Postcentral Regions Research Articles

Brain perfusion single photon emission computed tomography abnormality in MRI-negative stroke-like patients post COVID-19 vaccination.

Stroke-like symptoms after COVID-19 vaccination was thought to be functional if there was no anatomical image abnormality. We aimed to analyze brain perfusion changes in these patients. A case-control study of brain perfusion single photon emission computed tomography (SPECT) of 12 vaccinated patients with left-sided stroke-like symptoms were compared with 12 age- and gender-matched normal interictal brain SPECTs using voxel-based analysis. Significant hyperperfusion was seen on the right side in postcentral, inferior parietal, mid temporal, parahippocampal, and caudate regions, and on the left side in the thalamus, hippocampus, and mid temporal areas. In addition, there were hypoperfused bilateral superior frontal gyri and right mid/posterior cingulate cortex (Family-wise-error corrected p-values < .05). Both hypoperfusion and hyperperfusion in the brain are demonstrated. We hypothesize that these findings might be the result of the functional neurological disorder. However, based on other previous studies, circulating spike protein in the patients' plasma early after vaccination might also be the cause.

Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison

Background & aimWe examined group differences in cortical thickness and surface-parameters among age and handedness--matched persons with cannabis-induced psychosis (CIP), schizophrenia with heavy cannabis use (SZC), and healthy controls (HC). MethodsWe recruited 31 men with SZC, 28 with CIP, and 30 with HC. We used the Psychiatric Research Interview for Substance and Mental Disorders to differentiate between CIP and SZC. We processed and analyzed T1 MR images using the Surface-based Brain Morphometry (SBM) pipeline of the CAT-12 toolbox within the statistical parametric mapping. After pre-processing, volumes were segmented using surface and thickness estimation for the analysis of the region of interest. We used the projection-based thickness method to assess the cortical thickness and Desikan-Killiany atlas for cortical parcellation. ResultsWe observed the lowest cortical thickness, depth, and gyrification in the SZC, followed by CIP and the control groups. The differences were predominantly seen in frontal cortices, with limited parietal and temporal regions involvement. After False Discovery Rate (FDR) corrections and post-hoc analysis, SZC had reduced cortical thickness than HC in the middle and inferior frontal, right entorhinal, and left postcentral regions. Cortical thickness of SZC was also significantly lower than CIP in bilateral postcentral and right middle frontal regions. We found negative correlations (after FDR corrections) between the duration of cannabis use and cortical thickness in loci of parietal and occipital cortices. ConclusionOur study suggested cortical structural abnormalities in schizophrenia, in reference to healthy controls and cannabis-induced psychosis, indicating different pathophysiology of SZC and CIP.

Alterations in cerebral glucose metabolism measured by FDG PET in subjects performing a meditation practice based on clitoral stimulation

Background: The relationship between sexuality, or the libido, and spirituality or religion has long been debated in psychiatry. Recent studies have explored the neurophysiology of both sexual experiences and spiritual practices such as meditation or prayer. In the present study, we report changes in cerebral glucose metabolism in a unique meditation practice augmented by clitoral stimulation called, Orgasmic Meditation, in which a spiritual state is described to be attained by both male and female participants engaged in the practice as a pair. Methods: Male (N=20) and female (N=20) subjects had an intravenous catheter connected to a bag of normal saline inserted prior to the practice. During the practice, men stimulated their partner’s clitoris for exactly 15 minutes (he received no sexual stimulation). Midway through the practice, researchers injected 18F-fluorodeoxyglucose so the scan would reflect cerebral metabolism during the practice. Positron emission tomography (PET) imaging was performed approximately 30 minutes later. Results: In the female participants, the meditation state showed significant decreases in the left inferior frontal, inferior parietal, insula, middle temporal, and orbitofrontal regions as well as in the right angular gyrus, anterior cingulate and parahippocampus compared to a neutral state (p&lt;0.01). Male subjects had significant decreases in the left middle frontal, paracentral, precentral, and postcentral regions as well as the right middle frontal and paracentral regions during meditation (p&lt;0.01). Men also had significantly increased metabolism in the cerebellum and right postcentral and superior temporal regions (p&lt;0.01). Conclusions: These findings represent a distinct pattern of brain activity, for both men and women, that is a hybrid between that of other meditation practices and sexual stimulation. Such findings have potential psychotherapeutic implications and may deepen our understanding of the relationship between spiritual and sexual experience.

Examining the common and specific grey matter abnormalities in childhood maltreatment and peer victimisation.

Early-life interpersonal stress, particularly childhood maltreatment, is associated with neurobiological abnormalities. However, few studies have investigated the neural effects of peer victimisation. This study examines common and specific associations between childhood maltreatment, peer victimisation and brain structural alterations in youths. Grey matter volume (GMV) and cortical thickness data were collected from 105 age- and gender-matched youths (age range: 17-21 years). Region-of-interest and whole-brain analyses were conducted. For the region-of-interest analyses, the childhood maltreatment group had smaller GMV than controls in left inferior frontal gyrus, bilateral anterior insula, postcentral and lingual regions, which were associated with greater emotional abuse, along with smaller insular GMV than the peer victimisation group, who had smaller left lingual and postcentral GMV than controls. At the whole-brain level, both childhood maltreatment and peer victimisation groups had smaller GMV than controls in a cluster comprising left post/precentral, inferior frontal gyrus, insula, superior parietal and supramarginal gyri. The peer victimisation group alone had increased cortical thickness in a cluster comprising left superior frontal, anterior cingulate and medial orbitofrontal gyri, which was related to greater cyberbullying. Early-life interpersonal stress is associated with common structural alterations of the inferior frontal-limbic, sensory and lingual regions involved in cognitive control, emotion and sensory processing. The findings of childhood-maltreatment-related reduced anterior insular GMV and peer-victimisation-related increased cortical thickness in the left medial prefrontal-anterior cingulate cluster underscore the distinctive negative effects of childhood maltreatment and peer victimisation, and suggest that peer victimisation, particularly cyberbullying, could be as detrimental as childhood maltreatment.

Examining Grey Matter Structural Abnormalities in Young People Exposed to Childhood Maltreatment and Peer Victimisation

AimsEarly-life interpersonal stress, particularly childhood maltreatment (CM), is associated with neurobiological abnormalities. However, few studies have investigated the neural effects of peer victimisation (PV). This study examines the common and specific associations between CM, PV and brain structural alterations in healthy youths.MethodsGrey matter volume (GMV) and cortical thickness (CT) data were collected from 105 age-and gender-matched healthy youths (34 CM, 35 PV and 36 controls). Region-of-interest (ROI) and whole-brain analyses were conducted.ResultsFor the ROI, the CM group had smaller GMV than controls in left IFG, bilateral anterior insula, postcentral and lingual regions, which were associated with higher emotional abuse, along with smaller insular GMV than the PV group. The PV group had smaller left lingual GMV than controls, which was positively associated with age of bully onset. At the whole-brain level, both CM and PV groups had smaller GMV than controls in a cluster comprising left post/pre-central, inferior frontal, insula, superior parietal and supramarginal gyri. The PV group alone had increased CT in a cluster comprising left superior frontal, anterior cingulate and medial orbitofrontal gyri, which was related to greater cyberbullying.ConclusionEarly-life interpersonal stress from carers and peers is associated with common structural alterations of the inferior frontal-limbic, sensory and lingual regions involved in cognitive control, emotion and sensory processing. The findings of a CM-specific reduced anterior insular GMV and a PV-specific increased CT in the left medial prefrontal cluster is intriguing and underscores the unique negative effects of CM and PV, particularly cyberbullying.

Clinical and Imaging Determinants of Neurocognitive Disorders in Post-Acute COVID-19 Patients with Cognitive Complaints.

Neurocognitive disorders (NCDs) are a part of the post-acute coronavirus disease (COVID-19) syndrome. No study has specifically evaluated NCDs in post-acute COVID-19 patients with cognitive complaints or their MRI determinants. To characterize NCDs in post-acute COVID-19 patients with cognitive complaints. The secondary objectives were to assess their clinical and MRI determinants. We included 46 patients with a post-acute COVID-19 cognitive complaint referred to the Amiens University Hospital Memory Center. They underwent a neuropsychological assessment and 36 had cerebral MRI. The G3 overall summary score was the sum of the mean z scores for the executive function, language, and action speed domains. Neuropsychological profiles were compared in a general linear model. Clinical determinants were analyzed by stepwise linear regression. White matter hyperintensities (WMH) masks were analyzed using parcel-based WMH symptom mapping to identify the locations of WMHs associated with cognitive performance. Repeated ANOVA showed a group effect (p = 0.0001) due to overall lower performance for patients and a domain effect (p = 0.0001) due to a lower (p = 0.007) action speed score. The G3 overall summary score was significantly associated with solely the requirement for oxygen (R2 = 0.319, p = 0.031). WHMs were associated with the G3 overall summary score in the following structures, all right-sided (p < 0.01): superior frontal region, postcentral region, cingulum, cortico-spinal tract, inferior longitudinal fasciculus, internal capsule, and posterior segment of the arcuate fasciculus. Post-acute COVID-19 patients with cognitive complaints had NCD, with prominent action slowing, significantly associated with the acute phase oxygen requirement and a right-sided WMH structure pattern.

Imaging and genetics in Parkinson's disease: assessment of the GBA1 mutation.

Several genetic variants are associated with an increased risk for developing Parkinson's Disease (PD) and limited genotype/phenotype correlation. Specifically, mutations in GBA1, the gene coding for the lysosomal enzyme glucocerebrosidase, are associated with an earlier age of onset and faster disease progression. Given these phenotypic differences associated with GBA1 variants, we explored whether cortical thickness and other biomarkers of neurodegeneration differed in healthy controls and PD patients with and without GBA1 variants. To understand how different GBA1 variants influence PD phenotype early in the disease, we retrieved neuroimaging and biospecimen data from the Parkinson's Progression Markers Initiative database. Using FreeSurfer, we compared T1-weighted MRI images from healthy controls (N = 47) to PD patients with heterozygous N370S (N = 21), heterozygous E326K (N = 18) or heterozygous T369M (N = 8) variants, and GBA1 non-mutation carriers (N = 47). Cortical thickness in PD patients differed from controls in the parietal cortex, with E365K, T369M variants, and GBA1 non-mutation carriers showing more cortical thinning than N370S variants. Patients with N370S variants had significantly higher serum neurofilament light levels among all groups. Our results demonstrate significant cortical thinning in PD patients independent of genotype in superior parietal and postcentral regions when compared to the controls. They highlight the impact of GBA1 variants on cortical thickness in the parietal cortex. Finally, they suggest that recently diagnosed PD patients with N370S variants have a higher cortical thickness and increased active neurodegeneration when compared to PD patients without GBA1 mutations and PD patients with E326K or T369M variants.

Common abnormal connectivity in first-episode and chronic schizophrenia in pre- and post-central regions: Implications for neuromodulation targeting

Schizophrenia is a neurodevelopmental disorder manifesting differing impairments at early onset and chronic disease stages. Brain imaging research suggests a core pathological region in patients with first-episode schizophrenia is Broca's area. With disease progression, alterations in thalamic connectivity becomes more prevalent. Understanding the common circuitry underlying pathology in these two groups might highlight a critical common network and novel targets for treatment. In this study, 937 subject samples were collected including patients with first-episode schizophrenia and those with chronic schizophrenia. We used hypothesis-based voxel-level functional connectivity analyses to calculate functional connectivity using the left Broca's area and thalamus as regions of interest in those with first-episode and chronic schizophrenia, respectively. We show for the first time that in both patients with first-episode and chronic schizophrenia the greatest functional connectivity disruption ended in the pre- and postcentral regions. At the early-onset stage, the core brain region is abnormally connected to pre- and postcentral areas responsible for mouth movement, while in the chronic stage, it expanded to a wider range of sensorimotor areas. Our findings suggest that expanding the focus on the low-order sensory-motor systems beyond high-order cognitive impairments in schizophrenia may show potential for neuromodulation treatment, given the relative accessibility of these cortical regions and their functional and structural connections to the core region at different stages of illness.

Brain Activation During Active Balancing and Its Behavioral Relevance in Younger and Older Adults: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted. Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear. Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored. More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device. As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty. We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions. Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency. We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance. Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance. Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed.

Brain Global Structural and Network Topological Alterations in Long-term Nasopharyngeal Cancer Survivors

Purpose/Objective(s) Radiation and chemotherapy are highly effective treatments for patients with nasopharyngeal carcinoma (NPC), with a cure rate of 80% or higher. Long-term survivors, despite having normal MRIs, commonly suffer from memory impairment and neurocognitive dysfunction. The purpose of the study was to quantify the long-term impact of chemoradiation on brain function using general linear model (GLM) and brain connectivity and to identify brain regions which show significant functional changes after radiation. Materials/Methods Between 2002 and 2020, 26 NPC patients underwent IMRT or proton at our institution. The median age was 51 years (17 male). For all patients, high-resolution T1-W MRIs were obtained before radiation (pre-RT) and at least 5 years after (post-RT) (median 8 years). Open-source software for processing and analyzing brain MRI images was used to perform automated cortical region segmentation. Cortical area information was extracted from the 34 brain regions from both left and right brain to analyze. Age and gender were used as covariates. GLM was used to assess change in cortical regions. Simulations were used to correct for multiple comparisons. Graph theory-based brain connectome was evaluated to assess the connectivity between different regions of brain. Local efficiency and clustering coefficient were used to determine local region connectivity. Global efficiency, transitivity, and modularity were used to assess global connectivity. Hub regions (by regions of unusually high degree of connectivity) were identified. Results Five clusters were generated in the right brain: Cluster 1 and 3 (superiortemporal: p=0.05), Cluster 2 (supramarginal: p=0.001), Cluster 4 (precentral: p=0.003) and Cluster 5 (caudalanteriorcingulate: p= 0.04). Brain connectome was evaluated to analyze the brain region connectivity. After RT, patients presented an abnormal global network as reflected by increased modularity (p<0.001) and decreased global efficiency (p=0.004), clustering coefficient (p=0.002), and local efficiency (p=0.002). Reorganization of hubs was observed in post-RT. Pre-RT hubs: left (rostralanteriorcingulate, posteriorcingulate, parstriangularis, rostralmiddlefrontal, temporalpole, caudalanteriorcingulate, and pericalcarine) and right entorhinal, pericalcarine, and inferiorparietal) brain. Post-RT hubs: left (superiorfrontal, frontalpole, Lateralorbitofrontal, superiorparietal, parsopercularis, insula, posteriorcingulate, pericalcarine, and precuneus) and right (rostralmiddlefrontal, parsopercularis, and lingual) brain. Conclusion Global and permanent change in cortical areas can be seen after chemoradiation in long-term survivors. Postcentral, supramarginal, superiotemporal, and precentral regions showed the most change in cortical areas and the most disrupted connectivity. Reorganization of hubs was observed after chemoradiation. Radiation and chemotherapy are highly effective treatments for patients with nasopharyngeal carcinoma (NPC), with a cure rate of 80% or higher. Long-term survivors, despite having normal MRIs, commonly suffer from memory impairment and neurocognitive dysfunction. The purpose of the study was to quantify the long-term impact of chemoradiation on brain function using general linear model (GLM) and brain connectivity and to identify brain regions which show significant functional changes after radiation. Between 2002 and 2020, 26 NPC patients underwent IMRT or proton at our institution. The median age was 51 years (17 male). For all patients, high-resolution T1-W MRIs were obtained before radiation (pre-RT) and at least 5 years after (post-RT) (median 8 years). Open-source software for processing and analyzing brain MRI images was used to perform automated cortical region segmentation. Cortical area information was extracted from the 34 brain regions from both left and right brain to analyze. Age and gender were used as covariates. GLM was used to assess change in cortical regions. Simulations were used to correct for multiple comparisons. Graph theory-based brain connectome was evaluated to assess the connectivity between different regions of brain. Local efficiency and clustering coefficient were used to determine local region connectivity. Global efficiency, transitivity, and modularity were used to assess global connectivity. Hub regions (by regions of unusually high degree of connectivity) were identified. Five clusters were generated in the right brain: Cluster 1 and 3 (superiortemporal: p=0.05), Cluster 2 (supramarginal: p=0.001), Cluster 4 (precentral: p=0.003) and Cluster 5 (caudalanteriorcingulate: p= 0.04). Brain connectome was evaluated to analyze the brain region connectivity. After RT, patients presented an abnormal global network as reflected by increased modularity (p<0.001) and decreased global efficiency (p=0.004), clustering coefficient (p=0.002), and local efficiency (p=0.002). Reorganization of hubs was observed in post-RT. Pre-RT hubs: left (rostralanteriorcingulate, posteriorcingulate, parstriangularis, rostralmiddlefrontal, temporalpole, caudalanteriorcingulate, and pericalcarine) and right entorhinal, pericalcarine, and inferiorparietal) brain. Post-RT hubs: left (superiorfrontal, frontalpole, Lateralorbitofrontal, superiorparietal, parsopercularis, insula, posteriorcingulate, pericalcarine, and precuneus) and right (rostralmiddlefrontal, parsopercularis, and lingual) brain. Global and permanent change in cortical areas can be seen after chemoradiation in long-term survivors. Postcentral, supramarginal, superiotemporal, and precentral regions showed the most change in cortical areas and the most disrupted connectivity. Reorganization of hubs was observed after chemoradiation.

Altered Pain Processing Associated with Administration of Dopamine Agonist and Antagonist in Healthy Volunteers.

Striatal dopamine dysfunction is associated with the altered top-down modulation of pain processing. The dopamine D2-like receptor family is a potential substrate for such effects due to its primary expression in the striatum, but evidence for this is currently lacking. Here, we investigated the effect of pharmacologically manipulating striatal dopamine D2 receptor activity on the anticipation and perception of acute pain stimuli in humans. Participants received visual cues that induced either certain or uncertain anticipation of two pain intensity levels delivered via a CO2 laser. Rating of the pain intensity and unpleasantness was recorded. Brain activity was recorded with EEG and analysed via source localisation to investigate neural activity during the anticipation and receipt of pain. Participants completed the experiment under three conditions, control (Sodium Chloride), D2 receptor agonist (Cabergoline), and D2 receptor antagonist (Amisulpride), in a repeated-measures, triple-crossover, double-blind study. The antagonist reduced an individuals’ ability to distinguish between low and high pain following uncertain anticipation. The EEG source localisation showed that the agonist and antagonist reduced neural activations in specific brain regions associated with the sensory integration of salient stimuli during the anticipation and receipt of pain. During anticipation, the agonist reduced activity in the right mid-temporal region and the right angular gyrus, whilst the antagonist reduced activity within the right postcentral, right mid-temporal, and right inferior parietal regions. In comparison to control, the antagonist reduced activity within the insula during the receipt of pain, a key structure involved in the integration of the sensory and affective aspects of pain. Pain sensitivity and unpleasantness were not changed by D2R modulation. Our results support the notion that D2 receptor neurotransmission has a role in the top-down modulation of pain.

Data-driven study on resting-state functional magnetic resonance imaging during early abstinence of alcohol dependence in male patients and its predictive value for relapse

BackgroundAlcohol dependence is a mental disorder with a high relapse rate. However, specific neuroimaging biomarkers have not been determined for alcohol dependence and its relapse. We conducted data-driven research to investigate resting-state functional magnetic resonance imaging (rs-fMRI) during early abstinence from alcohol dependence and its potential ability to predict relapse.MethodsParticipants included 68 alcohol-dependent patients and 68 healthy controls (HCs). The regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were compared between the alcohol dependence group and the HCs and between the relapse group and the nonrelapse group. The brain regions that presented significantly different ReHo and/or fALFF between the alcohol-dependent patients and HCs and/or between the relapsed and nonrelapsed patients were selected as the seeds to calculate the functional connectivities (FCs).ResultsDuring a 6-month follow-up period, 52.24% of alcohol-dependent patients relapsed. A regression model for differentiating alcohol-dependent patients and HCs showed that reductions in ReHo in the left postcentral region, fALFF in the right fusiform region, and FC in the right fusiform region to the right middle cingulum were independently associated with alcohol dependence, with an area under the receiver operating characteristic curve (AUC) of 0.841. The baseline FC of the left precentral to the left cerebellum of the relapse group was significantly lower than that of the nonrelapse group. The AUC of this FC to predict relapse was 0.774.ConclusionsOur findings contribute to advancing research on the neurobiological etiology and predictive biomarkers for relapse associated with alcohol dependence.

Impaired Topographic Organization in Patients With Idiopathic Blepharospasm.

Background: Idiopathic blepharospasm (BSP) is a common adult-onset focal dystonia. Neuroimaging technology can be used to visualize functional and microstructural changes of the whole brain.Method: We used resting-state functional MRI (rs-fMRI) and graph theoretical analysis to explore the functional connectome in patients with BSP. Altogether 20 patients with BSP and 20 age- and gender-matched healthy controls (HCs) were included in the study. Measures of network topology were calculated, such as small-world parameters (clustering coefficient [Cp], the shortest path length [Lp]), network efficiency parameters (global efficiency [Eglob], local efficiency [Eloc]), and the nodal parameter (nodal efficiency [Enod]). In addition, the least absolute shrinkage and selection operator (LASSO) regression was adopted to determine the most critical imaging features, and the classification model using critical imaging features was constructed.Results: Compared with HCs, the BSP group showed significantly decreased Eloc. Imaging features of nodal centrality (Enod) were entered into the LASSO method, and the classification model was constructed with nine imaging nodes. The area under the curve (AUC) was 0.995 (95% CI: 0.973–1.000), and the sensitivity and specificity were 95% and 100%, respectively. Specifically, four imaging nodes within the sensorimotor network (SMN), cerebellum, and default mode network (DMN) held the prominent information. Compared with HCs, the BSP group showed significantly increased Enod in the postcentral region within the SMN, decreased Enod in the precentral region within the SMN, increased Enod in the medial cerebellum, and increased Enod in the precuneus within the DMN.Conclusion: The network model in BSP showed reduced local connectivity. Baseline connectomic measures derived from rs-fMRI data may be capable of identifying patients with BSP, and regions from the SMN, cerebellum, and DMN may provide key insights into the underlying pathophysiology of BSP.

Mechanical Affective Touch Therapy for Anxiety Disorders: Effects on Resting State Functional Connectivity

ObjectivesMechanical Affective Touch Therapy (MATT) is a safe, novel form of noninvasive peripheral nerve stimulation. Although mechanical stimulation activates nerves, we know little about its impact on psychiatric symptoms and their underlying cortical mechanisms. We examined the effects of open-label MATT on resting state functional connectivity (RSFC) and its relationship with anxiety and affective symptomatology (clinical results in separate report). Materials and MethodsA total of 22 adults with an Axis I anxiety disorder were recruited from the community. After two initial sessions assisted by research staff, participants self-administered 20-minute sessions of MATT at home at least twice daily for four weeks. Self-report measures of mood and anxiety severity were collected at baseline, two weeks, and four weeks. Resting state functional magnetic resonance imaging was collected before the initial MATT session (n = 20), immediately after the first session (n = 18), and following four weeks of MATT (n = 14). Seed-based whole-brain functional connectivity analyses identified brain connectivity patterns correlated with responsiveness to MATT. Seeds were based on Neurosynth meta-analytic maps for “anxiety” and “pain” given MATT’s hypothesized role in anxiety symptom amelioration and potential mechanism of action through C-tactile afferents, which play an important role in detecting pain and its affective components. Connectivity results were corrected for multiple comparisons (voxel p < 0.005, cluster p-FDR < 0.05). ResultsBaseline RSFC is predictive of symptom improvement with chronic MATT. Acute increases in insula connectivity were observed between mid-cingulate cortex and postcentral motor regions following the first MATT session. Chronic MATT was associated with increased connectivity between pain and anxiety regions of interest (ROIs) and posterior default mode network (DMN) regions involved in memory and self-reflection; the connectivity changes correlated with decreases in stress and depression symptoms. ConclusionsMATT is associated with alterations in RSFC in the DMN of anxiety disorder patients both acutely and after long-term administration, and baseline RSFC is predictive of post-treatment symptom improvement.

Sex Differences in Brain and Cognition in de novo Parkinson's Disease.

Background and Objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients.Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males: 78 females) and 69 healthy controls (40 males: 29 females) were obtained from the PPMI dataset.Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function.Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.

Longitudinal Changes in Brain Gyrification in Schizophrenia Spectrum Disorders.

Previous magnetic resonance imaging (MRI) studies reported increased brain gyrification in schizophrenia and schizotypal disorder, a prototypic disorder within the schizophrenia spectrum. This may reflect deviations in early neurodevelopment; however, it currently remains unclear whether the gyrification pattern longitudinally changes over the course of the schizophrenia spectrum. The present MRI study using FreeSurfer compared longitudinal changes (mean inter-scan interval of 2.7 years) in the local gyrification index (LGI) in the entire cortex among 23 patients with first-episode schizophrenia, 14 with schizotypal disorder, and 39 healthy controls. Significant differences were observed in longitudinal LGI changes between these groups; the schizophrenia group exhibited a progressive decline in LGI, predominantly in the fronto-temporal regions, whereas LGI increased over time in several brain regions in the schizotypal and control groups. In the schizophrenia group, a greater reduction in LGI over time in the right precentral and post central regions correlated with smaller improvements in negative symptoms during the follow-up period. The cumulative medication dosage during follow-up negatively correlated with a longitudinal LGI increase in the right superior parietal area in the schizotypal group, but did not affect longitudinal LGI changes in the schizophrenia group. Collectively, these results suggest that gyrification patterns in the schizophrenia spectrum reflect both early neurodevelopmental abnormalities as a vulnerability factor and active brain pathology in the early stages of schizophrenia.

A novel MRI approach for evaluation of microstructural neurodegeneration in early Alzheimer disease

AbstractBackgroundCurrently, brain tissue atrophy serves as in vivo structural MRI biomarker of neurodegeneration in Alzheimer Disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that AD‐related memory loss begins when neurons are lost. Hence, in vivo detection of neurodegeneration preceding detectable atrophy is essential for early AD diagnosis.MethodOur innovative approach to assessing neuronal damage in vivo is based on (a) quantitative Gradient Recalled Echo (qGRE) MRI technique and (b) genetically‐informed relationships between qGRE metrics and major components of brain tissue cellular structure (neurons/neurites and glia) that were obtained using gene expression profiles across the human brain provided by the Allen Human Brain Atlas. Seventy participants were recruited from the Knight Alzheimer Disease Research Center, representing three groups: Healthy controls [Clinical Dementia Rating® (CDR®)=0, amyloid β (Aβ)‐negative), n=34] HC; Preclinical AD (CDR=0, Aβ‐positive, n=19), PC; and mild AD (CDR=0.5 or 1, Aβ‐positive, n=17), AD.ResultPreliminary data show that qGRE identified new biomarkers in AD brain characterizing tissues with significantly lower (termed Dark Matter) and relatively preserved (termed Viable Tissue) concentrations of neurons. The fraction of Dark Matter showed clinically important and significant differences between HC and PC groups in hippocampus, middle temporal, fusiform, postcentral, and inferior parietal brain regions. However, no HC vs. PC group difference was detected by the volumetric measurements (Figure 1). Further, measurements of the Dark Matter fraction in the hippocampus showed strong associations with Cerebrospinal fluid (CSF) amyloid Aβ42 (r=‐0.52), CSF ptau (r=0.60), 18F‐AV1415‐PET tau imaging (r=0.60), and PiB‐PET amyloid imaging (r=0.60). These associations were significantly stronger compared with volumetric measurements: CSF amyloid Aβ42 (r=0.18), CSF ptau (r=‐0.24), PET tau imaging (r=‐0.39), and PiB‐PET amyloid imaging (r=‐0.17)). Importantly, the Dark Matter fraction had a significant inter‐regional association (r=0.87) with neuronal count in the hippocampal subfields obtained from histopathological study of one participant who underwent in vivo qGRE 14 months prior to expiration (Figure 2).ConclusionqGRE‐based measurements identify the microstructural changes in early AD‐related neurodegeneration that are not recognized by structural MRI atrophy measurements, therefore providing new biomarkers for early AD detection.

Cortical remodeling across the lifespan in healthy brain reveals structural network vulnerability to neurodegeneration

AbstractBackgroundAging is the main risk factor for most of the neurodegenerative diseases. The aim of this study was to investigate typical cortical thinning changes across lifespan in the healthy brain revealing structural network vulnerability to neurodegeneration.MethodThe cohort included 128 healthy individuals aged 20‐85 years that underwent an MRI scan. Structural T1‐weighted images were used to estimate vertex‐wise cortical thickness maps, then grouped into 83 regions. For each region, cortical thickness trajectory with advancing age was estimated, including sex as covariate. Additionally, all regions were ranked based on their relative thickness at the end of the observed lifetime, assessing regional changes over time. Finally, regional mean thickness was correlated with relative change over time.ResultThe highest cortical thinning was observed in the temporal lobe (parahippocampal, entorhinal, superior and middle temporal and fusiform), in the frontal lobe (lateral orbitofrontal, superior and inferior frontal and rostral anterior cingulate), in the parietal lobe (the isthmus of cingulate, precuneus, supramarginal and inferior parietal) and in the insular cortex. Interestingly, occipital regions (cuneus, lateral occipital, lingual, pericalcarine), and motor and premotor areas (precentral, postcentral and paracentral regions) showed the least cortical thickness change relative to the whole brain. Finally, positive correlation was found between mean regional thickness and its relative change over time.ConclusionThis study highlights structural vulnerability of brain regions to aging. Furthermore, results provide information concerning trajectories of normal brain aging, identifying those areas that might be more vulnerable to the attack of neurodegeneration. Supported by: European Research Council (StG‐2016_714388_NeuroTRACK).

Decreased Cortical Thickness and Local Gyrification in Individuals with Subjective Cognitive Impairment.

ObjectiveSubjective cognitive impairment (SCI) is associated with future cognitive decline. This study aimed to compare cortical thickness and local gyrification index (LGI) between individuals with SCI and normal control (NC) subjects.MethodsForty-seven participants (27 SCI and 20 NC) were recruited. All participants underwent brain magnetic resonance imaging scanning and were clinically assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery of tests. We compared cortical thickness and LGI between the two groups and analyzed correlations between cortical thickness/LGI and scores on CERAD protocol subtests in the SCI group for region of interests with significant between-group differences.ResultsCortical thickness reduction in the left entorhinal, superior temporal, insular, rostral middle frontal, precentral, superior frontal, and supramarginal regions, and right supramarginal, precentral, insular, postcentral, and posterior cingulate regions was observed in the SCI compared to the NC group. Cortical thickness in these regions correlated with scores of constructional praxis, word list memory, word list recall, constructional recall, trail making test A, and verbal fluency under the CERAD protocol. Significantly decreased gyrification was observed in the left lingual gyrus of the SCI group. In addition, gyrification of this region was positively associated with scores of constructional praxis.ConclusionOur results may provide an additional reference to the notion that SCI may be associated with future cognitive impairment. This study may help clinicians to assess individuals with SCI who may progress to mild cognitive impairment and Alzheimer’s dementia.

Offline tDCS modulates prefrontal-cortical-subcortical-cerebellar fear pathways in delayed fear extinction.

Transcranial direct current stimulation (tDCS) has been studied to enhance extinction-based treatments for anxiety disorders. However, the field shows conflicting results about its anxiolytic effect and only a few studies have observed the extinction of consolidated memories. We looked to study the effect of offline 1mA tDCS over the right dorsolateral pre-frontal cortex across the fear pathways, in consolidated fear response during delayed extinction. Participants (N = 34 women) underwent in a two-day fear conditioning procedure. On day 1, participants were assigned to the control group (N = 18) or the tDCS group (N = 16) and went through a fear acquisition procedure. On day 2, the tDCS group received 20min tDCS before extinction and while inside the MRI scanner. The control group completed the extinction procedure only. The tDCS session (for the tDCS group) and the fMRI scan (for both groups) were completed just on the second day. Univariate fMRI analysis showed stimulation-dependent activity during late extinction with the tDCS group showing decreased neural activity during the processing of threat cues (CS +) and increased activity during the processing of safety cues (CS-), in prefrontal, postcentral and paracentral regions, during late extinction. ROI to whole-brain psychophysiological interaction (PPI) analysis showed the tDCS effect on the connectivity between the left dorsolateral prefrontal cortex three cortical-amygdalo-hippocampal-cerebellar pathway clusters during the processing of the CS + in late extinction (TFCE corrected; p < 0.05). Increased neuronal activity during the processing of safety cues and stronger coupling during the processing of threat cues might be the mechanisms by which tDCS contributes to stimuli discrimination.