Altered cortical and subcortical connectivity due to infrasound administered near the hearing threshold – Evidence from fMRI

In the present study, the brain’s response towards near- and supra-threshold infrasound (IS) stimulation (sound frequency < 20 Hz) was investigated under resting-state fMRI conditions. The study involved two consecutive sessions. In the first session, 14 healthy participants underwent a hearing threshold—as well as a categorical loudness scaling measurement in which the individual loudness perception for IS was assessed across different sound pressure levels (SPL). In the second session, these participants underwent three resting-state acquisitions, one without auditory stimulation (no-tone), one with a monaurally presented 12-Hz IS tone (near-threshold) and one with a similar tone above the individual hearing threshold corresponding to a ‘medium loud’ hearing sensation (supra-threshold). Data analysis mainly focused on local connectivity measures by means of regional homogeneity (ReHo), but also involved independent component analysis (ICA) to investigate inter-regional connectivity. ReHo analysis revealed significantly higher local connectivity in right superior temporal gyrus (STG) adjacent to primary auditory cortex, in anterior cingulate cortex (ACC) and, when allowing smaller cluster sizes, also in the right amygdala (rAmyg) during the near-threshold, compared to both the supra-threshold and the no-tone condition. Additional independent component analysis (ICA) revealed large-scale changes of functional connectivity, reflected in a stronger activation of the right amygdala (rAmyg) in the opposite contrast (no-tone > near-threshold) as well as the right superior frontal gyrus (rSFG) during the near-threshold condition. In summary, this study is the first to demonstrate that infrasound near the hearing threshold may induce changes of neural activity across several brain regions, some of which are known to be involved in auditory processing, while others are regarded as keyplayers in emotional and autonomic control. These findings thus allow us to speculate on how continuous exposure to (sub-)liminal IS could exert a pathogenic influence on the organism, yet further (especially longitudinal) studies are required in order to substantialize these findings

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Neuropsychosocial profiles of current and future adolescent alcohol misusers

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention

Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms

BackgroundThe orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms.MethodsActivations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14.ResultsThe medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003).ConclusionsActivations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Results of the whole-brain analysis comparing regional homogeneity (ReHo) as derived from resting-state acquisitions during near-threshold vs. no-tone condition.

<p>Results of the whole-brain analysis comparing regional homogeneity (ReHo) as derived from resting-state acquisitions during near-threshold vs. no-tone condition.</p

Acoustical characterization of 14 participants according to hearing threshold and categorical loudness scaling measurements for an IS-pure tone at 12 Hz.

<p>Acoustical characterization of 14 participants according to hearing threshold and categorical loudness scaling measurements for an IS-pure tone at 12 Hz.</p

ReHo results.

<p>Statistical analysis of beta values extracted from the respective clusters observed in the whole-brain contrasts.</p

Significant condition differences in resting state fMRI of the ICA.

<p>Significant condition differences in resting state fMRI of the ICA.</p