A Gee Whiz! moment. Activating neurons with ultrasound.

Optogenetics, making nerve cells sensitive to light by a genetic manipulation, has the limitation that light doesn't penetrate living tissue very well, and so must be delivered by a invasive thin fiber optic stimulation. Frank and Gorman offer a video clip describing work of Ibsen et al., who show a nerve cell can be genetically altered to become sensitive to activation by non-invasive ultrasound, an approach they described as "sonogenetics." The video (I could do without the rock music sound track) shows a worm's movement changing direction as a nerve cell is stimulated by ultrasound.

1/f brain noise increases with aging.

From Gazzaley and collaborators, a description of what in going on in our aging brains:

Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging.

Methionine, an amino acid, enhances recovery from cocaine addiction.

Wright et al. use a mouse model to show that the common amino acid methionine - which can serve as a methyl group donor for the DNA methylation that regulates neural functions associated with learning, memory, and synaptic plasticity - can reduce addictive like behaviors such as drug seeking, and block a cocaine-induced marker of neuronal activation after reinstatement in the nucleus accumbens and the medial prefrontal cortex, two brain regions responsible for drug seeking and relapse. Here is the technical abstract:

Epigenetic mechanisms, such as histone modifications, regulate responsiveness to drugs of abuse, such as cocaine, but relatively little is known about the regulation of addictive-like behaviors by DNA methylation. To investigate the influence of DNA methylation on the locomotor-activating effects of cocaine and on drug-seeking behavior, rats receiving methyl supplementation via chronic L-methionine (MET) underwent either a sensitization regimen of intermittent cocaine injections or intravenous self-administration of cocaine, followed by cue-induced and drug-primed reinstatement. MET blocked sensitization to the locomotor-activating effects of cocaine and attenuated drug-primed reinstatement, with no effect on cue-induced reinstatement or sucrose self-administration and reinstatement. Furthermore, upregulation of DNA methyltransferase 3a and 3b and global DNA hypomethylation were observed in the nucleus accumbens core (NAc), but not in the medial prefrontal cortex (mPFC), of cocaine-pretreated rats. Glutamatergic projections from the mPFC to the NAc are critically involved in the regulation of cocaine-primed reinstatement, and activation of both brain regions is seen in human addicts when reexposed to the drug. When compared with vehicle-pretreated rats, the immediate early gene c-Fos (a marker of neuronal activation) was upregulated in the NAc and mPFC of cocaine-pretreated rats after cocaine-primed reinstatement, and chronic MET treatment blocked its induction in both regions. Cocaine-induced c-Fos expression in the NAc was associated with reduced methylation at CpG dinucleotides in the c-Fos gene promoter, effects reversed by MET treatment. Overall, these data suggest that drug-seeking behaviors are, in part, attributable to a DNA methylation-dependent process, likely occurring at specific gene loci (e.g., c-Fos) in the reward pathway.

Memory aging and brain maintenance

An open access article by Nyberg et al. notes

The association of intact memory functioning in old age with maintenance and preservation of a functionally young and healthy brain may seem obvious. However, up to the present the focus has largely been on possible forms of compensatory brain responses. This is so, even though it remains unclear whether memory performance in old age can benefit from altered patterns of brain activation, with almost as many studies showing positive as negative relationships.

Their abstract suggests the relevance of "brain maintenance":

Episodic memory and working memory decline with advancing age. Nevertheless, large-scale population-based studies document well-preserved memory functioning in some older individuals. The influential ‘reserve’ notion holds that individual differences in brain characteristics or in the manner people process tasks allow some individuals to cope better than others with brain pathology and hence show preserved memory performance. Here, we discuss a complementary concept, that of brain maintenance (or relative lack of brain pathology), and argue that it constitutes the primary determinant of successful memory aging. We discuss evidence for brain maintenance at different levels: cellular, neurochemical, gray- and white-matter integrity, and systems-level activation patterns. Various genetic and lifestyle factors support brain maintenance in aging and interventions may be designed to promote maintenance of brain structure and function in late life.

The figures are worth a look, for they illustrate how a fraction of older individuals have brains that, at different levels of brain organization, are similar to younger brains in their relative lack of brain pathology. They say very little about the "lifestyle factors" or "interventions" that might promote brain maintenance.

The wealthy are different from you and me...

The abstract from an article titled "The distributional preferences of an elite" by Fisman et al.:

We studied the distributional preferences of an elite cadre of Yale Law School students, a group that will assume positions of power in U.S. society. Our experimental design allows us to test whether redistributive decisions are consistent with utility maximization and to decompose underlying preferences into two qualitatively different tradeoffs: fair-mindedness versus self-interest, and equality versus efficiency. Yale Law School subjects are more consistent than subjects drawn from the American Life Panel, a diverse sample of Americans. Relative to the American Life Panel, Yale Law School subjects are also less fair-minded and substantially more efficiency-focused. We further show that our measure of equality-efficiency tradeoffs predicts Yale Law School students’ career choices: Equality-minded subjects are more likely to be employed at nonprofit organizations.

Watching sleep deprivation cause a decline in prefrontal control of emotion.

From Simon et al.:

Sleep deprivation has been shown recently to alter emotional processing possibly associated with reduced frontal regulation. Such impairments can ultimately fail adaptive attempts to regulate emotional processing (also known as cognitive control of emotion), although this hypothesis has not been examined directly. Therefore, we explored the influence of sleep deprivation on the human brain using two different cognitive–emotional tasks, recorded using fMRI and EEG. Both tasks involved irrelevant emotional and neutral distractors presented during a competing cognitive challenge, thus creating a continuous demand for regulating emotional processing. Results reveal that, although participants showed enhanced limbic and electrophysiological reactions to emotional distractors regardless of their sleep state, they were specifically unable to ignore neutral distracting information after sleep deprivation. As a consequence, sleep deprivation resulted in similar processing of neutral and negative distractors, thus disabling accurate emotional discrimination. As expected, these findings were further associated with a decrease in prefrontal connectivity patterns in both EEG and fMRI signals, reflecting a profound decline in cognitive control of emotion. Notably, such a decline was associated with lower REM sleep amounts, supporting a role for REM sleep in overnight emotional processing. Altogether, our findings suggest that losing sleep alters emotional reactivity by lowering the threshold for emotional activation, leading to a maladaptive loss of emotional neutrality.

Ig Nobel Prizes for 2015

This year’s Ig Nobel Prizes, awarded in an annual ceremony in Harvard University’s Sanders Theater:

Chemistry prize - for inventing a chemical recipe to partially un-boil an egg.

Physics prize - for testing the biological principle that nearly all mammals empty their bladders in about 21 seconds (bigger bladders gush faster on emptying).

Literature prize - for discovering that the word "huh?" (or its equivalent) seems to exist in every human language — and for not being quite sure why.

Economics prize - to the Bangkok, Thailand, Metropolitan Police, for offering to pay policemen extra cash if the policemen refuse to take bribes.

Medicine prize - for experiments to study the biomedical benefits or biomedical consequences of intense kissing (and other intimate, interpersonal activities).

Mathematics prize - for trying to use mathematical techniques to determine whether and how Moulay Ismael the Bloodthirsty, the Sharifian Emperor of Morocco, managed, during the years from 1697 through 1727, to father 888 children.

Biology prize - for observing that when you attach a weighted stick to the rear end of a chicken, the chicken then walks in a manner similar to that in which dinosaurs are thought to have walked.

Diagnostic Medicine prize - for determining that acute appendicitis can be accurately diagnosed by the amount of pain evident when the patient is driven over speed bumps.

Physiology and Entomology prize - Awarded jointly to two individuals: Justin Schmidt [USA, CANADA], for painstakingly creating the Schmidt Sting Pain Index, which rates the relative pain people feel when stung by various insects; and to Michael L. Smith [USA, UK, THE NETHERLANDS], for carefully arranging for honey bees to sting him repeatedly on 25 different locations on his body, to learn which locations are the least painful (the skull, middle toe tip, and upper arm). and which are the most painful (the nostril, upper lip, and penis shaft).

For a full description of recipients and journal references, see this link.

Brain system for mental orientation in space, time, and person.

Peer and collaborators show that mental orientation in space, time, and person produces a sequential posterior–anterior pattern of activity in each participant’s brain.

Processing of spatial, temporal, and social relations relies on mental cognitive maps, on which the behaving self is oriented relative to different places, events, and people. Using high-resolution functional MRI scanning in individual subjects, we show that mental orientation in space, time, and person produces a sequential posterior–anterior pattern of activity in each participant’s brain. These activations are adjacent and partially overlapping, highlighting the relation between mental orientation in these domains. Furthermore, the activity is highly overlapping with the brain’s default-mode network, a system involved in self-referential processing. These findings may shed new light on fundamental cognitive processing of space, time, and person and alter our understanding of disorientation phenomena in neuropsychiatric disorders such as Alzheimer’s disease.

Midsagittal cortical activity during orientation in space, time, and person. (A) Domain-specific activity in a representative subject, identified by contrasting activity between each orientation domain and the other two domains. The precuneus region is active in all three orientation domains, and the medial prefrontal cortex only in person and time orientation. Dashed black lines represent the limit of the scanned region in this subject. (B) Precuneus activity in four subjects, demonstrating a highly consistent posterior–anterior organization (white dashed line); all other subjects showed the same activity pattern (Fig. S1). (C) Group average (n = 16) of event-related activity in independent experimental runs demonstrates the specificity of each cluster to one orientation domain. Lines represent activity in response to space (blue), time (green), and person (red) conditions. Error bars represent SEM between subjects. (D) Group average of beta plots from volume-of-interest GLM analysis, showing highly significant domain-specific activity. Error bars represent SEM between subjects. P, person; S, space; T, time.

More exercise correlates with younger body cells.

Reynolds points to work by Loprinzi et al. showing physically active people have longer telomeres at the end of their chromosomes' DNA strands than sedentary people. (A telomere is a region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. It's length is a measure of a cell's biological age because it naturally shortens and frays with age.) Here is their abstract, complete with three (unnecessary) abbreviations, LTL (leukocyte telomere length), PA (physical activity) and MBB (Movement based behaviors), that you will have to keep in your short term memory for a few seconds:

INTRODUCTION: Short leukocyte telomere length (LTL) has become a hallmark characteristic of aging. Some, but not all, evidence suggests that physical activity (PA) may play an important role in attenuating age-related diseases and may provide a protective effect for telomeres. The purpose of this study was to examine the association between PA and LTL in a national sample of US adults from the National Health and Nutrition Examination Survey.

METHODS: National Health and Nutrition Examination Survey data from 1999 to 2002 (n = 6503; 20-84 yr) were used. Four self-report questions related to movement-based behaviors (MBB) were assessed. The four MBB included whether individuals participated in moderate-intensity PA, vigorous-intensity PA, walking/cycling for transportation, and muscle-strengthening activities. An MBB index variable was created by summing the number of MBB an individual engaged in (range, 0-4).

RESULTS: A clear dose-response relation was observed between MBB and LTL; across the LTL tertiles, respectively, the mean numbers of MBB were 1.18, 1.44, and 1.54 (Ptrend less than 0.001). After adjustments (including age) and compared with those engaging in 0 MBB, those engaging in 1, 2, 3, and 4 MBB, respectively, had a 3% (P = 0.84), 24% (P = 0.02), 29% (P = 0.04), and 52% (P = 0.004) reduced odds of being in the lowest (vs highest) tertile of LTL; MBB was not associated with being in the middle (vs highest) tertile of LTL.

CONCLUSIONS: Greater engagement in MBB was associated with reduced odds of being in the lowest LTL tertile.

Does exercise change your brain?

After yesterday's post suggesting no effects of common dietary supplements on cognitive changes with aging, I thought I would note work regarding exercise and brain health. mentioned by Reynolds, in particular a study by Burzynska et al. that monitored the daily activities of non-athletes:

...the most physically active elderly volunteers, according to their activity tracker data, had better oxygenation and healthier patterns of brain activity than the more sedentary volunteers — especially in parts of the brain, including the hippocampus, that are known to be involved in improved memory and cognition, and in connecting different brain areas to one another. Earlier brain scan experiments by Dr. Burzynska and her colleagues had established that similar brain activity in elderly people is associated with higher scores on cognitive tests.

Again, there is the caveat that a correlation does not prove a cause.

Can dietary supplements fight cognitive decline?

Maybe not...It is known that people who eat diets rich in fish and antioxidants have better brain health, but this association does not prove cause and effect. Rabin points to a recent massive NIH study of ~3,500 subjects that finds no cognitive effects of dietary supplementation wtih long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) (tested vs placebo in a factorial design). All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc. Participants,recruited by retinal specialists in 82 US academic and community medical centers as being at risk for developing late age-related macular degeneration, underwent cognitive tests every two years during the 5-year study. The bottom line: "A total of 89% (3741/4203) of the Age-Related Eye Disease Study 2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not."

Humanity as a Competitive Advantage

Some clips from a review by Tony Schwartz, of Geoff Colvin's new book “Humans Are Underrated: What High Achievers Know That Brilliant Machines Never Will.”

…computers are rapidly getting better – often far better — than humans are in dozens of areas…analyzing legal cases, providing financial advice, diagnosing illnesses, driving cars and even fighting wars, with battlefield robots and drones. “Affective” computing makes it possible for these machines to understand human emotions and measure levels of stress, often better than we can ourselves.

From Oxford Economics, a research firm: skills employers said they would need more of in the next five to 10 years were not so much analytic and technical ones as they were “relationship building, teaming, co-creativity, brainstorming, cultural sensitivity and ability to manage diverse employees – the skills… of “social interaction.”…organizations will build competitive advantage through qualities such as empathy, care, attunement, self-awareness and even generosity….The more valued, appreciated, cared for and taken care of we feel, the more secure and trusting we become, the less preoccupied by fear, and the more likely we are to generate our highest value.

…leaders in the workplace must become not just chief executive officers, but also chief energy officers, because their energy – and emotions – are so contagious, for better or for worse.

Is "gaydar" a myth?

Cox et al. contest work by Rule et al. that I mentioned in a previous post and suggest that the idea of "gaydar" is a myth. (Use gaydar as a search term in the search box in the left column for other posts on this topic.)

In the present work, we investigate the pop cultural idea that people have a sixth sense, called “gaydar,” to detect who is gay. We propose that “gaydar” is an alternate label for using stereotypes to infer orientation (e.g., inferring that fashionable men are gay). Another account, however, argues that people possess a facial perception process that enables them to identify sexual orientation from facial structure (Rule et al., 2008). We report five experiments testing these accounts. Participants made gay-or-straight judgments about fictional targets that were constructed using experimentally-manipulated stereotypic cues and real gay/straight people’s face cues. These studies revealed that orientation is not visible from the face—purportedly “face- based” gaydar arises from a third-variable confound. People do, however, readily infer orientation from stereotypic attributes (e.g., fashion, career). Furthermore, the folk concept of gaydar serves as a legitimizing myth: Compared to a control group, people stereotyped more when led to believe in gaydar, whereas people stereotyped less when told gaydar is an alternate label for stereotyping. Discussion focuses on the implications of the gaydar myth and why, contrary to some prior claims, stereotyping is highly unlikely to result in accurate judgments about orientation.

Consolidating motor skills in our sleep.

It is well known that sleep, in ourselves and in other animals, helps in consolidating learned motor tasks. (When I am learning difficult passage in a new piano piece I’m preparing for performance, during initial stages of waking I observe my mind playing through the notes.) Ramanathan et al. examine the neurophysiological basis for this by recording from single motor cells in the rat brain to examine the replay of synchronous neural activity during sleep that mediates large-scale neural plasticity and stabilizes kinematics during early motor learning:

Sleep has been shown to help in consolidating learned motor tasks. In other words, sleep can induce “offline” gains in a new motor skill even in the absence of further training. However, how sleep induces this change has not been clearly identified. One hypothesis is that consolidation of memories during sleep occurs by “reactivation” of neurons engaged during learning. In this study, we tested this hypothesis by recording populations of neurons in the motor cortex of rats while they learned a new motor skill and during sleep both before and after the training session. We found that subsets of task-relevant neurons formed highly synchronized ensembles during learning. Interestingly, these same neural ensembles were reactivated during subsequent sleep blocks, and the degree of reactivation was correlated with several metrics of motor memory consolidation. Specifically, after sleep, the speed at which animals performed the task while maintaining accuracy was increased, and the activity of the neuronal assembles were more tightly bound to motor action. Further analyses showed that reactivation events occurred episodically and in conjunction with spindle-oscillations—common bursts of brain activity seen during sleep. This observation is consistent with previous findings in humans that spindle-oscillations correlate with consolidation of learned tasks. Our study thus provides insight into the neuronal network mechanism supporting consolidation of motor memory during sleep and may lead to novel interventions that can enhance skill learning in both healthy and injured nervous systems.

More bad things about sleep debt.

This post is to point to two recent articles on pathologies induced by sleep debt. He et al. show that sleep restriction impairs blood-brain barrier function:

The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice.

And, Weljie et al. find cross-species molecular markers of sleep debt:

Reduced sleep duration is a hallmark of modern-day society and is increasingly associated with medical conditions, such as diabetes, obesity, metabolic syndrome, and cardiovascular disease. Here we present data from a rat model and human clinical study of chronic sleep restriction, both revealing that two metabolites in blood, oxalic acid and diacylglycerol 36:3, are quantitatively depleted under sleep-restricted conditions and restored after recovery sleep. Our findings also reveal a significant overall shift in lipid metabolism, with higher levels of phospholipids in both species and evidence of a systemic oxidative environment. This work provides a potential link between the known pathologies of reduced sleep duration and metabolic dysfunction.

Our nervous systems are lazy.

Selinger et al. show that the subconscious nervous processes that regulate our movement are constantly adapting to minimize the energy required for movement in a given situation. To show this, they had subjects wear robotic exoskeletons that could increase or decrease resistance to the knees, to change the difficulty of swinging the legs during walking. Within minutes, gate was adjusted to be energetically more optimal.

Highlights

•People readily adapt established gait patterns to minimize energy use 

•People converge on new energetic optima within minutes, even for small cost savings 

•Updated predictions about energetically optimal gaits allow re-convergence within seconds 

•Energetic cost is not just an outcome of movement, but also continuously shapes it

Summary

People prefer to move in ways that minimize their energetic cost. For example, people tend to walk at a speed that minimizes energy use per unit distance and, for that speed, they select a step frequency that makes walking less costly. Although aspects of this preference appear to be established over both evolutionary and developmental timescales, it remains unclear whether people can also optimize energetic cost in real time. Here we show that during walking, people readily adapt established motor programs to minimize energy use. To accomplish this, we used robotic exoskeletons to shift people’s energetically optimal step frequency to frequencies higher and lower than normally preferred. In response, we found that subjects adapted their step frequency to converge on the new energetic optima within minutes and in response to relatively small savings in cost (less than 5%). When transiently perturbed from their new optimal gait, subjects relied on an updated prediction to rapidly re-converge within seconds. Our collective findings indicate that energetic cost is not just an outcome of movement, but also plays a central role in continuously shaping it.

The social mysteries of the superior temporal sulcus

Michael Beauchamp does a summary of work by Deen et al. (open access), who use functional magnetic resonance imaging (fMRI) to show a regular anterior–posterior organization in the STS for different social tasks such as theory of mind, biological motion, faces, voices and language. Here is the summary graphic:

Organization of social perception and cognition within the superior temporal sulcus (STS). Results of Deen et al. are shown on an inflated cortical surface model of the left and right hemisphere. Filled circles show the location of the peak activation, averaged across subjects, for each contrast. Colored regions show the extent of the activation for each contrast (multiple colored regions for some contrasts). 

A final musical/social at Twin Valley - some Rachmaninoff

A personal posting: On Sunday Sept. 13, Len and I hosted our last musical/social at the 1860 stone school house we have lived in for 25 years (I have been doing affairs like these since 1971-72). The following Wednesday, the Steinway B left for our Fort Lauderdale condo. The school house will be offered for sale in the spring of 2016, as we contract our Madison WI footprint to a condo near the university campus. Good friend Roy Wesley did video recordings of the concert, using a simple camera whose automatic volume control for audio damped out dynamic volume changes. I've posted these on YouTube, commentary and glitches included, just to have a record for myself and a few friends. I thought I would pass on the concert program, some pictures, an embedded video of the final Rachmaninoff  pieces, and URLS of the others, to MindBlog readers.

Program 

Chopin Nocturne in C# minor No. 18 (post.), Trois Ecossaises Op. 72 (post.) No. 3 

J. Brahms Capriccio Op 76. No 2; Waltzes, Op. 39 Nos.1, 12, 13, 14, 15. 

C. Debussy - Preludes Livre I - Danseuse de Delphes, Minstrels , Les Collines d’Anacapri 

F. Poulenc - Valse, Improvisation No. 14, Nocturne No. 2 

S.  Rachmaninoff Morceaux de fantasie (Fantasy pieces) Op. 3, No. 1, Elegie; No. 4, Polichinelle

Here is a video of the Rachmaninoff:

And URLs:
J. Brahms Capriccio Op 76. No 2; Waltzes, Op. 39 Nos.1, 12, 13, 14, 15
C. Debussy - Preludes Livre I - Danseuse de Delphes, Minstrels , Les Collines d’Anacapri 
F. Poulenc - Valse, Improvisation No. 14, Nocturne No. 2 

Hormones and clothing choices.

Here is an interesting and curious bit from Eisenbruch et al.:

Recent evidence supports the idea that women use red clothing as a courtship tactic, and results from one study further suggested that women were more likely to wear red on days of high fertility in their menstrual cycles. Subsequent studies provided mixed support for the cycle-phase effect, although all such studies relied on counting methods of cycle-phase estimation and used between-subjects designs. By comparison, in the study reported here, we employed frequent hormone sampling to more accurately assess ovulatory timing and used a within-subjects design. We found that women were more likely to wear red during the fertile window than on other cycle days. Furthermore, within-subjects fluctuations in the ratio of estradiol to progesterone statistically mediated the within-subjects shifts in red-clothing choices. Our results appear to represent the first direct demonstration of specific hormone measurements predicting observable changes in women’s courtship-related behaviors. We also demonstrate the advantages of hormonal determination of ovulatory timing for tests of cycle-phase shifts in psychology or behavior.

Heritable risk of developing anxiety correlates with brain metabolism, not structure.

A group of Univ. of Wisconsin collaborators adds another installment to their series of articles on anxiety in a primate model for humans.

Significance

According to the World Health Organization, anxiety and depressive disorders are a leading source of disability, affecting hundreds of millions of people. Children can inherit an extremely anxious temperament, which is a prominent risk factor for the later development of anxiety, depression, and comorbid substance abuse. This study uses high-resolution functional and structural imaging in our well-established developmental nonhuman primate model to identify the heritable neural substrate that underlies extreme childhood anxious temperament. Using a large multigenerational family pedigree, genetic correlation analyses revealed a tripartite neural circuit where metabolism likely shares a genetic substrate with early-life dispositional anxiety. Interestingly, we found that brain function—not structure—is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

Abstract

Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism—not brain structure—that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.