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.
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.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 1 year ago
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.
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.
Lateralized brain regions subserve functions such as language and visuospatial processing. It has been conjectured that individuals may be left-brain dominant or right-brain dominant based on personality and cognitive style, but neuroimaging data has not provided clear evidence whether such phenotypic differences in the strength of left-dominant or right-dominant networks exist. We evaluated whether strongly lateralized connections covaried within the same individuals. Data were analyzed from publicly available resting state scans for 1011 individuals between the ages of 7 and 29. For each subject, functional lateralization was measured for each pair of 7266 regions covering the gray matter at 5-mm resolution as a difference in correlation before and after inverting images across the midsagittal plane. The difference in gray matter density between homotopic coordinates was used as a regressor to reduce the effect of structural asymmetries on functional lateralization. Nine left- and 11 right-lateralized hubs were identified as peaks in the degree map from the graph of significantly lateralized connections. The left-lateralized hubs included regions from the default mode network (medial prefrontal cortex, posterior cingulate cortex, and temporoparietal junction) and language regions (e.g., Broca Area and Wernicke Area), whereas the right-lateralized hubs included regions from the attention control network (e.g., lateral intraparietal sulcus, anterior insula, area MT, and frontal eye fields). Left- and right-lateralized hubs formed two separable networks of mutually lateralized regions. Connections involving only left- or only right-lateralized hubs showed positive correlation across subjects, but only for connections sharing a node. Lateralization of brain connections appears to be a local rather than global property of brain networks, and our data are not consistent with a whole-brain phenotype of greater “left-brained” or greater “right-brained” network strength across individuals. Small increases in lateralization with age were seen, but no differences in gender were observed.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 1 year ago
Modern medicine has generally viewed the concept of “psychosomatic” disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. The second, smaller network originates in regions of medial prefrontal cortex, including a major contribution from pregenual and subgenual regions of anterior cingulate cortex. These cortical areas are involved in higher-order aspects of cognition and affect. These results indicate that specific multisynaptic circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness.
Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli.
How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex.
Misophonia is an affective sound-processing disorder characterized by the experience of strong negative emotions (anger and anxiety) in response to everyday sounds, such as those generated by other people eating, drinking, chewing, and breathing [1-8]. The commonplace nature of these sounds (often referred to as “trigger sounds”) makes misophonia a devastating disorder for sufferers and their families, and yet nothing is known about the underlying mechanism. Using functional and structural MRI coupled with physiological measurements, we demonstrate that misophonic subjects show specific trigger-sound-related responses in brain and body. Specifically, fMRI showed that in misophonic subjects, trigger sounds elicit greatly exaggerated blood-oxygen-level-dependent (BOLD) responses in the anterior insular cortex (AIC), a core hub of the "salience network" that is critical for perception of interoceptive signals and emotion processing. Trigger sounds in misophonics were associated with abnormal functional connectivity between AIC and a network of regions responsible for the processing and regulation of emotions, including ventromedial prefrontal cortex (vmPFC), posteromedial cortex (PMC), hippocampus, and amygdala. Trigger sounds elicited heightened heart rate (HR) and galvanic skin response (GSR) in misophonic subjects, which were mediated by AIC activity. Questionnaire analysis showed that misophonic subjects perceived their bodies differently: they scored higher on interoceptive sensibility than controls, consistent with abnormal functioning of AIC. Finally, brain structural measurements implied greater myelination within vmPFC in misophonic individuals. Overall, our results show that misophonia is a disorder in which abnormal salience is attributed to particular sounds based on the abnormal activation and functional connectivity of AIC.
Noninvasive brain stimulation has shown considerable promise for enhancing cognitive functions by the long-term manipulation of neuroplasticity [1-3]. 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 [4, 5], 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.