Middle Prefrontal Gyrus Research Articles

Perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fMRI study.

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard clinical measures. Three groups of adolescents (N = 96; 78% females, age = 11.6-18.1) were included: patients with depressive disorders and previous suicide attempts (SA, n = 29); patient controls with depressive disorders but without anysuicide attempt history (PC, n = 35); and healthy controls (HC, n = 32). We scanned participants with 3T-MRI during social inclusion/exclusion (Cyberball Game) and response inhibition (Go-NoGo) tasks. Neural activation was indexed by the blood-oxygenation-level dependent (BOLD) of the hemodynamic response during three conditions in the Cyberball Game ("Control condition", "Social Inclusion", and "Social Exclusion"), and two conditions in Go-NoGo task ("Go" and "NoGo" blocks). ANCOVA-style analysis identified group effects across three whole-brain contrasts: 1) NoGo vs. Go, 2) Social inclusion vs. control condition, 3) Social exclusion vs. control condition. We found that SA had lower activation in the left insula during social inclusion vs. control condition compared to PC and HC. Moreover, SA compared to PC had higher activity in the right middle prefrontal gyrus during social exclusion vs. control condition, and in bilateral precentral gyri during NoGo vs. Go conditions. Task-related behavioral and self-report measures (Self-reported emotional reactivity in the Cyberball Game, response times and number of errors in the Go-NoGo Task) did not discriminate groups. In conclusion, adolescent suicidal behaviors are likely associated with neural alterations related to the processing of social perception and response inhibition. Further research, involving prospective designs and diverse cohorts of patients, is necessary to explore the potential of neuroimaging as a tool in understanding the emergence and progression of suicidal behaviors.

Combined Intrinsic Local Functional Connectivity With Multivariate Pattern Analysis to Identify Depressed Essential Tremor.

BackgroundAlthough depression is one of the most common neuropsychiatric symptoms in essential tremor (ET), the diagnosis biomarker and intrinsic brain activity remain unclear. We aimed to combine multivariate pattern analysis (MVPA) with local brain functional connectivity to identify depressed ET.MethodsBased on individual voxel-level local brain functional connectivity (regional homogeneity, ReHo) mapping from 41 depressed ET, 43 non-depressed ET, and 45 healthy controls (HCs), the binary support vector machine (BSVM) and multiclass Gaussian Process Classification (MGPC) algorithms were used to identify depressed ET patients from non-depressed ET and HCs, the accuracy and permutations test were used to assess the classification performance.ResultsThe MGPC algorithm was able to classify the three groups (depressed ET, non-depressed ET, and HCs) with a total accuracy of 84.5%. The BSVM algorithm achieved a better classification performance with total accuracy of 90.7, 88.64, and 90.48% for depressed ET vs. HCs, non-depressed ET vs. HCs, and depressed ET vs. non-depressed ET, and the sensitivity for them at 80.49, 76.64, and 80.49%, respectively. The significant discriminative features of depressed ET vs. HCs were primarily located in the cerebellar-motor-prefrontal gyrus-anterior cingulate cortex pathway, and for depressed ET vs. non-depressed ET located in the cerebellar-prefrontal gyrus-anterior cingulate cortex circuits. The partial correlation showed that the ReHo values in the bilateral middle prefrontal gyrus (positive) and the bilateral cerebellum XI (negative) were significantly correlated with clinical depression severity.ConclusionOur findings suggested that combined individual ReHo maps with MVPA not only could be used to identify depressed ET but also help to reveal the intrinsic brain activity changes and further act as the potential diagnosis biomarker in depressed ET patients.

Identifying Depressed Essential Tremor Using Resting-State Voxel-Wise Global Brain Connectivity: A Multivariate Pattern Analysis.

Background and Objective: Although depression is one of the most common non-motor symptoms in essential tremor (ET), its pathogenesis and diagnosis biomarker are still unknown. Recently, machine learning multivariate pattern analysis (MVPA) combined with connectivity mapping of resting-state fMRI has provided a promising way to identify patients with depressed ET at the individual level and help to reveal the brain network pathogenesis of depression in patients with ET.Methods: Based on global brain connectivity (GBC) mapping from 41 depressed ET, 49 non-depressed ET, 45 primary depression, and 43 healthy controls (HCs), multiclass Gaussian process classification (GPC) and binary support vector machine (SVM) algorithms were used to identify patients with depressed ET from non-depressed ET, primary depression, and HCs, and the accuracy and permutation tests were used to assess the classification performance.Results: While the total accuracy (40.45%) of four-class GPC was poor, the four-class GPC could discriminate depressed ET from non-depressed ET, primary depression, and HCs with a sensitivity of 70.73% (P < 0.001). At the same time, the sensitivity of using binary SVM to discriminate depressed ET from non-depressed ET, primary depression, and HCs was 73.17, 80.49, and 75.61%, respectively (P < 0.001). The significant discriminative features were mainly located in cerebellar-motor-prefrontal cortex circuits (P < 0.001), and a further correlation analysis showed that the GBC values of significant discriminative features in the right middle prefrontal gyrus, bilateral cerebellum VI, and Crus 1 were correlated with clinical depression severity in patients with depressed ET.Conclusion: Our findings demonstrated that GBC mapping combined with machine learning MVPA could be used to identify patients with depressed ET, and the GBC changes in cerebellar-prefrontal cortex circuits not only posed as the significant discriminative features but also helped to understand the network pathogenesis underlying depression in patients with ET.

The Association Between Resting State Functional Connectivity and the Trait of Impulsivity and Suicidal Ideation in Young Depressed Patients With Suicide Attempts.

Suicide is a leading cause of death among youth and is strongly associated with major depressive disorder (MDD). However, the neurobiological underpinnings of suicidal behaviour and the identification of risk for suicide in young depressed patients are not yet well-understood. In this study, we used a seed-based correlation analysis to investigate the differences in resting-state functional connectivity (RSFC) in depressed youth with or without a history of suicide attempts and healthy controls (HCs). Suicidal attempters (ATT group, n = 35), non-suicide attempters (NAT group, n = 18), and HCs exhibited significantly different RSFC patterns with the left superior prefrontal gyrus (L-SFG) and left middle prefrontal gyrus (L-MFG) serving as the regions of interest (ROIs). The ATT group showed decreased RSFC of the left middle frontal gyrus with the left superior parietal gyrus compared to the NAT and HC groups. Decreased RSFC between the left superior frontal gyrus and the right anterior cingulate cortex (rACC) was found in the ATT group compared to the NAT and HC groups. Furthermore, the left prefrontal-parietal connectivity was associated with suicidal ideation and levels of impulsivity, but RSFC of the left prefrontal cortex with the rACC was correlated exclusively with impulsivity levels and was not related to suicidal ideation in the ATT group. Our results demonstrated that altered RSFC of the prefrontal-parietal and prefrontal-rACC regions was associated with suicide attempts in depressed youth, and state-related deficits in their interconnectivity may contribute to traits, such as cognitive impairments and impulsivity to facilitate suicidal acts. Our findings suggest that the neural correlates of suicidal behaviours might be dissociable from those related to the severity of current suicidal ideation. Neural circuits underlying suicide attempts differ from those that underlie suicidal ideation.

Altered effective connectivity from the pregenual anterior cingulate cortex to the laterobasal amygdala mediates the relationship between internet gaming disorder and loneliness.

Individual with internet gaming disorder (IGD) often experience a high level of loneliness, and neuroimaging studies have demonstrated that amygdala function is associated with both IGD and loneliness. However, the neurobiological basis underlying these relationships remains unclear. In the current study, Granger causal analysis was performed to investigate amygdalar subdivision-based resting-state effective connectivity differences between 111 IGD subjects and 120 matched participants with recreational game use (RGUs). We further correlated neuroimaging findings with clinical measures. Mediation analysis was conducted to explore whether amygdalar subdivision-based effective connectivity mediated the relationship between IGD severity and loneliness. Compared with RGUs, IGD subjects showed inhibitory effective connections from the left pregenual anterior cingulate cortex (pACC) to the left laterobasal amygdala (LBA) and from the right medial prefrontal cortex (mPFC) to the left LBA, as well as an excitatory effective connection from the left middle prefrontal gyrus (MFG) to the right superficial amygdala. Further analyses demonstrated that the left pACC-left LBA effective connection was negatively correlated with both Internet Addiction Test and UCLA Loneliness scores, and it mediated the relationship between the two. IGD subjects and RGUs showed different connectivity patterns involving amygdalar subdivisions. These findings support a neurobiological mechanism for the relationship between IGD and loneliness, and suggest targets for therapeutic approaches that could be used to treat IGD.

Altered resting-state voxel-level whole-brain functional connectivity in multiple system atrophy patients with cognitive impairment

ObjectiveThere is increasing evidence of cognitive impairment (CI) frequently occurring in patients with multiple system atrophy (MSA); however, the neurobiological mechanisms underlying CI in patients with MSA remain unclear. MethodsWe enrolled 61 patients with probable MSA and 33 healthy controls (HC). We used degree centrality (DC) analysis to assess changes in the centrality level of MSA-CI related brain nodes. We conducted a secondary seed-based functional connectivity (FC) analysis to investigate dysfunctions in cognitive networks related to MSA. Further, we analysed the correlation between clinical symptoms and acquired connectivity measures. ResultsCompared with HC, patients with MSA-CI and those with MSA with normal cognition (MSA-NCI) exhibited lower DC values in the left calcarine and right postcentral regions and higher DC values in the bilateral caudate and left precuneus. There were significant differences in the DC values in the right middle prefrontal gyrus between the MSA-CI and MSA-NCI groups. The mean DC values in the right middle prefrontal gyrus (RMPFG) were correlated with clinical cognitive severity. Consequently, we used this brain region as a seed in secondary seed-based FC analysis and observed FC changes within the right precuneus, inferior parietal lobe, and right insula. ConclusionsDecreased middle prefrontal cortex activity and its altered functional connectivity with the precuneus, inferior parietal lobe, and insula are possible biomarkers of cognitive dysfunction in patients with MSA-CI. SignificanceCognitive impairment in MSA is associated with alterations in the dorsolateral prefrontal cortex network.

Altered resting-state voxel-level whole-brain functional connectivity in depressed Parkinson's disease

BackgroundDepression is one of the most common non-motor symptoms in Parkinson's disease (PD), but its pathogenesis is still not very clear. Recently, degree centrality, a voxel-level whole-brain functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging, has provided the most promising way to explore the neural network mechanisms underlying depressed PD. MethodsDegree centrality, voxel-wise image and clinical symptoms correlation and secondary seed-based FC analyses were performed in twenty-seven drug-naïve, early stage depressed PD patients, 27 non-depressed PD patients and 27 healthy controls (HCs) to reveal voxel-level whole-brain FC changes in depressed PD. ResultsCompared with the HCs, depressed PD and non-depressed PD patients shared similar brain degree centrality abnormalities mainly in the basal ganglia, insular cortex, motor cortices, default mode network, prefrontal gyrus and the cerebellum. However, compared with non-depressed PD, depressed PD showed degree centrality abnormalities in the right middle prefrontal gyrus, anterior cingulate cortices, supplementary motor cortices and cerebellum lobule VI. The right middle prefrontal gyrus degree centrality abnormalities were correlated with the clinical depression severity, and using it as a seed, a secondary seed-based FC analysis further revealed the FC changes in the anterior cingulate cortices and the cerebellum lobule VI. ConclusionsOur findings revealed that dysfunction in extensive brain areas were involved in depressed PD, and among these regions, the right middle prefrontal gyrus, anterior cingulate cortices and the cerebellum may pose as pathogenesis hubs underlying depressed PD.

Left prefrontal neuronavigated electrode localization in tDCS: 10–20 EEG system versus MRI-guided neuronavigation

Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral cephalic region above the eye, referred-to as the supraorbital region. Although the 10–20 EEG system is frequently used to locate the DLPFC, due to inter-subject brain variability, this method may lack accuracy. Therefore, we compared in forty participants left DLPFC-localization via the 10–20 EEG system to MRI-guided neuronavigation. In one participant, with individual electrode positions in close proximity to the mean electrode position across subjects, we also investigated whether distinct electrode localizations were associated with different tDCS-induced electrical field distributions. Furthermore, we aimed to examine which neural region is targeted when placing the reference-electrode on the right supraorbital region. Compared to the 10–20 EEG system, MRI-guided neuronavigation localizes the DLPFC-targeting anode more latero-posteriorly, targeting the middle prefrontal gyrus. tDCS-induced electric fields (n = 1) suggest that both localization methods induce significantly different electric fields in distinct brain regions. Considering the frequent application of tDCS as a neuropsychiatric treatment, an evaluation and direct comparison of the clinical efficacy of targeting methods is warranted.

Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy.

Nearly three out of four survivors experience Cancer-Related Cognitive Impairment (CRCI) for months or years following treatment. Both clinical and animal studies point to the hippocampus as a likely brain region affected in CRCI, however no previous study has investigated the functional connectivity of the hippocampus in CRCI. We compared hippocampal connectivity in cancer survivors and healthy controls and tested the relationship between functional connectivity differences and measures of objective and subjective cognition. Exploratory analysis of inflammatory markers was conducted in a small subset of participants as well. FMRI data were acquired during a memory task from 16 breast cancer survivors and 17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro-QoL was used to measure self-reported cognitive concerns. Whole-brain group-level comparisons identified clusters with different connectivity to the hippocampus in survivors versus controls during task. Average connectivity was extracted from clusters of significant difference between the groups and correlated with cognitive performance and subjective report. Survivors performed worse on a test of episodic memory and reported greater cognitive concern than controls. Exploratory analysis found higher IL6 in cancer survivors compared to controls. Cancer survivors demonstrated higher connectivity of hippocampus with left cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared with controls. In survivors, higher task-related hippocampal-cortical connectivity was related to worse subjective measures of cognitive concern. Of the four significant clusters, higher connectivity of the precuneus with hippocampus was significantly associated with worse cognitive concern in survivors. The observed greater hippocampal-cortical connectivity in survivors compared to controls is the first reported fMRI biomarker of subjective concern, and may represent a compensatory response to cancer and its treatments. This compensation could explain, in part, the subjective feelings of cognitive impairment that were reported by survivors.

Socioeconomic disadvantages and neural sensitivity to infant cry: role of maternal distress.

Socioeconomic disadvantage such as poverty can increase distress levels, which may further make low-income mothers more vulnerable to difficulties in the transition to parenthood. However, little is known about the neurobiological processes by which poverty and maternal distress are associated with risks for adaptations to motherhood. Thus, the current study examined the associations between income and neural responses to infant cry sounds among first-time new mothers (N = 28) during the early postpartum period. Lower income was associated with reduced responses to infant cry in the medial prefrontal gyrus (involved in evaluating emotional values of stimuli), middle prefrontal gyrus (involved in affective regulation) and superior temporal gyrus (involved in sensory information processing). When examining the role of maternal distress, we found a mediating role of perceived stress, but not depressive symptoms, in the links between income and prefrontal responses to infant cry. Reduced neural responses to infant cry in the right middle frontal gyrus and superior temporal gyrus were further associated with less positive perceptions of parenting. The results demonstrate that perceived stress associated with socioeconomic disadvantages may contribute to reduced neural responses to infant cry, which is further associated with less positive perceptions of motherhood.

Major Depressive Disorder and Heroin-dependent Patients Share Decreased Frontal Gray Matter Volumes: A Voxel-Based Morphometry Study

Background: Heroin addiction has been occurring in comorbidity with depression. These conditions are thought to result from common neurobiological basis. However, to date, little is known on the common volumetric changes in the multiple gray matter regions in these two patients groups. Methods: The study comprised samples of 15 depressed patients, 15 heroindependent subjects and 15, age- and sex-matched healthy controls. The gray matter volumes (GMV) abnormalities of these samples were identified and compared among them by using voxel-based morphometry method. The two resulted images were interpolated to locate the common areas of GMV alterations in the two subjects groups. Results: Common GMV abnormalities were found in superior frontal gyrus (SFG), right Middle prefrontal cortex (MPFC) and Middle frontal gyrus (MFG) in both heroin-dependent subjects and patients with depression. Moreover, we found decreased GMV in MPFC to positively correlate with HAMD scores. The decreased GMV in SFG was found to be positively correlated with daily doses of heroin in patients with heroin addiction. Conclusions: The Common disruptions of GMV in frontal lobe might be the neuroanatomical substrate for impairments of motivational drive, decision-making and behavioral control that characterizes individuals with heroin dependence and depression.

Neurobiology of Adult ADHD: Emerging Evidence for Network Dysfunctions.

FIGURE 1. Changes in cortical thickness provide one measure of brain maturation. A large longitudinal study found that for most areas of cortex, children with attention deficit hyperactivity disorder (ADHD) reach peak cortical thickness several years later than typically developing children, supporting presence of developmental delay. The rate of cortical thinning also differed between the group who continued to meet diagnostic criteria into adulthood (persistent ADHD) and those who did not (remitted ADHD). Areas of cortex in which the rate of thinning correlated with adult symptom level (green, more symptoms associated with more thinning) are approximated on medial and lateral simplified representations of cortex. An earlier study also identified multiple areas in which cortex was thinner in adults with persistent ADHD compared with controls (orange). In addition, this study noted some areas of thicker cortex in remitted ADHD when compared with persistent ADHD (blue).

Acute aerobic exercise increases cortical activity during working memory: a functional MRI study in female college students.

There is increasing evidence that acute aerobic exercise is associated with improved cognitive function. However, neural correlates of its cognitive plasticity remain largely unknown. The present study examined the effect of a session of acute aerobic exercise on working memory task-evoked brain activity as well as task performance. A within-subjects design with a counterbalanced order was employed. Fifteen young female participants (M = 19.56, SD = 0.81) were scanned using functional magnetic resonance imaging while performing a working memory task, the N-back task, both following an acute exercise session with 20 minutes of moderate intensity and a control rest session. Although an acute session of exercise did not improve behavioral performance, we observed that it had a significant impact on brain activity during the 2-back condition of the N-back task. Specifically, acute exercise induced increased brain activation in the right middle prefrontal gyrus, the right lingual gyrus, and the left fusiform gyrus as well as deactivations in the anterior cingulate cortexes, the left inferior frontal gyrus, and the right paracentral lobule. Despite the lack of an effect on behavioral measures, significant changes after acute exercise with activation of the prefrontal and occipital cortexes and deactivation of the anterior cingulate cortexes and left frontal hemisphere reflect the improvement of executive control processes, indicating that acute exercise could benefit working memory at a macro-neural level. In addition to its effects on reversing recent obesity and disease trends, our results provide substantial evidence highlighting the importance of promoting physical activity across the lifespan to prevent or reverse cognitive and neural decline.

From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder

From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder

Frequency dependent alterations in regional homogeneity of baseline brain activity in schizophrenia.

Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5∶0.01–0.027 Hz; slow-4∶0.027–0.08 Hz; and typical band: 0.01–0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent.

The alteration of gray matter volume in children with mental retardation: the differences between the patients presented with operation deficit predominantly and those presented with language deficit mainly

Objective To detect the differences of grey matter volume between the patients with mental retardation (MR) presented clinically as operation deficit (OD) or as language deficit (LD) and the children with typical normal development using optimal VBM.The developmental connections between brain gray matter and language or operation skills were examined.Methods Magnetic resonance imaging was obtained from 9 children with mental retardation presented as OD predominantly and 11 children with mental retardation presented as LD mainly,as well as the age-matched control group (11 and 14 normal children,respectively) on a 1.5 T scanner.Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the volume of grey matter between the two groups (OD VS.control; LD VS.control).Statistically,the total and local gray matter volumes were compared between the two groups with t test.Results The total gray matter volume of OD group was [(1.030 ± 0.078) × 106 mm3].Compared to that of controls [(0.984 ± 0.058) × 106 mm3],it was increased significantly (t =-2.6,P ＜ 0.05).And the gray matter volume in the posterior cingulated gyrus,left superior prefrontal gyrus,left cuneus,left middle prefrontal gyrus and the body of left caudate nucleus showed significantly increased.Meanwhile,the total gray matter volume of the MR children presented as LD [(1.002 ± 0.068) × 106 mm3] showed significantly increased(t =-3.0,P ＜ 0.05) compared with that of control group [(0.957 ±0.057) × 106 mm3].The gray matter volume in bilateral thalami,the left inferior temporal gyrus,the left inferior frontal gyrus,and the left cerebellum of the LD group was more than that of normal children.Conclusion As revealed by VBM,there are differences in alterations of gray matter volume between MR children presented with OD and with LD relative to control. Key words: Child ; Mental retardation ; Magnetic resonance imaging; Brain

Patterns of Brain Activation during Visually Evoked Sexual Arousal Differ between Homosexual and Heterosexual Men

Nowadays the mechanism of homosexuality is little known. Few studies have been carried out to explore the brain functional changes of homosexual men during sexual arousal. We used functional MR imaging (fMRI) to determine whether the patterns of brain activation in homosexual and heterosexual men differed during visually evoked sexual arousal. To all the subjects (10 homosexual and 10 heterosexual), real-time visual stimulation was provided by 3-minute exposure to 3 types of erotic film: heterosexual couples (F-M), male homosexual couples (M-M), and female homosexual couples (F-F) engaged in sexual activity, during which time fMRI was used to determine the patterns of brain activation. Self-reports of level of sexual arousal were collected immediately afterward. Statistical parametric mapping showed that viewing erotic film excerpts that induced sexual arousal was associated, in both groups, with activation of the middle prefrontal gyrus, bilateral temporal lobe and postcentral gyrus, thalamus, insula, vermis, left precuneus, occipital cortex, parietal cortex, and cerebellum. In homosexual men, the left angular gyrus, left caudate nucleus, and right pallidum were activated; in contrast, heterosexual men showed no activation in these regions. However, heterosexual men showed activation in the bilateral lingual gyrus, right hippocampus, and right parahippocampal gyrus, areas not activated in homosexual men. In both groups, region-of-interest analysis revealed no correlation between the magnitude of amygdala or thalamus activation and the reported level of sexual arousal. Our findings indicate that different neural circuits are active during sexual arousal in homosexual and heterosexual men and may contribute to a better understanding of the neural basis of male sexual orientation.

Prefrontal but not temporal grey matter changes in males with first-episode schizophrenia

Introduction Changes of brain morphology are now considered as a part of the pathology of schizophrenia. Voxel-based morphometry may be used to study regional changes of the grey matter in the whole brain. It is advantageous to study first-episode patients to prevent the influence of many possible biasing factors when trying to identify primary pathological processes underlying the manifestation of the illness. Objective To investigate regional grey matter changes in the first-episode schizophrenia patients. Methods Optimized voxel-based morphometry was used to detect changes in grey matter volume in 22 patients with first-episode schizophrenia compared with 18 healthy volunteers of comparable age, gender and handedness. Results The first-episode schizophrenia group had significantly reduced grey matter volume in the prefrontal cortex (inferior and middle prefrontal gyrus, cingulate gyrus). We identified no differences in the temporal cortex. Conclusion Our data support the theoretical assumption that prefrontal dysfunction underlines the primary pathology and clinical manifestation of schizophrenia. We are inclined to explain the differences in the pattern of morphological changes reported in other first-episode studies – especially the lack of changes in the temporal cortex – by heterogeneity of schizophrenia, potential progression and antipsychotic medication effect.

Voxel-based morphometry of patients with schizophrenia or bipolar disorder and their unaffected relatives

Structural brain abnormalities in schizophrenia are well replicated; many emerge before the onset of illness and are present in relatives who remain well. Structural changes in bipolar disorder are less clearly established. The possibility that structural abnormalities might provide a means by which the disorders might be separated is one that has attracted limited research effort. This study sought to examine these issues and clarify the associations of phenotypic expression and genetic liability. Forty-nine control subjects, 71 patients, and 72 unaffected relatives were recruited for the study. Patients included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone, and those with bipolar disorder from families affected by both bipolar disorder and schizophrenia. Unaffected relatives were recruited from the families of the three patient groups. Subjects underwent a magnetic resonance imaging scan of the brain, which was analyzed with a grey-matter-optimized, voxel-based morphometry technique. Compared with control subjects, all patient and relative groups showed evidence of reduced anterior thalamic gray matter. Reductions in middle prefrontal gyrus and dorsomedial thalamus were specific to participants with schizophrenia. Whereas prefrontal and dorsomedial thalamic gray matter reductions seem to be specific to schizophrenia, anterior thalamic reductions seem to be a marker of liability to psychosis in general. These results are discussed in the context of their functional role and in terms of their connections with other cortical and subcortical structures.

Metabolic brain pattern of sustained auditory discrimination.

Positron emission tomography of [18F]-2-fluorodeoxyglucose was used to assess the functional brain activity of normal subjects while performing auditory discrimination (CPT), while receiving an identical set of tones as in CPT, but with the instructions that they were background noise, or while at rest. The present study: (1) confirms earlier findings of an association between the functional activity of the right midprefrontal cortex and the performance of auditory discrimination, (2) localizes this increase in right prefrontal cortex activity to the middle prefrontal gyrus; and (3) provides a framework of specific testable hypotheses for the evaluation of the importance of certain limbic and paralimbic areas in the biological determination of sustained attention to be addressed in future studies. The framework accounts for the now confirmed finding that the middle cingulate has lower metabolic activity in CPT than at rest, and new findings of alterations in temporal lobe processing of tones in response to attention.