger adults were more efficient at selecting the options that yielded more points.

In the second experiment, the rewards received depended on the choices made previously.  The “decreasing option” gave a larger number of points on each trial, but caused rewards on future trials to be lower. The “increasing option” gave a smaller reward on each trial but caused rewards on future trials to increase.  In one version of the test, the increasing option led to more points earned over the course of the experiment; in another, chasing the increasing option couldn’t make up for the points that could be accrued grabbing the bigger bite on each trial.

The older adults did better on every permutation.

Understanding more complex scenarios is where experience tells. The difference in performance also may reflect the different ways younger and older adults use their brains. Decision-making can involve two different reward learning systems, according to recent thinking. In the model-based system, a cognitive model is constructed that shows how various actions and their rewards are connected to each other. Decisions are made by simulating how one decision will affect future decisions. In the model-free system, on the other hand, only values associated with each choice are considered.

These systems are rooted in different parts of the brain. The model-based system uses the intraparietal sulcus and lateral prefrontal cortex, while the model-free system uses the ventral striatum. There is some evidence that younger adults use the ventral striatum (involved in habitual, reflexive learning and immediate reward) for decision-making more than older adults, and older adults use the dorsolateral prefrontal cortex (involved in more rational, deliberative thinking) more than younger adults.

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Working memory capacity not 4 but 2+2

October, 2011

A monkey study finds that our very limited working memory capacity of around 4 items reflects two capacities of two items. The finding has practical implications for information presentation.

In the study, two rhesus monkeys were given a standard human test of working memory capacity: an array of colored squares, varying from two to five squares, was shown for 800 msec on a screen. After a delay, varying from 800 to 1000 msec, a second array was presented. This array was identical to the first except for a change in color of one item. The monkey was rewarded if its eyes went directly to this changed square (an infra-red eye-tracking system was used to determine this). During all this, activity from single neurons in the lateral prefrontal cortex and the lateral intraparietal area — areas critical for short-term memory and implicated in human capacity limitations — was recorded.

As with humans, the more squares in the array, the worse the performance (from 85% correct for two squares to 66.5% for 5). Their working memory capacity was calculated at 3.88 objects — i.e. the same as that of humans.

That in itself is interesting, speaking as it does to the question of how human intelligence differs from other animals. But the real point of the exercise was to watch what is happening at the single neuron level. And here a surprise occurred.

That total capacity of around 4 items was composed of two independent, smaller capacities in the right and left halves of the visual space. What matters is how many objects are in the hemifield an eye is covering. Each hemifield can only handle two objects. Thus, if the left side of the visual space contains three items, and the right side only one, information about the three items from the left side will be degraded. If the left side contains four items and the right side two, those two on the right side will be fine, but information from the four items on the left will be degraded.

Notice that the effect of more items than two in a hemifield is to decrease the total information from all the items in the hemifield — not to simply lose the additional items.

The behavioral evidence correlated with brain activity, with object information in LPFC neurons decreasing with increasing number of items in the same hemifield, but not the opposite hemifield, and the same for the intraparietal neurons (the latter are active during the delay; the former during the presentation).

The findings resolve a long-standing debate: does working memory function like slots, which we fill one by one with items until all are full, or as a pool that fills with information about each object, with some information being lost as the number of items increases? And now we know why there is evidence for both views, because both contain truth. Each hemisphere might be considered a slot, but each slot is a pool.

Another long-standing question is whether the capacity limit is a failure of perception or  memory. These findings indicate that the problem is one of perception. The neural recordings showed information about the objects being lost even as the monkeys were viewing them, not later as they were remembering what they had seen.

All of this is important theoretically, but there are also immediate practical applications. The work suggests that information should be presented in such a way that it’s spread across the visual space — for example, dashboard displays should spread the displays evenly on both sides of the visual field; medical monitors that currently have one column of information should balance it in right and left columns; security personnel should see displays scrolled vertically rather than horizontally; working memory training should present information in a way that trains each hemisphere separately. The researchers are forming collaborations to develop these ideas.

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[2335] Buschman, T. J., Siegel M., Roy J. E., & Miller E. K.
(2011).  Neural substrates of cognitive capacity limitations.
Proceedings of the National Academy of Sciences.

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Ability to remember memories' origin develops slowly

October, 2011

A study comparing the brains of children, adolescents, and young adults has found that the ability to remember the origin of memories is slow to mature. As with older adults, impaired source memory increases susceptibility to false memories.

In the study, 18 children (aged 7-8), 20 adolescents (13-14), and 20 young adults (20-29) were shown pictures and asked to decide whether it was a new picture or one they had seen earlier. Some of the pictures were of known objects and others were fanciful figures (this was in order to measure the effects of novelty in general). After a 10-minute break, they resumed the task — with the twist that any pictures that had appeared in the first session should be judged “new” if that was the first appearance in the second session. EEG measurements (event-related potentials — ERPs) were taken during the sessions.

ERPs at the onset of a test stimulus (each picture) are different for new and old (repeated) stimuli. Previous studies have established various old/new effects that reflect item and source memory in adults. In the case of item memory, recognition is thought to be based on two processes — familiarity and recollection — which are reflected in ERPs of different timings and location (familiarity: mid-frontal at 300-500 msec; recollection: parietal at 400-70 msec). Familiarity is seen as a fast assessment of similarity, while recollection varies according to the amount of retrieved information.

Source memory appears to require control processes that involve the prefrontal cortex. Given that this region is the slowest to mature, it would not be surprising if source memory is a problematic memory task for the young. And indeed, previous research has found that children do have particular difficulty in sourcing memories when the sources are highly similar.

In the present study, children performed more poorly than adolescents and adults on both item memory and source memory. Adolescents performed more poorly than adults on item memory but not on source memory. Children performed more poorly on source memory than item memory, but adolescents and adults showed no difference between the two tasks.

All groups responded faster to new items than old, and ERP responses to general novelty were similar across the groups — although children showed a left-frontal focus that may reflect the transition from analytic to a more holistic processing approach.

ERPs to old items, however, showed a difference: for adults, they were especially pronounced at frontal sites, and occurred at around 350-450 msec; for children and adolescents they were most pronounced at posterior sites, occurring at 600-800 msec for children and 400-600 msec for adolescents. Only adults showed the early midfrontal response that is assumed to reflect familiarity processing. On the other hand, the late old/new effect occurring at parietal sites and thought to reflect recollection, was similar across all age groups. The early old/new effect seen in children and adolescents at central and parietal regions is thought to reflect early recollection.

In other words, only adults showed the brain responses typical of familiarity as well as recollection. Now, some research has found evidence of familiarity processing in children, so this shouldn’t be taken as proof against familiarity processing in the young. What seems most likely is that children are less likely to use such processing. Clearly the next step is to find out the factors that affect this.

Another interesting point is the early recollective response shown by children and adolescents. It’s speculated that these groups may have used more retrieval cues — conceptual as well as perceptual — that facilitated recollection. I’m reminded of a couple of studies I reported on some years ago, that found that young children were better than adults on a recognition task in some circumstances — because children were using a similarity-based process and adults a categorization-based one. In these cases, it had more to do with knowledge than development.

It’s also worth noting that, in adults, the recollective response was accentuated in the right-frontal area. This suggests that recollection was overlapping with post-retrieval monitoring. It’s speculated that adults’ greater use of familiarity produces a greater need for monitoring, because of the greater uncertainty.

What all this suggests is that preadolescent children are less able to strategically recollect source information, and that strategic recollection undergoes an important step in early adolescence that is probably related to improvements in cognitive control. But this process is still being refined in adolescents, in particular as regards monitoring and coping with uncertainty.

Interestingly, source memory is also one of the areas affected early in old age.

Failure to remember the source of a memory has many practical implications, in particular in the way it renders people more vulnerable to false memories.

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Adolescent binge drinking can damage spatial working memory

August, 2011
  • This study finds that adolescent females are particularly vulnerable to the effects of binge drinking, and points to specific changes in brain activation patterns seen in binge drinkers.

Binge drinking occurs most frequently among young people, and there has been concern that consequences will be especially severe if the brain is still developing, as it is in adolescence. Because of the fact that it is only some parts of the brain — most crucially the prefrontal cortex and the hippocampus — that are still developing, it makes sense that only some functions will be affected.

I recently reported on a finding that binge drinking university students, performed more poorly on tests of verbal memory, but not on a test of visual memory. A new study looks at another function: spatial working memory. This task involves the hippocampus, and animal research has indicated that this region may be especially vulnerable to binge drinking. Spatial working memory is involved in such activities as driving, figural reasoning, sports, and navigation.

The study involved 95 adolescents (aged 16-19) from San Diego-area public schools: 40 binge drinking (27 males, 13 females) and 55 control (31 males, 24 females). Brain scans while performing a spatial working memory task revealed that there were significant gender differences in brain activation patterns for those who engaged in binge drinking. Specifically, in eight regions spanning the frontal cortex, anterior cingulate, temporal cortex, and cerebellum, female binge drinkers showed less activation than female controls, while male bingers exhibited greater activation than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances, while for male binge drinkers, greater activation was linked to better spatial performance.

The differences between male binge drinkers and controls were smaller than that seen in the female groups, suggesting that female teens may be particularly vulnerable. This is not the first study to find a gender difference in the brains’ response to excess alcohol. In this case it may have to do, at least partly, with differences in maturity — female brains mature earlier than males’.

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Neurofeedback offers hope for attention training

May, 2011

Receiving immediate feedback on the activity in a brain region enabled people to improve their control of that region’s activity, thus improving their concentration.

I’ve always been intrigued by neurofeedback training. But when it first raised its head, technology was far less sophisticated. Now a new study has used real-time functional Magnetic Resonance Imaging (fMRI) feedback from the rostrolateral prefrontal cortex to improve people's ability to control their thoughts and focus their attention.

In the study, participants performed tasks that either raised or lowered mental introspection in 30-second intervals over four six-minute sessions. Those with access to real-time fMRI feedback could see their RLPFC activity increase during introspection and decrease during non-introspective thoughts, such as mental tasks that focused on body sensations. These participants became significantly better at controlling their thoughts and performing the mental tasks. Moreover, the improved regulation was reflected only in activity in the rostrolateral prefrontal cortex. Those given inaccurate or no brain feedback showed no such improvement.

The findings point to a means of improving attentional control, and also raise hope for clinical treatments of conditions that can benefit from improved awareness and regulation of one's thoughts, including depression, anxiety, and obsessive-compulsive disorders.

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Advice vs. experience: Genes predict learning style

May, 2011

Three gene variants governing dopamine response in the prefrontal cortex and the striatum affect how likely we are to persist with inaccurate beliefs in the face of contradictory experience.

We learn from what we read and what people tell us, and we learn from our own experience. Although you would think that personal experience would easily trump other people’s advice, we in fact tend to favor abstract information against our own experience. This is seen in the way we commonly distort what we experience in ways that match what we already believe. But there is probably good reason for this tendency (reflected in confirmation bias), even if it sometimes goes wrong.

But of course individuals vary in the extent to which they persist with bad advice. A new study points to genes as a critical reason. Different brain regions are involved in the processing of these two information sources (advice vs experience): the prefrontal cortex and the striatum. Variants in the genes DARPP-32 and DRD2 affect the response to dopamine in the striatum. Variation in the gene COMT, on the other hand, affects dopamine response in the prefrontal cortex.

In the study, over 70 people performed a computerized learning task in which they had to pick the "correct" symbol, which they learned through trial and error. For some symbols, subjects were given advice, and sometimes that advice was wrong.

COMT gene variants were predictive of the degree to which participants persisted in responding in accordance with prior instructions even as evidence against their correctness grew. Variants in DARPP-32 and DRD2 predicted learning from positive and negative outcomes, and the degree to which such learning was overly inflated or neglected when outcomes were consistent or inconsistent with prior instructions.

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Adolescent brain vulnerable to binge drinking and tobacco

April, 2011

Binge drinking occurs most often in adolescents, and most smokers also begin at this time. Two new studies suggest that the impact of these activities on their still-developing brains is likely to be long-lasting.

Binge drinking is, unfortunately, most common among adolescents (12-20 years). But this is a time when brains are still developing. Does this make them more vulnerable to the detrimental effects of excessive alcohol?

A study involving adolescent mice has revealed that not only did an alcoholic binge reduce the activity of many neurotransmitter genes, but that gene expression in adulthood was even more seriously reduced. Although this deficit didn’t translate into problems with spatial learning, adult mice that had been exposed to excess alcohol in adolescence were significantly worse on a reversal learning task. Moreover, certain brain regions (the olfactory bulb and basal forebrain) were smaller.

In humans, it is thought that these impairments might translate into greater difficulty in adapting to changed situations, in evaluating consequences and controlling impulses.

Similarly, another recent study involving teenagers (15-21) has found that activity in the prefrontal cortex varied according to how heavily they smoked, with those who smoked most heavily having the least activity.

The 25 smokers and 25 non-smokers were tested on a Stop-Signal Task, which tests a person’s ability to inhibit an action. Despite the differences in activity level, smokers and non-smokers performed similarly on the task, suggesting that other brain areas are in some way compensating for the impaired prefrontal cortex. Nevertheless, reduced activity in the prefrontal cortex, which is still developing in adolescence, does suggest long-term consequences for decision-making and cognitive control.

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Learning ability is refreshed by sleep spindles

March, 2011

A new study confirms that learning ability declines with time awake, and shows that stage 2 non-REM sleep, achieved during a long afternoon nap, can re-invigorate your brain.

In a study involving 44 young adults given a rigorous memorizing task at noon and another such task at 6pm, those who took a 90-minute nap during the interval improved their ability to learn on the later task, while those who stayed awake found it harder to learn.

The degree to which the nappers were refreshed correlated with the amount of stage 2 non-REM sleep they experienced. This sleep phase is characterized by sleep spindles, which are associated with brain activity between the hippocampus and prefrontal cortex. Spindle-rich sleep occurs mostly in the second half of the night, so those who don’t get their quota of sleep are probably getting less.

The finding confirms the idea that learning ability decreases the more time you spend awake.

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[2144] Mander, B. A., Santhanam S., Saletin J. M., & Walker M. P.
(2011).  Wake deterioration and sleep restoration of human learning.
Current Biology. 21(5), R183-R184 - R183-R184.

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Exercise improves executive function and math in sedentary children

February, 2011
  • A three-month trial comparing the effects of exercise programs on cognitive function in sedentary, overweight children, has found dose-related benefits of regular aerobic exercise.

A study involving 171 sedentary, overweight 7- to 11-year-old children has found that those who participated in an exercise program improved both executive function and math achievement. The children were randomly selected either to a group that got 20 minutes of aerobic exercise in an after-school program, one that got 40 minutes of exercise in a similar program, or a group that had no exercise program. Those who got the greater amount of exercise improved more. Brain scans also revealed increased activity in the prefrontal cortex and reduced activity in the posterior parietal cortex, for those in the exercise group.

The program lasted around 13 weeks. The researchers are now investigating the effects of continuing the program for a full year. Gender, race, socioeconomic factors or parental education did not change the impact of the exercise program.

The effects are consistent with other studies involving older adults. It should be emphasized that these were sedentary, overweight children. These findings are telling us what the lack of exercise is doing to young minds. I note the report just previous, about counteracting what we have regarded as “normal” brain atrophy in older adults by the simple action of walking for 40 minutes three times a week. Children and older adults might be regarded as our canaries in the coal mine, more vulnerable to many factors that can affect the brain. We should take heed.

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