Superior Frontal Cortex Research Articles

Cortical correlates of speech intelligibility measured using functional near-infrared spectroscopy (fNIRS)

Functional neuroimaging has identified that the temporal, frontal and parietal cortex support core aspects of speech processing. An objective measure of speech intelligibility based on cortical activation in these brain regions would be extremely useful to speech communication and hearing device applications. In the current study, we used noise-vocoded speech to examine cortical correlates of speech intelligibility in normally-hearing listeners using functional near-infrared spectroscopy (fNIRS), a non-invasive, neuroimaging technique that is fully-compatible with hearing devices, including cochlear implants. In twenty-three normally-hearing adults we measured (1) activation in superior temporal, inferior frontal and inferior parietal cortex bilaterally and (2) behavioural speech intelligibility. Listeners heard noise-vocoded sentences targeting five equally spaced levels of intelligibility between 0 and 100% correct. Activation in superior temporal regions increased linearly with intelligibility. This relationship appears to have been driven in part by changing acoustic properties across stimulation conditions, rather than solely by intelligibility per se. Superior temporal activation was also predictive of individual differences in intelligibility in a challenging listening condition. Beyond superior temporal cortex, we identified regions in which activation varied non-linearly with intelligibility. For example, in left inferior frontal cortex, activation peaked in response to heavily degraded, yet still somewhat intelligible, speech. Activation in this region was linearly related to response time on a simultaneous behavioural task, suggesting it may contribute to decision making. Our results indicate that fNIRS has the potential to provide an objective measure of speech intelligibility in normally-hearing listeners. Should these results be found to apply similarly in the case of individuals listening through a cochlear implant, fNIRS would demonstrate potential for a clinically useful measure not only of speech intelligibility, but also of listening effort.

Smoking Cessation With 20 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) Applied to Two Brain Regions: A Pilot Study.

Chronic smoking impairs brain functions in the prefrontal cortex and the projecting meso-cortical limbic system. The purpose of this pilot study is to examine whether modulating the frontal brain activity using high-frequency repetitive transcranial magnetic stimulation (rTMS) can improve smoking cessation and to explore the changing pattern of the brain activity after treatment. Fourteen treatment-seeking smokers were offered a program involving 10 days of rTMS treatment with a follow-up for another 25 days. A frequency of 20 Hz rTMS was sequentially applied on the left dorso-lateral prefrontal cortex (DLPFC) and the superior medial frontal cortex (SMFC). The carbon monoxide (CO) level, withdrawal, craving scales, and neuroimaging data were collected. Ten smokers completed the entire treatment program, and 90% of them did not smoke during the 25-day follow-up time. A significant smoking craving reduction and resting brain activity reduction measured by the cerebral blood flow (CBF) and brain entropy (BEN) were observed after 10 days of 20 Hz rTMS treatments compared to the baseline. Although limited by sample size, these pilot findings definitely showed a high potential of multiple-target high-frequency rTMS in smoking cessation and the utility of fMRI for objectively assessing the treatment effects.

Does emotion regulation engage the same neural circuit as working memory? A meta-analytical comparison between cognitive reappraisal of negative emotion and 2-back working memory task

Research into cognitive emotion regulation (ER) extends our understanding of human cognition, which is capable of processing objective information and is crucial in maintaining subjective/internal homeostasis. Among various ER strategies, the alleviation of negative emotion via reappraisal is of particular importance for adaptation and psychological well-being. Although still debated, previous neuroimaging studies tend to infer that the reappraisal ER is mediated by the capability of working memory (WM), which has not been examined empirically. This meta-analytical study of published neuroimaging literature used activation likelihood estimation (ALE) to compare the neural circuits that regulate negative emotion (reappraisal tasks; 46 studies/1254 subjects) and execute WM (2-back tasks; 50 studies/1312 subjects), with special emphasis on the prefrontal cortex (PFC). Taking the canonical WM network as a reference, ALE results revealed that the dorsal midline PFC was partly shared by both ER and WM, whereas ER-specific PFC structures were delineated in the inferior, middle, and superior frontal cortices, as well as in the posterior brain regions. The peak coordinates of ER in the middle frontal cortex were dorsal to those of WM by 15.1 mm (left) and 21.6 mm (right). The results support specialized emotion-related neural substrates in the PFC, negating the assumption that reappraisal ER and WM rely on the same neural resources. The holistic picture of "emotional brain" may need to incorporate the emotion-related PFC circuit, together with subcortical and limbic emotion centers.

Cortical thickness and subcortical volumes alterations in euthymic bipolar I patients treated with different mood stabilizers.

Reported structural abnormalities of patients with bipolar disorder (BD) are inconsistent and the use of psychotropic medication is one of the sources of heterogeneity. A fairly small number of morphometric studies have involved comparison of BD on different mood stabilizers. Here in this study, we aimed to investigate the cortical thickness and subcortical volumes in euthymic BD patients on lithium and valproate and healthy controls (HC), and to elucidate the relationship between the use of medication and brain structure variations. We acquired structural magnetic resonance imaging data from 35 BD patients (19/valproate;16/lithium) and 30 HC subjects. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Group analyses revealed widespread thinning of the prefrontal cortex in BD. Compared with BD on valproate, BD on lithium showed significant increased cortical thickness of the left rostral middle frontal cortex and right superior frontal cortex, while cortical thickness was not significantly different between BD on lithium and HC in the bilateral rostral middle frontal cortex. Moreover, no significant difference was observed in subcortical volume. Limitations of this study comprise the possible effect of other psychotropic drugs, small sample size and the cross-sectional design. Therefore, the results suggest medication-related neurobiological difference between BD patients on different mood stabilizers, but no casual role can be proposed. Our findings provided new evidence about the effects of psychotropic medication upon neuroanatomy in BD, and could help to explain the inconsistency of existing studies as well as contribute to the extraction of reliable neuroimaging biomarkers in BD.

Increases in orbitofrontal cortex thickness following antidepressant treatment are associated with changes in resting state autonomic function in adolescents with major depression – Preliminary findings from a pilot study

In adults with major depressive disorder (MDD), effective treatment has been associated with increases in both heart rate variability (HRV) and cortical thickness. However, the impact of treatment on these indices has not yet been examined in adolescents. Cortical thickness and HRV were measured in twelve adolescents with MDD before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). We examined treatment-related changes in depression symptoms, HRV, heart rate (HR), and cortical thickness, and analyzed correlations among these change indices. At follow-up, patients showed significantly decreased depression severity, increased HRV and increased thickness of the left medial orbitofrontal cortex (OFC). Clinical improvement was associated with increased HRV and decreased HR. Increased HRV was associated with increased cortical thickness of left lateral OFC and superior frontal cortex. Due to the small sample size, results represent preliminary findings that need replication. Further, in the absence of a placebo arm, we cannot confirm that the observed effects are due solely to medication. These preliminary findings suggest that SSRI treatment in adolescents impacts both cortical thickness and autonomic functioning. Confirmation of these findings would support OFC thickness and HRV as neurobiological mediators of treatment outcome.

Correlations between exploratory eye movement, hallucination, and cortical gray matter volume in people with schizophrenia

BackgroundWidespread cortical gray matter alternations in people with schizophrenia are correlated with both psychotic symptoms and cognitive/behavioral abnormalities, including the impairments of exploratory eye movement (EEM). Particularly, the loss of gray matter density is specifically related to deficits of the responsive search score (RSS) of EEM in schizophrenia. It is unknown, however, whether the schizophrenia-related RSS deficits are associated with certain psychotic symptoms, such as hallucinations.MethodsIn 33 participants with schizophrenia, the measurement of EEM, assessment of the hallucination severity using Positive and Negative Syndrome Scale (PANSS) and a voxel-based morphometric analysis of cortical gray matter volume (GMV) were conducted to investigate the relationships between the RSS of EEM, symptom severity, and GMV. In 29 matched healthy controls, the measurement of EEM and a voxel-based morphometric analysis of cortical GMV were also conducted to investigate the relationship between the RSS of EEM and GMV.ResultsIn participants with schizophrenia, the hallucination severity was significantly negatively correlated with both the RSS and the GMV of a large number of brain regions in the frontal, temporal, parietal, orbitofrontal, calcarine, cingulate, and insular cortices, and rolandic operculum, hippocampus, parahippocampal gyrus, and thalamus. Also in participants with schizophrenia, the RSS was significantly positively correlated with the GMV in the left supplementary motor area (SMA), left superior frontal cortex (SFG), bilateral precentral gyri, bilateral postcentral gyri, and bilateral middle frontal cortices. More importantly, the GMV of the SMA, SFG, and precentral gyrus in the left hemisphere was not only significantly negatively correlated with the hallucination severity but also significantly positively correlated with the RSS. No significant correlation could be revealed between the RSS and the GMV of any brain regions in healthy controls.ConclusionsThere was a significantly negative association between the hallucination severity and the RSS of EEM, suggesting that the RSS may be a potential biomarker for predicting the hallucination severity of schizophrenia. Also, the GMV of the left SMA, SFG, and precentral gyrus may be the common substrates underlying both hallucination induction and the RSS in people with schizophrenia.

P29. Differential linear and nonlinear brain activation for probabilistic aversive outcomes in pathological gamblers and controls

Objective Functional imaging studies on decision making under uncertain risk of negative (aversive) outcomes are scarce. To get a better understanding of the underlying processes, we tested models of decision making including participants that were gambling regularly despite negative long-term consequences. Primarily, we sought to detect group differences in cortical and subcortical regions involved in decision processes. Also, we wanted to investigate, if current economic decision making models account for observable physiological data. Do we process aversive contingencies of decisions in a linear or a nonlinear manner, or both? Methods We studied 22 pathological and 18 habitual gamblers, as well as 23 control subjects, evaluated by psychologists with a semi-structured interview and self-reported Southern Oaks Gambling Scale. Participants were scanned with blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and engaged in a card game in which un-ambiguous situations of various risk levels for punishment (unpleasant, but not painful electric shocks) were created. Apart from neural responses to punishment, our paradigm allowed us to measure how neural activity during expectation of a punishment is modulated by the probability to be punished (risk) or the certainty of the outcome (certainty). Results Extending previous work and testing our hypothesis, based on economic studies, we modelled expected outcomes according to the prospect theory. Activations differed spatially when situations were modelled according to risk or certainty. With linearly increasing chances of avoiding punishment we found that the BOLD signal increased in the orbitofrontal cortex, caudate nucleus, precuneus, and the posterior cingulate cortex ( Fig. 1 a). Conversely, with increasing certainty of an outcome (U-shaped from most certain punishment to most certain avoidance), we could demonstrate nonlinear activations in medial superior frontal cortex, anterior cingulate cortex, anterior insula and angular gyrus ( Fig. 1 b). Interestingly, we found no group differences in cerebral activation during the task, which dovetailed with ‘offline’ behavioural analyses of decision making in the same groups. Conclusion Our results support the notion that economic decision making contains both linear and nonlinear cognitive processes largely following contingencies for risk and certainty and provide evidence that these cognitive processes are represented in different sets of brain regions. Correlates of the risk for punishment were found in areas known to be involved in dopaminergic reinforcement learning, while regions known to sub serve decision making, conflict monitoring and punishment show correlation with certainty of the outcome. While differences in reward perception in pathological gamblers are frequently described in the literature, we found no evidence for changes in punishment perception.

Bio-Inspired Model Learning Visual Goals and Attention Skills Through Contingencies and Intrinsic Motivations

Animal learning is driven not only by biological needs but also by intrinsic motivations (IMs) serving the acquisition of knowledge. Computational modeling involving IMs is indicating that learning of motor skills requires that autonomous agents self-generate tasks/goals and use them to acquire skills solving/leading to them. We propose a neural architecture driven by IMs that is able to self-generate goals on the basis of the environmental changes caused by the agent’s actions. The main novelties of the model are that it is focused on the acquisition of attention (looking) skills and that its architecture and functioning are broadly inspired by the functioning of relevant primate brain areas (superior colliculus, basal ganglia, and frontal cortex). These areas, involved in IM-based behavior learning, play important functions for reflexive and voluntary attention. The model is tested within a simple simulated pan-tilt camera robot engaged in learning to switch on different lights by looking at them, and is able to self-generate visual goals and learn attention skills under IM guidance. The model represents a novel hypothesis on how primates and robots might autonomously learn attention skills and has a potential to account for developmental psychology experiments and the underlying brain mechanisms.

Functional brain lateralization in schizophrenia based on the variability of resting-state fMRI signal

Abnormal brain lateralization has been implicated in schizophrenia but few studies have focused on the variability of resting-state fMRI signal and its lateralization in schizophrenia. Here we utilized standard deviations (SD) to quantify the variability of resting-state fMRI signal and measured the lateralization index (LI), on the basis of SD of the resting-state fMRI signal in order to assess the difference of brain signal variability across the hemispheres. We recruited 180 patients with schizophrenia and 358 age- and sex-matched healthy volunteers. Between-group comparison revealed that in comparison to healthy volunteers, schizophrenia patients have significantly higher SD of resting-state fMRI activity in left inferior temporal, left fusiform, and right superior medial frontal cortex, and lower SD in right precuneus, posterior cingulum on both sides, right lingual, and left calcarine in the occipital region. Using region of interest approach, most brain regions showed increased leftward lateralization in patients with schizophrenia, as compared with healthy controls. SD and LI were also found to be correlated to age of onset or duration of illness. These results provide further evidence that abnormal variability and lateralization exist in schizophrenia patients, and abnormality in fusiform, lingual and inferior temporal could have potential help to identify the dysfunctional brain lateralization in schizophrenia.

Volumetric brain magnetic resonance imaging predicts functioning in bipolar disorder: A machine learning approach

Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach.Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital status. There were significant differences between groups in gender, BMI, FAST score, and employment status. There was significant correlation between observed and predicted FAST score for patients with BD, but not for controls. According to the model, the brain structures volumes that could predict FAST scores were: left superior frontal cortex, left rostral medial frontal cortex, right white matter total volume and right lateral ventricle volume. The machine learning approach demonstrated that brain volume changes in MRI were predictors of FAST score in patients with BD and could identify specific brain areas related to functioning impairment.

Common proteomic profiles of induced pluripotent stem cell-derived three-dimensional neurons and brain tissue from Alzheimer patients

We established a unique platform for proteomic analysis of cultured three-dimensional (3D) neurons and brain tissue from Alzheimer's disease (AD) patients. We collected peripheral blood mononuclear cells (PBMC), converted PBMC to induced pluripotent stem cell (iPSC) lines, and differentiated the iPSC into human 3D neuro-spheroids. The postmortem brain tissue from the superior frontal cortex, inferior frontal cortex and cerebellum area of the AD patients was compared to the same regions from the control subjects. Proteomic analysis of 3D neuro-spheroids derived from AD subjects revealed the alteration of a number of proteins involved in axon growth, mitochondrial function, and antioxidant defense. Similar analysis of post-mortem AD brain tissue revealed significant alteration in proteins involved in oxidative stress, neuro-inflammation, along with proteins related to axonal injury. These results clearly indicate that the dysfunction of 3D neurons from AD patients in our in vitro environment is comparable to the post-mortem AD brain tissue in vivo. In conclusion, our study revealed a number of candidate proteins that have important implications in AD pathogenesis and supports the notion that the iPSC-derived 3D neuronal system functions as a model to examine novel aspects of AD pathology. SignificanceIn this study, we present a unique platform for proteomic analysis of induced pluripotent stem cell-derived three dimensional (3D) neurons and compare the results to those from three regions of post-mortem brain tissue from Alzheimer's disease patients and normal control subjects. Our results show that the dysfunction of 3D neurons from AD patients in our in vitro environment is comparable to the post-mortem AD brain tissue in vivo. Our results revealed several candidate proteins that have important implications in AD pathogenesis.

Cerebral processing of facial emotions in bipolar I and II disorders: An event-related potential study

BackgroundBehavioral results have shown that bipolar disorder patients have impaired recognition of facial emotions, but the detailed information processing of facial emotions in patients with bipolar I (BD I) and II (BD II) disorders remain unknown. MethodsWe tested the cerebral event-related potentials to the static facial expressions of Neutral, Happiness, Anger and Sadness in 39 adult patients with BD I, 22 BD II, and 54 healthy volunteers. Participants’ affective states were measured with the Mood Disorder Questionnaire, the Hypomania Checklist-32, and the Plutchik–van Praag Depression Inventory. ResultsOver-processed right occipitotemporal cortex during N1 time window to Neutral and Happiness, and during P3b window to Sadness were found in BD I; prolonged N1 latencies to Neutral and Happiness, declined P3b amplitude to Sadness, negative correlation between P3b latency to Sadness and depression, and attenuated superior frontal activity during P3b window to Sadness were found in BD II; and the right-side dominance during facial emotion processing were found in both BD I and BD II. LimitationsWe didn't record the personality traits or medication used in patients, nor included other facial emotions such as fear and disgust. ConclusionsWhen responding to facial emotions, both BD I and BD II showed a right-side processing dominance; BD I displayed enhanced processing in the right occipitotemporal cortex during structural encoding and categorical processing of facial emotions; while BD II displayed generalized impairments, less involvement of superior frontal cortex to negative emotions, and reduced ability to process negative emotions which was associated with depression.

T145. ALTERATIONS IN SUPERFICIAL WHITE MATTER IN THE FRONTAL CORTEX IN SCHIZOPHRENIA: A DWI STUDY USING A NOVEL ATLAS

BackgroundAlterations in brain connectivity are strongly implicated in the pathophysiology of schizophrenia (SZ). Very recently, evidence is mounting to suggest that changes in superficial white matter (SWM) U-shaped short range fibers are integral components of disease neuropathology, a theory that is supported by findings from postmortem studies and less often in vivo in patients with SZ. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in the frontal cortex in people with SZ.MethodsWhole brain tractography was performed in 31 people with SZ and 54 healthy controls using BrainVISA and Connectomist 2.0 software. Segmentation and labelling of superficial white matter tracts were performed using a novel atlas characterizing 100 bundles. Principal Components Analysis (PCA) using a varimax orthogonal rotation was performed on mean generalised fractional anisotropy (gFA) of bundles located in the frontal cortex. Composites scores were computed for each subject, reflecting a linear combination of mean gFA values.ResultsPCA revealed three components explaining 19.7 %, 5.8 %, and 5.4 % of the total variance. The mean score of the second component was significantly lower in the people with SZ compared with controls (p = 0.01) and included 13 bundles connecting regions in the pars orbitalis, insula, pars triangularis, pars opercularis, orbitofrontal cortex, anterior cingulate, superior frontal cortex and middle frontal cortex.DiscussionOur results support findings of reduced white matter integrity in the frontal cortex in people with SZ. Moreover, PCA may be helpful in identifying specific networks as the deficits do not appear to be widespread. Identifying patterns of superficial white matter dysconnectivity may be helpful in understanding the prominent symptoms and cognitive deficits and observed in SZ.

F148. A PILOT STUDY OF [11C] (R)-MEQAA PET BRAIN IMAGING ANALYSIS OF ALPHA 7 NICOTINIC ACETYLCHOLINE RECEPTORS AVAILABILITY IN SCHIZOPHRENIA

BackgroundA growing body of evidence suggests that the aberrant cholinergic system may underlie the pathophysiology in schizophrenia. Nicotinic acetylcholine receptor (nAChR) subtype α7 (henceforth ‘α7 nAChR’) is located in presynaptic and postsynaptic constructs in the cerebral cortex and considered to play a key role in the regulation of learning and memory. Additionally, α7 nAChR is deemed to exert neuroprotective effects. Therefore, α7 nAChR is one of the potent therapeutic targets for negative symptoms and cognitive impairment in schizophrenia. In effect, several randomised trials to assess the efficacy and safety of α7 nAChR agonists are currently underway.There is some evidence in support of aberrant α7 nAChR in schizophrenia. In postmortem studies, protein levels of α7 nAChR in the frontal cortex (Guan et al., 1999) have been reported to be decreased in patients with schizophrenia. However, the availability of α7 nAChR in individuals with schizophrenia has yet to be examined in vivo. In this pilot study, we aim to clarify availability of α7 nAChR in the brains of patients with schizophrenia using positron emission tomography (PET) with a ligand of [11C](R)-2-methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([11C](R)-MeQAA).MethodsAll participants provided informed consent. Inclusion criteria included diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5, 2013). Patients were excluded if they had (1) full IQ under 69 measured with the Wechsler Adult Intelligent Scale-III; (2) current or past history of tobacco smoking; (3) history of neurological disorder or structural brain abnormality; (4) use of benzodiazepines, antidepressants, or anticholinergics in the past 6 months; and (5) substance abuse. Although scanning drug-free or drug-naïve patients for investigation is optimal, it is extremely difficult to attain this. Consequently, participants with schizophrenia comprised medicated cases.We evaluated the availability of α7 nAChR by estimating non-displaceable binding potential (BPND) of the tracer using PET with [11C] (R)-MeQAA, a selective PET tracer for α7 nAChR. Four patients with schizophrenia (age: range 27–39; m/f: 2/2) and 5 age-matched healthy adults (age: range 22–32; m/f: 2/3) underwent the PET scan. The level of BPND in patients with schizophrenia was compared with that for control participants by applying regions of interest (ROIs) approach. In this pilot study, we opted for 4 cortical areas, the superior frontal, middle frontal, parietal, and temporal cortices, for ROIs. This study was approved by the Hamamatsu University School of Medicine Ethics Committee.ResultsWe found the levels of [11C] (R)-MeQAA BPND significantly lower in the middle frontal cortex (p = 0.036) in patients with schizophrenia. Additionally, there was a trend towards a decreased level of BPND in the temporal cortex (p = 0.067) and parietal cortex (p = 0.087) in the brains of schizophrenia patients, although it failed to reach statistical significance. There was no difference in the superior frontal cortex.DiscussionTo our knowledge, this represents the first demonstration of anomalies in the acetylcholinergic system in the in vivo brains of schizophrenia patients. However, this is regarded as a pilot study, and further recruitment of schizophrenia patients with a recent onset and minimal use of antipsychotic medication, followed by scanning and data analyses, will be continued.

The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder

BackgroundIntranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD.MethodsIn this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes.ResultsCentral analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards.ConclusionsThe effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

24-Impact of stress induced by long-lasting and life threating situation on the brain of holocaust survivors and their offspring. A neuroimaging study

Introduction This two-generation study focuses on stress influence transfer from holocaust survivors to the next generation. Control group consists of healthy volunteers without experience of long-term stress. Methods Data from 93 subjects were divided into 4 groups (stress and control groups; for each 1st and 2nd generation). Acquisition of structural T1-weighted and fMRI resting state data was performed on 3 T scanner. Voxel-based morphometry (VBM) and seed-based functional connectivity (FC) methods were used. Results The VBM revealed significant reduction of gray matter volume in the stress group in (all bilateral): insula, orbitofrontal area, anterior cingulate, superior and middle frontal gyri, entorhinal and perirhinal cortices. Significant decrease of FC in the stress group was observed for 2 seeds: right hippocampus FC with left insula, bilateral posterior cingulate/precuneus, right angular gyrus, left putamen and bilateral thalamus; middle cingulate FC (all bilateral) with insula, hippocampus, putamen and thalamus. Conclusion Differences between control and stress groups were detected especially in the areas belonging to the limbic system and memory neural network. Our results suggest partially altered structure and functionality; not only in the direct holocaust survivors group (1st generation), but also as a result of stress influence transition to the next generation.

Cognitive and psychopathology correlates of brain white/grey matter structure in severely psychotic schizophrenic inpatients

The brain structural correlates of cognitive and psychopathological symptoms within the active phase in severely psychotic schizophrenic inpatients have been rarely investigated. Twenty-eight inpatients with a DSM-5 diagnosis of Schizophrenia (SZ), admitted for acute psychotic decompensation, were assessed through a comprehensive neuropsychological and psychopathological battery. All patients underwent a high-resolution T1-weighted magnetic resonance imaging investigation.Increased psychotic severity was related to reduced grey matter volumes in the medial portion of the right superior frontal cortex, the superior orbitofrontal cortex bilaterally and to white matter volume reduction in the medial portion of the left superior frontal area. Immediate verbal memory performance was related to left insula and inferior parietal cortex volume, while long-term visuo-spatial memory was related to grey matter volume of the right middle temporal cortex, and the right (lobule VII, CRUS1) and left (lobule VI) cerebellum. Moreover, psychotic severity correlated with cognitive inflexibility and negative symptom severity was related to visuo-spatial processing and reasoning disturbances.These findings indicate that a disruption of the cortical-subcortical-cerebellar circuit, and distorted memory function contribute to the development and maintenance of psychotic exacerbation.

Difference in regional neural fluctuations and functional connectivity in Crohn's disease: a resting-state functional MRI study.

Patients with Crohn's disease (CD) are shown to have abnormal changes in brain structures. This study aimed to further investigate whether these patients have abnormal brain activities and network connectivity. Sixty patients with CD and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were used to assess differences in spontaneous regional brain activity and functional connectivity. Compared to the HCs, patients with CD showed significantly higher ALFF values in hippocampus and parahippocampus (HIPP/paraHIPP), anterior cingulate cortex, insula, superior frontal cortex and precuneus. The ALFF values were significantly lower in secondary somatosensory cortex (S2), precentral gyrus, and medial prefrontal cortex. Functional connectivities between left HIPP and left inferior temporal cortex, and right middle cingulate cortex, HIPP, and fusiform area were significantly lower. The functional connectivities between right HIPP and right inferior orbitofrontal cortex and left HIPP were also significantly lower. Patients with CD showed higher or lower spontaneous activity in multiple brain regions. Altered activities in these brain regions may collectively reflect abnormal function and regulation of visceral pain and sensation, external environmental monitoring, and cognitive processing in these patients. Lower functional connectivity of the hippocampus-limbic system was observed in these patients. These findings may provide more information to elucidate the neurobiological mechanisms of the disease.

Functional connectivity corresponding to the tonotopic differentiation of the human auditory cortex.

Recent research has demonstrated that resting-state functional connectivity (RS-FC) within the human auditory cortex (HAC) is frequency-selective, but whether RS-FC between the HAC and other brain areas is differentiated by frequency remains unclear. Three types of data were collected in this study, including resting-state functional magnetic resonance imaging (fMRI) data, task-based fMRI data using six pure tone stimuli (200, 400, 800, 1,600, 3,200, and 6,400 Hz), and structural imaging data. We first used task-based fMRI to identify frequency-selective cortical regions in the HAC. Six regions of interest (ROIs) were defined based on the responses of 50 participants to the six pure tone stimuli. Then, these ROIs were used as seeds to determine RS-FC between the HAC and other brain regions. The results showed that there was RS-FC between the HAC and brain regions that included the superior temporal gyrus, dorsolateral prefrontal cortex (DL-PFC), parietal cortex, occipital lobe, and subcortical structures. Importantly, significant differences in FC were observed among most of the brain regions that showed RS-FC with the HAC. Specifically, there was stronger RS-FC between (1) low-frequency (200 and 400 Hz) regions and brain regions including the premotor cortex, somatosensory/-association cortex, and DL-PFC; (2) intermediate-frequency (800 and 1,600 Hz) regions and brain regions including the anterior/posterior superior temporal sulcus, supramarginal gyrus, and inferior frontal cortex; (3) intermediate/low-frequency regions and vision-related regions; (4) high-frequency (3,200 and 6,400 Hz) regions and the anterior cingulate cortex or left DL-PFC. These findings demonstrate that RS-FC between the HAC and other brain areas is frequency selective.

Empathy by default: Correlates in the brain at rest.

Empathy, defined as the ability to access and respond to the inner world of another person, is a multidimensional construct involving cognitive, emotional and self-regulatory mechanisms. Neuroimaging studies report that empathy recruits brain regions which are part of the social cognition network. Among the different resting state networks, the Default Mode Network (DMN) may be of particular interest for the study of empathy since it has been implicated in social cognition tasks. The current study compared the cognitive and emotional empathy scores, as measured by the Interpersonal Reactivity Index, with the patterns of activation within the DMN, through the neuroimaging methodology of resting-state functional magnetic resonance. Results suggest a significant positive correlation between cognitive empathy and activation of the bilateral superior medial frontal cortex nodes of the DMN. Contrastingly, a negative correlation was found between emotional empathy and the same brain region. Overall, this data highlights a critical role of the medial cortical regions of the DMN, specifically its anterior node, for both cognitive and emotional domains of the empathic process.