Human Brain Magnetic Resonance Imaging Studies for Psychiatric Disorders: The Current Progress and Future Directions.

With the prevalence of psychiatric disorders and the limitations of the diagnostic scheme and treatment options of these disorders, magnetic resonance imaging (MRI) studies play a significant role in uncovering the pathological basis of psychiatric disorders and potentially using biological markers in clinical settings. The use of MRI in clinical research has grown over the past three decades, and current MRI research continues to provide an avenue to guide the development of diagnostic approaches and therapeutic solutions. However, the current shortcomings of MRI studies derive not only from technical limitations (i.e., the range of contrasts that MRI probes or sensors can create) but also from confounding factors in the current methodological approaches of case-control studies for psychiatric disorders. Thus, by reviewing the recent literature on MRI research on psychiatric disorders, we explain the current progress and limitations of brain MRI methodologies used to study psychiatric disorders. We consider the growing use of cross-disorder methods to identify shared and disease-specific pathological features across psychiatric disorders. In addition, we need to outline healthy developmental and aging changes of the brain and investigate the disorder difference as a deviation of the trajectory. Although these methods have provided us with new insights, the demarcation between psychiatric disorders based on a definitive set of pathologies remains limited. This challenge of disease stratification is further complicated by the presence of multiple different sets of disorder pathologies within a single disorder and the different progressive timelines of different disorders. As such, we introduce the ongoing research projects in Japan, namely, the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) and the Strategic International Brain Science Research Promotion Program (Brain/MINDS Beyond). These collaborative research initiatives across Japan use neuroimaging and travel-subject harmonization to conduct nationwide MRI studies capable of providing large-scale coherent results, which may address the current limitations of MRI psychiatric disorder research.

A comparative study of the dorsolateral prefrontal cortex targeting approaches for transcranial magnetic stimulation treatment: Insights from the healthy control data.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for medication-resistant depression. Several targeting methods for the left DLPFC have been proposed including identification with resting-state functional magnetic resonance imaging (rs-fMRI) neuronavigation, stimulus coordinates based on structural MRI, or electroencephalography (EEG) F3 site by Beam F3 method. To date, neuroanatomical and neurofunctional differences among those approaches have not been investigated on healthy subjects, which are structurally and functionally unaffected by psychiatric disorders. This study aimed to compare the mean location, its dispersion, and its functional connectivity with the subgenual cingulate cortex (SGC), which is known to be associated with the therapeutic outcome in depression, of various approaches to target the DLPFC in healthy subjects. Fifty-seven healthy subjects underwent MRI scans to identify the stimulation site based on their resting-state functional connectivity and were measured their head size for targeting with Beam F3 method. In addition, we included two fixed stimulus coordinates over the DLPFC in the analysis, as recommended in previous studies. From the results, the rs-fMRI method had, as expected, more dispersed target sites across subjects and the greatest anticorrelation with the SGC, reflecting the known fact that personalized neuronavigation yields the greatest antidepressant effect. In contrast, the targets located by the other methods were relatively close together with less dispersion, and did not differ in anticorrelation with the SGC, implying their limitation of the therapeutic efficacy and possible interchangeability of them.

Dissecting Mismatch Negativity: Early and Late Subcomponents for Detecting Deviants in Local and Global Sequence Regularities.

Mismatch negativity (MMN) is commonly recognized as a neural signal of prediction error evoked by deviants from the expected patterns of sensory input. Studies show that MMN diminishes when sequence patterns become more predictable over a longer timescale. This implies that MMN is composed of multiple subcomponents, each responding to different levels of temporal regularities. To probe the hypothesized subcomponents in MMN, we record human electroencephalography during an auditory local-global oddball paradigm where the tone-to-tone transition probability (local regularity) and the overall sequence probability (global regularity) are manipulated to control temporal predictabilities at two hierarchical levels. We find that the size of MMN is correlated with both probabilities and the spatiotemporal structure of MMN can be decomposed into two distinct subcomponents. Both subcomponents appear as negative waveforms, with one peaking early in the central-frontal area and the other late in a more frontal area. With a quantitative predictive coding model, we map the early and late subcomponents to the prediction errors that are tied to local and global regularities, respectively. Our study highlights the hierarchical complexity of MMN and offers an experimental and analytical platform for developing a multitiered neural marker applicable in clinical settings.

Macronutrient intake is associated with intelligence and neural development in adolescents.

Introduction: Macronutrient intake can be one of the most influential factors in cognitive and neural development in adolescents. Adolescence is a specific period of cognitive and neural development, and nutritional effects during this period could be life-long. Therefore, understanding the effects of macronutrient intake on cognitive and neural development in adolescents is crucially important. We thus examined the association across macronutrient intake, intelligence, and neural development using population-based cohort data. Methods: We conducted two studies. In study 1, we included a total of 1,734 participants (boys, 907, age [mean ± standard deviation] 171.9 ± 3.44 months; range 163.0-186.0 months) from the Tokyo TEEN Cohort (TTC) to examine the association between macronutrient intake and intelligence quotient (IQ). In study 2, we included a total of 63 participants (boys, 38, age 174.4 ± 7.7 months; range 160.7-191.6 months) to investigate the effect of nutrition intake on neural development using graph theory analysis for resting-state functional magnetic resonance imaging (rs-fMRI) derived from a subset of the TTC. Results: TTC data revealed that a higher IQ was associated in boys with increased protein intake (ß = 0.068, p = 0.031), and in girls, with reduced carbohydrate intake (ß = -0.076, p = 0.024). Graph theory analysis for rs-fMRI at approximately age 12 has shown that impaired local efficiency in the left inferior frontal gyrus was associated with higher carbohydrate and fat intake ([x, y, z] = [-51, 23, 8], pFDR-corrected = 0.00018 and 0.02290, respectively), whereas increased betweenness centrality in the left middle temporal gyrus was associated with higher carbohydrate, fat, and protein intake ([x, y, z] = [-61, -43, -13], pFDR-corrected = 0.0027, 0.0029, and 0.00075, respectively). Moreover, we identified a significant moderating effect of fat and protein intake on the relationship between change in betweenness centrality over a 2-year measurement gap in the left middle temporal gyrus and intelligence (ß = 12.41, p = 0.0457; ß = 12.12, p = 0.0401, respectively). Conclusion: Our study showed the association between macronutrient intake and neural development related to intelligence in early adolescents. Appropriate nutritional intake would be a key factor for healthy cognitive and neural development.

Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia.

The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (ß = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (ß = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia.

Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues' magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility-volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group's nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

Parent-Child Associations in COVID-19-Related Preventive Behaviors and Efficacy Expectations: A One-Year Longitudinal Survey.

PURPOSE: It is necessary to identify the variables that explain the variance in preventive behaviors against COVID-19 to increase adolescents' engagement in these behaviors. We focused on efficacy expectations of preventive behaviors and their associations within families. This study examined the associations between efficacy expectations and preventive behaviors, and between adolescents and their parents in terms of efficacy expectations and preventive behaviors. METHODS: A cross-lagged panel model was employed to analyze 281 parent-child pairs consisting of 245 children (118 girls, mean age = 17.4 years), 277 mothers (median age = 49.3 years), and 211 fathers (median age = 51.5 years). Participants completed the Prevention of COVID-19 Infection Scale at baseline (October 2020 to April 2021) and one-year follow-up to assess efficacy expectations and preventive behaviors for sanitization, contact, and hoarding factors. RESULTS: Efficacy expectations of preventive behaviors at baseline were positively associated with preventive behaviors at one-year follow-up regarding the sanitization and contact factors. Additionally, for parents, efficacy expectations of preventive behaviors at baseline were positively associated with subsequent preventive behaviors regarding the hoarding factor. Parental efficacy expectation scores for contact at baseline were positively associated with their children's scores at one-year follow-up. DISCUSSION: The findings highlight the association between parental efficacy expectations at an initial time point and adolescents' efficacy expectations at one-year follow-up toward COVID-19 preventive measures, particularly contact-related behaviors. These insights can inform public health interventions targeting individual expectations and parental involvement to promote effective preventive practices during future health crises.

Drastic changes in ground-dwelling beetle communities following high-intensity deer culling: insights from an island ecosystem.

The overabundance of large herbivores can have detrimental effects on the local environment due to overgrazing. Culling is a common management practice implemented globally that can effectively control herbivore populations and allow vegetation communities to recover. However, the broader indirect effects of culling large herbivores remain relatively unknown, particularly on insect species such as ground-dwelling beetles that perform key ecosystem processes such as decomposition. Here we undertook a preliminary investigation to determine how culling sika deer on an island in North Japan impacted ground-beetle community dynamics. We conducted pitfall trapping in July and September in 2012 (before culling) and again in 2019 (after culling). We compared beetle abundance and community composition within 4 beetle families (Carabidae, Scarabaeidae, Geotrupidae, and Silphidae), across seasons and culling treatments. We found each family responded differently to deer culling. Scarabaeidae displayed the greatest decline in abundance after culling. Silphidae also had reduced abundance but to a lesser extent compared to Scarabaeidae. Carabidae had both higher and lower abundance after culling, depending on the season. We found beetle community composition differed between culling and season, but seasonal variability was reduced after culling. Overall, the culling of large herbivores resulted in a reduction of ground-dwelling beetle populations, particularly necrophagous species dependent on dung and carrion for survival. Our preliminary research highlights the need for long-term and large-scale experiments to understand the indirect ecological implications of culling programs on ecosystem processes.

Hippocampal Structures Among Japanese Adolescents Before and After the COVID-19 Pandemic.

Importance: Few studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus. Objective: To examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development. Design, Setting, and Participants: The population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan. Due to the SoE, data collection was suspended between March 27, 2020, and July 30, 2020. Analyzed data, comprising 1149 brain structural scans obtained from 479 participants, of whom 336 participants had undergone 2 or more scans, were collected between October 2013 and November 2021. Data were analyzed from August 2022 to December 2023. Exposures: Japan's first SoE (April 7 to May 25, 2020). Main Outcomes and Measures: Hippocampal volume, 12 hippocampal subfield volumes, and 7 microstructural measures of the hippocampus. Results: A total of 1060 brain scans from 459 participants (214 female participants [47%]) including 246 participants from wave 1 (median [IQR] age, 11.3 [11.1-11.7] years), 358 from wave 2 (median [IQR] age, 13.8 [13.3-14.5] years), 304 from wave 3 (median [IQR] age, 15.9 [15.4-16.5] years), and 152 from wave 4 (median [IQR] age, 17.9 [17.5-18.4] years) were included in the final main analysis. The generalized additive mixed model showed a significant associations of the SoE with the mean hippocampal volume (ß = 102.19; 95% CI, 0.61-203.77; P = .049). The generalized linear mixed models showed the main associations of the SoE with hippocampal subfield volume (granule cell and molecular layer of the dentate gyrus: ß = 18.19; 95% CI, 2.97-33.41; uncorrected P = .02; CA4: ß = 12.75; 95% CI, 0.38-25.12; uncorrected P = .04; hippocampus-amygdala transition area: ß = 5.67; 95% CI, 1.18-10.17; uncorrected P = .01), and fractional anisotropy (ß = 0.03; 95% CI, 0.00-0.06; uncorrected P = .04). Conclusions and Relevance: After the first SoE, a volumetric increase in the hippocampus and trend increase in 3 subfield volumes and microstructural integration of the hippocampus were observed, suggesting that the transient plasticity of the adolescent hippocampus was affected by a major life event along with the typical developmental trajectory.

Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

Gamma-band harmonic responses for beta-band auditory steady-state response are intact in patients with early stage schizophrenia.

Gamma oscillations, thought to arise from the activity of ɣ-aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma-band auditory steady-state responses (ASSRs) are notably reduced in both chronic and early-stage schizophrenia patients. Furthermore, alterations in gamma-band ASSRs have been demonstrated in animal models through translational research. However, the 40-Hz harmonic responses of the 20-Hz ASSR are not as well-characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40-Hz harmonic response to the 20-Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra-high-risk (UHR) for psychosis, 13 patients with first-episode schizophrenia (FES), and 21 healthy controls (HCs). The 40-Hz harmonic responses of the 20-Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40-Hz ASSRs, the 40-Hz harmonic responses of the 20-Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma-band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia.

Data-mining analysis of media frame effects on social perception of schizophrenia renaming in Korea.

BACKGROUND: In 2011, Korean Neuropsychiatric Association renamed schizophrenia from 'mind split disorder' ('Jungshinbunyeolbyung' in Korean) to 'attunement disorder' ('Johyeonbyung' in Korean), in a strategic way to reduce social stigma toward people with schizophrenia. However, there remains an elusive consensus that how the renaming effort has contributed to changes in the social perception of schizophrenia in Korea. METHODS: With this regard, we explored whether media frames alter the social perception, in ways of respecting or disrespecting schizophrenia patients before and after the renaming. This study extensively investigated media keywords related to schizophrenia across the time by applying both language and epidemiologic analyses. RESULTS: In results, the media keywords have been negatively described for schizophrenia patients both before and after the renaming. Further, from an analysis using the regression model, a significant correlation was observed between the frequency of negative keywords and the hospitalization frequency of schizophrenia patients. CONCLUSIONS: These findings suggest that the social perception of schizophrenia has been scarcely changed, but rather remained negatively biased against schizophrenia patients, in spite of the renaming effort. Notably, the biased media frames have been demonstrated to negatively impact on the social perception, and even on the medical use patterns of general schizophrenia patients. In conclusion, we suggest that the unbiased media frames along with the renaming effort may collectively help reduce the negative social perception of schizophrenia. TRIAL REGISTRATION: This study was approved from the Institute of Review Board (IRB) of the Yoing-In Mental Hospital (IRB No. YIMH-IRB-2019-02).

Traveling Subject-Informed Harmonization Increases Reliability of Brain Diffusion Tensor and Neurite Mapping.

Diffusion-weighted magnetic resonance imaging (dMRI) of brain has helped elucidate the microstructural changes of psychiatric and neurodegenerative disorders. Inconsistency between MRI models has hampered clinical application of dMRI-based metrics. Using harmonized dMRI data of 300 scans from 69 traveling subjects (TS) scanning the same individuals at multiple conditions with 13 MRI models and 2 protocols, the widely-used metrics such as diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) were evaluated before and after harmonization with a combined association test (ComBat) or TS-based general linear model (TS-GLM). Results showed that both ComBat and TS-GLM significantly reduced the effects of the MRI site, model, and protocol for diffusion metrics while maintaining the intersubject biological effects. The harmonization power of TS-GLM based on TS data model is more powerful than that of ComBat. In conclusion, our research demonstrated that although ComBat and TS-GLM harmonization approaches were effective at reducing the scanner effects of the site, model, and protocol for DTI and NODDI metrics in WM, they exhibited high retainability of biological effects. Therefore, we suggest that, after harmonizing DTI and NODDI metrics, a multisite study with large cohorts can accurately detect small pathological changes by retaining pathological effects.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Daily fat intake is associated with basolateral amygdala response to high-calorie food cues and appetite for high-calorie food.

OBJECTIVES: Animal studies have indicated that fat intake mediates amygdala activation, which in turn promotes fat intake, while amygdala activation increases the preference for fat and leads to increased fat intake. However, the association among fat intake, amygdala activation, and appetite for high-calorie foods in humans remains unclear. Thus, to examine this association, we conducted a functional magnetic resonance imaging (fMRI) experiment. METHODS: Fifty healthy-weight adults (18 females; mean age: 22.9 ± 3.02 years) were included. Participants were shown images of high-calorie and low-calorie foods and were instructed to rate their desire to eat the food items during fMRI. All participants provided information on their daily fat intake using a self-reported questionnaire. Associations among fat intake, the desire to eat high-calorie or low-calorie food items, and amygdala responses to food items were examined. RESULTS: The basolateral amygdala (BLA) response was positively associated with fat intake ([x, y, z] = [24, -6, -16], z = 3.91, pFWE-corrected = 0.007) and the desire to eat high-calorie food items ([26, -4, -16], z = 3.75, pFWE-corrected = 0.010). Structural equation modeling showed that the desire for high-calorie food items was predicted by BLA response to high-calorie food items (p = 0.013, ß = 3.176), and BLA response was predicted by fat intake (p < 0.001, ß = 0.026). DISCUSSION: Fat intake influences BLA response to high-fat food, which in turn increases the desire to eat palatable high-fat food. This may lead to additional fat intake and increase the risk of weight gain.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Alterations of auditory-evoked gamma oscillations are more pronounced than alterations of spontaneous power of gamma oscillation in early stages of schizophrenia.

Several animal models of schizophrenia and patients with chronic schizophrenia have shown increased spontaneous power of gamma oscillations. However, the most robust alterations of gamma oscillations in patients with schizophrenia are reduced auditory-oscillatory responses. We hypothesized that patients with early-stage schizophrenia would have increased spontaneous power of gamma oscillations and reduced auditory-oscillatory responses. This study included 77 participants, including 27 ultra-high-risk (UHR) individuals, 19 patients with recent-onset schizophrenia (ROS), and 31 healthy controls (HCs). The auditory steady-state response (ASSR) and spontaneous power of gamma oscillations measured as induced power during the ASSR period were calculated using electroencephalography during 40-Hz auditory click-trains. The ASSRs were lower in the UHR and ROS groups than in the HC group, whereas the spontaneous power of gamma oscillations in the UHR and ROS groups did not significantly differ from power in the HC group. Both early-latency (0-100 ms) and late-latency (300-400 ms) ASSRs were significantly reduced and negatively correlated with the spontaneous power of gamma oscillations in the ROS group. In contrast, UHR individuals exhibited reduced late-latency ASSR and a correlation between the unchanged early-latency ASSR and the spontaneous power of gamma oscillations. ASSR was positively correlated with the hallucinatory behavior score in the ROS group. Correlation patterns between the ASSR and spontaneous power of gamma oscillations differed between the UHR and ROS groups, suggesting that the neural dynamics involved in non-stimulus-locked/task modulation change with disease progression and may be disrupted after psychosis onset.

Timing and distance of natal dispersal in Asian black bears.

Dispersal has important implications for population ecology and genetics of a species through redistribution of individuals. In most mammals, males leave their natal area before they reach sexual maturity, whereas females are commonly philopatric. Here, we investigate the patterns of natal dispersal in the Asian black bear (Ursus thibetanus) based on data from 550 bears (378 males, 172 females) captured or removed in Gunma and Tochigi prefectures on central Honshu Island, Japan in 2003-2018. We used genetic data and parentage analysis to investigate sex-biased differences in the distance of natal dispersal. We further investigated the age of dispersal using spatial autocorrelation analysis, that is, the change in the correlation between genetic and geographic distances in each sex and age group. Our results revealed that male dispersal distances (mean ± SE = 17.4 ± 3.5 km) were significantly farther than female distances (4.8 ± 1.7 km), and the results were not affected by years of mast failures, a prominent forage source for this population. Based on an average adult female home range radius of 1.8 km, 96% of the males and 50% of the females dispersed. In the spatial autocorrelation analysis, the changes in the relationship between genetic and geographic distances were more pronounced in males compared to females. Males seem to mostly disperse at age 3 regardless of mast productivity, and they gradually disperse far from their home range, but young and inexperienced males may return to their natal home range in years with poor food conditions. The results suggest that factors driving the dispersal process seem to be population structure-based instead of forage availability-based. In females, a significant genetic relationship was observed among all individuals in the group with a minimum age of 6 years within a distance of 2 km, which resulted in the formation of matrilineal assemblages.