Psilocybin desynchronizes our brains during ego dissolution

From Siegel et al (open source).:

A single dose of psilocybin, a psychedelic that acutely causes distortions of space–time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials^1,2,3,4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus^5,6,7,8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg - a placebo in the form of methylphenidate, (Ritalin)), and brought back for an additional psilocybin dose 6–12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

Why music training slows cognitive aging

A team of Chinese collaborators has reported experiments in the Oxford academic journal Cerebral Cortex titled "Functional gradients in prefrontal regions and somatomotor networks reflect the effect of music training experience on cognitive aging" which are stated to show that music training enhances the functional separation between regions across prefrontal and somatomotor networks, delaying deterioration in working memory performance and prefrontal suppression of prominant but irrelevant information. I'm passing on the abstract and a clip from the paper's conclusion, and can send interested readers the whole article. I think it is an important article but I find it is rendered almost unintelligble by Chinese to English translation issues. I'm surprised the journal let this article appear without further editing.

Studies showed that the top-down control of the prefrontal cortex (PFC) on sensory/motor cortices changes during cognitive aging. Although music training has demonstrated efficacy on cognitive aging, its brain mechanism is still far from clear. Current music intervention studies have paid insufficient attention to the relationship between PFC and sensory regions. Functional gradient provides a new perspective that allows researchers to understand network spatial relationships, which helps study the mechanism of music training that affects cognitive aging. In this work, we estimated the functional gradients in four groups, young musicians, young control, older musicians, and older control. We found that cognitive aging leads to gradient compression. Compared with young subjects, older subjects presented lower and higher principal gradient scores in the right dorsal and medial prefrontal and the bilateral somatomotor regions, respectively. Meanwhile, by comparing older control and musicians, we found a mitigating effect of music training on gradient compression. Furthermore, we revealed that the connectivity transitions between prefrontal and somatomotor regions at short functional distances are a potential mechanism for music to intervene in cognitive aging. This work contributes to understanding the neuroplasticity of music training on cognitive aging.

From the conclusion paragraph:

In a nutshell, we demonstrate the top-down control of prefrontal regions to the somatomotor network, which is associated with inhibitory function and represents a potential marker of cognitive aging, and reveal that music training may work by affecting the connectivity between the two regions. Although this work has investigated the neuroplasticity of music on cognitive aging by recruiting subjects of different age spans, the present study did not include the study of longitudinal changes of the same group. Further studies should include longitudinal follow-up of the same groups over time to more accurately evaluate the effect of music intervention on the process of cognitive aging.

Possible mechanism of psychedelic therapeutic effects

From the latest issue of Science Magazine:  

The mechanism underlying psychedelic action

Psychedelic compounds promote cortical structural and functional neuroplasticity through the activation of serotonin 2A receptors. However, the mechanisms by which receptor activation leads to changes in neuronal growth are still poorly defined. Vargas et al. found that activation of intracellular serotonin 2A receptors is responsible for the plasticity-promoting and antidepressant-like properties of psychedelic compounds, but serotonin may not be the natural ligand for those intracellular receptors (see the Perspective by Hess and Gould). —PRS

Abstract

Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.

Lack of mathematical education impacts brain development and future attainment

From Zacharopoulos et al.:  

 Significance

Our knowledge of the effect of a specific lack of education on the brain and cognitive development is currently poor but is highly relevant given differences between countries in their educational curricula and the differences in opportunities to access education. We show that within the same society, adolescent students who specifically lack mathematical education exhibited reduced brain inhibition levels in a key brain area involved in reasoning and cognitive learning. Importantly, these brain inhibition levels predicted mathematical attainment ∼19 mo later, suggesting they play a role in neuroplasticity. Our study provides biological understanding of the impact of the lack of mathematical education on the developing brain and the mutual play between biology and education.

Abstract

Formal education has a long-term impact on an individual’s life. However, our knowledge of the effect of a specific lack of education, such as in mathematics, is currently poor but is highly relevant given the extant differences between countries in their educational curricula and the differences in opportunities to access education. Here we examined whether neurotransmitter concentrations in the adolescent brain could classify whether a student is lacking mathematical education. Decreased γ-aminobutyric acid (GABA) concentration within the middle frontal gyrus (MFG) successfully classified whether an adolescent studies math and was negatively associated with frontoparietal connectivity. In a second experiment, we uncovered that our findings were not due to preexisting differences before a mathematical education ceased. Furthermore, we showed that MFG GABA not only classifies whether an adolescent is studying math or not, but it also predicts the changes in mathematical reasoning ∼19 mo later. The present results extend previous work in animals that has emphasized the role of GABA neurotransmission in synaptic and network plasticity and highlight the effect of a specific lack of education on MFG GABA concentration and learning-dependent plasticity. Our findings reveal the reciprocal effect between brain development and education and demonstrate the negative consequences of a specific lack of education during adolescence on brain plasticity and cognitive functions.

Looking at pictures makes your brain’s visual cortex swell!

Wow, talk about dynamic neuroplasticity...Mansson et al (open source) take observations of how rapidly our brains can change to a whole new level. They show that our visual cortex gets bigger when viewing a picture versus a simple fixation cross.

Measuring brain morphology with non-invasive structural magnetic resonance imaging is common practice, and can be used to investigate neuroplasticity. Brain morphology changes have been reported over the course of weeks, days, and hours in both animals and humans. If such short-term changes occur even faster, rapid morphological changes while being scanned could have important implications. In a randomized within-subject study on 47 healthy individuals, two high-resolution T1-weighted anatomical images were acquired (á 263 s) per individual. The images were acquired during passive viewing of pictures or a fixation cross. Two common pipelines for analyzing brain images were used: voxel-based morphometry on gray matter (GM) volume and surface-based cortical thickness. We found that the measures of both GM volume and cortical thickness showed increases in the visual cortex while viewing pictures relative to a fixation cross. The increase was distributed across the two hemispheres and significant at a corrected level. Thus, brain morphology enlargements were detected in less than 263 s. Neuroplasticity is a far more dynamic process than previously shown, suggesting that individuals’ current mental state affects indices of brain morphology. This needs to be taken into account in future morphology studies and in everyday clinical practice.

A brain area crucial to coping with stress.

Sinha et al. show that “neuroflexibility” in a specific region of our ventromedial prefrontal cortex enhances resilience to stress - an increase in its activity dampens down brain areas initially activated by stress. Subjects showing lower levels of this flexibility exhibited higher levels of maladaptive coping behaviors in real life.

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping.

Exercise and intermittent fasting improve brain plasticity and health

I have had numerous requests for a PDF of the article referenced in a Dec. 29, 2014 post - on how exercise and fasting stimulate brain plasticity and resilience - with the same title as this post.  It turns out that the reference pointed to by the link is open source. Readers should be able to download the article for themselves. Here is the text of the original post:

I thought it might be useful to point to this brief review by Praag et al. that references several recent pieces of work presented at a recent Soc. for Neuroscience Meeting symposium. The experiments indicate that exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases by enhancing neurogenesis, synaptic plasticity and neuronal stress robustness.  (Motivated readers can obtain the article from me.) Here is their central summary figure:

Exercise and IER/fasting exert complex integrated adaptive responses in the brain and peripheral tissues involved in energy metabolism. As described in the text, both exercise and IER enhance neuroplasticity and resistance of the brain to injury and disease. Some of the effects of exercise and IER on peripheral organs are mediated by the brain, including increased parasympathetic regulation of heart rate and increased insulin sensitivity of liver and muscle cells. In turn, peripheral tissues may respond to exercise and IER by producing factors that bolster neuronal bioenergetics and brain function. Examples include the following: mobilization of fatty acids in adipose cells and production of ketone bodies in the liver; production of muscle-derived neuroactive factors, such as irisin; and production of as yet unidentified neuroprotective “preconditioning factors.” Suppression of local inflammation in tissues throughout the body and the nervous system likely contributes to prevention and reversal of many different chronic disease processes.

Video games for Neuro-Cognitive Optimization

Continuing the MindBlog thread on brain games (cf. here), I pass on the introduction to a brief review by Mishra, Anguera, and Gazzaley on designing the next generation of closed-loop video games (CLVGs) that offer the prospect of enhancing cognition:

Humans of all ages engage deeply in game play. Game-based interactive environments provide a rich source of enjoyment, but also generate powerful experiences that promote learning and behavioral change (Pellegrini, 2009). In the modern era, software-based video games have become ubiquitous. The degree of interactivity and immersion in these video games can now be further enhanced like never before with the advent of consumer-accessible technologies like virtual reality, augmented reality, wearable physiological devices, and motion capture, all of which can be readily integrated using accessible game engines. This technological revolution presents a huge opportunity for neuroscientists to design targeted, novel game-based tools that drive positive neuroplasticity, accelerate learning, and strengthen cognitive function, and thereby promote mental wellbeing in both healthy and impaired brains.

In fact, there is now a burgeoning brain-training industry that already claims to have achieved this goal. However, many commercial claims are unsubstantiated and dismissed by the scientific community (Max Planck Institute for Human Development/Stanford Center on Longevity, 2014, Underwood, 2016). It seems prudent for us to slow down and approach this opportunity with scientific rigor and conservative optimism. Enhancing brain function should not be viewed as a clever, profitable start-up idea that can be conquered with a large marketing budget. If the field continues to be led by overinflated claims, we will jeopardize the careful and iterative process of evidence-based innovations in brain training and thereby risk throwing out the baby with the bathwater.

To strike the right balance, the path to commercialization needs to be accomplished via cutting-edge, neuroscientifically informed video game development tightly coupled with refinement and validation of the software in well-controlled empirical studies. Additionally, to separate the grain from the chaff, these studies and the claims based on them need verification and approval by independent regulatory agencies and the broader scientific community. High-level video game development and rigorous scientific validation need to become the twin pillar foundations of the next generation of closed-loop video games (CLVGs). Here, we define CLVGs as interactive video games that incorporate rapid, real-time, performance-driven, adaptive game challenges and performance feedback. The time is ideal for intensified effort in this important endeavor; CLVGs that are methodically developed and validated have the potential to benefit a broad array of disciplines in need of effective tools to enhance brain function, including education, medicine, and wellness.

Exercise helps your brain rewire.

Our brains are most capable of changing in response to experience when we are young, then this ability abruptly declines into adulthood. Lunghi and Sale do an interesting experiment showing how the plasticity that does remain can be enhanced by exercise. Covering one eye and watching a movie while relaxing in a chair boosts brain responses to the deprived eye. If study participants instead watched the movie while alternating 10 min. intervals of rest and cycling on a stationary bike, this enhancement of the deprived eye became much larger. A figure, followed by their abstract:

Brain plasticity, defined as the capability of cerebral neurons to change in response to experience, is fundamental for behavioral adaptability, learning, memory, functional development, and neural repair. The visual cortex is a widely used model for studying neuroplasticity and the underlying mechanisms. Plasticity is maximal in early development, within the so-called critical period, while its levels abruptly decline in adulthood. Recent studies, however, have revealed a significant residual plastic potential of the adult visual cortex by showing that, in adult humans, short-term monocular deprivation alters ocular dominance by homeostatically boosting responses to the deprived eye. In animal models, a reopening of critical period plasticity in the adult primary visual cortex has been obtained by a variety of environmental manipulations, such as dark exposure, or environmental enrichment, together with its critical component of enhanced physical exercise. Among these non-invasive procedures, physical exercise emerges as particularly interesting for its potential of application to clinics, though there has been a lack of experimental evidence available that physical exercise actually promotes visual plasticity in humans. Here we report that short-term homeostatic plasticity of the adult human visual cortex induced by transient monocular deprivation is potently boosted by moderate levels of voluntary physical activity. These findings could have a bearing in orienting future research in the field of physical activity application to clinical research.

Musical expertise changes the brain's functional connectivity during audiovisual integration

Music notation reading encapsulates auditory, visual, and motor information in a highly organized manner and therefore provides a useful model for studying multisensory phenomena. Paraskevopoulos et al. show that large-scale functional brain networks underpinning audiovisual integration are organized differently in musicians and nonmusicians. They examine brain responses to congruent (sound played corresponding to musical notation) and incongruent (sound played different from notation) stimuli.

Multisensory integration engages distributed cortical areas and is thought to emerge from their dynamic interplay. Nevertheless, large-scale cortical networks underpinning audiovisual perception have remained undiscovered. The present study uses magnetoencephalography and a methodological approach to perform whole-brain connectivity analysis and reveals, for the first time to our knowledge, the cortical network related to multisensory perception. The long-term training-related reorganization of this network was investigated by comparing musicians to nonmusicians. Results indicate that nonmusicians rely on processing visual clues for the integration of audiovisual information, whereas musicians use a denser cortical network that relies mostly on the corresponding auditory information. These data provide strong evidence that cortical connectivity is reorganized due to expertise in a relevant cognitive domain, indicating training-related neuroplasticity.

Figure - Paradigm of an audiovisual congruent and incongruent trial. (A) A congruent trial. (B) An incongruent trial. The line “time” represents the duration of the presentation of the auditory and visual part of the stimulus. The last picture of each trial represents the intertrial stimulus in which subjects had to answer if the trial was congruent or incongruent.

Figure - Cortical network underpinning audiovisual integration. (Upper) Statistical parametric maps of the significant networks for the congruent > incongruent comparison. Networks presented are significant at P less than 0.001, FDR corrected. The color scale indicates t values. (Lower) Node strength of the significant networks for each comparison. Strength is represented by node size.

After Phrenology: Neural Reuse and the Interactive Brain

I've been reading through an interesting article by Michael Anderson, a précis of a book accepted for publication and available as a PDF through BBS. I pass on the abstract:

Neural reuse is a form of neuroplasticity whereby neural elements originally developed for one purpose are put to multiple uses. A diverse behavioral repertoire is achieved via the creation of multiple, nested, and overlapping neural coalitions, in which each neural element is a member of multiple different coalitions and cooperates with a different set of partners at different times. This has profound implications for how we think about our continuity with other species, for how we understand the similarities and differences between psychological processes, and for how best to pursue a unified science of the mind. After Phrenology surveys the terrain and advocates for a series of reforms in psychology and cognitive neuroscience. The book argues that, among other things, we should capture brain function in a multi-dimensional manner, develop a new, action-oriented vocabulary for psychology, and recognize that higher-order cognitive processes are built from complex configurations of already evolved circuitry.

Music training offsets decline in speech recognition on aging.

From Bidelman and Alain:

Musicianship in early life is associated with pervasive changes in brain function and enhanced speech-language skills. Whether these neuroplastic benefits extend to older individuals more susceptible to cognitive decline, and for whom plasticity is weaker, has yet to be established. Here, we show that musical training offsets declines in auditory brain processing that accompanying normal aging in humans, preserving robust speech recognition late into life. We recorded both brainstem and cortical neuroelectric responses in older adults with and without modest musical training as they classified speech sounds along an acoustic–phonetic continuum. Results reveal higher temporal precision in speech-evoked responses at multiple levels of the auditory system in older musicians who were also better at differentiating phonetic categories. Older musicians also showed a closer correspondence between neural activity and perceptual performance. This suggests that musicianship strengthens brain-behavior coupling in the aging auditory system. Last, “neurometric” functions derived from unsupervised classification of neural activity established that early cortical responses could accurately predict listeners' psychometric speech identification and, more critically, that neurometric profiles were organized more categorically in older musicians. We propose that musicianship offsets age-related declines in speech listening by refining the hierarchical interplay between subcortical/cortical auditory brain representations, allowing more behaviorally relevant information carried within the neural code, and supplying more faithful templates to the brain mechanisms subserving phonetic computations. Our findings imply that robust neuroplasticity conferred by musical training is not restricted by age and may serve as an effective means to bolster speech listening skills that decline across the lifespan.

Exercise and intermittent fasting improve brain plasticity and health

I thought it might be useful to point to this brief review by Praag et al. that references several recent pieces of work presented at a recent Soc. for Neuroscience Meeting symposium. The experiments indicate that exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases by enhancing neurogenesis, synaptic plasticity and neuronal stress robustness.  (Motivated readers can obtain the article from me.) Here is their central summary figure:

Exercise and IER/fasting exert complex integrated adaptive responses in the brain and peripheral tissues involved in energy metabolism. As described in the text, both exercise and IER enhance neuroplasticity and resistance of the brain to injury and disease. Some of the effects of exercise and IER on peripheral organs are mediated by the brain, including increased parasympathetic regulation of heart rate and increased insulin sensitivity of liver and muscle cells. In turn, peripheral tissues may respond to exercise and IER by producing factors that bolster neuronal bioenergetics and brain function. Examples include the following: mobilization of fatty acids in adipose cells and production of ketone bodies in the liver; production of muscle-derived neuroactive factors, such as irisin; and production of as yet unidentified neuroprotective “preconditioning factors.” Suppression of local inflammation in tissues throughout the body and the nervous system likely contributes to prevention and reversal of many different chronic disease processes.

Trajectories of aging.

This post points to another of the articles in the Science special issue on aging. Lindenberger summarizes key features of human cognitive aging from the combined perspectives of life-span psychology and the cognitive neuroscience of aging, and notes a number of longitudinal studies that suggest that leading an intellectually challenging, physically active, and socially engaged life may mitigate losses and consolidate gains during cognitive aging. Here is a summary figure from the article:

Figure. An individual’s range of possible cognitive developmental trajectories from early to late adulthood.

The blue curve shows the most likely developmental path under normal circumstances. The fading of the background color indicates that more extreme paths are less likely. The functional threshold represents a level of functioning below which goal-directed action in the individual’s ecology will be severely compromised. The red curve represents the hope that changes in organism-environment interactions during adulthood move the individual onto a more positive trajectory. Beneficial changes may consist in the mitigation of risk factors, such as vascular conditions, metabolic syndrome, or chronic stress; the strengthening of enhancing factors, such as neuroplasticity; or both.

Long-term improvement of brain function and cognition with brain stimulation and cognitive training.

A group of collaborators from the University of Oxford and Innsbruck Medical University have published an observation that simple transcranial random noise stimulation (TRNS) of the bilateral (both sides of the brain) dorsolateral prefrontal cortex (DLPFC) applied during cognitive training over five days causes improvement in learning and performance of complex arithmetic tasks (both calculation and drill leaning) that still persist on testing 6 months later. This correlates with long lasting oxygenated blood flow changes measured by near-infrared spectroscopy that suggests more efficient neurovascular coupling within the left DLPFC. Here is their complete abstract:

Noninvasive brain stimulation has shown considerable promise for enhancing cognitive functions by the long-term manipulation of neuroplasticity. However, the observation of such improvements has been focused at the behavioral level, and enhancements largely restricted to the performance of basic tasks. Here, we investigate whether transcranial random noise stimulation (TRNS) can improve learning and subsequent performance on complex arithmetic tasks. TRNS of the bilateral dorsolateral prefrontal cortex (DLPFC), a key area in arithmetic , was uniquely coupled with near-infrared spectroscopy (NIRS) to measure online hemodynamic responses within the prefrontal cortex. Five consecutive days of TRNS-accompanied cognitive training enhanced the speed of both calculation- and memory-recall-based arithmetic learning. These behavioral improvements were associated with defined hemodynamic responses consistent with more efficient neurovascular coupling within the left DLPFC. Testing 6 months after training revealed long-lasting behavioral and physiological modifications in the stimulated group relative to sham controls for trained and nontrained calculation material. These results demonstrate that, depending on the learning regime, TRNS can induce long-term enhancement of cognitive and brain functions. Such findings have significant implications for basic and translational neuroscience, highlighting TRNS as a viable approach to enhancing learning and high-level cognition by the long-term modulation of neuroplasticity.

For those of you who might well ask "How exactly is TRNS done?" here is a clip from their experimental procedures section. The photograph suggests a rather imposing device!:

Subjects received TRNS while performing the learning task each day. Two electrodes (5 cm × 5 cm) were positioned over areas of scalp corresponding to the DLPFC (F3 and F4, identified in accordance with the international 10-20 EEG procedure; see the figure). Electrodes were encased in saline-soaked synthetic sponges to improve contact with the scalp and avoid skin irritation. Stimulation was delivered by a DC-Stimulator-Plus device (DC-Stimulator-Plus, neuroConn). Noise in the high-frequency band (100–600Hz) was chosen as it elicits greater neural excitation than lower frequency stimulation. For the TRNS group, current was administered for 20 min, with 15 s increasing and decreasing ramps at the beginning and end, respectively, of each session of stimulation. In the sham group current was applied for 30 s after upward ramping and then terminated.

Decreased amygdala neuroplasticity linked to early-life anxious temperament.

Some interesting work from the research groups of my University of Wisconsin colleagues Ned Kalin and Richard Davidson that suggests that altered amygdala neuroplasticity may play a role the early dispositional risk to develop anxiety and depression.:

Children with anxious temperament (AT) are particularly sensitive to new social experiences and have increased risk for developing anxiety and depression. The young rhesus monkey is optimal for studying the origin of human AT because it shares with humans the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning. In vivo imaging in young monkeys demonstrated that central nucleus of the amygdala (Ce) metabolism is relatively stable across development and predicts AT. Transcriptome-wide gene expression, which reflects combined genetic and environmental influences, was assessed within the Ce. Results support a maladaptive neurodevelopmental hypothesis linking decreased amygdala neuroplasticity to early-life dispositional anxiety. For example, high AT individuals had decreased mRNA expression of neurotrophic tyrosine kinase, receptor, type 3 (NTRK3). Moreover, variation in Ce NTRK3 expression was inversely correlated with Ce metabolism and other AT-substrates. These data suggest that altered amygdala neuroplasticity may play a role the early dispositional risk to develop anxiety and depression.

How childhood musical training shapes the adult brain.

From Skoe and Kraus:

Playing a musical instrument changes the anatomy and function of the brain. But do these changes persist after music training stops? We probed this question by measuring auditory brainstem responses in a cohort of healthy young human adults with varying amounts of past musical training. We show that adults who received formal music instruction as children have more robust brainstem responses to sound than peers who never participated in music lessons and that the magnitude of the response correlates with how recently training ceased. Our results suggest that neural changes accompanying musical training during childhood are retained in adulthood. These findings advance our understanding of long-term neuroplasticity and have general implications for the development of effective auditory training programs.

Mechanisms of white matter changes induced by meditation.

Diffusion tensor imaging (DTI) is a noninvasive MRI-based technique that can delineate white matter fibers in vivo, measure white matter’s structural plasticity to demonstrate that training or learning alters brain white matter. Fractional anisotropy (FA) is an important index for measuring the integrity of white matter fibers. In general, a higher FA value has been related to improved performance, and reduced FA has been found in normal aging and in neurological or psychiatric disorders. Posner and collaborators now show more details about changes that occur with only 4 weeks of meditation training (One suspects these changes might reverse after cessation of meditation practice?):

Using diffusion tensor imaging, several recent studies have shown that training results in changes in white matter efficiency as measured by fractional anisotropy (FA). In our work, we found that a form of mindfulness meditation, integrative body–mind training (IBMT), improved FA in areas surrounding the anterior cingulate cortex after 4-wk training more than controls given relaxation training. Reductions in radial diffusivity (RD) have been interpreted as improved myelin but reductions in axial diffusivity (AD) involve other mechanisms, such as axonal density. We now report that after 4-wk training with IBMT, both RD and AD decrease accompanied by increased FA, indicating improved efficiency of white matter involves increased myelin as well as other axonal changes. However, 2-wk IBMT reduced AD, but not RD or FA, and improved moods. Our results demonstrate the time-course of white matter neuroplasticity in short-term meditation. This dynamic pattern of white matter change involving the anterior cingulate cortex, a part of the brain network related to self-regulation, could provide a means for intervention to improve or prevent mental disorders.

Here is their description of the integrative body-mind training (IBMT) used:

IBMT involves body relaxation, mental imagery, and mindfulness training, accompanied by selected music background. Cooperation between the body and the mind is emphasized in facilitating and achieving a meditative state. The trainees concentrated on achieving a balanced state of body and mind guided by an IBMT coach and the compact disk. The method stresses no effort to control thoughts, but instead a state of restful alertness that allows a high degree of awareness of body, mind, and external instructions (5, 16, 19). RT involves the relaxing of different muscle groups over the face, head, shoulders, arms, legs, chest, back, and abdomen, guided by a tutor and compact disk. With eyes closed and in a sequential pattern, one is forced to concentrate on the sensation of relaxation, such as the feelings of warmth and heaviness. This progressive training helps the participant achieve physical and mental relaxation and calmness.

Our brain structure changes after two hours of learning.

Sagi and colleagues have provided the first evidence that rapid structural plasticity can be detected in humans after just 2 hr of playing a video game. To assess brain structure they used diffusion magnetic resonance imaging, a technique sensitive to the self-diffusion of water molecules that depends on tissue architecture (how freely water diffuses depends on the space between the objects such as neurons, glia, and blood vessels, that it is moving through). They showd that only two hours of learning can cause a mean diffusivity reduction in the human hippocampus. In a similar supporting study on rats, the authors were able to show that changes in brain derived neurotropic growth (BDNF) factor correlated with the structural change measured by MRI. I'm passing on the abstract, and for those of you who like data, one of the figures from their paper.

The timescale of structural remodeling that accompanies functional neuroplasticity is largely unknown. Although structural remodeling of human brain tissue is known to occur following long-term (weeks) acquisition of a new skill, little is known as to what happens structurally when the brain needs to adopt new sequences of procedural rules or memorize a cascade of events within minutes or hours. Using diffusion tensor imaging (DTI), an MRI-based framework, we examined subjects before and after a spatial learning and memory task. Microstructural changes (as reflected by DTI measures) of limbic system structures (hippocampus and parahippocampus) were significant after only 2 hr of training. This observation was also found in a supporting rat study. We conclude that cellular rearrangement of neural tissue can be detected by DTI, and that this modality may allow neuroplasticity to be localized over short timescales.

Figure (Click on figure to enlarge it) - Structural Remodeling of Brain Tissue, Measured by DTI as Changes in MD after 2 hr of Training on a Spatial Learning and Memory TaskThe following statistical analyses were employed: paired t tests between the MD maps before and after the task in the learning group (A and F); planned comparisons analysis of the learning versus control groups with respect to scan time with predicated effect in the learning group only (B and G); and linear effect between groups (C and H) as well as a group by time interaction following ANOVA (D and I). The effects were found in the left hippocampus (A–D) and right parahippocampus (F–I). The parametric maps in these images were generated at a significance level of p less than 0.005 (uncorrected). The enlarged subset in those images indicates the significant voxels following correction for multiple comparisons (p less than 0.05, corrected). In the enlarged subset the corrected p value color scale is between 0.005 and 0.05. L indicates the left side of the brain. (E) and (J) show the MD values in the clusters in the subset of (A) and (F) (mean ± SEM). (K) shows the correlation analysis between subjects' improvement rates (see Figure 1) and decrease in MD in the right parahippocampus (of the cluster in F).

Cognitive enhancement is in our futures.

I want to point to three articles on brain enhancement that have accumulated in my queue of potential items for posting:

Benedict Carey discusses work showing that deep brain stimulation delivered through electrodes inserted into the brains of epilepsy patients being prepared for surgery sharply improved performance on a virtual driving game that tests spatial memory, the neural mapping ability that allows people to navigate a new city without a GPS:

Ross Andersen does an article in The Atlantic that describes ethical debates that have risen over the use of transcranial direct current stimulation (TDCS) to improve cognition in human beings.

Recent years have seen some encouraging, if preliminary, lab results involving TDCS, a deep brain stimulation technique that uses electrodes placed outside the head to direct tiny painless currents across the brain. The currents are thought to increase neuroplasticity, making it easier for neurons to fire and form the connections that enable learning. There are signs that the technology could improve language acumen, math ability, and even memory.

Finally in PloS Biology Knafo et al. note that a pharmacological cognitive enhancer that improves spatial learning and memory (in rats) by enhancing synaptic transmission in the hippocampus.