Rostral Middle Frontal Cortex Research Articles

The prefrontal cortex, but not the medial temporal lobe, is associated with episodic memory in middle-aged persons with HIV.

Identifying persons with HIV (PWH) at increased risk for Alzheimer's disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined. We examined 92 PWH from the CHARTER Program, ages 45-68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years). At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall. Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

The Role of 3' Regulatory Region Flanking Kinectin 1 Gene in Schizophrenia.

Schizophrenia is often associated with volumetric reductions in cortices and expansions in basal ganglia, particularly the putamen. Recent genome-wide association studies have highlighted the significance of variants in the 3' regulatory region adjacent to the kinectin 1 gene (KTN1) in regulating gray matter volume (GMV) of the putamen. This study aimed to comprehensively investigate the involvement of this region in schizophrenia. We analyzed 1136 single-nucleotide polymorphisms (SNPs) covering the entire 3' regulatory region in 4 independent dbGaP samples (4604 schizophrenia patients vs. 4884 healthy subjects) and 3 independent Psychiatric Genomics Consortium samples (107 240 cases vs. 210 203 controls) to identify consistent associations. Additionally, we examined the regulatory effects of schizophrenia-associated alleles on KTN1 mRNA expression in 16 brain areas among 348 subjects, as well as GMVs of 7 subcortical nuclei in 38 258 subjects, and surface areas (SA) and thickness (TH) of the entire cortex and 34 cortical areas in 36 936 subjects. The major alleles (f > 0.5) of 25 variants increased (β > 0) the risk of schizophrenia across 2 to 5 independent samples (8.4 × 10-4 ≤ P ≤ .049). These schizophrenia-associated alleles significantly elevated (β > 0) GMVs of basal ganglia, including the putamen (6.0 × 10-11 ≤ P ≤ 1.1 × 10-4), caudate (8.7 × 10-4 ≤ P ≤ 9.4 × 10-3), pallidum (P = 6.0 × 10-4), and nucleus accumbens (P = 2.7 × 10-5). Moreover, they potentially augmented (β > 0) the SA of posterior cingulate and insular cortices, as well as the TH of frontal (pars triangularis and medial orbitofrontal), parietal (superior, precuneus, and inferior), and temporal (transverse) cortices, but potentially reduced (β < 0) the SA of the whole, frontal (medial orbitofrontal), and temporal (pole, superior, middle, and entorhinal) cortices, as well as the TH of rostral middle frontal and superior frontal cortices (8.9 × 10-4 ≤ P ≤ .050). Our findings identify significant and functionally relevant risk alleles in the 3' regulatory region adjacent to KTN1, implicating their crucial roles in the development of schizophrenia.

Culture, prefrontal volume, and memory.

Prior cross-cultural studies have demonstrated differences among Eastern and Western cultures in memory and cognition along with variation in neuroanatomy and functional engagement. We further probed cultural neuroanatomical variability in terms of its relationship with memory performance. Specifically, we investigated how memory performance related to gray matter volume in several prefrontal lobe structures, including across cultures. For 58 American and 57 Taiwanese young adults, memory performance was measured with the California Verbal Learning Test (CVLT) using performance on learning trial 1, on which Americans had higher scores than the Taiwanese, and the long delayed free recall task, on which groups performed similarly. MRI data were reconstructed using FreeSurfer. Across both cultures, we observed that larger volumes of the bilateral rostral anterior cingulate were associated with lower scores on both CVLT tasks. In terms of effects of culture, the relationship between learning trial 1 scores and gray matter volumes in the right superior frontal gyrus had a trend for a positive relationship in Taiwanese but not in Americans. In addition to the a priori analysis of select frontal volumes, an exploratory whole-brain analysis compared volumes-without considering CVLT performance-across the two cultural groups in order to assess convergence with prior research. Several cultural differences were found, such that Americans had larger volumes in the bilateral superior frontal and lateral occipital cortex, whereas Taiwanese had larger volumes in the bilateral rostral middle frontal and inferior temporal cortex, and the right precuneus.

Sex versus gender associations with brain structure

In contrast to sex (a biological distinction), little is known about the associations between gender (a societal construct) and brain structure in the general population. In response to this knowledge gap, we examined the associations of sex vs. gender with FreeSurfer-generated cortical thickness and proportion-adjusted subcortical brain volume regions-of-interest (ROIs) in healthy adults (n = 88) screened for general medical conditions, mental illness, substance abuse, and intracranial pathologies. Gender role endorsement was assessed using the well-established and validated Bem Sex Role Inventory. For our main objectives, we calculated a continuum score as a composite measure of gender. For our secondary objectives, we examined sex-specific associations of the masculine vs. feminine gender role endorsement domains with brain structural outcomes. We found that female sex, independent of continuum scores, was associated with larger proportion-adjusted volumes for the basal ganglia, hippocampus, and ventral diencephalon. Higher continuum scores, independent of sex, were associated with thicker cortical thickness for the left and right superior frontal cortex, caudal and rostral middle frontal cortex, and right pars orbitalis. Female sex and higher continuum scores were independently associated with larger corpus callosum volumes. Post-hoc testing showed sex-specific associations between higher femininity scores and thicker prefrontal cortical thickness for the ROIs in females, but not in males. In conclusion, sex and gender showed semi-independent associations with brain structure in a general population sample. Our research supports the disaggregation of sex and gender to provide a more nuanced perspective on brain structural differences between men and women.

Association between mild behavioral impairment and hippocampal structural covariance in amnestic mild cognitive impairment

AbstractBackgroundOur previous work reported that mild cognitive impairment (MCI) patients with multiple mild behavioral impairment (MBI) domain symptoms (complex group) revealed a higher risk of developing Alzheimer’s disease (AD) compared with those with no MBI symptoms (asymptomatic group) and cortical thinning in the parietal and frontal areas. However, MCI patients with only affective dysregulation (affective dysregulation group) were not associated with the risk of AD and revealed relative cortical thickening (Yoon EJ, Front Aging Neurosci 2023). To clarify relationships of cortical thickness changes and risk of progression to AD in MCI patients, we compared structural covariance patterns between hippocampal volume and cortical thickness among the MBI subgroups.MethodA total 201 older adults with amnestic MCI were classified based on profiles of MBI domain symptoms into asymptomatic, affective dysregulation, and complex groups. The FreeSurfer was used to estimate cortical thickness and volumes of hippocampal subfields (Fig 1). A vertex‐wise general linear interaction model was used to compare group map of covariance between volumes of hippocampus subfields and thickness at each of vertices. Correlations between the thickness in regions showing significant group differences and mini‐mental state examination (MMSE) scores were also assessed.ResultIn the affective dysregulation group, the structural covariance of left CA1, CA4/DG and molecular layer were increased in the left superior and inferior parietal cortex (Fig 2a), and the thickness of this region showed positive correlation with MMSE (spearman’s rho = 0.302, p‐value = 0.046). The structural covariance of left hippocampal tail for the affective dysregulation group was increased in left lateral occipital cortex, and those for the complex group was increased in left inferior parietal and lateral occipital cortex compared with the asymptomatic group (Fig 2b). Also, the complex group revealed decreased structural covariance of right subiculum with left rostral middle frontal cortex (Fig 2c).ConclusionOur findings suggest that the lateral parietal area might have an important role in compensatory mechanisms in the affective dysregulation group. On the other hand, the complex group may be associated with more advanced stages of disease in which the patterns of increased covariance of hippocampal subfields were disappeared or inversed.

The effect of dopamine replacement therapy on cortical structure in Parkinson's disease.

To explore the cortical structural reorganization in Parkinson's disease (PD) patients under chronic dopamine replacement therapy (DRT) in cross-sectional and longitudinal data and determine whether these changes were associated with clinical alterations. A total of 61 DRT-treated, 60 untreated PD patients, and 61 normal controls (NC) were retrospectively included. Structural MRI scans and neuropsychological tests were conducted. Cortical thickness and volume were extracted based on FreeSurfer and were analyzed using general linear model to find statistically significant differences among three groups. Correlation analyses were performed among significant cortical areas, medication treatment (duration and dosage), and neuropsychological tests. Longitudinal cortical structural changes of patients who initiated DRT were analyzed using linear mixed-effect model. Significant cortical atrophy was primarily observed in the prefrontal cortex in treated patients, including the cortical thickness of right pars opercularis and the volume of bilateral superior frontal cortex (SFC), left rostral anterior cingulate cortex (rACC), right lateral orbital frontal cortex, right pars orbitalis, and right rostral middle frontal cortex. A negative correlation was detected between the left SFC volume and levodopa equivalent dose (LED) (r = -0.316, p = 0.016), as well as the left rACC volume and medication duration (r = -0.329, p = 0.013). In the patient group, the left SFC volume was positively associated with digit span forward score (r = 0.335, p = 0.017). The left SFC volume reduction was longitudinally correlated with increased LED (standardized coefficient = -0.077, p = 0.001). This finding provided insights into the influence of DRT on cortical structure and highlighted the importance of drug dose titration in DRT.

Changed cortical thickness and sulcal depth in pediatric acute lymphoblastic leukemia survivors treated with chemotherapy only.

The purpose of this study is to observe the changes of cortical morphological characteristics and their potential contribution to cognitive function in ALL survivors by using surface-based morphometry (SBM). Using SBM analysis, we calculated and compared group differences in cortical thickness, sulcal depth, gyrification, and fractal dimension of the cerebral cortex between 18 pediatric ALL survivors treated on chemotherapy-only protocols and off treatment within 2years, and 18 healthy controls (HCs) with two-sample t-tests [P < 0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical characteristic values and cognitive function parameters were investigated with partial correlation analysis, taking age as a covariate. We found decreased cortical thickness mainly located in the prefrontal and temporal region, and increased sulcal depth in left rostral middle frontal cortex and left pars orbitalis in the ALL survivors compared to HCs. There were no statistically significant differences in the gyrification and fractal dimension between the two groups. In ALL survivors, cortical thickness and sulcal depth of above areas values revealed no significant correlation with the cognitive function parameters. In conclusion, pediatric ALL survivors show decreased cortical thickness in prefrontal and temporal regions, and increased sulcal depth in prefrontal region. These results suggest that SBM-based approach can be used to assess changes of cortical morphological characteristics in pediatric ALL survivors.

Lower fractional dimension in Alzheimer's disease correlates with reduced locus coeruleus signal intensity

This study aimed to determine the pattern of fractional dimension (FD) in Alzheimer's disease (AD) patients, and investigate the relationship between FD and the locus coeruleus (LC) signal intensity.A total of 27 patients with AD and 25 healthy controls (HC) were collected to estimate the pattern of fractional dimension (FD) and cortical thickness (CT) using the Computational Anatomy Toolbox (CAT12), and statistically analyze between groups on a vertex level using statistical parametric mapping 12. In addition, they were examined by neuromelanin sensitive MRI(NM-MRI) technique to calculate the locus coeruleus signal contrast ratios (LC-CRs). Additionally, correlations between the pattern of FD and LC-CRs were further examined.Compared to HC, AD patients showed widespread lower CT and FD Furthermore, significant positive correlation was found between local fractional dimension (LFD) of the left rostral middle frontal cortex and LC-CRs. Results suggest lower cortical LFD is associated with LCCRs that may reflect a reduction due to broader neurodegenerative processes. This finding may highlight the potential utility for advanced measures of cortical complexity in assessing brain health and early identification of neurodegenerative processes.

Altered Emotion Perception Linked to Structural Brain Differences in Youth With Congenital Adrenal Hyperplasia.

Congenital adrenal hyperplasia (CAH) is a genetic disorder that results in hormonal imbalances and decreased brain volumes in regions important for emotional processing. To examine whether emotion perception differs between youth with CAH and control youth, and if these differences relate to brain volumes. In this cross-sectional study of 27 youths with CAH (mean age = 12.63 years, 16 female) and 35 age- and sex-matched controls (mean age = 13.03 years, 20 female), each participant rated picture stimuli and completed a 3T structural brain scan. Valence and arousal ratings and reaction times of 61 affective images were assessed. Gray matter volumes were measured by MRI. Youth with CAH had lower valence ratings for negative (P = .007) and neutral (P = .019) images. Controls showed differences in reaction times and arousal ratings across stimuli conditions, but youth with CAH did not. Brain volumes of the right amygdala (P = .025) and left hippocampus (P = .002) were associated with valence ratings. Left rostral middle frontal (P < .001) and right medial orbitofrontal cortex (P = .002) volumes were negatively related to valence scores only in youth with CAH, whereas left medial orbitofrontal cortex (P < .001) volumes were associated with valence scores positively in youth with CAH and negatively in controls. Findings suggest that youth with CAH perceive emotive stimuli as more unpleasant. Decreased brain volumes in the amygdala, hippocampus, and prefrontal cortex are associated with these measures of altered emotion perception in youth with CAH.

Morphometric similarity network alterations in COVID-19 survivors correlate with behavioral features and transcriptional signatures

ObjectivesTo explore the differences in the cortical morphometric similarity network (MSN) between COVID-19 survivors and healthy controls, and the correlation between these differences and behavioralfeatures and transcriptional signatures. Materials & methods39 COVID-19 survivors and 39 age-, sex- and education years-matched healthy controls (HCs) were included. All participants underwent MRI and behavioral assessments (PCL-17, GAD-7, PHQ-9). MSN analysis was used to compute COVID-19 survivors vs. HCs differences across brain regions. Correlation analysis was used to determine the associations between regional MSN differences and behavioral assessments, and determine the spatial similarities between regional MSN differences and risk genes transcriptional activity. ResultsCOVID-19 survivors exhibited decreased regional MSN in insula, precuneus, transverse temporal, entorhinal, para-hippocampal, rostral middle frontal and supramarginal cortices, and increased regional MSN in pars triangularis, lateral orbitofrontal, superior frontal, superior parietal, postcentral, and inferior temporal cortices. Regional MSN value of lateral orbitofrontal cortex was positively associated with GAD-7 and PHQ-9 scores, and rostral middle frontal was negatively related to PHQ-9 scores. The analysis of spatial similarities showed that seven risk genes (MFGE8, MOB2, NUP62, PMPCA, SDSL, TMEM178B, and ZBTB11) were related to regional MSN values. ConclusionThe MSN differences were associated with behavioral and transcriptional signatures, early psychological counseling or intervention may be required to COVID-19 survivors. Our study provided a new insight into understanding the altered coordination of structure in COVID-19 and may offer a new endophenotype to further investigate the brain substrate.

ALTERATIONS IN FUNCTIONAL CONNECTIVITY: BEING WATCHED AS AN INDICATOR OF STATE ANXIETY

Anxiety increases self-focused attention and rumination. Individuals with anxiety are sensitive to being watched by others, as being watched provokes self-referential processing and induces thoughts regarding others perceptions of oneself. However, whether the neural sensitivity to being watched depends on the level of anxiety remains unclear.We investigated the relationship between anxiety and the neural sensitivity to being watched by others.The anxiety of 25 healthy participants (mean age standard deviation, 23.08 1.71 years; 12 men and 13 women) was evaluated using the Spielberger StateTrait Anxiety Inventory. Resting state electroencephalography data was collected under the alone condition and the condition of being watched by another person. By subtracting the phase lag value between the two conditions, we determined the alterations in participants functional networks when they were being watched. We then found the correlation between the Spielberger StateTrait Anxiety Inventory scores and reactivity of functional connectivity when being watched.The score of state anxiety was significantly correlated with increased phase lag values in the left precuneus, bilateral caudal anterior cingulate cortex, and right rostral middle frontal cortex in the beta band (p&lt; 0.05). We found no significant correlation between the trait anxiety scores and altered phase lag values.Functional connectivity may be involved in the default mode network relevant to self-referential processing and the dorsal attentional network. Our results suggest that self-focused mental processing and sensitivity to being watched by others could be common in people with anxiety, thus expanding the current understanding of the cognitive mechanisms behind anxiety.

No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes

Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across childhood until age 9 years in Generation R and 11 years in MARS. Protective factors (temperament, cognition, self-esteem, maternal sensitivity, friendship quality) were assessed at various time-points during childhood. Global brain volumes and volumes of amygdala, hippocampus, and the anterior cingulate, medial orbitofrontal and rostral middle frontal cortices were assessed with anatomical scans at 10 years in Generation R and at 25 years in MARS. Childhood adversity was related to smaller cortical grey matter, cerebral white matter, and cerebellar volumes in children. Also, no buffering effects of protective factors on the association between adversity and the brain outcomes survived multiple testing correction. We found no robust evidence for an interaction between protective factors and childhood adversity on broad brain structural measures. Small interaction effects observed in one cohort only warrant further investigation.

Functional brain changes using electroencephalography after a 24-week multidomain intervention program to prevent dementia.

Quantitative electroencephalography (QEEG) has proven useful in predicting the response to various treatments, but, until now, no study has investigated changes in functional connectivity using QEEG following a lifestyle intervention program. We aimed to investigate neurophysiological changes in QEEG after a 24-week multidomain lifestyle intervention program in the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN). Participants without dementia and with at least one modifiable dementia risk factor, aged 60–79 years, were randomly assigned to the facility-based multidomain intervention (FMI) (n = 51), the home-based multidomain intervention (HMI) (n = 51), and the control group (n = 50). The analysis of this study included data from 44, 49, and 34 participants who underwent EEG at baseline and at the end of the study in the FMI, HMI, and control groups, respectively. The spectrum power and power ratio of EEG were calculated. Source cortical current density and functional connectivity were estimated by standardized low-resolution brain electromagnetic tomography. Participants who received the intervention showed increases in the power of the beta1 and beta3 bands and in the imaginary part of coherence of the alpha1 band compared to the control group. Decreases in the characteristic path lengths of the alpha1 band in the right supramarginal gyrus and right rostral middle frontal cortex were observed in those who received the intervention. This study showed positive biological changes, including increased functional connectivity and higher global efficiency in QEEG after a multidomain lifestyle intervention.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT03980392] identifier [NCT03980392].

Disruptions in Structural and Functional Connectivity Relate to Poststroke Fatigue.

Introduction: Poststroke fatigue (PSF) is a disabling condition with unclear etiology. The brain lesion is thought to be an important causal factor in PSF, although focal lesion characteristics such as size and location have not proven to be predictive. Given that the stroke lesion results not only in focal tissue death but also in widespread changes in brain networks that are structurally and functionally connected to damaged tissue, we hypothesized that PSF relates to disruptions in structural and functional connectivity. Materials and Methods: Twelve patients who incurred an ischemic stroke in the middle cerebral artery (MCA) territory 1-3 years prior, and currently experiencing a range of fatigue severity, were enrolled. The patients underwent structural and resting-state functional magnetic resonance imaging (MRI). The structural MRI data were used to measure structural disconnection of gray matter resulting from lesion to white matter pathways. The functional MRI data were used to measure network functional connectivity. Results: The patients showed structural disconnection in varying cortical and subcortical regions. Fatigue severity correlated significantly with structural disconnection of several frontal cortex regions in the ipsilesional (IL) and contralesional hemispheres. Fatigue-related structural disconnection was most severe in the IL rostral middle frontal cortex. Greater structural disconnection of a subset of fatigue-related frontal cortex regions, including the IL rostral middle frontal cortex, trended toward correlating significantly with greater loss in functional connectivity. Among identified fatigue-related frontal cortex regions, only the IL rostral middle frontal cortex showed loss in functional connectivity correlating significantly with fatigue severity. Conclusion: Our results provide evidence that loss in structural and functional connectivity of bihemispheric frontal cortex regions plays a role in PSF after MCA stroke, with connectivity disruptions of the IL rostral middle frontal cortex having a central role. Impact statement Poststroke fatigue (PSF) is a common disabling condition with unclear etiology. We hypothesized that PSF relates to disruptions in structural and functional connectivity secondary to the focal lesion. Using structural and resting-state functional connectivity magnetic resonance imaging (MRI) in patients with chronic middle cerebral artery (MCA) stroke, we found frontal cortex regions in the ipsilesional (IL) and contralesional hemispheres with greater structural disconnection correlating with greater fatigue. Among these fatigue-related cortices, the IL rostral middle frontal cortex showed loss in functional connectivity correlating with fatigue. These findings suggest that disruptions in structural and functional connectivity play a role in PSF after MCA stroke.

Quantification of Brain β-Amyloid Load in Parkinson's Disease With Mild Cognitive Impairment: A PET/MRI Study.

BackgroundMild cognitive impairment in Parkinson's disease (PD-MCI) is associated with faster cognitive decline and conversion to dementia. There is uncertainty about the role of β-amyloid (Aβ) co-pathology and its contribution to the variability in PD-MCI profile and cognitive progression.ObjectiveTo study how presence of Aβ affects clinical and cognitive manifestations as well as regional brain volumes in PD-MCI.MethodsTwenty-five PD-MCI patients underwent simultaneous PET/3T-MRI with [18F]flutemetamol and a clinical and neuropsychological examination allowing level II diagnosis. We tested pairwise differences in motor, clinical, and cognitive features with Mann–Whitney U test. We calculated [18F]flutemetamol (FMM) standardized uptake value ratios (SUVR) in striatal and cortical ROIs, and we performed a univariate linear regression analysis between the affected cognitive domains and the mean SUVR. Finally, we investigated differences in cortical and subcortical brain regional volumes with magnetic resonance imaging (MRI).ResultsThere were 8 Aβ+ and 17 Aβ- PD-MCI. They did not differ for age, disease duration, clinical, motor, behavioral, and global cognition scores. PD-MCI-Aβ+ showed worse performance in the overall executive domain (p = 0.037). Subcortical ROIs analysis showed significant Aβ deposition in PD-MCI-Aβ+ patients in the right caudal and rostral middle frontal cortex, in precuneus, in left paracentral and pars triangularis (p < 0.0001), and bilaterally in the putamen (p = 0.038). Cortical regions with higher amyloid load correlated with worse executive performances (p < 0.05). Voxel-based morphometry (VBM) analyses showed no between groups differences.ConclusionsPresence of cerebral Aβ worsens executive functions, but not motor and global cognitive abilities in PD-MCI, and it is not associated with middle-temporal cortex atrophy. These findings, together with the observation of significant proportion of PD-MCI-Aβ-, suggest that Aβ may not be the main pathogenetic determinant of cognitive deterioration in PD-MCI, but it would rather aggravate deficits in domains vulnerable to Parkinson primary pathology.

Frontotemporal thalamic connectivity in schizophrenia and schizotypal personality disorder

Schizotypal personality disorder (SPD) resembles schizophrenia, but with attenuated brain abnormalities and the absence of psychosis. The thalamus is integral for processing and transmitting information across cortical regions and widely implicated in the neurobiology of schizophrenia. Comparing thalamic connectivity in SPD and schizophrenia could reveal an intermediate schizophrenia-spectrum phenotype to elucidate neurobiological risk and protective factors in psychosis. We used rsfMRI to investigate functional connectivity between the mediodorsal nucleus (MDN) and pulvinar, and their connectivity with frontal and temporal cortical regions, respectively in 43 healthy controls (HCs), and individuals in the schizophrenia-spectrum including 45 psychotropic drug-free individuals with SPD, and 20 individuals with schizophrenia-related disorders [(schizophrenia (n = 10), schizoaffective disorder (n = 8), schizophreniform disorder (n = 1) and psychosis NOS (n = 1)]. Individuals with SPD had greater functional connectivity between the MDN and pulvinar compared to individuals with schizophrenia. Thalamo-frontal (i.e., between the MDN and rostral middle frontal cortex) connectivity was comparable in SPD and HCs; in SPD greater connectivity was associated with less symptom severity. Individuals with schizophrenia had less thalamo-frontal connectivity and thalamo-temporal (i.e., pulvinar to the transverse temporal cortex) connectivity compared with HCs. Thalamo-frontal functional connectivity may be comparable in SPD and HCs, but abnormal in schizophrenia, and that this may be protective against psychosis in SPD.

Symposium

Objective:Neuromodulatory interventions like transcranial direct current stimulation (tDCS) is an emerging and potential therapeutic strategy to help in reducing craving and relapse prevention in patients of alcohol dependence syndrome (1–4). The potential target for alcohol dependence is the dorsolateral pre-frontal cortex (dlPFC) as frontal dysfunction is a hallmark of alcoholism, even in alcohol dependence subjects with no major clinical and global cognitive deficits (5). In this context, this study was designed to explore the effect of tDCS treatment on craving and relapse prevention and its correlation to dorsolateral prefrontal cortex (DLPFC) activation in alcohol dependent patients.Methodology:This study was a double blinded randomized sham control trial, conducted at National Institute of Mental Health and Neurosciences, Bangalore after approval by the Institute Ethics Committee. Twenty-four patients of alcohol dependence syndrome were recruited after informed consent. After detoxification patients underwent baseline fMRI scans. Followed by tDCS with intensity of 2mA and duration of 20 minutes per day was administered for 5 consecutive days with cathode over left dorsolateral prefrontal cortex (DLPFC) and anode over right DLPFC. On the 5th day post fMRI scans were repeated. Both investigator and subjects remained blind throughout the study period. During scans patients were exposed to visual alcohol cues using VICE (visual image- Induced craving for ethanol) paradigm. Pre- treatment and post-treatment scans were analysed using SPM-12 software.Results:At the beginning of the study, 24 subjects were selected but 2 subjects dropped out before post fMRI scan. The baseline comparison of socio-demographic and clinical variables found to have no differences among both groups.fMRI results: At baseline, the true and sham tDCS groups had comparable BOLD activation patterns and there were no between-group differences in activation pattern noted for alcohol vs. neutral cues contrast. Following 5 sessions of tDCS, there is significantly increased activation observed in true tDCS group, from Pre- to Post- treatment scans. Brain activity at DLPFC (Post-Pre) was positively associated with time to first alcohol lapse (p=0.048, Spearman’s rho =0.426). This suggests that greater the increase in brain activity at DLPFC after treatment with bilateral repetitive tDCS longer was the time to first lapse. Conclusion:This study has shown bilateral repetitive transcranial direct current stimulation in alcohol dependent subjects, activates dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) along with increase in the connectivity strength between medial frontal gyrus (MFG) and sub cortical reward centre (NAc), which facilitated abstinence from alcohol. So from this study we better understood the mechanism of tDCS in preventing relapse to alcohol by activation of dorsolateral prefrontal cortex and anterior cingulated cortex. Though the fMRI results were statistically significant for relapse and DLPFC activation, but it would be difficult to establish the clinical significance of the improvement in craving in the background of small sample size. Hence further studies with larger sample size are required in near future. Referrences: 1. Klauss J, Penido Pinheiro LC, Silva Merlo BL, Correia Santos GDA, Fregni F, Nitsche MA, et al. A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. Int J Neuropsychopharmacol. 2014;17(11):1793–803.2. Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, et al. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study. Drug Alcohol Depend. 2008;92(1–3):55–60.3. Nakamura-Palacios EM, Lopes IBC, Souza RA, Klauss J, Batista EK, Conti CL, et al. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction. J Neural Transm. 2016;123(10):1179–94.4. da Silva MC, Conti CL, Klauss J, Alves LG, do Nascimento Cavalcante HM, Fregni F, et al. Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. J Physiol. 2013;107(6):493–502.5. Nakamura-Palacios EM, Souza RSM, Zago-Gomes MP, de Melo AMF, Braga FS, Kubo TTA, et al. Gray Matter Volume in Left Rostral Middle Frontal and Left Cerebellar Cortices Predicts Frontal Executive Performance in Alcoholic Subjects. Alcohol Clin Exp Res [Internet]. 2014 Apr 1 ;38(4):1126–33. Available from: http://doi.wiley.com/10.1111/ acer.12308

Structural abnormalities in adolescents with conduct disorder and high versus low callous unemotional traits.

There may be distinct conduct disorder (CD) etiologies and neural morphologies in adolescents with high callous unemotional (CU) traits versus low CU traits. Here, we employed surface-based morphometry methods to investigate morphological differences in adolescents diagnosed with CD [42 with high CU traits (CD-HCU) and 40 with low CU traits (CD-LCU)] and healthy controls (HCs, N = 115) in China. Whole-brain analyses revealed significantly increased cortical surface area (SA) in the left inferior temporal cortex and the right precuneus, but decreased SA in the left superior temporal cortex in the CD-LCU group, compared with the HC group. There were no significant cortical SA differences between the CD-HCU and the HC groups. Compared to the CD-HCU group, the CD-LCU group had a greater cortical thickness (CT) in the left rostral middle frontal cortex. Region-of-interest analyses revealed significant group differences in the right hippocampus, with CD-HCU group having lower righthippocampal volumes than HCs. We did not detect significant group differences in the amygdalar volume, however, the right amygdalar volume was found to be a significant moderator of the correlation between CU traits and the proactive aggression in CD patients. The present results suggested that the manifestations of CD differ between those with high CU traits versus low CU traits, and underscore the importance of sample characteristics in understanding the neural substrates of CD.

Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults

Small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH), is associated with cognitive decline and risk of clinical Alzheimer disease (AD). One way in which small vessel cerebrovascular disease could contribute to AD is through the promotion of neurodegeneration; the effect of small vessel cerebrovascular disease on neurodegeneration may differ across racial and ethnic groups. To examine whether WMH volume is associated with cortical thinning over time and subsequent memory functioning and whether the association between WMH volume and cortical thinning differs among racial and ethnic groups. This longitudinal community-based cohort study included older adults from northern Manhattan who were participants in the Washington Heights-Inwood Columbia Aging Project. Participants underwent two 3T magnetic resonance imaging (MRI) scans a mean of 4 years apart. Data were collected from March 2011 to January 2020. Total and regional WMH volumes. The association of total and regional WMH volumes with cortical thinning over time was tested using general linear models in a vertexwise analysis. Cortical thinning was measured vertexwise by symmetrized percent change between 2 time points. The association of changes in cortical thickness with memory and whether this association differed by race and ethnicity was also analyzed. Delayed memory was a secondary outcome. In 303 participants (mean [SD] age, 73.16 [5.19] years, 181 [60%] women, 96 [32%] non-Hispanic White, 113 [37%] Non-Hispanic Black, 94 [31%] Hispanic), baseline WMH volumes were associated with cortical thinning in medial temporal and frontal/parietal regions. Specifically, total WMH volume was associated with cortical thinning in the right caudal middle frontal cortex (P = .001) and paracentral cortex (P = .04), whereas parietal WMH volume was associated with atrophy in the left entorhinal cortex (P = .03) and right rostral middle frontal (P < .001), paracentral (P < .001), and pars triangularis (P = .02) cortices. Thinning of the right caudal middle frontal and left entorhinal cortices was related to lower scores on a memory test administered closest to the second MRI visit (right caudal middle frontal cortex: standardized β = 0.129; unstandardized b = 0.335; 95% CI, 0.055 to 0.616; P = .01; left entorhinal cortex: β = 0.119; b = 0.290; 95% CI, 0.018 to 0.563; P = .03). The association of total WMH with thinning in the right caudal middle frontal and right paracentral cortex was greater in non-Hispanic Black participants compared with White participants (right caudal middle frontal cortex: β = -0.222; b = -0.059; 95% CI, -0.114 to -0.004; P = .03; right paracentral cortex: β = -0.346; b = -0.155; 95% CI, -0.244 to -0.066; P = .001). The association of parietal WMH with cortical thinning of the right rostral middle frontal, right pars triangularis, and right paracentral cortices was also stronger among non-Hispanic Black participants compared with White participants (right rostral middle frontal cortex: β = -0.252; b = -0.202; 95% CI, -0.349 to -0.055; P = .007; right pars triangularis cortex: β = -0.327; b = -0.253; 95% CI, -0.393 to -0.113; P < .001; right paracentral cortex: β = -0.263; b = -0.337; 95% CI, -0.567 to -0.107; P = .004). In this study, small vessel cerebrovascular disease, operationalized as WMH, was associated with subsequent cortical atrophy in regions that overlap with typical AD neurodegeneration patterns, particularly among non-Hispanic Black older adults. Cerebrovascular disease may affect risk and progression of AD by promoting neurodegeneration and subsequent memory decline.

S158. URBANICITY INDEX AND CORTICAL GYRIFICATION IN SCHIZOPHRENIA

BackgroundUrban birth and upbringing are considered to be risk factors for schizophrenia, but recent studies do not support the same. While several hypotheses are suggested, the pathogenic mechanisms are not known. Notably, no study has examined brain changes, if any, associated with an urban upbringing in schizophrenia. Hence, in this study, we examined the effect of urban upbringing on the cortical gyrification in schizophrenic patients.MethodsWe recruited 108 persons with DSM-IV schizophrenia and 74 healthy volunteers. Study participants underwent clinical assessments using Positive and negative syndrome scale, Calgary depression scale to measure severity of clinical symptoms. All participants were scanned using 3T MRI scanner and a high resolution T1 structural scan was obtained. Cortical gyrification measurements were conducted on these images using Freesurfer software. Statistical maps were generated in Query, design, Estimate, Contrast (QDEC) interface. A Monte Carlo Simulation (MCS) was run for FWE correction with the threshold 1.3 (p<0.05) in QDEC. Participants upbringing place was noted with respect to the place where they lived for the first 15 years of life. Based on Census India of 2011, the places were categorized into 1) rural 2) statutory town and 3) census town. These 3 groups and assigned values 1,2 and 3, respectively, which were then rated for each year of life (1–15) and urbanicity index was calculated using a previously used method (range from 15 to 45). A regression analysis was implemented in QDEC with age, sex, education and demean ICV as covariates to examine the relation between Urban upbringing and cortical gyrification index.ResultsIn the overall population, HV had higher gyrification index in the left superior parietal cortex (p<0.008) than SCZ. There was a significant negative correlations between gyrification index and urbanicity index in left postcentral (p<0.0001), left insula (p<0.0001), left fusiform (p<0.0005), left rostral middle frontal (p<0.01), right supramarginal (p<0.0001), right fusiform (p<0.0001), and right superior temporal (p<0.005) cortices.DiscussionThe results indicate a significant effect of urbanicity on cortical gyrification in patients with SCZ as well as HV. The presence of deficits in frontal areas indicate the likely effect of urban upbringing on growth and maturation of the frontal cortex. Interestingly, the presence of difference in areas implicated in schizophrenia provides support to the possible increased risk of urban upbringing on schizophrenia. The preliminary evidence from this analysis provides the necessary rationale to further examine the impact of urban upbringing on brain structure/ function and the risk of developing schizophrenia.