Where our brains compute musical reward.

Yet another fascinating chunk from Zatorre and collaborators:

We used functional magnetic resonance imaging to investigate neural processes when music gains reward value the first time it is heard. The degree of activity in the mesolimbic striatal regions, especially the nucleus accumbens, during music listening was the best predictor of the amount listeners were willing to spend on previously unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value, which was instead predicted by increasing functional connectivity of these regions with the nucleus accumbens as the reward value increased. Thus, aesthetic rewards arise from the interaction between mesolimbic reward circuitry and cortical networks involved in perceptual analysis and valuation.

Quiet - the world of introverts.

I recently visited my year old grandson in Austin, TX., who turns out to be my opposite on Jerome Kagan's scale of temperamental introversion/extraversion. Like his mother, he is outgoing and gregarious, and wears me out very quickly with his intensity in play activities. Against this background I was struck by reading a book review by Judith Warner of Susan Cain's new book "Quiet", listed by the NY Times as one of the 10 major popular science books of the past year. Some clips from the review:

Too often denigrated and frequently overlooked in a society that’s held in thrall to an “Extrovert Ideal — the omnipresent belief that the ideal self is gregarious, alpha and comfortable in the spotlight,” Cain’s introverts are overwhelmed by the social demands thrust upon them. They’re also underwhelmed by the example set by the voluble, socially successful go-getters in their midst who “speak without thinking,” in the words of a Chinese software engineer whom Cain encounters in Cupertino, Calif.

Many of the self-avowed introverts she meets in the course of this book.. ape extroversion...some fake it well enough to make it, going along to get along in a country that rewards the out­going...Unchecked extroversion — a personality trait Cain ties to ebullience, excitability, dominance, risk-taking, thick skin, boldness and a tendency toward quick thinking and thoughtless action — has actually, she argues, come to pose a real menace of late. The outsize reward-seeking tendencies of the hopelessly ­outer-directed helped bring us the bank meltdown of 2008...she claims....it’s time to establish “a greater balance of power” between those who rush to speak and do and those who sit back and think. Introverts — who, according to Cain, can count among their many virtues the fact that “they’re relatively immune to the lures of wealth and fame” — must learn to “embrace the power of quiet.” And extroverts should learn to sit down and shut up.

Her accounts of introverted kids misunderstood and mishandled by their parents should give pause, for she rightly notes that introversion in children (often incorrectly viewed as shyness) is in some ways threatening to the adults around them. Indeed, in an age when kids are increasingly herded into classroom “pods” for group work, Cain’s insights into the stresses of nonstop socializing for some children are welcome; her advice that parents should choose to view their introverted offspring’s social style with understanding rather than fear is well worth hearing.

A...problem with Cain’s argument is her assumption that most introverts are actually suffering in their self-esteem. This may be true in the sorts of environments — Harvard Business School, corporate boardrooms, executive suites — that she knows best and appears to spend most of her time thinking about. Had she spent more time in other sorts of places, among other types of people — in research laboratories, for example, or among economists rather than businessmen and -women — she would undoubtedly have discovered a world of introverts quite contented with who they are, and who feel that the world has been good to them.

Free Will, continued - Prior unconscious brain activity predicts choices for abstract intentions!

I've been running a thread on free will and neuroscience in this blog, recently noting comments by Nahmias:

...As long as people understand that discoveries about how our brains work do not mean that what we think or try to do makes no difference to what happens, then their belief in free will is preserved. What matters to people is that we have the capacities for conscious deliberation and self-control that I’ve suggested we identify with free will.

...None of the evidence marshaled by neuroscientists and psychologists suggests that those neural processes involved in the conscious aspects of such complex, temporally extended decision-making are in fact causal dead ends. It would be almost unbelievable if such evidence turned up.

Almost unbelievable appears to have happened, with this from Soon et al.. Interestingly, they identified a partial spatial and temporal overlap of choice-predictive signals with activity in the default mode network I reviewed in this past Monday's post. The abstract:

Unconscious neural activity has been repeatedly shown to precede and potentially even influence subsequent free decisions. However, to date, such findings have been mostly restricted to simple motor choices, and despite considerable debate, there is no evidence that the outcome of more complex free decisions can be predicted from prior brain signals. Here, we show that the outcome of a free decision to either add or subtract numbers can already be decoded from neural activity in medial prefrontal and parietal cortex 4 s before the participant reports they are consciously making their choice. These choice-predictive signals co-occurred with the so-called default mode brain activity pattern that was still dominant at the time when the choice-predictive signals occurred. Our results suggest that unconscious preparation of free choices is not restricted to motor preparation. Instead, decisions at multiple scales of abstraction evolve from the dynamics of preceding brain activity.

And, a chunk from their discussion:

It is interesting that mental calculation, the more complex task, had less predictive lead time than a simple binary motor choice in our previous study. This could tentatively reflect a general limitation of unconscious processing in the sense that unconscious processes might be restricted in their ability to develop or stabilize complex representations such as abstract intentions. It is also worth noting that both studies showed the same dissociation between cortical regions that were predictive of the content versus the timing of the decision. This implies that the formation of an intention to act depends on interactions between the choice-predictive and time-predictive regions. The temporal profile of this interaction is likely to determine when the earliest choice-predictive information is available and might differ between tasks.

There was a partial spatial overlap between the choice-predictive brain regions and the DMN. Interestingly, the state of the DMN (default mode network) during the early preparatory phase still resembled that during off-task or “resting” periods. This lends further credit to the notion that the preparatory signals were not a result of conscious engagement with the task. Furthermore, the spatial and temporal overlap hints at a potential involvement of the DMN in unconscious choice preparation.

To summarize, we directly investigated the formation of spontaneous abstract intentions and showed that the brain may already start preparing for a voluntary action up to a few seconds before the decision enters into conscious awareness. Importantly, these results cannot be explained by motor preparation or general attentional mechanisms. We found that frontopolar and precuneus/posterior cingulate encoded the content of the upcoming decision, but not the timing. In contrast, the pre-SMA predicted the timing of the decision, but not the content.

Showing where moral intent is determined in our brains.

Interesting work from Koster-Hale et al:

Intentional harms are typically judged to be morally worse than accidental harms. Distinguishing between intentional harms and accidents depends on the capacity for mental state reasoning (i.e., reasoning about beliefs and intentions), which is supported by a group of brain regions including the right temporo-parietal junction (RTPJ). Prior research has found that interfering with activity in RTPJ can impair mental state reasoning for moral judgment and that high-functioning individuals with autism spectrum disorders make moral judgments based less on intent information than neurotypical participants. Three experiments, using multivoxel pattern analysis, find that (i) in neurotypical adults, the RTPJ shows reliable and distinct spatial patterns of responses across voxels for intentional vs. accidental harms, and (ii) individual differences in this neural pattern predict differences in participants’ moral judgments. These effects are specific to RTPJ. By contrast, (iii) this distinction was absent in adults with autism spectrum disorders. We conclude that multivoxel pattern analysis can detect features of mental state representations (e.g., intent), and that the corresponding neural patterns are behaviorally and clinically relevant.

Brain training games don't actually make you smarter.

Wow...after having done several posts uncritically passing on studies by Jaeggi and others claiming that games to improve working memory, such as the n-Back game, increase cognitive skills in other areas, a number of studies have failed to replicate these phenomena. Gareth Cook has done an interesting article on this in The New Yorker, suggesting that claims made by commercial software sites like Cogmen, Lumosity, and CogniFit are bogus.

Over the last year, however, the idea that working-memory training has broad benefits has crumbled. One group of psychologists, lead by a team at Georgia Tech, set out to replicate the Jaeggi findings, but with more careful controls and seventeen different cognitive-skills tests. Their subjects showed no evidence whatsoever for improvement in intelligence. They also identified a pattern of methodological problems with experiments showing positive results, like poor controls and a reliance on a single measure of cognitive improvement. This failed replication was recently published in one of psychology’s top journals, and another, by a group at Case Western Reserve University, has been published since.

The recent meta-analysis, led by Monica Melby-Lervåg, of the University of Oslo, and also published in a top journal, is even more damning. Some studies are more convincing than others, because they include more subjects and show a larger effect. Melby-Lervåg’s paper laboriously accounts for this, incorporating what Jaeggi, Klingberg, and everyone else had reported. The meta-analysis found that the training isn’t doing anyone much good. If anything, the scientific literature tends to overstate effects, because teams that find nothing tend not to publish their papers. (This is known as the “filedrawer” effect.) A null result from meta-analysis, published in a top journal, sends a shudder through the spine of all but the truest of believers. In the meantime, a separate paper by some of the Georgia Tech scientists looked specifically at Cogmed’s training, which has been subjected to more scientific scrutiny than any other program. “The claims made by Cogmed,” they wrote, “are largely unsubstantiated.”

Older brains - just as much nerve firing, but scrambled connections?

A group of colleagues at Imperial College London and Tsinghua University in Beijing have fitted glass windows on the skulls of old and young mice. Contrary to expectation they observe that older mice have more firing points than younger ones, but they are more erratic in their activity than in younger mice, with high turnover rates and wavering firing strengths. The older mice also performed less well on a memory test. The suggestion then is that the mental decline seen in aging may be due more do disorderly wiring than to loss of nerve cells. Their abstract:

Aging is a major risk factor for many neurological diseases and is associated with mild cognitive decline. Previous studies suggest that aging is accompanied by reduced synapse number and synaptic plasticity in specific brain regions. However, most studies, to date, used either postmortem or ex vivo preparations and lacked key in vivo evidence. Thus, whether neuronal arbors and synaptic structures remain dynamic in the intact aged brain and whether specific synaptic deficits arise during aging remains unknown. Here we used in vivo two-photon imaging and a unique analysis method to rigorously measure and track the size and location of axonal boutons in aged mice. Unexpectedly, the aged cortex shows circuit-specific increased rates of axonal bouton formation, elimination, and destabilization. Compared with the young adult brain, large (i.e., strong) boutons show 10-fold higher rates of destabilization and 20-fold higher turnover in the aged cortex. Size fluctuations of persistent boutons, believed to encode long-term memories, also are larger in the aged brain, whereas bouton size and density are not affected. Our data uncover a striking and unexpected increase in axonal bouton dynamics in the aged cortex. The increased turnover and destabilization rates of large boutons indicate that learning and memory deficits in the aged brain arise not through an inability to form new synapses but rather through decreased synaptic tenacity. Overall our study suggests that increased synaptic structural dynamics in specific cortical circuits may be a mechanism for agerelated cognitive decline.

A review - Mindfulness meditation and our brain's default versus attentional networks.

I've been doing some homework on potential topics to work up into a lecture, one of them being brain correlates of various meditative, attentional, or default mode states. The vocabulary used is sometimes contradictory between papers, but two categories emerge. One uses terms for thought like default, narrative focus, phenomenal, social reasoning, theory of mind, baseline setting, self referential, introspective, and stimulus independent. The contrasting descriptors are attentional, direct experience, experiential focus, task positive network, physical cause/effect reasoning.

This cooks down roughly to distinguishing between brain networks whose primary activity occurs during internal narrative focus versus those activated during direct attentional experience.

In reviewing previous mindblog posts on the default network I come up with a partial bibliography of reviews and experiments, and thought some readers might find it useful, a list in no particular order, with brief notes:

Reciprocal repression (mutual inhibition) between networks - nice graphics  - some muddying of definitions

Relationship of this mutual inhibition to mindfulness meditation , which notes Farb et al., 2007

Review (NYTimes) on power of concentration - mindfulness training causing increased connectivity in attentional and default networks. 

Review with graphics of MRI of default network activated by autobiographical memory, envisioning future, theory of mind, moral decision making. 

Tierney - virtues of a wandering mind.  (context, larger agenda, creativity)

Review of varieties of resting state activity

Change between operating systems during eyeblink.

Different components of default mode active in different kinds of memory.

Mental time travel and default network.

Synchronization of both modes between individuals.

Default network can be realized by multiple architectures (split brain patients).

Default network as underpinning of cerebral ‘connectome‘  - good graphic.

Development of human default network from being sparsely functionally connected at 7-9  years.







Default mode in Chimps and Monkeys

Association of default network with midline structures.

Why old folks more easy lose their way,

Wiener et al. make observations that shed light on why older people have more difficulty finding their car in a shopping mall's large parking lot if they exit the mall by a different door than they used to enter it (or follow directions involving an intersection if they approach the intersection from a different direction than the one used for learning them.) From their introduction:

Everyday navigation can be based on different strategies. The hippocampus plays a key role in cognitive map or place strategies that rely on allocentric processing, whereas the parietal cortex and striatal circuits are involved in route or response strategies...To test the hypothesis that cognitive aging not only results in a shift away from allocentric strategies but in a specific preference for beacon-based strategies, we developed a novel experimental paradigm: participants first learned a route along a number of intersections and were then asked to rejoin the original route approaching the intersections from different directions. Trials in which participants approached the intersections from a direction different from that during training (see Fig. 1) allowed us (1) to compare the use and adoption of route-learning strategies between young and older participants and (2) to test for specific preferences for beacon-based strategies in older participants.

The abstract:

Efficient spatial navigation requires not only accurate spatial knowledge but also the selection of appropriate strategies. Using a novel paradigm that allowed us to distinguish between beacon, associative cue, and place strategies, we investigated the effects of cognitive aging on the selection and adoption of navigation strategies in humans. Participants were required to rejoin a previously learned route encountered from an unfamiliar direction. Successful performance required the use of an allocentric place strategy, which was increasingly observed in young participants over six experimental sessions. In contrast, older participants, who were able to recall the route when approaching intersections from the same direction as during encoding, failed to use the correct place strategy when approaching intersections from novel directions. Instead, they continuously used a beacon strategy and showed no evidence of changing their behavior across the six sessions. Given that this bias was already apparent in the first experimental session, the inability to adopt the correct place strategy is not related to an inability to switch from a firmly established response strategy to an allocentric place strategy. Rather, and in line with previous research, age-related deficits in allocentric processing result in shifts in preferred navigation strategies and an overall bias for response strategies. The specific preference for a beacon strategy is discussed in the context of a possible dissociation between beacon-based and associative-cue-based response learning in the striatum, with the latter being more sensitive to age-related changes.

Defining when a visual stimulus become conscious to us.

Llinás and collaborators do a nice dissection of our conscious versus unconscious visual processing and note the timing (240 milliseconds) of a brain signal that correlates with our conscious awareness of a stimulus. (This is the same time epoch that I evoke in the "millisecond manager" term I use in several of my essays in the left column of this blog - a period during which we can note the onset of a visual or emotional perception before further action or interpretation begins.)

At perceptual threshold, some stimuli are available for conscious access whereas others are not. Such threshold inputs are useful tools for investigating the events that separate conscious awareness from unconscious stimulus processing. Here, viewing unmasked, threshold-duration images was combined with recording magnetoencephalography to quantify differences among perceptual states, ranging from no awareness to ambiguity to robust perception. A four-choice scale was used to assess awareness: “didn’t see” (no awareness), “couldn’t identify” (awareness without identification), “unsure” (awareness with low certainty identification), and “sure” (awareness with high certainty identification). Stimulus-evoked neuromagnetic signals were grouped according to behavioral response choices. Three main cortical responses were elicited. The earliest response, peaking at ∼100 ms after stimulus presentation, showed no significant correlation with stimulus perception. A late response (∼290 ms) showed moderate correlation with stimulus awareness but could not adequately differentiate conscious access from its absence. By contrast, an intermediate response peaking at ∼240 ms was observed only for trials in which stimuli were consciously detected. That this signal was similar for all conditions in which awareness was reported is consistent with the hypothesis that conscious visual access is relatively sharply demarcated.

Your smartphone, your social brain, and your vagus nerve.

I am always struck, when I go a local Starbucks for my noon coffee or do a happy hour at a local bar, that the great majority of those present are staring intently at their smartphones or tablets, while sitting in an environment meant to encourage interaction. As we spend less and less time engaging in face to face positive social contact in public places, what are we losing? The increasing aversion to human contact exhibited by people addicted to staring at their small screens suggests that our social brain follows the same rule as the rest of our brain and body: "Use it or loose it." I've done a post pointing to how modern hi-tech dialog devices fail to engage the evolved brain and body synchronization that accompanies face-to-face dialog.

In a recent NYTimes piece, Barabara Fredricksen describes some of her recent work on countering the toxic effects of isolation from direction person-to-person contact. Some clips, to which I have added a few reference links:

My research team and I conducted a longitudinal field experiment on the effects of learning skills for cultivating warmer interpersonal connections in daily life. Half the participants, chosen at random, attended a six-week workshop on an ancient mind-training practice known as metta, or “lovingkindness,” that teaches participants to develop more warmth and tenderness toward themselves and others....We discovered that the meditators not only felt more upbeat and socially connected; but they also altered a key part of their cardiovascular system called vagal tone. Scientists used to think vagal tone was largely stable, like your height in adulthood. Our data show that this part of you is plastic, too, and altered by your social habits.

To appreciate why this matters, here’s a quick anatomy lesson. Your brain is tied to your heart by your vagus nerve. Subtle variations in your heart rate reveal the strength of this brain-heart connection, and as such, heart-rate variability provides an index of your vagal tone. By and large, the higher your vagal tone the better. It means your body is better able to regulate the internal systems that keep you healthy, like your cardiovascular, glucose and immune responses.

Beyond these health effects, the behavioral neuroscientist Stephen Porges has shown that vagal tone is central to things like facial expressivity and the ability to tune in to the frequency of the human voice. By increasing people’s vagal tone, we increase their capacity for connection, friendship and empathy.

In short, the more attuned to others you become, the healthier you become, and vice versa. This mutual influence also explains how a lack of positive social contact diminishes people. Your heart’s capacity for friendship also obeys the biological law of “use it or lose it.” If you don’t regularly exercise your ability to connect face to face, you’ll eventually find yourself lacking some of the basic biological capacity to do so.

Mindfulness training improves working memory and cognitive performance while reducing mind wandering.

Yet another study, by Mrazek et al., on the salutary effects of mindfulness:

Given that the ability to attend to a task without distraction underlies performance in a wide variety of contexts, training one’s ability to stay on task should result in a similarly broad enhancement of performance. In a randomized controlled investigation, we examined whether a 2-week mindfulness-training course would decrease mind wandering and improve cognitive performance. Mindfulness training improved both GRE reading-comprehension scores and working memory capacity while simultaneously reducing the occurrence of distracting thoughts during completion of the GRE and the measure of working memory. Improvements in performance following mindfulness training were mediated by reduced mind wandering among participants who were prone to distraction at pretesting. Our results suggest that cultivating mindfulness is an effective and efficient technique for improving cognitive function, with wide-reaching consequences.

(The GRE is the Graduate Record Examination meant to test cognitive capacity of graduate school applicants. Readers interested in the details of the experiment, performed on the usual batch of ~50 college undergraduates, can email me.)

Alteration of paralimbic self awareness circuits in behavioral addiction.

Changeux and collaborators look at the brain correlates of pathological gambling, evaluating whether addictions might occur because of a predisposition linked to abnormal functioning of a frontal circuitry associated with self awareness, preceding any use of drugs. Some clips:

The introduction of magnetoencephalography (MEG) has made it possible to study neural mechanisms even in deeper parts of the cortex with a high degree of temporal resolution in combination with a decent spatial resolution. This allows investigation of one of the major networks of the brain, the paralimbic interaction between the medial prefrontal/anterior cingulate (ACC) and medial parietal/posterior cingulate (PCC) cortices. This interaction has in several recent studies been associated with self-awareness.

Schematic representation of the medial cortical components of the paralimbic network of self-awareness. Schematic localization of the medial sources for MEG registration. Red, ACC; Blue, PCC.

They compared 14 pathological gamblers and 11 age- and sex-matched controls using a stop-signal task consisting of “go” and “nogo” trials. In go trials, the participant is instructed to press a button as soon as an “O” appears on the screen. In nogo trials, the O is followed by an “X,” and the participant is instructed to withhold his response. The task can be used to measure a number of variables associated with impulsivity such as the stop-signal reaction time (SSRT), which is the time required for the stop signal to be processed so a response can be withheld. In particular, the SSRT has been widely used as a valid measure of impulsivity in general, and in studies of patients suffering from addiction.

The main finding of the present study was that behavioral addiction is linked to abnormal activity in, and communication between, nodal regions of the paralimbic network of self-awareness, the ACC and PCC, which are effective in different aspects of self-awareness processing. Pathological gamblers had lower synchronization between the ACC and PCC at rest in the high gamma band compared with controls, and failed to show an increase in gamma synchronization during rest compared with the task (as observed in controls). These findings could not be attributed to previous drug abuse or smoking habits. Furthermore, pathological gamblers without previous drug abuse had lower PCC power than controls and gamblers with previous stimulant abuse during the stop-signal task. In contrast, a history of stimulant abuse in gamblers caused a marked increase in power across regions and frequencies both at rest and during the stop-signal task.

Training our emotional brain - improving affective control.

Schweizer et al. suggest that our ability to keep a cool head in emotionally charged situations can be enhanced by working memory training, because both functions are associated with the same frontoparietal neural circuitry, including the dorsolateral prefrontal cortex (PFC), the inferior parietal and the anterior cingulate cortices, that can exert downregulatory effects on experienced emotional distress through projections to the amygdala and midbrain nuclei from the lateral and medial PFC components. Here is their abstract, followed by a description of the emotional working memory (not regular working memory) training that was evaluated.

Affective cognitive control capacity (e.g., the ability to regulate emotions or manipulate emotional material in the service of task goals) is associated with professional and interpersonal success. Impoverished affective control, by contrast, characterizes many neuropsychiatric disorders. Insights from neuroscience indicate that affective cognitive control relies on the same frontoparietal neural circuitry as working memory (WM) tasks, which suggests that systematic WM training, performed in an emotional context, has the potential to augment affective control. Here we show, using behavioral and fMRI measures, that 20 d of training on a novel emotional WM protocol successfully enhanced the efficiency of this frontoparietal demand network. Critically, compared with placebo training, emotional WM training also accrued transfer benefits to a “gold standard” measure of affective cognitive control–emotion regulation. These emotion regulation gains were associated with greater activity in the targeted frontoparietal demand network along with other brain regions implicated in affective control, notably the subgenual anterior cingulate cortex. The results have important implications for the utility of WM training in clinical, prevention, and occupational settings.

A description of the training:

The emotional working memory training... comprised an affective dual n-back task consisting of a series of trials each of which simultaneously presented a face (for 500 ms) on a 4 × 4 grid on a monitor and a word (for 500–950 ms) over headphones. Each picture-word pair was followed by a 2500 ms interval during which participants responded via button press if either/both stimuli from the pair matched the corresponding stimuli presented n positions back; 60% of the words (e.g., evil, rape) and faces (fearful, angry, sad, or disgusted expressions) were emotionally negative with the others affectively neutral in tone. Trial presentation order was randomized across training sessions.

Impersonating your younger self makes your body physiologically younger - a rediscovered post.

For several years I've been trying to find or recall a MindBlog post or an article read, and couldn't come up with it. A blog reader sent an email recalling it, and I couldn't find it. FINALLY, on doing a string search in this blog (for 'mindfulness') I found it, an August 2010 post that I had given the misleading title of "The Psychology of Possibility." It referenced an article in Harvard Magazine on the work of Ellen Langer (1,2,3). Some of her early work is fascinating, and the post is worth repeating here:

An interesting article in the Harvard Magazine describes the life work of Ellen Langer, her demonstrations that our social self image (old versus young, for example) strongly patterns our actual vitality and physiology, her work on Mindfulness, unconscious processing, etc. I recommend that you read the article. Here are some clips from its beginning that hooked me (I actually did my own mini-repeat of the experiment described, a simple self-experiment of pretending that I had been transported back in time to 40 years ago, and convinced myself I was experiencing some of the effects described)...

In 1981, early in her career at Harvard, Ellen Langer and her colleagues piled two groups of men in their seventies and eighties into vans, drove them two hours north to a sprawling old monastery in New Hampshire, and dropped them off 22 years earlier, in 1959. The group who went first stayed for one week and were asked to pretend they were young men, once again living in the 1950s. The second group, who arrived the week afterward, were told to stay in the present and simply reminisce about that era. Both groups were surrounded by mid-century mementos—1950s issues of Life magazine and the Saturday Evening Post, a black-and-white television, a vintage radio—and they discussed the events of the time: the launch of the first U.S. satellite, Castro’s victory ride into Havana, Nikita Khrushchev and the need for bomb shelters.

...Before and after the experiment, both groups of men took a battery of cognitive and physical tests, and after just one week, there were dramatic positive changes across the board. Both groups were stronger and more flexible. Height, weight, gait, posture, hearing, vision—even their performance on intelligence tests had improved. Their joints were more flexible, their shoulders wider, their fingers not only more agile, but longer and less gnarled by arthritis. But the men who had acted as if they were actually back in 1959 showed significantly more improvement. Those who had impersonated younger men seemed to have bodies that actually were younger.

Do we need an Apollo moon project for the brain?

I have collected a sampling of the many commentaries on the Brain Activity Map project to which Barack Obama alluded in his State of the Union address which is becoming a high profile 3-billion dollar endeavor. For a few examples, see the NYTimes, The Altantic, and Plos Blogs. I finally want to put in my two cents worth to say that such an effort is completely misguided. But first, clips from a Science article contributed by 'big science' luminaries who would profit from such a project.

...the mechanisms of perception, cognition, and action remain mysterious because they emerge from the real-time interactions of large sets of neurons in densely interconnected, widespread neural circuits. It is time for a large-scale effort in neuroscience to create and apply a new generation of tools to enable the functional mapping and control of neural activity in brains with cellular and millisecond resolution...This initiative, the Brain Activity Map (BAM), could put neuroscientists in a position to understand how the brain produces perception, action, memories, thoughts, and consciousness

The last phrase, in particular, is borderline delusional. As John Horgan points out, we don't even see the side of the barn yet. Apart from the fact that we don’t know what to include in a simulation and what to leave out, we already have conclusive evidence that a search for a road map of stable neural pathways that can represent brain functions is futile. Edited from Horgan:

...the brain is radically unlike and more complex than any existing computer. A typical brain contains 100 billion cells, and each cell is linked via synapses to as many as 100,000 others. Synapses are awash in neurotransmitters, hormones, modulatory peptide (small proteins), neural-growth factors and other chemicals that affect the transmission of signals, and synapses constantly form and dissolve, weaken and strengthen, in response to new experiences...not only do old brain cells die, new ones can form via neurogenesis...many genes are constantly turning on and off and thereby further altering operations of brain nerve cells...the brain may be processing information at many levels below and above that of individual neurons and synapses...each individual neuron, rather than resembling a transistor, maybe be more like a computer in its own right, engaging in complex information-processing.

I fear that these big, much-hyped initiatives will turn out to be as disappointing as the Decade of the Brain. Rather than boosting the status of neuroscience, they may harm its credibility.

A particularly telling story comes from my long time friend and colleague Tony Stretton at the University of Wisconsin, who studies the very simple nervous system of the parasitic nematode Ascaaris suum, that has only 298 neurons, for which a functional circuit from the morphological synapses, scored by electron microscopy, has been obtained. This is just the sort of information the Brain Activity Map project is trying to obtain for our brains. So, do we know how the Ascaris nervous system works? No, we're not even close, because Stretton has discovered that their are numerous peptides (as many as 250) that modulate the activity of neurons. Go figure how neurons in that complex modulatory soup work!! And multiply the problem by at least a billion for our brains.

To be fair, the vigorous discussion over the merits of a big push has led, as Markoff and Gorman describe in the NYTimes, to cast the enterprise as trying to better define the playing field, rather than assuming that we now know what it is.  

A next generation of antidepressants?

Russo and Charney do a brief write up on recent work of Nasca et al., who find that a common dietary supplement, L-acetylcarnitine, is a potential rapidly acting antidepressant:

Over the past 50 y, there have been few mechanistically distinct drugs for the treatment of major depressive disorders, despite the fact that nearly two-thirds of patients do not achieve full remission of symptoms on currently available antidepressants. In addition, even when adequate remission is achieved, patients require 2–4 wk of treatment before any significant effects, increasing the risk for complications, such as suicide. This delay in effectiveness has resulted in a major push to identify and develop novel therapeutics with more rapid effects. The recent identification of ketamine as a rapid antidepressant effective in treatment-resistant patients has been groundbreaking.

Nasca et al.  describe in PNAS a unique potential rapidly acting antidepressant, l-acetylcarnitine (LAC), which is a dietary supplement that acts by acetylating protein targets to control their function. LAC is reported to be well tolerated and can readily cross the blood-brain barrier. A recent study suggests it has promise in the treatment of Parkinson disease because of its neroprotective properties. Strikingly, LAC exhibits antidepressant efficacy within 2–3 d following intraperitoneal administration in rodents, compared with 2–3 wk with a standard antidepressant treatment, such as chlorimipramine. Although LAC is relatively nonspecific and can target many biological pathways, it is suggested by Nasca et al.  to promote rapid antidepressant responses by acetylation of histone proteins that control the transcription of BDNF and metabotropic glutamate 2 (mGlu2) receptors in the hippocampus (Hipp) and prefrontal cortex (PFC).

One of the more impressive aspects of this article is that Nasca et al. verify rapid antidepressant efficacy of LAC in both a genetic rat model of susceptibility [Flinders Sensitive Line (FSL)] and following chronic stress exposure, factors that are thought to be the primary cause of depression in humans. Although there is clearly far more work necessary to understand the mechanisms of antidepressant action of LAC in rodents, and the dose and relative safety profile for depression treatment in humans, these exciting results are a first step toward that goal.

What are philosophers good for?

Perhaps an appropriate post for April 1st...If you are looking for a good headache, take yourself to Gary Gutting's rehashing of the "can consciousness be explained in physical terms?" debate by dragging out the classic "Mary, the color blind scientist who knows all the physical facts about colors and their perception" and the "philosophical zombie, defined as physically identical to you or me but utterly lacking in internal subjective experience." Gutting solicits comments on his article, and in a subsequent article presents a selection of the responses. From Gutting's final paragraph:

...my conclusion is that neither the Mary nor the Zombie Argument makes a decisive case against physicalism...professional philosophers have uncovered a number of subtle and complex problems for both arguments. For anyone interested in pursuing the discussion further, I would recommend the Stanford Encyclopedia of Philosophy articles “Qualia: The Knowledge Argument” (by Martine Nida-Rümelin) and “Zombies” (by Robert Kirk).

I like Metzinger's stance that consciousness is epistemologically irreducible (see his book "The Ego Tunnel"). There is one reality, one kind of fact, but two kinds of knowledge: first-person knowledge and third-person knowledge, that never can be conflated. There is a long list of ideas on why consciousness evolved, what it is good for, doing goal hierarchies and long-terms plans, enhancement of social coordination, etc. I like Metzinger's description of consciousness as a as a new kind of virtual organ - unlike the permanent hardware of the liver, kidney, or heart it is always present. Virtual organs form for a certain time when needed (like desire, courage, anger, an immune response)..."they are a new computational strategy, that makes classes of facts globally available and allows attending, flexible reacting, within context." "Reality generation" allowed animals to represent explicitly the fact that something is actually the case, the world is present. (conscious color gives information about nutritional value, red berries among green leaves, empathy gives information about the emotional state of conspecifics).

For those of you who like this sort of stuff I point out "A darwinist lynch mob goes after a philosopher" by Leon Wieseltier in the March 11 New Republic, on some outraged reactions to Nagel's new book: "Mind and Cosmos: Why the Materialist Neo-Darwinian Conception of Nature Is Almost Certainly False."

Also,"Was Wittgenstein Right? by Paul Horwich:

Wittgenstein claims that there are no realms of phenomena whose study is the special business of a philosopher, and about which he or she should devise profound a priori theories and sophisticated supporting arguments. There are no startling discoveries to be made of facts, not open to the methods of science, yet accessible “from the armchair” through some blend of intuition, pure reason and conceptual analysis. Indeed the whole idea of a subject that could yield such results is based on confusion and wishful thinking.

To which Michael Lynch makes a rejoinder.

 I have to end by repeating another old chestnut:

Philosophy, n. A route of many roads leading from nowhere to nothing. -AMBROSE BIERCE, The Devil's Dictionary

Brain activity associated with the "Cocktail Party Effect."

Zion et al. do interesting experiments, with an array of sub-dural electrodes implanted in surgical epilepsy patients, to show what is happening as we attend to one of several simultaneously talking voices. From a commentary by Miller:

The data clearly show that both low-frequency phase (delta-theta, 1–7 Hz) and high gamma power (70–150 Hz) yield consistent trial-to-trial responses to speech. Other frequency bands do not, nor does low frequency power—adding weight to the argument that speech tracking is partly due to entrainment of endogenous rhythms. However, these effects are not equally distributed across cortical areas. The high-gamma tracking tends to be clustered in the superior temporal lobe and the low-frequency phase response is more widespread, including superior and anterior temporal regions and inferior parietal and frontal lobes. Across electrodes though, both the low-frequency phase and high-gamma power showed more consistent responses to the attended versus the ignored speech. Corroborating this observation, speech envelope acoustics could only be reconstructed from neural responses for the attended talker, not the unattended.

The Zion et al. abstract:

The ability to focus on and understand one talker in a noisy social environment is a critical social-cognitive capacity, whose underlying neuronal mechanisms are unclear. We investigated the manner in which speech streams are represented in brain activity and the way that selective attention governs the brain’s representation of speech using a “Cocktail Party” paradigm, coupled with direct recordings from the cortical surface in surgical epilepsy patients. We find that brain activity dynamically tracks speech streams using both low-frequency phase and high-frequency amplitude fluctuations and that optimal encoding likely combines the two. In and near low-level auditory cortices, attention “modulates” the representation by enhancing cortical tracking of attended speech streams, but ignored speech remains represented. In higher-order regions, the representation appears to become more “selective,” in that there is no detectable tracking of ignored speech. This selectivity itself seems to sharpen as a sentence unfolds.

The perils of perfectionism, and the world we are losing.

I want to mention one of the many items in my queue of articles for potential posts that I have neglected so far.  Vgeny Morozov does a precis of his new book “To Save Everything, Click Here: The Folly of Technological Solutionism.”

Silicon Valley’s technophilic gurus and futurists have embarked on a quest to develop the ultimate patch to the nasty bugs of humanity…Facebook’s former marketing director, enthused about a trendy app to “crowdsource absolutely every decision in your life.” Called Seesaw, the app lets you run instant polls of your friends and ask for advice on anything…Jean-Paul Sartre, the existentialist philosopher who celebrated the anguish of decision as a hallmark of responsibility, has no place in Silicon Valley.

All these efforts to ease the torments of existence might sound like paradise to Silicon Valley. But for the rest of us, they will be hell. They are driven by a pervasive and dangerous ideology that I call “solutionism”: an intellectual pathology that recognizes problems as problems based on just one criterion: whether they are “solvable” with a nice and clean technological solution at our disposal. Thus, forgetting and inconsistency become “problems” simply because we have the tools to get rid of them — and not because we’ve weighed all the philosophical pros and cons…Given Silicon Valley’s digital hammers, all problems start looking like nails, and all solutions like apps…Whenever technology companies complain that our broken world must be fixed, our initial impulse should be to ask: how do we know our world is broken in exactly the same way that Silicon Valley claims it is? What if the engineers are wrong and frustration, inconsistency, forgetting, perhaps even partisanship, are the very features that allow us to morph into the complex social actors that we are?

In the same apocalyptic spirit Edward Hoagland writes a lyrical elegy to the natural world we are losing:

Aesop, the fabulist and slave who, like Scheherazade, may have won his freedom by the magic of his tongue and who supposedly shared the Greek island of Samos with Pythagoras 2,500 years ago, nailed down our fellowship with other beasties of the animal kingdom. Yet we seem to have reached an apogee of separation since then. The problem is, we find ourselves quite ungovernable when operating solo, shredding our habitat, while hugging our dogs and cats as if for consolation and dieting on whole-food calories if we are affluent enough. Google Earth and genome games also lend us a fitful confidence that everything is under control.

It’s a steeplechase, hell-for-leather and exhilarating, for the highest stakes, but not knowing where we’re going. Call it progress or metastasizing, what we have done as a race, a species or a civilization is dumbfounding. Every inch of the planet is ours, we claim, and elements of clear improvement are intertwined with cancerous excess

…Aesopian metaphors were artesian if not prehistoric. The tortoise and the hare, the lion saved by the mouse, the monkey who would be king, the dog in the manger, the dog and his shadow, the country mouse and the city mouse, the wolf in sheep’s clothing, the raven and the crow, the heron and the fish, the peacock and the crane. From where will we draw replacement similes and language? Pop culture somersaults “bad” to mean good, “cool” to mean warm, and bustles and bodices segue into tank tops and cargo pants, as in a robust society they should. But will a natural keel remain, as we face multiflex, multiplex change? “Hogging” the spotlight, playing possum, resembling a deer in the headlights, being buffaloed or played like a fish: will the clarity of what is said hold? A “tiger,” a “turtle,” a “toad.” After the oceans have been vacuumed of protein and people are eating farmed tilapia and caked algae, will Aesop’s platform of markers remain?

Ambivalence and Body Movement

Schneider et al. make interesting observations about circulation correlations between our thoughts and body movements. We sway more from side to when we feel ambivalent about a choice or situation, and if we apply a swaying motion to our bodies, that makes us feel more ambivalent about a topic on which we are already uncertain.

Prior research exploring the relationship between evaluations and body movements has focused on one-sided evaluations. However, people regularly encounter objects or situations about which they simultaneously hold both positive and negative views, which results in the experience of ambivalence. Such experiences are often described in physical terms: For example, people say they are “wavering” between two sides of an issue or are “torn.” Building on this observation, we designed two studies to explore the relationship between the experience of ambivalence and side-to-side movement, or wavering. In a first study, we used a Wii Balance Board to measure movement and found that people who are experiencing ambivalence move from side to side more than people who are not experiencing ambivalence. In a second study, we induced body movement to explore the reverse relationship and found that when people are made to move from side to side, their experiences of ambivalence are enhanced.

If you use Google Reader to follow Deric's MindBlog, please read on....

This blog has ~2,500 RSS subscribers. As I write this, 2,240 subscribers are obtaining the feed via Feedfetcher, which is how Google grabs RSS or Atom feeds when users subscribe to them in Google Reader or iGoogle. Feedfetcher collects and periodically refreshes these user-initiated feeds.

Because it doesn't make the billions of dollars that Google requires for a service, Google has announced that it is shutting it down on July 1. If you want to continue getting MindBlog's RSS feed you will need to use an alternative reader. This Lifehacker post suggests five of the best alternatives - a few further suggestions are here. (I use my My Yahoo home page to obtain RSS feeds from blogs I follow.) Also, a note: There are more petitions floating around the web to keep Google Reader alive than it is possible to count.

(added note, comment from blog re3ader: "It should be noted that you don't need to use unreliable web services to aggregate rss/atom feeds. There are lots of excellent software programs to do so. By using actual software instead of a third party web service you have both insured access and offline access. I use rssowl, a program that runs on the big three OSes (http://www.rssowl.org/)." )

Are there trendy parts of the brain?

Behrens et al. do an interesting analysis, asking:

Are there really trendy parts of the brain? Or does each scientist falsely believe their own research area to be underrepresented in the top journals, and their friend's recent Nature paper to be the result of a passing fad? The maturity of functional brain imaging allows us to perform a rigorous test of this instinctual feeling. There have now been many thousands of imaging papers published across the journal spectrum. Are some brain regions really overrepresented in this literature? In addition, are papers reporting activation in some brain regions preferentially published in high-impact journals, whereas others are published in low-impact ones? To answer these questions, we examined 7342 functional contrasts published between 1985 and 2008 and documented in the BrainMap database.

Figure - (a) Distributions of activation frequency across the brain. Popular voxels are portrayed in red; unpopular ones in blue. (b) Frequency distribution of keywords describing experimental domains, paradigms, and functional contrasts. The size of each word is proportional to its frequency in the BrainMap database.

Journal impact factor strongly predicted activity in several different brain areas. With one exception in the primary visual cortex, we suspect these brain regions would largely confirm anecdotal hypotheses. For example, researchers who find activity in a prescribed part of the fusiform gyrus should be confident of having their article selected for publication in a high-impact journal, perhaps due to the role of the region in face processing. Other regions with proposed roles in emotional processing returned similarly stellar performances, including both the ventral and dorsal portions of the rostral medial prefrontal cortex, the anterior insular cortex, the anterior cingulate gyrus, and the amygdala. The recent interest in reward prediction errors might explain impactful peaks in the mid-brain and ventral striatum, areas that exhibited independent significant effects of impact factor, publication date, and their interaction: studies reporting activation in these regions are published in high-impact journals, and are increasing in number (as a proportion of all studies) over time.

A Cornucopia of Mind Blog sites.

Scientific American has announced that its daughter magazine Scientific American Mind has set up a Blogs site that lists a number of psychology, neuroscience, etc. blogs dealing with the Mind. Just starting to sample from the blogs listed is an overwhelming experience. Keeping up with blogs dealing with mind in the current blogosphere would be more than a full time job. My own list of "Other Mind Blogs" in the right hand column of this blog is several years old, and now doesn't include many excellent current efforts. I occasionally find this blog listed in "Top Psychology Blogs" on other sites.  We could all easily spend all our time "taking in each other's laundry," to become aggregators of aggregators of aggregators ad infinitum. This is why I don't look much at other Mind Blogs, but rather stick to looking through recent original research articles in the major journals. The efforts of each of us who labor away passing on some small fraction of the research world are appreciated by a sufficient number of readers to motivate us to continue.

Having said I don't look at other mind blogs,  I'll pass on this gem from "Brain Pickings" (click to enlarge and see text more clearly: "Friendship-The Silent Places-Where Speech Ends"

The brain basis of our superiority illusion.

One of the most robustly documented findings of psychology is the "optimism" bias, which leads us to put rose-colored glasses on past, future, and our own abilities. (Did you know that a spectacular 94% of college professors rate themselves to have teaching abilities that are above average?.) Equally well documented is the fact the people who have a fully realistic view of their abilities and their importance to groups tend to be depressed. It seems clear that most of us are completely unequipped to function without a vast array of positive delusions about our abilities, our futures, etc.

There is a large literature on this. Dan Dennett and McKay have written a treatise in Brain and Behavioral Science that examines possible evolutionary rationales for mistaken beliefs, bizarre delusions, instances of self-deception, etc., they conclude that only positive illusions meet their criteria for being adaptive. Johnson and his colleagues have produced an evolutionary model suggesting that overconfidence maximizes individual fitness and that populations tend to become overconfident as long as benefits from contested resources are sufficiently large compared with the cost of competition.

 Yamada et al. now look at resting state functional connectivity between brain regions whose activity correlates with the superiority illusion. Their abstract, and one figure from their paper:

The majority of individuals evaluate themselves as superior to average. This is a cognitive bias known as the “superiority illusion.” This illusion helps us to have hope for the future and is deep-rooted in the process of human evolution. In this study, we examined the default states of neural and molecular systems that generate this illusion, using resting-state functional MRI and PET. Resting-state functional connectivity between the frontal cortex and striatum regulated by inhibitory dopaminergic neurotransmission determines individual levels of the superiority illusion. Our findings help elucidate how this key aspect of the human mind is biologically determined, and identify potential molecular and neural targets for treatment for depressive realism.

Influence of striatal D2 availability on superiority illusion is mediated through dorsal anterior cingulate - striatal functional connectivity. Assuming an inverse relationship between D2 receptor availability and presynaptic dopamine release, dopamine likely acts on striatal D2 receptors to suppress functional connectivity between the dorsal striatum and dACC (2). This connectivity predicts individual differences in the superiority illusion  The indirect effect of striatal D2 receptor availability on the superiority illusion is significantly mediated through dACC-striatal functional connectivity . “+” indicates a positive relationship; “–,” a negative relationship.

Would Tarzan believe in God?

Some clips from Konika Banerjee and Paul Bloom:

Would someone raised without exposure to religious views nonetheless come to believe in the existence of God, an afterlife, and the intentional creation of humans and other animals? Many scholars would answer yes, proposing that universal cognitive biases generate religious ideas anew within each individual mind. Drawing on evidence from developmental psychology, we argue here that the answer is no: children lack spontaneous theistic views and the emergence of religion is crucially dependent on culture.

...if universal, early-emerging cognitive biases generate religious ideas, we would expect to see these ideas emerge spontaneously. This would be akin to the process of creolization, such as when deaf children who are exposed to non-linguistic communication systems create their own sign language. However, such cases are, as best we know, non-existent. There are many examples where children are quick to endorse religious beliefs, often surprising their atheist parents. But this is consistent with receptivity, not generativity, as these beliefs correspond to those endorsed within the social environment in which children are raised.

Findings from developmental psychology support the following theory of the emergence of religious belief: humans possess a suite of sophisticated cognitive adaptations for social life, which make accessible certain concepts that are associated with religion, including design, purpose, agency, and body–soul dualism. However, more is needed to generate fully-fledged, sustained, and conscious religious beliefs, including a belief in gods, in divine creation of natural entities, and in life after death. Such beliefs require cultural support.

Negativity bias and political ideology

I've just received a reviewer's copy of an upcoming article in Brain and Behavioral Science in the vein of several MindBlog posts mentioning work on the brains of conservatives versus liberals: "Differences in Negativity Bias Underlie Variations in Political Ideology" by J. R. Hibbing, K.B. Smith, and John R. Alford. I thought MindBlog readers might be interested in their abstract:

Disputes between those holding differing political views are ubiquitous, deep-seated, and often follow common, recognizable lines, with the supporters of tradition and stability, sometimes referred to as conservatives, doing battle with the supporters of innovation and reform, sometimes referred to as liberals. Understanding the correlates of these distinct political orientations is likely a prerequisite for managing political disputes, a source of social conflict often leading to frustration and even bloodshed. A rapidly growing body of empirical evidence documents a multitude of ways in which liberals and conservatives differ from each other in purviews of life with little direct connection to politics, from tastes in art to desire for closure and from disgust sensitivity to the tendency to pursue new information, but the central theme of these differences is a matter of debate. In this article, we argue that one organizing element of the many differences between liberals and conservatives is the nature of their physiological and psychological responses to features of the environment that are negative. Compared to liberals, conservatives tend to register greater physiological responses to such stimuli and also to devote more psychological resources to them. Operating from this point of departure, we suggest future approaches for refining understanding of the broad relationship between political views and response to the negative. We conclude with a discussion of normative implications, stressing that identifying differences across ideological groups is not tantamount to declaring one ideology superior to another.

Reversal of hearing decline with aging.

It is known that life-long musical experience partially offsets age-related neural timing delays. Such delays make it harder to process speech in noisy environments, and hearing aids don't help. (This is one reason I keep giving piano recitals). In a fascinating recent article, Anderson et al. show a partial reversal of these age-related neural timing delays can be partially reversed by cognitive auditory training. Edited from their text (in which the data show the indicated expectation were confirmed):

An auditory training group (n = 35) completed an adaptive computer-based auditory training program that combines bottom-up perceptual discrimination exercises with top-down cognitive demands. The second group (active control; n = 32) participated in a general educational stimulation program that was matched for time and computer use to that of the auditory training group. We recorded auditory brainstem responses to the speech syllable [da] presented in quiet and noise and assessed speech-in-noise perception, short-term memory, and speed of processing before and after 8 wk of training. We expected that auditory training would induce earlier brainstem peak latencies at posttest compared with pretest, and that the effects of noise on response timing would be reduced. Given previously demonstrated cognitive and perceptual gains from both short-term and long-term auditory training, we expected that auditory training would also improve speech-in-noise perception, short-term memory, and speed of processing.

The abstract:

Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills.

By the way, on this topic, Miller has a recent interesting article on the brain basis of the "cocktail party effect', how we single out a single voice in a room full of conversations.

How to dress to say it is wrong to be gay!

I had to pass this on.....

FABULOUS! The Pope Emeritus, wearing a fabulous vintage chiffon-lined Dior gold lame gown
over a silk Vera Wang empire waist tulle cocktail dress,
accessorized with a three-foot House of Whoville hat
and the ruby slippers Judy Garland wore in the Wizard of Oz,
on his way to tell us it's wrong to be gay.

Stay plain and simple, Francis! Stay plain and simple!

Does cannabis use cause lower IQ?

Rogeberg offers a critique of a recent suggestion by Meyer et. al. of a neurotoxic effect of cannabis on developing brains that permanently lowers IQ, based on on a correlation between persistent cannabis use initiated in adolescence and a decline in IQ-scores between the ages of 13 and 38. The data come  the" Dunedin cohort," 1,037 individuals followed from birth (1972/1973) to age 38 y. An alternative confounding model can be based on time-varying effects of socioeconomic status on IQ.

Does cannabis use have substantial and permanent effects on neuropsychological functioning? Renewed and intense attention to the issue has followed recent research on the Dunedin cohort, which found a positive association between, on the one hand, adolescent-onset cannabis use and dependence and, on the other hand, a decline in IQ from childhood to adulthood [Meier et al. (2012) Proc Natl Acad Sci USA 109(40):E2657–E2664]. The association is given a causal interpretation by the authors, but existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the Dunedin cohort, suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero. Further analyses of the Dunedin cohort are proposed to distinguish between the competing interpretations. Although it would be too strong to say that the results have been discredited, the methodology is flawed and the causal inference drawn from the results premature.

Observing regulatory connections correlating with emotion control during transition to adolescence.

Interesting work from Gee et al. showing some brain changes that correlate with the inhibition of emotional reactivity that occurs during human adolescence:

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. Although tracing studies have suggested changes in amygdala–cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala–prefrontal circuitry across the ages of 4–22 years using task-based functional magnetic resonance imaging. Results suggest positive amygdala–prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala–medial prefrontal cortex functional connectivity was significantly positive (greater than zero) among participants younger than 10 years, whereas functional connectivity was significantly negative (less than zero) among participants 10 years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.

How do alligators get errections?

I couldn't resist passing on this Discoblog pointer to Kelly's article. Most birds, reptiles, and mammals have penises that become erect by filling with fluid, but the alligator penis does not change shape or stiffness before sex. Kelly suggests it is popped out of the cloaca by muscles evolved for this purpose:

The intromittent organs of most amniotes contain variable-volume hydrostatic skeletons that are stored in a flexible state and inflate with fluid before or during copulation. However, the penis in male crocodilians is notable because its shaft does not seem to change either its shape or bending stiffness as blood enters its vascular spaces before copulation. Here I report that crocodilians may have evolved a mechanism for penile shaft erection that does not require inflation and detumescence. Dissections of the cloaca in sexually mature male American alligators (Alligator mississippiensis) show that the cross section of the proximal shaft of the alligator penis contains dense collagenous tissues that do not significantly change shape when fluid is added to the central vascular space. The large amount of collagen in the wall and central space of the alligator penis stiffen the structure so it can be simply everted for copulation and rapidly retracted at its completion. Because no muscles insert directly onto the penis, eversion and retraction must be produced indirectly. My results suggest that the contraction of paired levator cloacae muscles around the anterior end of the cloaca rotates the penis out of the cloacal opening and strains the ligamentum rami that connect the base of the penis to the ischia. When the cloacal muscles relax, the elastic recoil of the ligamentum rami can return the penis to its original position inside the cloaca.

Anti-aging drugs - Clarification on Resveratrol and SIRT1 activators

Resveratrol, the natural compound in red wine, and other small molecules are allosteric activators of SIRT1, an enzyme with roles in many biological processes (including DNA repair, metabolism, programmed cell death, and inflammation) that affect human life span. Studies have shown that Sirtuin activators like resveratrol can extend the lifespan of yeast, worms, and flies. From an editor's summary of work by Hubbard et al in the latest issue of Science:

Intense attention has focused on the SIRT1 deacetylase as a possible target for anti-aging drugs. But unexpected complications in assays of SIRT1 activity have made it unclear whether compounds thought to be sirtuin-activating compounds (STACs) are really direct regulators of the enzyme. Further exploration of these effects by Hubbard et al. revealed that interaction of SIRT1 with certain substrates allows activation of SIRT1 by STACs and identified critical amino acids in SIRT1 required for these effects. Mouse myoblasts reconstituted with SIRT1 mutated at this amino acid lost their responsiveness to STACs.

The Hubbard et al abstract:

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu230, located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.

The mental cost of cognitive enhancement.

There has been quite a bit of interest lately in the prospect of enhancing various brain operations by the use of trans-cranial electrical stimulation (TES). Iuculano and Kadosh make the fascinating observation that enhancing one activity with TES can compromise another:

Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.

And you thought you knew the data on wealth inequality?

I found this a jaw-dropping clarification of wealth inequality in the U.S.

Can the Catholic Church evolve?

Maureen Dowd discusses gay author Colin Toibin’s “The Testament of Mary,” a one-woman show with Fiona Shaw previewing later this month on Broadway, and I pass on this fascinating clip on Toibin’s thoughts about the Church and homosexuality (I was fascinated to learn about Benedict's “Gorgeous Georg”, who he takes with him into retirement.):

Benedict may have given up his flashy red loafers, downgrading to brown ones made for him in Mexico, but he is taking “Gorgeous Georg,” as the younger German is known, to live in his new home, a monastery in the Vatican. Some cardinals are worried about the arrangement of having Gänswein serve two pontiffs, by day as prefect of the new pope’s household and at night as secretary to the emeritus pope.

“An 85-year-old man having such a beautiful companion with him morning and night to talk to and walk with,” Toibin said. “It’s like the end of a novel. It’s what all of us want for ourselves, straight or gay. It’s better than sex.”

I ask him whether he thinks the church will evolve under a new pope.

“Everyone is hoping for some change,” he said. “If you could see nuns making sermons. Clerical celibacy has to be abolished and soon. And we must quickly begin the process of allowing women into the priesthood.

“They need to think very carefully about not recognizing that gay people, like all other people, are made in God’s image. It’s just possible that they have more gay priests than they know. I think most gay priests are very good people in the priesthood for very good reasons, and actually faithful to the vows of celibacy. On the issue of gays, Benedict made things even worse.”

As Cardinal Ratzinger, Benedict called homosexuality a “more or less strong tendency ordered towards an intrinsic moral evil.” As pope, he reiterated the church view that homosexuals were “objectively disordered” and that men who had such tendencies could not be allowed into seminaries. He called gay marriage a threat to “the future of humanity itself.”

Toibin says that the church must have tolerance, and that its leaders have lost any sense of how their sanctimonious denunciations clash with their scandals and imagery, causing nothing but pain.

“I remember being at the Vatican at Easter 1994,” he recalled, “and watching all the cardinals and bishops, wonderfully powerful old men with great chins, sitting nobly with a long row of extraordinarily beautiful young seminarians standing behind, shading them with different colored sun umbrellas, some of which were pink."

“It was remarkable that none of them seemed to know what it looked like, and I watched it thinking, somebody must tell them.”

Neural mechanisms of stress vulnerability and resilience.

Two interesting papers in the Journal of Neuroscience  deal with what is happening to nerve cells in mouse brains as they either do or don't recover from stress. Lehmann et al. demonstrate that glucocorticoid-dependent declines in neurogenesis drive changes in mood after social defeat and that glucocorticoids secreted during enrichment promote hippocampal neurogenesis and restore normal behavior after defeat, suggesting that treatments promoting neurogenesis can enhance stress resilience. Gourley et al. looked at the elimination of dendritic spines in the hippocampus caused by chronic stress exposure, and show that resilience, or recovery from stress, correlates with spine proliferation.

In praise of the unexamined, unlived life?

I was sufficiently interested by two reviews of a new book by British psychoanalyst Adam Phillips (“Missing Out: In Praise of the Unlived Life”), one in the NYTimes (Sheila Heti), one in The New Yorker (Joan Acocella), that I downloaded a Kindle version to look over. I totally regret having spent the 11 bucks. There are two main messages noted by reviewers, one is the dressing up of homily common to many self help books. From Acocella:

Instead of feeling that we should have a better life, he says, we should just live, as gratifyingly as possible, the life we have.  Otherwise, we are setting ourselves up for bitterness.  What makes us think that we could have been a contender?  Yet, in the dark of night, we do think this, and grieve that it wasn’t possible.  “And what was not possible all too easily becomes the story of our lives,” Phillips writes.  “Out lived lives might become a protracted mourning for, or an endless trauma about, the lives we were unable to live.”

OK, fair enough. It can be an error to spend our  time thinking on what we might have been or want to be or ought to be or be doing, rather than just living  and being who we are, getting on with it.  Just doing things. The rub is that Phillips is completely unwilling to write simple sentences with simple ideas. He generates complex elliptical sentences designed more to illustrate his erudition and mental pyrotechnics than to inform, lost in a world of abstraction.

I completely lost it with his second chapter "On Not Getting It," where he essentially argues that we are better off not understanding ourselves, or others. His correct contention that we can never really understand ourselves or others is beside the point. Our illusions of understanding ourselves and others are a feature evolved by our social brains that has proven its utility in enhancing and passing on the genes of groups of humans who share common illusions. And, we sure have gotten a lot of mileage out of trying to understand. Otherwise we wouldn't be attempting to read psychoanalytic babble like Philips' or write things like MindBlogs.

Is the insula necessary for our feelings? If not, where are they?

I have been fairly uncritical in passing on simplifications like “The insula is the sensory cortex for our internal visceral feelings” and so was grateful to see, in Damasio’s recent review article “The nature of feelings: evolutionary and neurobiological origins” a critique of this idea:

Feelings and the insula. Interoceptive information mapped in the brainstem is projected rostrally to the subcortical basal forebrain and to the cortical telencephalon, where it is remapped in the insula and somatosensory cortices SI and SII.

Contemporary neuroscience has identified the insula as the main cortical target for signals from the interoceptive system, and functional neuroimaging studies consistently implicate the human insula in both interoceptive and emotional feelings.

Recently, it has been proposed that the insula is not merely involved in human feelings but is their sole platform and, by extension, the critical provider of human awareness. Several findings suggest that this hypothesis is problematic. First, given that several topographically organized nuclei of the upper brainstem, which are obligatory relay stations for most signals conveyed from the body to the insula, can produce elaborate representations of multiple parameters of body states, these regions should not be excluded a priori as platforms for feelings. Second, children born without cerebral cortex exhibit behaviours compatible with feeling states. Third, bilateral insular damage does not abolish all feelings. Specifically, complete bilateral destruction of the insula as a result of herpes simplex encephalitis does not abolish either body or emotional feelings, including pain, pleasure, itch, tickle, happiness, sadness, apprehension, irritation, caring and compassion, in addition to hunger, thirst, and bladder and colon distension. In fact, feelings seem to dominate the mental landscape of patients with bilateral insular damage. Immediate comfort appears to be their main concern, fairly unbridled by cognitive constraints.

These observations do not support a view of the insula as a necessary substrate for feeling states. Thus, the generation of feelings must also rely on the brainstem and possibly on the SI and SII somatosensory cortices of the parietal lobe, which are spared in some patients that lack the insular cortices but remain fully capable of feeling. Indeed, damage to the posterior half of the upper brainstem is associated with coma or vegetative state — two conditions in which feelings and sentience are abolished.

After reviewing data on how feelings persist after lesions to other cortical regions suggested central to feelings, Damasio suggests that subcortical regions such as the upper brainstem and hypothalamus are most central in the generation of feelings, and that this has resounding evolutionary implications:

...the fundamental elements of body state mapping, sentience and feelings imbued with valence are likely to be far older than our species, and probably even older than the advent of cerebral cortices. There is good reason to believe that the primate brain inherited the neural instruments for feeling from its ancestors and elaborated upon them.

Watching our auditory brain, like a radio, switch hearing frequency channels.

From Da Costa et al.:

Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand.

Amygdala damage can make us more generous

From van Honk et al.:

Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the basolateral amygdala (BLA) subserves instrumental behaviors and regulates the central-medial amygdala, which subserves impulsive behaviors. The human amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.

Here is the anatomical location of the human lesions:

MR images (coronal view) of the three subjects with Urbach–Wiethe disease (UWD), with their year of birth and red crosshairs indicating the calcified brain damage...the lesions of the three patients are located in the BLA...the functional method shows activation during emotion matching in the superficial amygdala (SFA) and CMA, but not in the BLA.

How our viscera influence our brain and behavior

I want to pass on this fascinating and useful open source review by Critchley and Harrison in the journal Neuron. Having just had the flu, I found their presentation of visceral regulation of sickness behaviors very relevant! The article is worthwhile especially for the summary figures showing functional and anatomical pathways. (I resist the urge to paste them into this post, you can look at them by clicking on the link above. Here is their abstract:

Mental processes and their neural substrates are intimately linked to the homeostatic control of internal bodily state. There are a set of distinct interoceptive pathways that directly and indirectly influence brain functions. The anatomical organization of these pathways and the psychological/behavioral expressions of their influence appear along discrete, evolutionarily conserved dimensions that are tractable to a mechanistic understanding. Here, we review the role of these pathways as sources of biases to perception, cognition, emotion, and behavior and arguably the dynamic basis to the concept of self.

And, two clips from the text:

The internal state of the body motivates our desire to walk in the shade on a warm summer’s day and inhibits the desire to eat or socialize when feeling off-color. Communication from the viscera to brain is continuous and pervasive, yet we rarely give it a second thought. Visceral fluctuations and reactions accessible to introspective appraisal represent only the visible tip of the iceberg.

A comprehensive understanding of the integration of internal bodily signals in health is ultimately required for effective management of physical and psychological symptoms in illness. Such a goal can only be achieved through coordinated experimental approaches and perhaps a move away from treating physiological changes as irrelevant confounds in neuropsychological experiments. Together, these observations make “us realize more deeply than ever how much of our mental life is knit up in our corporeal frame” (James, 1890).