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Concept: Brain

1046

Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.

Concepts: Longitudinal study, Epidemiology, Brain, Magnetic resonance imaging, Cognition, Cerebrum, White matter, Corpus callosum

928

Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

Concepts: Central nervous system, Neuroanatomy, Brain, Male, Gender, Human brain, Sex, Cerebellum

802

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Concepts: Nervous system, Brain, Human brain, Cerebral cortex, Lysergic acid diethylamide, Psychedelic drug, Psychedelics, dissociatives and deliriants, Timothy Leary

732

Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

Concepts: Brain, Magnetic resonance imaging, Cerebral cortex, Cerebrum, Hippocampus, Serotonin, Schizophrenia, Major depressive disorder

717

The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer’s disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer’s disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep.

Concepts: Central nervous system, Neuron, Neuroanatomy, Brain, Human brain, Cerebral cortex, Cerebrum, Apolipoprotein E

589

A brain-to-brain interface (BTBI) enabled a real-time transfer of behaviorally meaningful sensorimotor information between the brains of two rats. In this BTBI, an “encoder” rat performed sensorimotor tasks that required it to select from two choices of tactile or visual stimuli. While the encoder rat performed the task, samples of its cortical activity were transmitted to matching cortical areas of a “decoder” rat using intracortical microstimulation (ICMS). The decoder rat learned to make similar behavioral selections, guided solely by the information provided by the encoder rat’s brain. These results demonstrated that a complex system was formed by coupling the animals' brains, suggesting that BTBIs can enable dyads or networks of animal’s brains to exchange, process, and store information and, hence, serve as the basis for studies of novel types of social interaction and for biological computing devices.

Concepts: Brain, Cerebral cortex, Emergence, Visual perception, The Animals, Activity, Behavior, Task

548

Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among friends reflect deeper similarities in how we perceive, interpret, and respond to the world? To test whether friendship, and more generally, social network proximity, is associated with increased similarity of real-time mental responding, we used functional magnetic resonance imaging to scan subjects' brains during free viewing of naturalistic movies. Here we show evidence for neural homophily: neural responses when viewing audiovisual movies are exceptionally similar among friends, and that similarity decreases with increasing distance in a real-world social network. These results suggest that we are exceptionally similar to our friends in how we perceive and respond to the world around us, which has implications for interpersonal influence and attraction.

Concepts: Psychology, Brain, Sociology, Magnetic resonance imaging, Similarity, Friendship, Social network

536

People often discount evidence that contradicts their firmly held beliefs. However, little is known about the neural mechanisms that govern this behavior. We used neuroimaging to investigate the neural systems involved in maintaining belief in the face of counterevidence, presenting 40 liberals with arguments that contradicted their strongly held political and non-political views. Challenges to political beliefs produced increased activity in the default mode network-a set of interconnected structures associated with self-representation and disengagement from the external world. Trials with greater belief resistance showed increased response in the dorsomedial prefrontal cortex and decreased activity in the orbitofrontal cortex. We also found that participants who changed their minds more showed less BOLD signal in the insula and the amygdala when evaluating counterevidence. These results highlight the role of emotion in belief-change resistance and offer insight into the neural systems involved in belief maintenance, motivated reasoning, and related phenomena.

Concepts: Psychology, Brain, Truth, Neuroscience, Cerebrum, Philosophy of mind, Limbic system, Frontal lobe

517

Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence.

Concepts: Nervous system, Neuron, Brain, Human brain, Bird, Cerebrum, Mammal, Computational neuroscience

513

 To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic.

Concepts: Brain, Medical imaging, Nuclear magnetic resonance, Radiography, Magnetic resonance imaging, Radiology, Virtopsy, Case series