Tuesday, March 18, 2008

Awaress and attention: different brain processes

Most of the proposed neural correlates of visual awareness do not explicitly distinguish top-down attention from awareness per se. However, several authors have started to point at the need to disambiguate visual awareness and spatial attention. Experimental evidence supporting their possible neural dissociation has remained sparse. Such evidence is now provided by a nice piece of work from Wyart and Tallon-Baudry:
To what extent does what we consciously see depend on where we attend to? Psychologists have long stressed the tight relationship between visual awareness and spatial attention at the behavioral level. However, the amount of overlap between their neural correlates remains a matter of debate. We recorded magnetoencephalographic signals while human subjects attended toward or away from faint stimuli that were reported as consciously seen only half of the time. Visually identical stimuli could thus be attended or not and consciously seen or not. Although attended stimuli were consciously seen slightly more often than unattended ones, the factorial analysis of stimulus-induced oscillatory brain activity revealed distinct and independent neural correlates of visual awareness and spatial attention at different frequencies in the gamma range (30–150 Hz). Whether attended or not, consciously seen stimuli induced increased mid-frequency gamma-band activity over the contralateral visual cortex, whereas spatial attention modulated high-frequency gamma-band activity in response to both consciously seen and unseen stimuli. A parametric analysis of the data at the single-trial level confirmed that the awareness-related mid-frequency activity drove the seen–unseen decision but also revealed a small influence of the attention-related high-frequency activity on the decision. These results suggest that subjective visual experience is shaped by the cumulative contribution of two processes operating independently at the neural level, one reflecting visual awareness per se and the other reflecting spatial attention.

Monday, March 17, 2008

Upset? Reduce your blood pressure by switching to 3rd person view.

How we view our own stories, immersed within them or viewing them as outside observer, can have a big effect on our ability to change (see 5/30/07 post). Negative feelings and stress are known to enhance vulnerability to cardiac disease, and a problem with ruminating over these negative feelings or events is that the effort can backfire, and instead maintain or enhance negativity. Ayduk and
Kross ask
whether the outcome of self analysis depends on the type of self-perspective that is adopted, self-immersed (1st person) or self-distanced (3rd person).

Their experiments recruited 90 undergraduates who:
...were cued to recall an experience when they were angry and indicated that they had recalled an appropriate experience by pressing the space bar (i.e., recall phase); the computer recorded their recall times. Then they were told, "Go back to the time and place of the conflict and see the scene in your mind's eye." They were then randomly assigned to one of two perspective conditions (the manipulation phase). In the self-immersed condition, participants were told: "Relive the situation as if it were happening to you all over again … Reexperience the interaction as it progresses in your mind's eye."

In the self-distanced condition, participants were told: "Take a few steps back … . Move away from the situation to a point where you can now watch the conflict from a distance … . Watch the conflict unfold as if it were happening all over again to the distant you. Replay the interaction as it progresses in your mind's eye."

At the end students filled out a questionnaires (the recovery phase) rating the extent to which and the intensity with which they re-experienced their original feelings during the experiment. Blood pressure (mean arterial pressure, or MAP) was monitored throughout the three phases of the experiments.

The authors expected and found no difference between the two groups in MAP reactivity during recall. In contrast, participants in the self-distanced group showed lower MAP reactivity than those in the self-immersed group during both the manipulation and the recovery phases of the experiment. (That is, they were more chilled out, had lower blood pressure.)

Watching yourself during a brain stroke...

This widely circulating video has some fascinating insights into the experience of having a stroke. Jill Bolte Taylor gives an very simplified description of left versus right hemisphere function and then describes the consequences of a hemmorage in her left hemisphere that formed a large clot pressing against the language area. She watched a flickering back and forth between having a self with thoughts and a la-la land or nirvana of pure awareness as she gradually lost motor and sensory control :

Friday, March 14, 2008

Our innate number sense.

Jim Holt has written an excellent article in the New Yorker focusing on the work of Stanislas Dehaene, who argues that humans (and higher animals) have an inbuilt “number sense” capable of some basic calculations and estimates. Evidence from cognitive deficits in brain-damaged patients has shown that we have a sense of number that is independent of language, memory, and reasoning in general.
When we see numerals or hear number words, our brains appear to automatically map them onto a number line that grows increasingly fuzzy above 3 or 4. A few chunks from Holt's article:
... it is generally agreed that infants come equipped with a rudimentary ability to perceive and represent number. (The same appears to be true for many kinds of animals, including salamanders, pigeons, raccoons, dolphins, parrots, and monkeys.) And if evolution has equipped us with one way of representing number, embodied in the primitive number sense, culture furnishes two more: numerals and number words. These three modes of thinking about number, Dehaene believes, correspond to distinct areas of the brain. The number sense is lodged in the parietal lobe, the part of the brain that relates to space and location; numerals are dealt with by the visual areas; and number words are processed by the language areas.

Dehaene has been able to bring together the experimental and the theoretical sides of his quest, and, on at least one occasion, he has even theorized the existence of a neurological feature whose presence was later confirmed by other researchers. In the early nineteen-nineties, working with Jean-Pierre Changeux, he set out to create a computer model to simulate the way humans and some animals estimate at a glance the number of objects in their environment. In the case of very small numbers, this estimate can be made with almost perfect accuracy, an ability known as “subitizing” (from the Latin word subitus, meaning “sudden”). Some psychologists think that subitizing is merely rapid, unconscious counting, but others, Dehaene included, believe that our minds perceive up to three or four objects all at once, without having to mentally “spotlight” them one by one. Getting the computer model to subitize the way humans and animals did was possible, he found, only if he built in “number neurons” tuned to fire with maximum intensity in response to a specific number of objects. His model had, for example, a special four neuron that got particularly excited when the computer was presented with four objects. The model’s number neurons were pure theory, but almost a decade later two teams of researchers discovered what seemed to be the real item, in the brains of macaque monkeys that had been trained to do number tasks. The number neurons fired precisely the way Dehaene’s model predicted—a vindication of theoretical psychology. “Basically, we can derive the behavioral properties of these neurons from first principles,” he told me. “Psychology has become a little more like physics.”

Thursday, March 13, 2008

Innate fear of snakes in young humans

Monkeys very rapidly learn to fear snakes simply from seeing another monkey react fearfully to the presence of a snake. There has been a question of whether our human aversion to snake forms requires such learning, or might develop autonomously. Experiments by LoBue and DeLoache support the idea that our visual systems employ an innate developmental sequence to develop a heightened awareness of snake like forms very early in development, independent of actual direct or indirect experience of snakes. 3-5 year olds preferentially attended to snake pictures, even compared with pictures of caterpillars (as well as pictures of flowers or frogs), and this preference was the same in the presence or absence of previous exposure to snakes or snake images.
A preschool child identifying the single flower target among eight snake distractors by touching the flower image on a touch-screen monitor.

Wednesday, March 12, 2008

Why smoking pot chills you out...

The title of the article by Phan et al. in J. Neuroscience is "Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans" and their abstract says it clearly:
The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear learning in both animals and humans. The anxiolytic effects of {Delta}9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are believed to be mediated through direct and selective agonism of CB1 receptors localized within the basolateral amygdala, a critical brain region for threat perception. However, little is known about the effects of THC on amygdala reactivity in humans. We used functional magnetic resonance imaging and a well validated task to probe amygdala responses to threat signals in 16 healthy, recreational cannabis users after a double-blind crossover administration of THC or placebo. We found that THC significantly reduced amygdala reactivity to social signals of threat but did not affect activity in primary visual and motor cortex. The current findings fit well with the notion that THC and other cannabinoids may have an anxiolytic role in central mechanisms of fear behaviors and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid system for disorders of anxiety and social fear.


Figure - THC effects on amygdala activation. A, B, Statistical t maps overlaid on a canonical brain rendering (MNI coronal y-plane = 0) showing right lateral amygdala activation to threat (>nonthreat) faces is present during the PBO session but absent during the THC session. C, Statistical t map overlaid on a canonical brain rendering (MNI coronal y-plane = 0) showing greater threat-related amygdala reactivity in the PBO relative to the THC session (PBO > THC). For additional information, see Results. Statistical t score scale is shown at the bottom of the brain rendering. R, Right.

The Genetics of Personality and Well-Being

Some support for our folk wisdom that happiness is a personal(ity) thing: Weiss et al. have used standard verbal and written questionnaires to examine personality and subjective well-being in 973 twin pairs. The written personality questionnaire used the five factor model (FFM) rating neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness. Numerous studies of personality have shown that genetic effects account for approximately 50% of the variance in these FFM domains. The 'happiness' measure was by a telephone interview that asked three questions: how satisfied participants were with life at the present, how much control subjects felt they had over their lives, and how satisfied they were with life overall.

They found that the genetic structure of the FFM and subjective well-being could be modeled without genetic influences specific to subjective well-being. Subjective well-being was genetically indistinct from personality traits, especially those reflecting, in part, emotional stability (low neuroticism), social and physical activity (high extraversion), and constraint (high conscientiousness). The close genetic relationship between positive personality traits and happiness traits is the mirror image of comorbidity in psychopathology. Weiss et al. suggest that their findings indicate that subjective well-being is linked to personality by common genes and that personality may form an "affective reserve" relevant to set-point maintenance and changes in set point over time.

Tuesday, March 11, 2008

The age of American unreason

A Kakutani review of Susan's Jacoby's book with the title of this post is worth a look.

Adolescent outbursts related to prefrontal and amygdala sizes

Whittle et al. have done fMRI experiments on adolescents that focused on three key brain regions which are known to represent critical nodes in neural networks supporting affective regulation: the amygdala, anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Increased amygdala volume and a relative decrease of left versus right paralimbic ACC volumes were associated with increased duration of aggressive behaviors during parent-child interactions, with the latter association being apparent in males but not females. Decreased relative volume of left vs. right OFC was associated with greater reciprocity of dysphoric behaviors, the association also being specific to males. An absence of mean gender differences in affective behaviors suggests that the neural circuits underlying affective behaviors may differ for male and female adolescents during this age period. Here are some (slightly edited) comments by the authors:
The maturation of the prefrontal cortex and its inhibitory connections with the subcortex are key outcomes of the adolescent neurodevelopment that underlies the development of emotional and behavioral regulatory abilities. The associations of increased amygdala volume and decreased left frontal asymmetries with more negative affective behaviors may represent a delay in brain maturation. Longitudinal research would be needed to examine whether these findings have implications for the development of affective and behavioral dysregulation later in life.

The male specificity of this finding adds to a growing body of evidence that the neural mechanisms underlying affective processing differ between males and females. Males have been found to exhibit structural and functional brain asymmetries to a greater extent than females in a number of prefrontal areas, including the cingulate region. It has been suggested that these asymmetries may render males more vulnerable to certain disorders involving dysfunction of the frontal lobes such as ADHD, autism, and dyslexia. Although males in the present study did not display more aggressive behavior than females, the more pronounced relationship between ACCP asymmetry and aggressive affective behaviors in males suggests that aggressive affect in male adolescents may function as a mechanism by which their brain asymmetry is implicated in their risk for psychopathology.
Here is a useful figure that shows you the locations and variations in the anatomy of the cingulate structures being discussed:

Figure-Example of changes in the location and extent of the limbic (ACCL; highlighted in green) and paralimbic (ACCP; highlighted in blue) anterior cingulate cortices as a function of variations in the cingulate sulcus (CS; green arrow, Upper row) and paracingulate sulcus (PCS; blue arrow, Upper row). A PCS is absent in the left-hand case and present in the right-hand case. The Upper row presents parasagittal slices through an individual's T1-weighted image. The coronal section illustrates the distinction between absent (left-hand side) and present (right-hand side) cases. Notice that the ACCP is buried in the depths of the CS when the PCS is absent and extends over the paracingulate gyrus when the PCS is present. The same principle applies throughout consecutive coronal sections.

Brain imaging of our parental instinct

A group of collaborators reports in PLOS ONE a specific and rapid neural signature for our parental instinct:
Darwin originally pointed out that there is something about infants which prompts adults to respond to and care for them, in order to increase individual fitness, i.e. reproductive success, via increased survivorship of one's own offspring. Lorenz proposed that it is the specific structure of the infant face that serves to elicit these parental responses, but the biological basis for this remains elusive. Here, we investigated whether adults show specific brain responses to unfamiliar infant faces compared to adult faces, where the infant and adult faces had been carefully matched across the two groups for emotional valence and arousal, as well as size and luminosity. The faces also matched closely in terms of attractiveness. Using magnetoencephalography (MEG) in adults, we found that highly specific brain activity occurred within a seventh of a second in response to unfamiliar infant faces but not to adult faces. This activity occurred in the medial orbitofrontal cortex (mOFC), an area implicated in reward behaviour, suggesting for the first time a neural basis for this vital evolutionary process. We found a peak in activity first in mOFC and then in the right fusiform face area (FFA)....These findings provide evidence in humans of a potential brain basis for the “innate releasing mechanisms” described by Lorenz for affection and nurturing of young infants.


The group analysis reveals a significant peak in the medial orbitofrontal cortex in the 10–30 Hz band in the 0–250 ms (first two columns), 100–350 ms (third column) and 200–450 ms (fourth column) windows when participants viewed infant (upper row) and not when they viewed adult faces (lower row). The fifth column shows the integrated map over the three time windows...In order to see the extent of the spread of activity over the fusiform cortices elicited by faces, the group activity is superimposed on a ventral view of the human brain (with the cerebellum removed).

Monday, March 10, 2008

More on Brain Enhancement

Have a look at Benedict Carey's article, "Brain Enhancement Is Wrong, Right?," in the NY Times Week in Review of 3/9/08. It continues the topic of using performance enhancing drugs, following up on a Nature article that I mentioned in my Feb. 1 post on the same subject. By the way, I have been meaning to point you to Chris Chatham's excellent post on how to use caffeine properly, obtaining effects on cognitive performance equivalent to those of modifanil. Here are some clips from the Carey article:
...two Cambridge University researchers reported that about a dozen of their colleagues had admitted to regular use of prescription drugs like Adderall, a stimulant, and Provigil, which promotes wakefulness, to improve their academic performance. The former is approved to treat attention deficit disorder, the latter narcolepsy, and both are considered more effective, and more widely available, than the drugs circulating in dorms a generation ago.

Francis Fukuyama raises the broader issue of performance enhancement: “The original purpose of medicine is to heal the sick, not turn healthy people into gods.” He and others point out that increased use of such drugs could raise the standard of what is considered “normal” performance and widen the gap between those who have access to the medications and those who don’t — and even erode the relationship between struggle and the building of character.

People already use legal performance enhancers, he said, from high-octane cafe Americanos to the beta-blockers taken by musicians to ease stage fright, to antidepressants to improve mood. “So the question with all of these things is, Is this enhancement, or a matter of removing the cloud over our better selves?”.

“You can imagine a scenario in the future, when you’re applying for a job, and the employer says, ‘Sure, you’ve got the talent for this, but we require you to take Adderall.’ Now, maybe you do start to care about the ethical implications.”

Moral Neuropolitics

Gary Olson, who is Chair of the Dept. of Political Science of Maravian College in Bethlehm, PA., sent me a latest draft of his article "From Mirror Neuron to Moral Neuropolitics." It does a nice job with the literature on mirror neurons and its implications, as well as political and cultural factors that enhance and inhibit moral behaviors. Gary is willing to pass on the draft article to blog readers for further comment (web version here; PDF download here).

My main comment was that the article might - in addition to covering cultural and political factors that work against moral behaviors between groups of distant people - add more data from evolutionary and developmental biology studies that also offer some evidence for factors working against morality and compassion. There is evidence for xenophobia and aggression between groups of animals (intra-group morality and cooperation, but also inter-group aggression and warfare), well documented in Chimps (cf. Feb. 19 Killer Instincts post), and other social animals (cf. March 8 post on Hyenas). Also, experiments show that that groups of children spontaneously invent not only language, but also in-groups and out-groups (cf. July 31 post) that can become competitive.

Friday, March 07, 2008

A voice region in the monkey brain

Both human and monkey brains have visual regions that are activated most strongly by the faces of conspecifics. Our brains also have have a region that is specialized for processing human voices that is located anteriorly on the temporal lobe, on the upper bank of the superior-temporal sulcus. Logothetis and his colleagues have now found a corresponding region in monkey brains. Their abstract and a portion of one of the figures:
For vocal animals, recognizing species-specific vocalizations is important for survival and social interactions. In humans, a voice region has been identified that is sensitive to human voices and vocalizations. As this region also strongly responds to speech, it is unclear whether it is tightly associated with linguistic processing and is thus unique to humans. Using functional magnetic resonance imaging of macaque monkeys (Old World primates, Macaca mulatta) we discovered a high-level auditory region that prefers species-specific vocalizations over other vocalizations and sounds. This region not only showed sensitivity to the 'voice' of the species, but also to the vocal identify of conspecific individuals. The monkey voice region is located on the superior-temporal plane and belongs to an anterior auditory 'what' pathway. These results establish functional relationships with the human voice region and support the notion that, for different primate species, the anterior temporal regions of the brain are adapted for recognizing communication signals from conspecifics.

Figure - The color code from orange to red indicates voxels with a clear and significant preference for macaque vocalizations. The cyan-to-blue color code identifies voxels with no preference for MVocs. The slice orientation and position are shown in the lower inset

The social brains of Hyenas

There is a correlation between brain size, particularly the newer frontal lobes, and the size of the social group an animal lives in. This rule works for our primate lineage and, it turns out, also for hyenas: those with the simplest social systems have the tiniest frontal cortices. The spotted hyena, which lives in the most complex societies, has far and away the largest frontal cortex. The brown and striped hyenas, with intermediate social systems, have intermediate brains. It appears that primates are not unique in the complexity of their social lives. An article by Zimmer describes the work of Holekamp and colleagues, who have found an array of complex social behaviors in spotted hyenas that are as complex as those of baboons. The groups are comprised of 60 to 80 individuals who all know each other individually. There are alliances, rivalries, and social hierarchies headed by an alpha female. Cubs undergo an education period. Hyena clans patrol their territory borders together against neighboring clans, kills near these borders can provoke clan conflicts. These behaviors are accomplished by brains with frontal lobes that are as easily distinguished as those of social primates (see figure.)

Thursday, March 06, 2008

Watching musical improvisation in the brain

Limb and Braun have done a fascinating functional MRI study of brain activity changes distinctively associated with improvisation in professional jazz pianists (compared to production of learned musical sequences). They suggest that a pattern of focal activation of the medial prefrontal (frontal polar) cortex, along with extensive deactivation of dorsolateral prefrontal and lateral orbital regions, may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance.

The patterns they observe suggest cognitive dissociations that may be intrinsic to the creative process: the innovative, internally motivated production of novel material (at once rule based and highly structured) that can apparently occur outside of conscious awareness and beyond volitional control.

You can check out the experimental paradigms used and also listen to audio samples of the musical excerpts provided in supporting information.

Three-dimensional surface projection of activations and deactivations associated with improvisation during the Jazz paradigm. Medial prefrontal cortex activation, dorsolateral prefrontal cortex deactivation, and sensorimotor activation can be seen. The scale bar shows the range of t-scores; the axes demonstrate anatomic orientation. Abbreviations: a, anterior; p, posterior; d, dorsal; v, ventral; R, right; L, left.

Wednesday, March 05, 2008

The Advantages of Closing a Few Doors

John Tierney has a fascinating short article with the title of this post in the NY Times - noting studies that show most of us insist on keeping options open even when doing this is irrational and against our best interests. The article focuses on the work of Dan Ariely at M.I.T. and relates an interesting experiment which I suspect you will be able to relate to your own behavior:
They played a computer game that paid real cash to look for money behind three doors on the screen. (You can play it yourself, without pay, at tierneylab.blogs.nytimes.com.) After they opened a door by clicking on it, each subsequent click earned a little money, with the sum varying each time...As each player went through the 100 allotted clicks, he could switch rooms to search for higher payoffs, but each switch used up a click to open the new door. The best strategy was to quickly check out the three rooms and settle in the one with the highest rewards.

Even after students got the hang of the game by practicing it, they were flummoxed when a new visual feature was introduced. If they stayed out of any room, its door would start shrinking and eventually disappear...They should have ignored those disappearing doors, but the students couldn’t. They wasted so many clicks rushing back to reopen doors that their earnings dropped 15 percent. Even when the penalties for switching grew stiffer — besides losing a click, the players had to pay a cash fee — the students kept losing money by frantically keeping all their doors open.

Why were they so attached to those doors? The players...would probably say they were just trying to keep future options open. But that’s not the real reason, according to Dr. Ariely and his collaborator in the experiments, Jiwoong Shin, an economist who is now at Yale.

They plumbed the players’ motivations by introducing yet another twist. This time, even if a door vanished from the screen, players could make it reappear whenever they wanted. But even when they knew it would not cost anything to make the door reappear, they still kept frantically trying to prevent doors from vanishing...Apparently they did not care so much about maintaining flexibility in the future. What really motivated them was the desire to avoid the immediate pain of watching a door close.

“Closing a door on an option is experienced as a loss, and people are willing to pay a price to avoid the emotion of loss,” Dr. Ariely says. In the experiment, the price was easy to measure in lost cash. In life, the costs are less obvious — wasted time, missed opportunities. If you are afraid to drop any project at the office, you pay for it at home.

Tuesday, March 04, 2008

Reasoning about our irrational ways

Elizabert Kolbert writes an interesting review in The New Yorker of several books on our irrational economic and political behaviors, the field of behavioral economics. It seems very likely that as politicians and governments become more knowledgeable about the patterns and emotional mechanisms governing our blunders, they will begin to nudge people towards more rational choices. The 'opt out' plans for increasing the numbers of people with health insurance plans or retirement savings are one example of this. Obama's campaign is making very good use of some basic neuro-economics and some of his people are aware of Westin's work (see my July 11 post), as well as Lakoff's (see Jan 31 post). Hillary doesn't seem to have a clue......

A test for Alzheimer's risk

A news piece by Jennifer Couzin in the Feb. 22 Science notes that starting in about a month, for ~$400, you can send a saliva sample to Smart Genetics in Philadelphia for their "Alzheimer's Mirror" test that determines whether you have a variant of the APOE gene that indicates a risk of Alzheimer's that's 3 to 15 times higher than normal. The company plans plan to screen out those who seem emotionally unstable and provide a genetic counseling session by telephone before giving out APOE results.

Not surprisingly many physicians and researchers are expressing reservations about making this gene test widely available. What are the mental health consequences of being told you may get a disease that's neither preventable nor treatable and is invariably fatal? (It's the only genetic information that James Watson, the DNA discoverer who recently had his entire genome sequenced, kept secret.) Would it turn out that people who had this information were more likely experience depression?

An officer at Smart Genetics argues that knowing one is at higher risk might trigger practical responses, including regular memory screenings or making certain financial decisions such as buying long-term care insurance.

Monday, March 03, 2008

Chill out, and your wounds will heal faster.

It is known that anger expression can be associated with increases in cortisol secretion and lowered immune function of the sort seen with other kinds of stress. Gouin et al. at Ohio State Univ. have examined the effect of anger on wound healing by following 98 community volunteers who agreed to receive a standardized blister wound on their non-dominant forearm. They found that wounds of those who expressed little anger or displayed anger in a controlled fashion healed more rapidly than the hotheads. The hotheads exhibited higher cortisol reactivity during the blistering procedure. This enhanced cortisol secretion was in turn related to longer time to heal.

The data show more rapid wound healing in subjects with high anger control.
Measurement of the rate of transepidermal water loss (TEWL) through human skin provides a noninvasive method to monitor changes in the stratum corneum barrier function of the skin. TEWL was measured using a vapor pressure gradient estimation method. TEWL decreased as the barrier was restored; thus, monitoring of TEWL over time allowed objective evaluation of wound healing.

The Fires of Aging

Donna Holmes offers an interesting review with the title of this post, of Caleb Finch's new book "The Biology of Human Longevity." Here are a few edited clips from that review:
Metabolically speaking, we're all on fire. Current thinking in the biology of aging suggests that the normal processes cells use to burn fuel, providing energy for life, indirectly lead to much of the disease and disability that characterize aging in humans and other animals. Chemically unstable by-products of cellular oxidation--especially free oxygen radicals--can initiate the deterioration of cell membranes and macromolecules. As small "hits" causing cellular injury accumulate, the results can range from uncorrected mutations and cancers to forms of tissue damage leading to vascular pathology and Alzheimer's disease.

Oxidative damage remains a central player in the drama Fitch unfolds, but now it shares the stage with several lesser-known, equally important accomplices: inflammation, damage during development, and the hazards of overnutrition.

Finch proposes that increases in brain size and the human life span over the past million years occurred in concert with changing nutritional priorities, slower developmental rates, and a tolerance for inflammation in "dirty, invasive, and stingy" prehistoric environments. The integration of more meat into the human diet, he argues, provided protein needed for larger brains but involved new physiological and genetic trade-offs between fitness and liability for long-term damage. This scenario provides a satisfying rationale for why variants of some genes for metabolizing animal fat that are linked to a human predilection for atherosclerosis, some cancers, and the amyloid plaques characteristic of Alzheimer's disease (such as those of the ApoE gene family) are not shared by our closest primate relatives.