The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats.

Persistent postsurgical pain affects 20% of youth undergoing a surgical procedure, with females exhibiting increased prevalence of chronic pain compared with males. This study sought to examine the sexually-dimorphic neurobiological changes underlying the transition from acute to persistent pain following surgery in adolescence. Male and female Sprague Dawley rats were randomly allocated to a sham or injury (plantar-incision surgery) condition and assessed for pain sensitivity while also undergoing magnetic resonance imaging at both an acute and chronic timepoint within adolescence. We found that injury resulted in persistent pain in both sexes, with females displaying most significant sensitivity. Injury resulted in significant gray matter density increases in brain areas including the cerebellum, caudate putamen/insula, and amygdala and decreases in the hippocampus, hypothalamus, nucleus accumbens, and lateral septal nucleus. Gray matter density changes in the hippocampus and lateral septal nucleus were driven by male rats whereas changes in the amygdala and caudate putamen/insula were driven by female rats. Overall, our results indicate persistent behavioral and neurobiological changes following surgery in adolescence, with sexually-dimorphic and age-specific outcomes, highlighting the importance of studying both sexes and adolescents, rather than extrapolating from male adult literature.

A brain-wide genome-wide association study of candidate quantitative trait loci associated with structural and functional phenotypes of pain sensitivity.

Individual pain sensitivity is modulated by the brain's structural and functional features, but its heritability remains unclear. This paper conducted a brain-wide genome-wide association study (GWAS) to explore the genetic bases of neuroimage phenotypes of pain sensitivity. In total, 432 normal participants were divided into high and low pain sensitivity groups according to the laser quantitative test threshold. Then, the brain's gray matter density (GMD) features correlated with pain sensitivity were identified. Next, GWAS was performed on each GMD phenotype using quality-controlled genotypes. Based on the heatmap and hierarchical clustering results, the right insula was identified for further refined analysis in terms of subregions GMD and resting-state functional connectivity (rs-FC) phenotypes. The results indicate that the right insula GMD in the high sensitivity group is significantly lower than that in the low sensitivity group. Also, the TT/TC group at locus rs187974 has lower right insula GMD than the CC group. Further, loci at gene CYP2D6 may lead to a variation of rs-FC between the right insula and left putamen. In conclusion, our study suggests that the right insula and multiple candidate loci may be importantly involved in pain sensitivity modulation, which may guide the future development of precision pain therapeutics.

Cholinergic nucleus degeneration and its association with gait impairment in Parkinson's disease.

BACKGROUND: The contribution of cholinergic degeneration to gait disturbance in Parkinson's disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD. METHODS: This cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association. RESULTS: PD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1-2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side. CONCLUSIONS: Our study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei's impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

Anticholinergic drugs and forebrain magnetic resonance imaging changes in cognitively normal people and those with mild cognitive impairment.

BACKGROUND AND PURPOSE: Anticholinergic (AC) medication use is associated with cognitive decline and dementia, which may be related to an AC-induced central hypocholinergic state, but the exact mechanisms remain to be understood. We aimed to further elucidate the putative link between AC drug prescription, cognition, and structural and functional impairment of the forebrain cholinergic nucleus basalis of Meynert (NBM). METHODS: Cognitively normal (CN; n = 344) and mildly cognitively impaired (MCI; n = 224) Alzheimer's Disease Neuroimaging Initiative Phase 3 participants with good quality 3-T magnetic resonance imaging were included. Structural (regional gray matter [GM] density) and functional NBM integrity (functional connectivity [FC]) were compared between those on AC medication for > 1 year (AC+ ) and those without (AC- ) in each condition. AC burden was classed as mild, moderate, or severe. RESULTS: MCI AC+ participants (0.55 ± 0.03) showed lower NBM GM density compared to MCI AC- participants (0.56 ± 0.03, p = 0.002), but there was no structural AC effect in CN. NBM FC was lower in CN AC+ versus CN AC- (3.6 ± 0.5 vs. 3.9 ± 0.6, p = 0.001), and in MCI AC+ versus MCI AC- (3.3 ± 0.2 vs. 3.7 ± 0.5, p < 0.001), with larger effect size in MCI. NBM FC partially mediated the association between AC medication burden and cognition. CONCLUSIONS: Our findings provide novel support for a detrimental effect of mild AC medication on the forebrain cholinergic system characterized as functional central hypocholinergic that partially mediated AC-related cognitive impairment. Moreover, structural tissue damage suggests neurodegeneration, and larger effect sizes in MCI point to enhanced susceptibility for AC medication in those at risk of dementia.

Regional brain tissue changes in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) patients present with a variety of symptoms, including mood and cognition deficits, in addition to classical respiratory, and autonomic issues. This suggests that brain injury, which can be examined with non-invasive magnetic resonance imaging (MRI), is a manifestation of this condition. However, brain tissue integrity in sites that regulate cognitive, autonomic, respiratory, and mood functions in CF patients is unclear. Our aim was to assess regional brain changes using high-resolution T1-weighted images based gray matter (GM) density and T2-relaxometry procedures in CF over control subjects. METHODS: We acquired high-resolution T1-weighted images and proton-density (PD) and T2-weighted images from 5 CF and 15 control subjects using a 3.0-Tesla MRI. High-resolution T1-weighted images were partitioned to GM-tissue type, normalized to a common space, and smoothed. Using PD- and T2-weighted images, whole-brain T2-relaxation maps were calculated, normalized, and smoothed. The smoothed GM-density and T2-relaxation maps were compared voxel-by-voxel between groups using analysis of covariance (covariates, age and sex; SPM12, p < 0.001). RESULTS: Significantly increased GM-density, indicating tissues injury, emerged in multiple brain regions, including the cerebellum, hippocampus, amygdala, basal forebrain, insula, and frontal and prefrontal cortices. Various brain areas showed significantly reduced T2-relaxation values in CF subjects, indicating predominant acute tissue changes, in the cerebellum, cerebellar tonsil, prefrontal and frontal cortices, insula, and corpus callosum. CONCLUSIONS: Cystic fibrosis subjects show predominant acute tissue changes in areas that control mood, cognition, respiratory, and autonomic functions and suggests that tissue changes may contribute to symptoms resulting from ongoing hypoxia accompanying the condition.

Regional dissociation between the cerebral blood flow and gray matter density alterations in idiopathic normal pressure hydrocephalous: results from SINPHONI-2 study.

PURPOSE: The purpose of this study was to elucidate the specific regional cerebral blood flow (rCBF) alterations for idiopathic normal pressure hydrocephalus (iNPH) by comparing the proportional rCBF and gray matter change from those of a normal database at the same point of SPECT and MRI examinations. METHODS: Thirty subjects with iNPH underwent both CBF SPECT and MRI. After normalization, voxel-wise two-sample t tests between patients and 11 normal controls were conducted to compare the regional alteration in the gray matter density and rCBF. RESULTS: The rCBF reduction and the gray matter decrease were seen in almost similar regions surrounding Sylvian fissure, the left parietotemporal region and frontal lobes, whereas we did not find rCBF increase at the top of the high convexity, where the increase of the gray matter density was the highest (p < 0.05). CONCLUSION: Our study showed regional associations and dissociations between the relative gray matter density and rCBF in patients with iNPH.

Longitudinal Alterations of Frontoparietal and Frontotemporal Networks Predict Future Creative Cognitive Ability.

Creative cognition is important to academic performance and career success during late adolescence and adulthood. However, there is a lack of longitudinal data on whether brain structural development could predict improvements in creative thinking, and how such changes interact with other cognitive abilities to support creative performance. Here we examined longitudinal alterations of brain structure and their relation to creative cognitive ability in a sample of 159 healthy young adults who were scanned using magnetic resonance imaging 2-3 times over the course of 3 years. The most robust predictor of future creative ability was the right dorsolateral prefrontal cortex (DLPFC), which in conjunction with baseline creative capacity showed a 31% prediction rate. Longitudinal analysis revealed that slower decreases in gray matter density within left frontoparietal and right frontotemporal clusters predicted enhanced creative ability. Moreoever, the relationship between longitudinal alterations within frontal-related clusters and improved creative ability was moderated by the right DLPFC and working memory ability. We conclude that continuous goal-directed planning and accumulated knowledge are implemented in the right DLPFC and temporal areas, respectively, which in turn support longitudinal gains in creative cognitive ability.

Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood.

Developmental structural neuroimaging studies in humans have long described decreases in gray matter volume (GMV) and cortical thickness (CT) during adolescence. Gray matter density (GMD), a measure often assumed to be highly related to volume, has not been systematically investigated in development. We used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to study age-related effects and sex differences in four regional gray matter measures in 1189 youths ranging in age from 8 to 23 years. Custom T1 segmentation and a novel high-resolution gray matter parcellation were used to extract GMD, GMV, gray matter mass (GMM; defined as GMD × GMV), and CT from 1625 brain regions. Nonlinear models revealed that each modality exhibits unique age-related effects and sex differences. While GMV and CT generally decrease with age, GMD increases and shows the strongest age-related effects, while GMM shows a slight decline overall. Females have lower GMV but higher GMD than males throughout the brain. Our findings suggest that GMD is a prime phenotype for the assessment of brain development and likely cognition and that periadolescent gray matter loss may be less pronounced than previously thought. This work highlights the need for combined quantitative histological MRI studies.SIGNIFICANCE STATEMENT This study demonstrates that different MRI-derived gray matter measures show distinct age and sex effects and should not be considered equivalent but complementary. It is shown for the first time that gray matter density increases from childhood to young adulthood, in contrast with gray matter volume and cortical thickness, and that females, who are known to have lower gray matter volume than males, have higher density throughout the brain. A custom preprocessing pipeline and a novel high-resolution parcellation were created to analyze brain scans of 1189 youths collected as part of the Philadelphia Neurodevelopmental Cohort. A clear understanding of normal structural brain development is essential for the examination of brain-behavior relationships, the study of brain disease, and, ultimately, clinical applications of neuroimaging.

Gastric-bypass surgery induced widespread neural plasticity of the obese human brain.

Bariatric surgery has become the gold standard for the treatment of morbid obesity (body mass index (BMI) ≥ 40 kg/m2), but only few studies investigated its plastic influences on the obese brain. In this longitudinal study, we combined structural and functional magnetic resonance brain imaging (MRI) in 27 patients (BMI 47.8 ± 5.5 kg/m2) undergoing gastric-bypass surgery and 14 non-obese matched controls (BMI 24.7 ± 3.4 kg/m2). Over the first year after surgery, patients presented widespread changes in white matter density (WMD) as well as gray matter density (GMD) in the cerebral cortex of all lobes, subcortical structures, the brainstem as well as the cerebellum, but no changes in white matter water diffusivity throughout the brain. Voxel-by-voxel regression analyses revealed that all GMD and WMD changes were well associated with elevated regional homogeneity of spontaneous neural activity (ReHo) in blood-oxygenation level-dependent signals. Spatial-temporal integration of structural and functional MRI suggests that gastric-bypass surgery induces widespread plastic changes in brain structure that concurrently homogenizes the functional profile of the cortex, subcortical regions as well as white matter structures.

Inferring distinct mechanisms in the absence of subjective differences: Placebo and centrally acting analgesic underlie unique brain adaptations.

Development and maintenance of chronic pain is associated with structural and functional brain reorganization. However, few studies have explored the impact of drug treatments on such changes. The extent to which long-term analgesia is related to brain adaptations and its effects on the reversibility of brain reorganization remain unclear. In a randomized placebo-controlled clinical trial, we contrasted pain relief (3-month treatment period), and anatomical (gray matter density [GMD], assessed by voxel-based morphometry) and functional connectivity (resting state fMRI nodal degree count [DC]) adaptations, in 39 knee osteoarthritis (OA) patients (22 females), randomized to duloxetine (DLX, 60 mg once daily) or placebo. Pain relief was equivalent between treatment types. However, distinct circuitry (GMD and DC) could explain pain relief in each group: up to 85% of variance for placebo analgesia and 49% of variance for DLX analgesia. No behavioral measures (collected at entry into the study) could independently explain observed analgesia. Identified circuitry were outside of nociceptive circuitry and minimally overlapped with OA-abnormal or placebo response predictive brain regions. Mediation analysis revealed that changes in GMD and DC can influence each other across remote brain regions to explain observed analgesia. Therefore, we can conclude that distinct brain mechanisms underlie DLX and placebo analgesia in OA. The results demonstrate that even in the absence of differences in subjective pain relief, pharmacological treatments can be differentiated from placebo based on objective brain biomarkers. This is a crucial step to untangling mechanisms and advancing personalized therapy approaches for chronic pain.

Gray matter density reduction associated with adjuvant chemotherapy in older women with breast cancer.

PURPOSE: The purpose of this study was to evaluate longitudinal changes in brain gray matter density (GMD) before and after adjuvant chemotherapy in older women with breast cancer. METHODS: We recruited 16 women aged ≥ 60 years with stage I-III breast cancers receiving adjuvant chemotherapy (CT) and 15 age- and sex-matched healthy controls (HC). The CT group underwent brain MRI and the NIH Toolbox for Cognition testing prior to adjuvant chemotherapy (time point 1, TP1) and within 1 month after chemotherapy (time point 2, TP2). The HC group underwent the same assessments at matched intervals. GMD was evaluated with the voxel-based morphometry. RESULTS: The mean age was 67 years in the CT group and 68.5 years in the HC group. There was significant GMD reduction within the chemotherapy group from TP1 to TP2. Compared to the HC group, the CT group displayed statistically significantly greater GMD reductions from TP1 to TP2 in the brain regions involving the left anterior cingulate gyrus, right insula, and left middle temporal gyrus (pFWE(family-wise error)-corrected < 0.05). The baseline GMD in left insula was positively correlated with the baseline list-sorting working memory score in the HC group (pFWE-corrected < 0.05). No correlation was observed for the changes in GMD with the changes in cognitive testing scores from TP1 to TP2 (pFWE-corrected < 0.05). CONCLUSIONS: Our findings indicate that GMD reductions were associated with adjuvant chemotherapy in older women with breast cancer. Future studies are needed to understand the clinical significance of the neuroimaging findings. This study is registered on ClinicalTrials.gov (NCT01992432).

Gray matter morphological anomalies in the cerebellar vermis in first-episode schizophrenia patients with cognitive deficits.

BACKGROUND: Cognitive deficits are a core feature of early schizophrenia. However, the pathological foundations underlying cognitive deficits are still unknown. The present study examined the association between gray matter density and cognitive deficits in first-episode schizophrenia. METHOD: Structural magnetic resonance imaging of the brain was performed in 34 first-episode schizophrenia patients and 21 healthy controls. Patients were divided into two subgroups according to working memory task performance. The three groups were well matched for age, gender, and education, and the two patient groups were also further matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to estimate changes in gray matter density in first-episode schizophrenia patients with cognitive deficits. The relationships between gray matter density and clinical outcomes were explored. RESULTS: Patients with cognitive deficits were found to have reduced gray matter density in the vermis and tonsil of cerebellum compared with patients without cognitive deficits and healthy controls, decreased gray matter density in left supplementary motor area, bilateral precentral gyrus compared with patients without cognitive deficits. Classifier results showed GMD in cerebellar vermis tonsil cluster could differentiate SZ-CD from controls, left supplementary motor area cluster could differentiate SZ-CD from SZ-NCD. Gray matter density values of the cerebellar vermis cluster in patients groups were positively correlated with cognitive severity. CONCLUSIONS: Decreased gray matter density in the vermis and tonsil of cerebellum may underlie early psychosis and serve as a candidate biomarker for schizophrenia with cognitive deficits.

The impact of parent-child interaction on brain structures: cross-sectional and longitudinal analyses.

There is a vast amount of evidence from psychological studies that the amount of parent-child interaction affects the development of children's verbal skills and knowledge. However, despite the vast amount of literature, brain structural development associated with the amount of parent-child interaction has never been investigated. In the present human study, we used voxel-based morphometry to measure regional gray matter density (rGMD) and examined cross-sectional correlations between the amount of time spent with parents and rGMD among 127 boys and 135 girls. We also assessed correlations between the amount of time spent with parents and longitudinal changes that occurred a few years later among 106 boys and 102 girls. After correcting for confounding factors, we found negative effects of spending time with parents on rGMD in areas in the bilateral superior temporal gyrus (STG) via cross-sectional analyses as well as in the contingent areas of the right STG. We also confirmed positive effects of spending time with parents on the Verbal Comprehension score in cross-sectional and longitudinal analyses. rGMD in partly overlapping or contingent areas of the right STG was negatively correlated with age and the Verbal Comprehension score in cross-sectional analyses. Subsequent analyses revealed verbal parent-child interactions have similar effects on Verbal Comprehension scores and rGMD in the right STG in both cross-sectional and longitudinal analyses. These findings indicate that parent-child interactions affect the right STG, which may be associated with verbal skills.

Structural and functional associations of the rostral anterior cingulate cortex with subjective happiness.

Happiness is one of the most fundamental human goals, which has led researchers to examine the source of individual happiness. Happiness has usually been discussed regarding two aspects (a temporary positive emotion and a trait-like long-term sense of being happy) that are interrelated; for example, individuals with a high level of trait-like subjective happiness tend to rate events as more pleasant. In this study, we hypothesized that the interaction between the two aspects of happiness could be explained by the interaction between structure and function in certain brain regions. Thus, we first assessed the association between gray matter density (GMD) of healthy participants and trait-like subjective happiness using voxel-based morphometry (VBM). Further, to assess the association between the GMD and brain function, we conducted functional magnetic resonance imaging (MRI) using the task of positive emotion induction (imagination of several emotional life events). VBM indicated that the subjective happiness was positively correlated with the GMD of the rostral anterior cingulate cortex (rACC). Functional MRI demonstrated that experimentally induced temporal happy feelings were positively correlated with subjective happiness level and rACC activity. The rACC response to positive events was also positively correlated with its GMD. These results provide convergent structural and functional evidence that the rACC is related to happiness and suggest that the interaction between structure and function in the rACC may explain the trait-state interaction in happiness.

Brains of verbal memory specialists show anatomical differences in language, memory and visual systems.

We studied a group of verbal memory specialists to determine whether intensive oral text memory is associated with structural features of hippocampal and lateral-temporal regions implicated in language processing. Professional Vedic Sanskrit Pandits in India train from childhood for around 10years in an ancient, formalized tradition of oral Sanskrit text memorization and recitation, mastering the exact pronunciation and invariant content of multiple 40,000-100,000 word oral texts. We conducted structural analysis of gray matter density, cortical thickness, local gyrification, and white matter structure, relative to matched controls. We found massive gray matter density and cortical thickness increases in Pandit brains in language, memory and visual systems, including i) bilateral lateral temporal cortices and ii) the anterior cingulate cortex and the hippocampus, regions associated with long and short-term memory. Differences in hippocampal morphometry matched those previously documented for expert spatial navigators and individuals with good verbal working memory. The findings provide unique insight into the brain organization implementing formalized oral knowledge systems.

Cortical plasticity between the pain and pain-free phases in patients with episodic tension-type headache.

BACKGROUND: State-related brain structural alterations in patients with episodic tension-type headache (ETTH) are unclear. We aimed to conduct a longitudinal study to explore dynamic gray matter (GM) changes between the pain and pain-free phases in ETTH. METHODS: We recruited 40 treatment-naïve ETTH patients and 40 healthy controls. All participants underwent brain structural scans on a 3.0-T MRI system. ETTH patients were scanned in and out of pain phases. Voxel-based morphometry analysis was used to determine the differences in regional gray matter density (GMD) between groups. Additional regression analysis was used to identify any associations between regional GMD and clinical symptoms. RESULTS: ETTH patients exhibited reduced GMD in the bilateral primary somatosensory cortex, and increased GMD in the bilateral anterior cingulate cortex (ACC) and anterior insula for the in pain phase compared with the out of pain phase. The out of pain phase of ETTH patients exhibited no regions with higher or lower GMD compared with healthy controls. GMD in the left ACC and left anterior insula was negatively correlated with headache days. GMD in the left ACC was negatively correlated with anxiety and depressive symptoms in ETTH patients. CONCLUSIONS: This is the first study to demonstrate dynamic and reversible GMD changes between the pain and pain-free phases in ETTH patients. However, this balance might be disrupted by increased headache days and progressive anxiety and depressive symptoms.

Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users.

Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.

Beyond classical inheritance: the influence of maternal genotype upon child's brain morphology and behavior.

Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior.

Comprehensive neural networks for guilty feelings in young adults.

Feelings of guilt are associated with widespread self and social cognitions, e.g., empathy, moral reasoning, and punishment. Neural correlates directly related to the degree of feelings of guilt have not been detected, probably due to the small numbers of subjects, whereas there are growing numbers of neuroimaging studies of feelings of guilt. We hypothesized that the neural networks for guilty feelings are widespread and include the insula, inferior parietal lobule (IPL), amygdala, subgenual cingulate cortex (SCC), and ventromedial prefrontal cortex (vmPFC), which are essential for cognitions of guilt. We investigated the association between regional gray matter density (rGMD) and feelings of guilt in 764 healthy young students (422 males, 342 females; 20.7 ± 1.8 years) using magnetic resonance imaging and the guilty feeling scale (GFS) for the younger generation which comprises interpersonal situation (IPS) and rule-breaking situation (RBS) scores. Both the IPS and RBS were negatively related to the rGMD in the right posterior insula (PI). The IPS scores were negatively correlated with rGMD in the left anterior insula (AI), right IPL, and vmPFC using small volume correction. A post hoc analysis performed on the significant clusters identified through these analyses revealed that rGMD activity in the right IPL showed a significant negative association with the empathy quotient. These findings at the whole-brain level are the widespread comprehensive neural network regions for guilty feelings. Interestingly, the novel finding in this study is that the PI was implicated as a common region for feelings of guilt with interaction between the IPS and RBS. Additionally, the neural networks including the IPL were associated with empathy and with regions implicated in moral reasoning (AI and vmPFC), and punishment (AI).

Neural basis underlying the association between thought control ability and happiness: The moderating role of the amygdala.

Thought control ability (TCA) plays an important role in individuals' health and happiness. Previous studies demonstrated that TCA was closely conceptually associated with happiness. However, empirical research supporting this relationship was limited. In addition, the neural basis underlying TCA and how this neural basis influences the relationship between TCA and happiness remain unexplored. In the present study, the voxel-based morphometry (VBM) method was adopted to investigate the neuroanatomical basis of TCA in 314 healthy subjects. The behavioral results revealed a significant positive association between TCA and happiness. On the neural level, there was a significant negative correlation between TCA and the gray matter density (GMD) of the bilateral amygdala. Split-half validation analysis revealed similar results, further confirming the stability of the VBM analysis findings. Furthermore, gray matter covariance network and graph theoretical analyses showed positive association between TCA and both the node degree and node strength of the amygdala. Moderation analysis revealed that the GMD of the amygdala moderated the relationship between TCA and happiness. Specifically, the positive association between TCA and self-perceived happiness was stronger in subjects with a lower GMD of the amygdala. The present study indicated the neural basis underlying the association between TCA and happiness and offered a method of improving individual well-being.