Left Lateral Orbitofrontal Cortex Research Articles

NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1’s activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder’s clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation.

History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment.

To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment(MCI). 85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences inbaseline cortical thickness and longitudinalchange, as well as group differences in neuropsychological measures of executive function. At baseline, theMCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortexareas bilaterally. Longitudinally, theMCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontalareas sover the span of 2years (median = 1-2%, 90%HDI [-0.01%: -0.001%], probability of direction(PD) = 90-99%). The MCI[TBI+] group also displayedgreater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [-5.17%: 43.2%], PD = 91.7%). Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displayinggreatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI.

Exploratory analysis of cortical thickness in low- and high-fit young adults.

Studies have shown changes in the human brain associated with physical activity and cardiorespiratory fitness (CRF). The effects of CRF on cortical thickness have been well-described in older adults, where a positive association between CRF and cortical thickness has been reported, but the impact of sustained aerobic activity in young adults remains poorly described. Here, exploratory analysis was performed on cortical thickness data that was collected in groups of fit and sedentary young adults. Twenty healthy sedentary individuals (<2 h/week physical activity) were compared to 20 active individuals (>6 h/week physical activity) and cortical thickness was measured in 34 cortical areas. Cortical thickness values were compared between groups, and correlations between cortical thickness and VO2 max were tested. Cardiorespiratory fitness was significantly higher in active individuals compared to sedentary individuals. Cortical thickness was lower in regions of the left (lateral and medial orbitofrontal cortex, pars orbitalis, pars triangularis, rostral anterior cingulate cortex, superior temporal cortex and frontal pole) and right (lateral and medial orbitofrontal cortex and pars opercularis) hemispheres. Only the left frontal pole and right lateral orbitofrontal cortical thickness remained significant after false discovery rate correction. Negative correlations were observed between VO2 max and cortical thickness in the left (frontal pole) and right (caudal anterior cingulate and medial orbitofrontal cortex) hemispheres. The present exploratory analysis supports previous findings suggesting that neuroplastic effects of cardiorespiratory fitness may be attenuated in young compared with older individuals, underscoring a moderating effect of age on the relationship between fitness and cortical thickness.

Negative association between DNA methylation in brain-derived neurotrophic factor exon VI and left superior parietal gyrification in major depressive disorder

ObjectiveWe have recently reported significantly higher DNA methylation in brain-derived neurotrophic factor (BDNF) exon VI in major depressive disorder (MDD). This study aimed to investigated cortical changes and their associations with DNA methylations in BDNF exon VI in MDD. MethodsData of 93 patients with MDD and 59 controls were involved in statistics. General linear regressions (GLM) were performed to analyze thickness and gyrification changes in MDD and their association with DNA methylation in BDNF exon VI in patients with MDD and controls. ResultsSignificantly decreased cortical thickness (CT) in left lateral orbitofrontal cortex (LOFC), left superior temporal lobe (ST) and right frontal pole (FP) and decreased local gyrification index (lGI) in left superior parietal lobe (SP) were found in MDD. The associations between DNA methylation in 3 CpG sites in BDNF exon VI and lGI in left SP were significantly different in patients and controls. DNA methylations in BDNF132 (β = –0.359, P < 0.001), BDNF137 (β = –0.214, P = 0.032), and BDNF151 (β = –0.223, P = 0.025) were significantly negatively associated with lGI in left SP in MDD. ConclusionThe negative association between BDNF exon VI methylation and lGI in left SP might imply a potential epigenetic marker associated with cortical gyrification reduction in patients with MDD.

Physical symptoms and brain morphology: a population neuroimaging study in 12,286 pre-adolescents

Physical symptoms, also known as somatic symptoms, are those for which medical examinations do not reveal a sufficient underlying root cause (e.g., pain and fatigue). The extant literature of the neurobiological underpinnings of physical symptoms is largely inconsistent and primarily comprises of (clinical) case-control studies with small sample sizes. In this cross-sectional study, we studied the association between dimensionally measured physical symptoms and brain morphology in pre-adolescents from two population-based cohorts; the Generation R Study (n = 2649, 10.1 ± 0.6 years old) and ABCD Study (n = 9637, 9.9 ± 0.6 years old). Physical symptoms were evaluated using continuous scores from the somatic complaints syndrome scale from the parent-reported Child Behavior Checklist (CBCL). High‐resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Linear regression models were fitted for global brain metrics (cortical and subcortical grey matter and total white matter volume) and surface-based vertex-wise measures (surface area and cortical thickness). Results were meta-analysed. Symptoms of anxiety/depression were studied as a contrasting comorbidity. In the meta-analyses across cohorts, we found negative associations between physical symptoms and surface area in the (i) left hemisphere; in the lateral orbitofrontal cortex and pars triangularis and (ii) right hemisphere; in the pars triangularis, the pars orbitalis, insula, middle temporal gyrus and caudal anterior cingulate cortex. However, only a subset of regions (left lateral orbitofrontal cortex and right pars triangularis) were specifically associated with physical symptoms, while others were also related to symptoms of anxiety/depression. No significant associations were observed for cortical thickness. This study in preadolescents, the most representative and well-powered to date, showed that more physical symptoms are modestly related to less surface area of the prefrontal cortex mostly. While these effects are subtle, future prospective research is warranted to understand the longitudinal relationship of physical symptoms and brain changes over time. Particularly, to elucidate whether physical symptoms are a potential cause or consequence of distinct neurodevelopmental trajectories.

Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder.

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.

Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study.

Despite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Our main objective was to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior. We analyzed 7,860 magnetic resonance images of children 9-11 years of age from the Adolescent Brain Cognitive Development (ABCD) dataset in order to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also obtained several behavioral data (cognition, behavioral problems, prodromal psychotic experiences, prosociality, impulsivity) to explore the potential mediatory role of brain volumes on behavior. In the 7,860 children analyzed (median age=9 years and 11 months; 49.9% female), whole-brain voxel-based morphometry analyses revealed an association mainly between breastfeeding duration and larger bilateral volumes of the pars orbitalis and the lateral orbitofrontal cortex. In particular, the association with the left pars orbitalis and the left lateral orbitofrontal cortex proved to be very robust to the addition of potentially confounding covariates, random selection of siblings, and splitting the sample in two. The volume of the left pars orbitalis and the left lateral orbitofrontal cortex appeared to mediate the relationship between breastfeeding duration and the negative urgency dimension of the UPPS-P Impulsive Behavior Scale. Global gray matter volumes were also significant mediators for behavioral problems as measured with the Child Behavior Checklist. Our findings suggest that breastfeeding is a relevant factor in the proper development of the brain, particularly for the pars orbitalis and lateral orbitofrontal cortex regions. This, in turn, may impact impulsive personality and mental health in early puberty.

Orbitofrontal cortex functional connectivity changes in patients with binge eating disorder and bulimia nervosa.

We aimed to define the shared and unshared functional neurobiological underpinnings of binge eating disorder (BED) and bulimia nervosa (BN). These disorders both involve loss of control over binge eating, but differ based on purging behavior and body image distortion. BED and BN have also been found to show differences in brain activation patterns in reward sensitivity. We enrolled 13 and 12 drug-naive and medication-free women with BED and BN, respectively, and 22 age- and sex-matched healthy controls. We performed an orbitofrontal cortex (OFC)-seeded resting-state whole brain functional connectivity (FC) analysis among the groups. In this study, BED patients exhibited significantly higher impulsivity than controls, whereas the difference in impulsivity between BN and controls was not significant. Participants with BED and BN showed weaker FC between the left lateral OFC and the right precuneus than controls. In the BED only group, the FC strength between these regions was negatively correlated with self-reported impulsivity. In both BED and BN, FC between the left lateral OFC and the right dorsolateral prefrontal cortex was weaker than that in controls. In BED, FC between the left medial OFC and the right cerebellar lobule IV was stronger than that of other groups. Our current results suggest similarities and differences between BED and BN in OFC-seeded FC with respect to reward processing. In particular, FC of the OFC in BED patients showed a significant correlation with their high impulsivity, which may reflect a decline in executive control over binge eating.

Neuroanatomical correlates of social approach in Williams Syndrome and down syndrome

Individuals with Williams Syndrome (WS) or Downs Syndrome (DS) are often described as hypersociable, friendly and overly trusting of others. This hypersociability is a major concern for parents/caregivers due to the associated increased risk of exploitation and victimisation. Two brain regions - the amygdala and the orbitofrontal cortex (OFC) - have been implicated in driving this hypersociability in WS, and in the general population and have associations with emotional evaluation, threat detection and social motivation. However, there has been little neuroimaging research on this topic, especially in DS, to date. The aim of the present study was to investigate the potential neuroanatomical and neuropsychological correlates of hypersociability in WS and DS. Twelve individuals with WS (M = 22 years of age) and eleven individuals with DS (M = 26 years of age) completed a neuropsychological battery of executive functioning and social measures, including informant ratings on an ecologically measure of social approach. Clinical groups and twelve typically developing controls (M = 23 years) underwent a magnetic resonance imaging scan to investigate volumetric differences in the OFC and the amygdala. As expected, WS individuals displayed the highest overall social approach, especially in relation to need to approach strangers and drive to interact with strangers, as well as inappropriate/overfriendly behaviours. Both groups rated similarly in terms of social trust and unconditional positive regard. Emotion recognition abilities were similar across groups, with the DS group displaying some difficulties with negative emotions (especially anger). Inhibition and flexibility were similarly impaired across WS and DS. Compared to neurotypical controls, the DS group showed increased amygdala volumes bilaterally, while the WS group showed an enlarged right medial OFC. Approach ratings were significantly correlated with left amygdala and medial and left lateral OFC volumes in WS, and with these same regions bilaterally in DS. Results provide potential biological explanations for the hypersociability seen in WS and DS. Future research should focus on other potential neural correlates, as well as potential genetic and hormonal contributions to approach.

Neuroanatomical Correlates of Emotion-Related Impulsivity

BackgroundEmotion-related impulsivity (ERI) refers to chronically poor self-control during periods of strong emotion. ERI robustly predicts psychiatric disorders and related problems, yet its neuroanatomical correlates are largely unknown. We tested whether local brain morphometry in targeted brain regions that integrate emotion and control could explain ERI severity. MethodsOne hundred twenty-two adults (ages 18–55 years) with internalizing or externalizing psychopathology completed a structural magnetic resonance imaging (MRI) scan, the Three-Factor Impulsivity Index, and the Structured Clinical Interview for DSM-5. The Three-Factor Impulsivity Index measures two types of ERI and a third type of impulsivity not linked to emotion. Cortical reconstruction yielded cortical thickness and local gyrification measurements. We evaluated whether morphometry in the orbitofrontal cortex (OFC), insula, amygdala, and nucleus accumbens was associated with ERI severity. Hypotheses and analyses were preregistered. ResultsLower cortical gyrification in the right lateral OFC was associated with high ERI severity in a full, preregistered model. Separate examinations of local gyrification and cortical thickness also showed a positive association between gyrification in the left lateral OFC and ERI. An integrated measure of hemispheric imbalance in lateral OFC gyrification (right < left) correlated with ERI severity. These findings were specific to ERI and did not appear with non–emotion-related impulsivity. ConclusionsLocal gyrification in the lateral OFC is associated with ERI severity. The current findings fit with existing theories of OFC function, strengthen the connections between the transdiagnostic literature in psychiatry and neuroscience, and may guide future treatment development.

Altered Prefrontal Blood Flow Related With Mild Cognitive Impairment in Parkinson's Disease: A Longitudinal Study.

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.

Brain Responses to Food Choices and Decisions Depend on Individual Hedonic Profiles and Eating Habits in Healthy Young Women.

The way different food consumption habits in healthy normal-weight individuals can shape their emotional and cognitive relationship with food and further disease susceptibility has been poorly investigated. Documenting the individual consumption of Western-type foods (i.e., high-calorie, sweet, fatty, and/or salty) in relation to psychological traits and brain responses to food-related situations can shed light on the early neurocognitive susceptibility to further diseases and disorders. We aimed to explore the relationship between eating habits, psychological components of eating, and brain responses as measured by blood oxygen level-dependent functional magnetic resonance imaging (fMRI) during a cognitive food choice task and using functional connectivity (FC) during resting-state fMRI (rsfMRI) in a population of 50 healthy normal-weight young women. A Food Consumption Frequency Questionnaire (FCFQ) was used to classify them on the basis of their eating habits and preferences by principal component analysis (PCA). Based on the PCA, we defined two eating habit profiles, namely, prudent-type consumers (PTc, N = 25) and Western-type consumers (WTc, N = 25), i.e., low and high consumers of western diet (WD) foods, respectively. The first two PCA dimensions, PCA1 and PCA2, were associated with different psychological components of eating and brain responses in regions involved in reward and motivation (striatum), hedonic evaluation (orbitofrontal cortex, OFC), decision conflict (anterior cingulate cortex, ACC), and cognitive control of eating (prefrontal cortex). PCA1 was inversely correlated with the FC between the right nucleus accumbens and the left lateral OFC, while PCA2 was inversely correlated with the FC between the right insula and the ACC. Our results suggest that, among a healthy population, distinct eating profiles can be detected, with specific correlates in the psychological components of eating behavior, which are also related to a modulation in the reward and motivation system during food choices. We could detect different patterns in brain functioning at rest, with reduced connectivity between the reward system and the frontal brain region in Western-type food consumers, which might be considered as an initial change toward ongoing modified cortico-striatal control.

Fibromyalgia impact in the prefrontal cortex subfields: An assessment with MRI

IntroductionPrevious studies have associated brain abnormalities in people with fibromyalgia with accelerated brain ageing. The prefrontal cortex is located in the anterior pole of the mammalian brain. It is defined as the part of the cerebral cortex that receives projections from the mediodorsal nucleus of the thalamus. AimThis study aimed to evaluate the volumetric differences in the prefrontal cortex subfields between healthy women and women with fibromyalgia using magnetic resonance imaging (MRI) and controlling for age, estimated intracranial volume, depression, and cognitive impairment. Material and methodsA total of 47 women with fibromyalgia (recruited from a fibromyalgia local association) and 43 healthy women (retrieved from the Open Access Series of Imaging Studies database) participated in this cross-sectional study. Multiple linear regressions were used to predict the value of the prefrontal cortex subfields as well as to determine if there were volumetric differences between the groups. ResultsVolume of all prefrontal cortex regions decreased with each year of age. Healthy women showed higher volume in all the prefrontal cortex subfields than women with fibromyalgia. Regarding partial correlations performed, no significant relation were found between the fibromyalgia impact and the brain volumes analyzed, controlling for depression. ConclusionsWomen with fibromyalgia showed reduced volume in the right caudal middle frontal gyrus, rostral middle frontal gyrus, left inferior frontal gyrus pars opercularis, inferior frontal gyrus pars triangularis, inferior frontal gyrus pars orbitalis, lateral orbitofrontal cortex, right medial orbitofrontal cortex, right rostral anterior cingulate gyrus subfields of the prefrontal cortex and total gray matter compared to healthy women. Furthermore, through an analysis of multiple linear regressions, the left rostral middle frontal gyrus and left lateral orbitofrontal cortex showed significantly volumetric decreases related to depression levels. The total gray matter also shows a significant decrease related to age observed through the analysis of multiple linear regressions. No significant relation were found between the impact of the disease and the brain volumes analyzed, controlling for depression in women with fibromyalgia.

Associations between BMI and brain structures involved in food intake regulation in first-episode schizophrenia spectrum disorders and healthy controls

Structural brain differences have been described in first-episode schizophrenia spectrum disorders (FES), and often overlap with those evident in the metabolic syndrome (MetS). We examined the associations between body mass index (BMI) and brain structures involved in food intake regulation in minimally treated FES patients (n = 117) compared to healthy controls (n = 117). The effects of FES diagnosis, BMI and their interactions on our selected prefrontal cortical thickness and subcortical gray matter volume regions of interest (ROIs) were investigated with hierarchical multivariate regressions, followed by post-hoc regressions for the individual ROIs. In a secondary analysis, we examined the relationships of other MetS risk factors and psychopathology with the brain ROIs. Both illness and BMI significantly predicted the grouped prefrontal cortical thickness ROIs, whereas only BMI predicted the grouped subcortical volume ROIs. For the individual ROIs, schizophrenia diagnosis predicted thinner left and right frontal pole and right lateral OFC thickness, and increased BMI predicted thinner left and right caudal ACC thickness. There were no significant main or interaction effects for diagnosis and BMI on any of the individual subcortical volume ROIs. Secondary analyses suggest associations between several brain ROIs and individual MetS risk factors, but not with psychopathology. Our findings indicate differential, independent effects for FES diagnosis and BMI on brain structures. Limited evidence suggests that the BMI effects are more prominent in FES. Exploratory analyses suggest associations between other MetS risk factors and some brain ROIs.

Differences in Cortical Thickness in Schizophrenia Patients With and Without Auditory Verbal Hallucinations.

Auditory verbal hallucinations (AVHs) are one of the most common and severe symptoms of schizophrenia (SCZ), but the neuroanatomical mechanisms underlying AVHs remain unclear. This study aimed to investigate whether persistent AVHs (pAVH) are associated with cortical thinning of certain brain regions in patients with SCZ. With the use of the 3T magnetic resonance imaging (MRI) technology, we acquired and analyzed data from 79 SCZ patients with pAVH (pAVH group), 60 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group). The severity of pAVH was assessed by the P3 hallucination items in the Positive and Negative Syndrome Scale (PANSS) and the Auditory Hallucinations Rating Scale (AHRS). Cortical thickness analysis was used to compare the region of interest (ROI) cortical thickness between the groups. The relationship between the severity of pAVH and cortical thickness was also explored. Compared with the non-AVH and HC groups, the pAVH group exhibited significantly reduced cortical thickness in the bilateral lateral orbitofrontal region (p < 0.0007, after Bonferroni correction); no significant difference was found between the non-AVH group and the HC group. The cortical thickness of the left lateral orbitofrontal cortex (P3: r = −0.44, p < 0.001; AHRS: r = −0.45, p < 0.001) and the right lateral orbitofrontal cortex (P3: r = −0.36, p = 0.002; AHRS: r = −0.33, p = 0.004) were negatively correlated with the severity of pAVH (after Bonferroni correction, p < 0.0125). Therefore, abnormal thickness of the bilateral lateral orbitofrontal cortices might be associated with pAVHs in SCZ patients.

Disassociated and concurrent structural and functional abnormalities in the drug-naïve first-episode early onset schizophrenia

Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS.

Resting-state functional connectivity graph-properties correlate with bipolar disorder-risk in young medication-free depressed subjects: Bipolar-risk Resting State Functional Connectivity in Major Depression

BackgroundMajor Depressive Disorder (MDD) is frequently associated with risk factors for the development of Bipolar Disorder (BD). Using graph theory, we investigated brain network properties associated with BD risk factors in young MDD subjects. MethodsResting-state fMRI was acquired from a large cohort (N= 104) of medication-free currently depressed participants (25 BD depression (BDD), 79 MDD). Lifetime mania symptom count (LMSC), current Young Mania Rating Scale (YMRS) score, and family history of mood disorders (FHMD) were examined as BD risk factors. Functional connectivity matrices from 280 regions of interests (ROIs) were first entered into the Network Based Statistic (NBS) toolbox to identify connections that varied with each risk factor. Next, within the correlated network for each risk factor, global and nodal graph properties for the top five linked nodes were calculated. Last, using identified graph properties, machine learning classification (MLC) between BDD, MDD with BD risk factors (MDD+), and without BD risk factors (MDD-) was conducted. ResultsLMSC positively correlated with left lateral orbitofrontal cortex (LOFC) Communication Efficiency and with left middle temporal Eigenvector Centrality. Current YMRS score positively correlated with right amygdala Communication Efficiency and Closeness Centrality. FHMD positively correlated with right insula Eigenvector Centrality. Acceptable MLC accuracy was seen between BDD and MDD- using middle temporal Eigenvector Centrality, whereas moderate accuracy was seen between MDD+ and MDD- using OFC Communication Efficiency. LimitationAlthough participants were medication-free, they were not medication-naïve. ConclusionFunctional connectome graph properties may serve as BD vulnerability biomarkers in young individuals with MDD.

Ruminative reflection is associated with anticorrelations between the orbitofrontal cortex and the default mode network in depression: implications for repetitive transcranial magnetic stimulation

Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex. Repetitive pulse transcranial magnetic stimulation of the prefrontal cortex has been shown to alter functional connectivity, suggesting that the abnormal connectivity associated with rumination could potentially be altered. This study examined potential repetitive pulse transcranial magnetic stimulation prefrontal cortical targets that could modulate one or both of these rumination subtypes. Forty-three patients who took part in a trial of repetitive pulse transcranial magnetic stimulation completed the Rumination Response Scale questionnaire and resting-state functional magnetic resonance imaging. Seed to voxel functional connectivity analyses identified an anticorrelation between the left lateral orbitofrontal cortex (−44, 26, −8; k = 172) with the default mode network-subgenual region in relation to higher levels of reflection. Parallel analyses were not significant for brooding or the RRS total score. These findings extend previous studies of rumination and identify a potential mechanistic model for symptom-based neuromodulation of rumination.

Amyloid and anatomical correlates of executive functioning in middle-aged offspring of patients with late-onset Alzheimer's disease.

A traditional hallmark of cognitive impairment associated with late-onset Alzheimer´s disease (LOAD) is episodic memory impairment. However, early alterations have been identified in brain regions associated with executive function in asymptomatic, middle-age offspring of patients with LOAD (O-LOAD) compared to those with no family history. We hypothesized that executive function among O-LOAD would correlate with structural and amyloid brain imaging differently from those without a family history of LOAD (control subjects, CS). Executive function, cortical thickness, and in-vivo Aβ deposits were quantified in 30 O-LOAD and 25 CS. Associations were observed among O-LOAD only. Cortical thickness in the left lateral orbitofrontal cortex was positively associated with Design Fluency. The Stroop Color and Word Test, correlated positively with right rostral mid-frontal cortex thickness. Trails Making Test-B was inversely related to left medial orbitofrontal thickness. Tower of London total time was positively associated with β-amyloid deposition in the right precuneus. These results support previous evidence that early executive dysfunction might reflect subtle, early changes in persons at risk of LOAD and suggests that executive function alterations deserve further exploration in the LOAD literature.

Structural connectivity changes in the cerebral pain matrix in burning mouth syndrome: a multi-shell, multi-tissue-constrained spherical deconvolution model analysis.

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome. Previous studies have attempted to determine the brain connectivity features in BMS using functional and structural magnetic resonance imaging. However, no study has investigated the structural connectivity using multi-shell, multi-tissue-constrained spherical deconvolution (MSMT-CSD), anatomically constrained tractography (ACT), and spherical deconvolution informed filtering of tractograms (SIFT). Therefore, this study aimed to assess the differences in brain structural connectivity of patients with BMS and healthy controls using probabilistic tractography with these methods, and graph analysis. Fourteen patients with BMS and 11 age- and sex-matched healthy volunteers underwent 3-T magnetic resonance imaging. MSMT-CSD-based probabilistic structural connectivity was computed using the second-order integration over fiber orientation distributions algorithm based on nodes set in 84 anatomical cortical regions with ACT and SIFT. A t-test was performed for comparisons between the BMS and healthy control brain networks. The betweenness centrality was significantly higher in the left insula, right amygdala, and right lateral orbitofrontal cortex and significantly lower in the right inferotemporal cortex in the BMS group than that in healthy controls. However, no significant difference was found in the clustering coefficient, node degree, and small-worldness between the two groups. Graph analysis of brain probabilistic structural connectivity, based on diffusion imaging using an MSMT-CSD model with ACT and SIFT, revealed alterations in the regions comprising the pain matrix and medial pain ascending pathway. These results highlight the emotional-affective profile of BMS, which is a type of chronic pain syndrome.