Left Orbitofrontal Cortex Research Articles

Do the negative symptoms of schizophrenia reflect reduced responsiveness to reward? Examination using a reward prediction error (RPE) task.

A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations. Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS, N = 27) or absent negative symptoms (ANS, N = 27) and healthy controls (HC, N = 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE. In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI. The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.

Elevated serum platelet count inhibits the effects of brain functional changes on cognitive function in patients with mild cognitive impairment: A resting-state functional magnetic resonance imaging study.

Brain function remodeling has been observed in patients with mild cognitive impairment (MCI) and is closely associated with cognitive performance. However, it is not clear if this relationship is influenced by complete blood counts. This study investigated the role of complete blood counts in the relationship between brain function and cognitive performance. Twenty-two MCI patients and eighteen controls were enrolled. All subjects underwent resting-state functional magnetic resonance imaging. A neuropsychological battery [Mini-Mental Status Examination, Auditory Verbal Learning Test (AVLT), Symbol Digit Modalities Test, Boston Naming Test (BNT), Shape Trails Test B (STT-B), Rey Complex Figure Test (RCFT), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Scale] was used to assess cognitive function, and MCI patients received complete blood counts tests for red blood cells (RBC), white blood cells, hemoglobin (HGB), monocytes, and platelet counts (PLT). Compared with controls, MCI patients demonstrated significantly decreased amplitude of low-frequency fluctuation (ALFF) values in the left dorsolateral superior frontal gyrus, left post orbitofrontal cortex, right medial superior frontal gyrus, right insula, and left triangular inferior frontal gyrus. In the MCI group, there were associations between ALFF values of the left hippocampus (HIP.L) and AVLT (p = 0.003) and AVLT-N5 scores (p = 0.001); ALFF values of the right supramarginal gyrus (SMG.R) and BNT scores (p = 0.044); ALFF values of the right superior temporal gyrus (STG.R) and BNT scores (p = 0.022); ALFF values of the left precuneus (PCUN.L) and STT-B time (p = 0.012); and ALFF values of the left caudate nucleus (CAU.L) and RCFT-time (p = 0.036). Moreover, the HAMA scores were negatively correlated with RBC and HGB levels, and positively correlated with monocyte count. The PLT count was positively correlated with STT-B time. Additionally, high PLT count inhibited the effect of ALFF values of the PCUN. L on STT-B performance in MCI patients (p = 0.0207). ALFF values of the HIP. L, SMG.R, STG. R, PCUN.L, and CAU. L were associated with decreased memory, language, executive function, and visuospatial ability in MCI patients. Notably, elevated PLT count could inhibit the effect of brain functional changes in the PCUN.L on executive function in MCI patients.

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.

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.

White matter and gray matter changes related to cognition in community populations.

Further studies are needed to improve the understanding of the pathological process underlying cognitive impairments. The purpose of this study is to investigate the global and topographic changes of white matter integrity and cortical structure related to cognitive impairments in a community-based population. A cross-sectional analysis was performed based on 995 subjects (aged 56.8 ± 9.1 years, 34.8% males) from the Shunyi study, a community-dwelling cohort. Cognitive status was accessed by a series of neurocognitive tests including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), category Verbal Fluency Test (VFT), Digit Span Test (DST), and Trail Making Tests A and B (TMT-A and TMT-B). Structural and diffusional MRI data were acquired. White matter integrity was assessed using fractional anisotropy (FA), mean diffusivity (MD), and peak width of skeletonized mean diffusivity (PSMD). Cortical surface area, thickness, and volume were measured using Freesurfer. Probabilistic tractography was further conducted to track the white matter fibers connecting to the cortical regions related to cognition. General linear models were used to investigate the association between brain structure and cognition. Global mean FA and MD were significantly associated with performances in VFT (FA, β 0.119, p < 0.001; MD, β -0.128, p < 0.001). Global cortical surface area, thickness, and volume were not related to cognitive scores. In tract-based spatial statistics analysis, disruptive white matter integrity was related to cognition impairment, mainly in visuomotor processing speed, semantic memory, and executive function (TMT-A and VFT), rather than verbal short-term memory and working memory (DST). In the whole brain vertex-wise analysis, surface area in the left orbitofrontal cortex, right posterior-dorsal part of the cingulate gyrus, and left central sulcus were positively associated with MMSE and MoCA scores, and the association were independent of the connecting white matter tract. Disrupted white matter integrity and regional cortical surface area were related to cognition in community-dwelling populations. The associations of cortical surface area and cognition were independent of the connecting white matter tract.

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p<0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p<0.05, from whole brain statistical parametric map analysis). This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies. This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

Physical Activity Alters Functional Connectivity of Orbitofrontal Cortex Subdivisions in Healthy Young Adults: A Longitudinal fMRI Study.

Physical activity (PA) plays an important role in affect processing. Studies describe the orbitofrontal cortex (OFC) as a major hub for emotion processing and the pathophysiology of affective disorders. Subregions of the OFC show diverse functional connectivity (FC) topographies, but the effect of chronic PA on subregional OFC FC still lacks scientific understanding. Therefore, we aimed at investigating the effects of regular PA on the FC topographies of OFC subregions in healthy individuals within a longitudinal randomized controlled exercise study. Participants (age: 18-35 years) were randomly assigned to either an intervention group (IG; N = 18) or a control group (CG; N = 10). Fitness assessments, mood questionnaires, and resting state functional magnetic resonance imaging (rsfMRI) were performed four times over the duration of 6 months. Using a detailed parcellation of the OFC, we created subregional FC topography maps at each time point and applied a linear mixed model to assess the effects of regular PA. The posterior-lateral right OFC showed a group and time interaction, revealing decreased FC with the left dorsolateral prefrontal cortex in the IG, while FC in the CG increased. Group and time interaction in the anterior-lateral right OFC with the right middle frontal gyrus was driven by increased FC in the IG. The posterior-lateral left OFC showed a group and time interaction based on differential change in FC to the left postcentral gyrus and the right occipital gyrus. This study emphasized regionally distinctive FC changes induced by PA within the lateral OFC territory, while providing aspects for further research.

The complexity of cortical folding is reduced in chronic cocaine users.

Cocaine use is a worldwide health problem with psychiatric, somatic and socioeconomic complications, being the second most widely used illicit drug in the world. Despite several structural neuroimaging studies, the alterations in cortical morphology associated with cocaine use and addiction are still poorly understood. In this study, we compared the complexity of cortical folding (CCF), a measure that aims to summarize the convoluted structure of the cortex between patients with cocaine addiction (n = 52) and controls (n = 36), and correlated it with characteristics of addiction and impulsivity. We found that patients with cocaine addiction had greater impulsivity and showed reduced CCF in a cluster that encompassed the left insula and the supramarginal gyrus (SMG) and in one in the left medial orbitofrontal cortex. Finally, the CCF in the left medial orbitofrontal cortex was correlated with the age of onset of cocaine addiction and with attentional impulsivity. Overall, our findings suggest that chronic cocaine use is associated with changes in the cortical surface in the fronto-parieto-limbic regions that underlie emotional regulation and these changes are associated with earlier cocaine use. Future longitudinal studies are warranted to unravel the association of these changes with the diathesis for the disorder and with the chronic use of this substance.

Assessing dynamic brain activity during verbal associative learning using MEG/fMRI co-processing

BackgroundThe abilities of individual neuroimaging methods to resolve spatial and temporal contributions of brain regions during cognitive processes are limited. Co-processing of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) may overcome some of the limitations by utilizing Multiple Sparse Priors (MSP) in a Bayesian framework that takes advantage of the temporal resolution of MEG and spatial resolution of fMRI. Methods24 healthy participants were recruited to perform a paired-associate verbal learning task during fMRI and MEG scans. FMRI data were processed within Group ICA fMRI Toolbox. Independent components (ICs) were temporally sorted by task time series (|r|>0.30 threshold identified task-related ICs). Task-positive (“generate”) ICs were retained as spatial priors for MEG analyses. MEG data were processed by an event-related potential (ERP) approach and with a theta power approach. MEG source reconstructions were constrained within the task-positive ICs for both ERP and theta-power approaches. ResultsFor fMRI, five networks were identified as task-related. Four ICs underlying active generation spanned bilateral parietal, orbitofrontal, medial frontal and superior temporal regions, and occipital lobe. FMRI-constrained MEG source reconstructions using the ERP approach yielded early visual cortex activity followed by left inferior frontal gyrus (IFG) and orbito-frontal cortex (OFC) recruitment to coalesce in the left inferior temporal lobe. For the theta approach, MEG source reconstructions showed a progression of activity from bilateral temporal areas to left OFC and middle temporal gyrus, followed by right IFG. DiscussionMSP analyses informed by fMRI produced more focused regional activity than reconstructions without priors suggesting this approach may result in identifying more relevant semantic information during active generation. Constraining MEG source reconstruction to fMRI priors during active generation indicates fronto-temporal and fronto-parietal networks are interconnected across time and space.

Adolescent Parvalbumin Expression in the Left Orbitofrontal Cortex Shapes Sociability in Female Mice.

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the left orbitofrontal cortex (OFCL), and decreased socially evoked activity in the OFCL Moreover, parvalbumin (PV) deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. MethodsFEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a ‘washout’ period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. ResultsClinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = −0.5 [95% CI −1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. ConclusionstDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step.Trial registration: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049

Transcutaneous electrical acupoint stimulation induced sedative effects in healthy volunteers: A resting-state fMRI study.

Previous studies indicated the sedative effect of acupoint stimulation. However, its mechanism remains unclear. This study aimed to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) and to explore the brain regions involved in this effect in healthy volunteers using functional magnetic resonance imaging (fMRI) techniques. In this randomized trial, 26 healthy volunteers were randomly assigned to the TEAS group (receiving 30 min of acupoint stimulation at HT7/PC4) and the control group. fMRI was conducted before and after the intervention. The primary outcome was the BIS value during the intervention. Secondary outcomes included the amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) showed by fMRI. In healthy volunteers, compared with the control group, ALFF values in the TEAS-treated volunteers decreased in the left thalamus, right putamen, and midbrain, while they increased in the left orbitofrontal cortex. More FC existed between the thalamus and the insula, middle cingulate cortex, somatosensory cortex, amygdala, and putamen in subjects after TEAS treatment compared with subjects that received non-stimulation. In addition, ALFF values of the thalamus positively correlated with BIS in both groups. Transcutaneous electrical acupoint stimulation could induce a sedative effect in healthy volunteers, and inhibition of the thalamus was among its possible mechanisms. www.ClinicalTrials.gov; identifier: NCT01896063.

The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder

BackgroundCACNA1C rs1006737 A allele, identified as a genetic risk variant for bipolar disorder (BD), is associated with anomalous functional connectivity in adults with and without BD. Studies have yet to investigate the association of CACNA1C rs1006737 with resting-state functional connectivity (rsFC) in youth BD.MethodsParticipants included 139 youth with BD-I, -II, or -not otherwise specified, ages 13–20 years, including 27 BD A-carriers, 41 BD non-carriers, 32 healthy controls (HC) A-carriers, and 39 HC non-carriers. Anterior cingulate cortex (ACC), amygdala, and orbitofrontal cortex (OFC) were examined as regions-of-interest in seed-to-voxel analyses. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and race.ResultsWe observed a main effect of BD diagnosis on rsFC between the right amygdala and the right occipital pole (p = 0.02), and a main effect of rs1006737 genotypes on rsFC between the right OFC and bilateral occipital cortex (p < 0.001). Two significant BD diagnosis-by-CACNA1C rs1006737 interactions were also identified. The A allele was associated with positive rsFC between the right ACC and right amygdala in BD but negative rsFC in HC (p = 0.01), and negative rsFC between the left OFC and left putamen in BD but positive rsFC in HC (p = 0.01).ConclusionThis study found that the rs1006737 A allele, identified as a genetic risk variant for BD in adults, was differentially associated with rsFC in youth with BD in regions relevant to emotion, executive function, and reward. Future task-based approaches are warranted to better understand brain connectivity in relation to CACNA1C in BD.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study

Introduction: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. Methods: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. Results: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. Conclusion: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Continuous theta burst stimulation-induced suppression of the right fronto-thalamic-cerebellar circuit accompanies improvement in language performance in poststroke aphasia: A resting-state fMRI study.

Continuous theta burst stimulation (cTBS) is a specific paradigm of repetitive transcranial magnetic stimulation (rTMS) with an inhibitory effect on cortical excitability for up to 60 min after less than 1 min of stimulation. The right posterior superior temporal gyrus (pSTG), homotopic to Wernicke's area in the left hemisphere, may be a potential stimulation target based on its critical role in semantic processing. The objective of this study was to explore whether cTBS over the right pSTG can promote language improvements in aphasic patients and the underlying mechanism. A total of 34 subjects with aphasia were randomly assigned to undergo 15 sessions of either 40-s inhibitory cTBS over the right pSTG (the cTBS group) or sham stimulation (the sham group), followed by 30 min of speech and language therapy. Subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI), and the aphasia quotient (AQ) of the Chinese version of the Western Aphasia Battery (WAB) was calculated before and after the intervention. This randomized controlled trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR210052962). After treatment, the language performance of the cTBS group was higher than that of the sham group in terms of the WAB-AQ score (p = 0.010) and the WAB scores for auditory comprehension (p = 0.022) and repetition (p = 0.035). The fractional amplitude of low-frequency fluctuations (fALFF) was significantly decreased in the pars triangularis of the inferior frontal gyrus (IFG), right middle frontal gyrus, right thalamus, and left cerebellar crus I. Clusters in the left orbitofrontal cortex exhibited increased fALFF. The change in WAB comprehension scores were significantly correlated with the change in the fALFF of the right IFG pars triangularis in both groups. Greatly increased functional connectivity was observed between the right pars triangularis and left paracingulate gyrus and between the right pSTG and right angular gyrus and the posterior cingulate gyrus with pre-and post-treatment between the two groups. Our findings indicate that cTBS of the right pSTG may improve language production by suppressing intrinsic activity of the right fronto-thalamic-cerebellar circuit and enhancing the involvement of the right temporoparietal region.

Neuromapping olfactory stimulation using magnetoencephalography - visualizing smell, a proof-of-concept study.

Currently, clinical assessment of olfaction is largely reliant on subjective methods that require patient participation. The objective method for measuring olfaction, using electroencephalogram (EEG) readings, can be supplemented with the improved temporal resolution of magnetoencephalography (MEG) for olfactory measurement that can delineate cortical and peripheral olfactory loss. MEG provides high temporal and spatial resolution which can enhance our understanding of central olfactory processing compared to using EEG alone. To determine the feasibility of building an in-house portable olfactory stimulator paired with electrophysiological neuroimaging technique with MEG to assess olfaction in the clinical setting. This proof-of-concept study utilized a paired MEG-olfactometer paradigm to assess olfaction in three normosmic participants. We used a two-channel olfactory stimulator to deliver odorants according to a programmed stimulus-rest paradigm. Two synthetic odorants: 2% phenethyl alcohol (rose) and 0.5% amyl acetate (banana) were delivered in increasing increments of time followed by periods of rest. Cortical activity was measured via a 306-channel MEG system. Primary outcome measure was the relative spectral power for each frequency band, which was contrasted between rest and olfactory stimulation. Compared to rest, olfactory stimulation produced a 40% increase in relative alpha power within the olfactory cortex bilaterally with both odorants. A 25%-30% increase in relative alpha power occurred in the left orbitofrontal cortex and precentral gyrus with phenethyl alcohol stimulation but not amyl acetate. In this proof-of-concept study, we demonstrate the feasibility of olfactory measurement via an olfactometer-MEG paradigm. We found that odorant-specific cortical signatures can be identified using this paradigm, setting the basis for further investigation of this system as a prognostic tool for olfactory loss.

Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy.

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).

Effects of a probiotic add-on treatment on fronto-limbic brain structure, function, and perfusion in depression: Secondary neuroimaging findings of a randomized controlled trial

BackgroundProbiotics are suggested to improve depressive symptoms via the microbiota-gut-brain axis. We have recently shown a beneficial clinical effect of probiotic supplementation in patients with depression. Their underlying neural mechanisms remain unknown. MethodsA multimodal neuroimaging approach including diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling was used to investigate the effects of a four-weeks probiotic supplementation on fronto-limbic brain structure, function, and perfusion and whether these effects were related to symptom changes. ResultsThirty-two patients completed both imaging assessments (18 placebo and 14 probiotics group). Probiotics maintained mean diffusivity in the left uncinate fasciculus, stabilized it in the right uncinate fasciculus, and altered resting-state functional connectivity (rsFC) between limbic structures and the temporal pole to a cluster in the precuneus. Moreover, a cluster in the left superior parietal lobule showed altered rsFC to the subcallosal cortex, the left orbitofrontal cortex, and limbic structures after probiotics. In the probiotics group, structural and functional changes were partly related to decreases in depressive symptoms. LimitationsThis study has a rather small sample size. An additional follow-up MRI session would be interesting for seeing clearer changes in the relevant brain regions as clinical effects were strongest in the follow-up. ConclusionProbiotic supplementation is suggested to prevent neuronal degeneration along the uncinate fasciculus and alter fronto-limbic rsFC, effects that are partly related to the improvement of depressive symptoms. Elucidating the neural mechanisms underlying probiotics' clinical effects on depression provide potential targets for the development of more precise probiotic treatments.

Altered regional homogeneity and its association with cognitive function in adolescents with borderline personality disorder.

Adolescents with borderline personality disorder often have cognitive impairment, but the underlying mechanism for this is not clear. This study was aimed at assessing alterations in regional homogeneity using resting-state functional MRI (fMRI) in adolescents with borderline personality disorder, and evaluating the associations between regional homogeneity and cognitive testing scores. We enrolled 50 adolescents with borderline personality disorder (age 12-17 years) and 21 age- and sex-matched healthy controls. We performed regional homogeneity and seed-based functional connectivity analysis for both groups. We also performed correlative analysis for regional homogeneity and cognitive testing scores. Compared with healthy controls, adolescents with borderline personality disorder had reduced regional homogeneity values in the frontal cortex (including the left inferior orbitofrontal cortex and the bilateral superior frontal cortex) as well as in the left precuneus in the default mode network. Adolescents with borderline personality disorder also had higher regional homogeneity values in several cortical regions: the right middle temporal gyrus, the right cuneus, the right precentral gyrus and the left middle occipital gyrus. Regional homogeneity values in the left middle occipital gyrus, left inferior orbitofrontal cortex and right superior frontal gyrus were associated with cognitive testing scores in adolescents with borderline personality disorder. We also found increased functional connectivity between the left middle occipital gyrus and right superior frontal gyrus in adolescents with borderline personality disorder. This study had a modest sample size, with a possible case selection bias for patients with more severe illness. This cohort also included patients with comorbidities or taking psychotropic medications, which may have confounded study results. Alterations in regional homogeneity and functional connectivity in brain regions that involve the limbic-cortical circuit could be neural correlates for cognitive impairment in adolescents with borderline personality disorder.

Differential Orbitofrontal Cortex Responses to Chocolate Images While Performing an Approach-Avoidance Task in the MRI Environment.

Background: Chocolate is one of the most frequently craved foods, and it often challenges self-regulation. These cravings may be underpinned by a neural facilitation of approach behavior toward chocolate. This preregistered study investigated the behavioral and neural correlates of such a bias using functional magnetic resonance imaging (fMRI) and reaction times (RTs). Methods: A total of n = 30 frequent chocolate eaters performed a relevant-feature approach-avoidance task (AAT) in the MRI scanner using buttons to enlarge (approach) or to shrink (avoid) pictures of chocolate and inedible control objects. We tested (a) whether implicit RT-based approach biases could be measured in a supine position in the scanner, (b) whether those biases were associated with activity in reward-related brain regions such as the insula, amygdala, striatum, and orbitofrontal cortex (OFC), and (c) whether individual RT-based bias-scores correlated with measures of chocolate craving. Results: Behaviorally, we found a highly reliable approach bias toward chocolate, defined by faster RTs in the compatible conditions (approach chocolate, avoid objects) compared to the incompatible conditions (avoid chocolate, approach objects). Neurally, this compatibility effect involved activity in the left medial OFC, a neural response that was positively correlated with individual approach bias scores. Conclusions: This study shows that the relevant feature AAT can be implemented in an fMRI setting in a supine position using buttons. An approach bias toward chocolate seems related to medial OFC activation that might serve to devalue chocolate when it has to be avoided. Our demonstration of neural and behavioral approach biases for chocolate underscores the need for stimulus-specific cognitive trainings to support healthy consumption and successful self-regulation.