Showing papers on "Superior frontal gyrus published in 2019"

Gender-related functional connectivity and craving during gaming and immediate abstinence during a mandatory break: Implications for development and progression of internet gaming disorder.

Abstract: Background Although males more frequently develop Internet gaming disorder (IGD) as compared with females, few studies have examined gender-related neurocognitive differences in IGD. Task and design fMRI and subjective data were collected from 119 subjects (IGD, male 29, female 25; recreational game use (RGU), male 34, female 31) when they were actively playing games and during a forced mandatory break. Analyses investigating effects of group (IGD, RGU) and gender (male, female) on the functional connectivity (FC) of executive control and reward systems linked to the dorsolateral prefrontal cortex (DLPFC) and striatum, respectively, were performed. Correlations between FC and subjective craving measures were also calculated. Results Gaming-group-by-gender interactions were observed. During gaming in males but not in females, the FC between the DLPFC and superior frontal gyrus was relatively decreased, and that between the striatum and thalamus was relatively increased. During the mandatory break, changes in the FC between DLPFC and superior frontal gyrus and the FC between the striatum and thalamus varied by gender with greater RGU-IGD differences observed in females. Significant correlations between FC and self-reported craving were observed. Conclusions During both gaming and a forced mandatory break, brain regions implicated in executive control and reward processing showed changes in FC that varied by gender. Brain regions implicated in executive control showed differential FC in males during gaming, and FC during the forced mandatory break appeared relevant to both genders, and perhaps particularly for females. The findings suggest possible neural mechanisms for why males appear more likely to develop IGD, and why it may be particularly difficult for individuals with IGD to cease gaming.

Influence of 4-week multi strain probiotic administration on resting-state functional connectivity in healthy volunteers

Abstract: Experimental investigations in rodents have contributed significantly to our current understanding of the potential importance of the gut microbiome and brain interactions for neurotransmitter expression, neurodevelopment, and behaviour. However, clinical evidence to support such interactions is still scarce. The present study used a double-blind, randomized, pre- and post-intervention assessment design to investigate the effects of a 4-week multi-strain probiotic administration on whole-brain functional and structural connectivity in healthy volunteers. Forty-five healthy volunteers were recruited for this study and were divided equally into three groups (PRP: probiotic, PLP: placebo, and CON: control). All the participants underwent resting-state functional MRI and diffusion MRI brain scans twice during the course of study, at the beginning (time point 1) and after 4 weeks (time point 2). MRI data were acquired using a 3T whole-body MR system (Magnetom Skyra, Siemens, Germany). Functional connectivity (FC) changes were observed in the default mode network (DMN), salience network (SN), and middle and superior frontal gyrus network (MFGN) in the PRP group as compared to the PLP and CON groups. PRP group showed a significant decrease in FC in MFGN (in frontal pole and frontal medial cortex) and in DMN (in frontal lobe) as compared to CON and PLP groups, respectively. Further, significant increase in FC in SN (in cingulate gyrus and precuneus cortex) was also observed in PRP group as compared to CON group. The significance threshold was set to p < 0.05 FWE corrected. No significant structural differences were observed between the three groups. This work provides new insights into the role of a multi-strain probiotic administration in modulating the behaviour, which is reflected as changes in the FC in healthy volunteers. This study motivates future investigations into the role of probiotics in context of major depression and stress disorders.

Stress and the brain: Perceived stress mediates the impact of the superior frontal gyrus spontaneous activity on depressive symptoms in late adolescence

Abstract: Identifying factors for the prediction of depression is a long-standing research topic in psychiatry and psychology. Perceived stress, which reflects the tendency to appraise one's life situations as stressful and overwhelming, has emerged as a stable predictor for depressive symptoms. However, the neurobiological bases of perceived stress and how perceived stress influences depressive symptoms in the healthy brain remain largely unknown. Here, we investigated these issues in 217 healthy adolescents by estimating the fractional amplitude of low-frequency fluctuations (fALFFs) via resting-state functional magnetic resonance imaging. A whole-brain correlation analysis showed that higher levels of perceived stress were associated with greater fALFF in the left superior frontal gyrus (SFG), which is a core brain region for cognitive control and emotion regulation-related processes. Mediation analysis further indicated that perceived stress mediated the link between the fALFF in the left SFG and depressive symptoms. Importantly, our results remained significant even when excluding the influences of head motion, anxiety, SFG gray matter structure, and school environment. Altogether, our findings suggested that the fALFF in the left SFG is a neurofunctional marker of perceived stress in adolescents and revealed a potential indirect effect of perceived stress on the association between the SFG spontaneous activity and depressive symptoms.

Anatomy and white matter connections of the inferior frontal gyrus

Abstract: The inferior frontal gyrus (IFG) is involved in the evaluation of linguistic, interoceptive, and emotional information. A detailed understanding of its subcortical white matter anatomy could improve postoperative morbidity related to surgery in and around this gyrus. Through GQI-based fiber tracking validated by gross anatomical dissection as ground truth, we characterized the fiber tracts of the IFG based on relationships to other well-known neuroanatomic structures. Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for fiber tracking analysis. We evaluated the IFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts. We identified four major connections of the IFG: a white matter bundle corresponding the frontal aslant tract connecting to the superior frontal gyrus; the superior longitudinal fasciculus connecting to the inferior parietal lobule, lateral occipital area, posterior temporal areas, and the temporal pole; the inferior fronto-occipital fasciculus connecting to the cuneus and lingual gyrus; and the uncinate fasciculus connecting to the temporal pole. A callosal fiber bundle connecting the inferior frontal gyri bilaterally was also identified. The IFG is an important region implicated in a variety of tasks including language processing, speech production, motor control, interoceptive awareness, and semantic processing. Postsurgical outcomes related to this region may be better understood in the context of the fiber-bundle anatomy highlighted in this study. Clin. Anat. 32:546-556, 2019. © 2019 Wiley Periodicals, Inc.

Distinct Disruptive Patterns of Default Mode Subnetwork Connectivity Across the Spectrum of Preclinical Alzheimer's Disease

Abstract: Background: The early progression continuum of Alzheimer's disease (AD) has been considered to advance through subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI). Altered functional connectivity (FC) in the default mode network (DMN) is regarded as a hallmark of AD. Furthermore, the DMN can be divided into two subnetworks, the anterior and posterior subnetworks. However, little is known about distinct disruptive patterns in the subsystems of the DMN across the preclinical AD spectrum. This study investigated the connectivity patterns of anterior DMN (aDMN) and posterior DMN (pDMN) across the preclinical AD spectrum. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in the DMN subnetworks in 20 healthy controls (HC), eight SCD, 11 naMCI, and 28 aMCI patients. Moreover, a correlation analysis was used to examine associations between the altered connectivity of the DMN subnetworks and the neurocognitive performance. Results: Compared to the HC, SCD patients showed increased FC in the bilateral superior frontal gyrus (SFG), naMCI patients showed increased FC in the left inferior parietal lobule (IPL), and aMCI patients showed increased FC in the bilateral IPL in the aDMN; while SCD patients showed decreased FC in the precuneus, naMCI patients showed increased FC in the left middle temporal gyrus (MTG), and aMCI patients also showed increased FC in the right middle frontal gyrus (MFG) in the pDMN. Notably, the FC between the ventromedial prefrontal cortex (vmPFC) and the left MFG and the IPL in the aDMN was associated with episodic memory in the SCD and aMCI groups. Interestingly, the FC between the posterior cingulated cortex (PCC) and several regions in the pDMN was associated with other cognitive functions in the SCD and naMCI groups. Conclusions: This study demonstrates that the three preclinical stages of AD exhibit distinct FC alternations in the DMN subnetworks. Furthermore, the patient group data showed that the altered FC involves cognitive function. These findings can provide novel insights for tailored clinical intervention across the preclinical AD spectrum.

Connectome analysis of functional and structural hemispheric brain networks in major depressive disorder.

Abstract: Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional–structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.

Altered voxel-wise gray matter structural brain networks in schizophrenia: Association with brain genetic expression pattern

Abstract: Previous seed- and atlas-based structural covariance/connectivity analyses have demonstrated that patients with schizophrenia is accompanied by aberrant structural connection and abnormal topological organization. However, it remains unclear whether this disruption is present in unbiased whole-brain voxel-wise structural covariance networks (SCNs) and whether brain genetic expression variations are linked with network alterations. In this study, ninety-five patients with schizophrenia and 95 matched healthy controls were recruited and gray matter volumes were extracted from high-resolution structural magnetic resonance imaging scans. Whole-brain voxel-wise gray matter SCNs were constructed at the group level and were further analyzed by using graph theory method. Nonparametric permutation tests were employed for group comparisons. In addition, regression modes along with random effect analysis were utilized to explore the associations between structural network changes and gene expression from the Allen Human Brain Atlas. Compared with healthy controls, the patients with schizophrenia showed significantly increased structural covariance strength (SCS) in the right orbital part of superior frontal gyrus and bilateral middle frontal gyrus, while decreased SCS in the bilateral superior temporal gyrus and precuneus. The altered SCS showed reproducible correlations with the expression profiles of the gene classes involved in therapeutic targets and neurodevelopment. Overall, our findings not only demonstrate that the topological architecture of whole-brain voxel-wise SCNs is impaired in schizophrenia, but also provide evidence for the possible role of therapeutic targets and neurodevelopment-related genes in gray matter structural brain networks in schizophrenia.

Mapping the Supratentorial Cerebral Arterial Territories Using 1160 Large Artery Infarcts.

Abstract: Importance Cerebral vascular territories are of key clinical importance in patients with stroke, but available maps are highly variable and based on prior studies with small sample sizes. Objective To update and improve the state of knowledge on the supratentorial vascular supply to the brain by using the natural experiment of large artery infarcts and to map out the variable anatomy of the anterior, middle, and posterior cerebral artery (ACA, MCA, and PCA) territories. Design, Setting, and Participants In this cross-sectional study, digital maps of supratentorial infarcts were generated using diffusion-weighted magnetic resonance imaging (MRI) of 1160 patients with acute ( Main Outcomes and Measures The 3 vascular territories were mapped individually by affected vessel, generating 3 data sets for which infarct frequency is defined for each voxel in the data set. By mapping these 3 vascular territories collectively, we generated data sets showing the Certainty Index (CI) to reflect the likelihood of a voxel being a member of a specific vascular territory, calculated as either ACA, MCA, or PCA infarct frequency divided by total infarct frequency in that voxel. Results Of the 1160 patients (mean [SD] age, 67.0 [13.3] years old), 623 were men (53.7%). When the cutoff CI was set as 90%, the volume of the MCA territory (approximately 54% of the supratentorial parenchymal brain volume) was about 4-fold bigger than the volumes of the ACA and PCA territories (each approximately 13%). Quantitative studies showed that the medial frontal gyrus, superior frontal gyrus, and anterior cingulate were involved mostly in ACA infarcts, whereas the middle frontal gyrus and caudate were involved mostly by MCA infarcts. The PCA infarct territory was smaller and narrower than traditionally shown. Border-zone maps could be defined by using either relative infarct frequencies or CI differences. Conclusions and Relevance We have generated statistically rigorous maps to delineate territorial border zones and lines. The new topographic brain atlas can be used in clinical care and in research to objectively define the supratentorial arterial territories and their borders.

A Longitudinal Study of Local Gyrification Index in Young Boys With Autism Spectrum Disorder.

Abstract: Local gyrification index (LGI), a metric quantifying cortical folding, was evaluated in 105 boys with autism spectrum disorder (ASD) and 49 typically developing (TD) boys at 3 and 5 years-of-age. At 3 years-of-age, boys with ASD had reduced gyrification in the fusiform gyrus compared with TD boys. A longitudinal evaluation from 3 to 5 years revealed that while TD boys had stable/decreasing LGI, boys with ASD had increasing LGI in right inferior temporal gyrus, right inferior frontal gyrus, right inferior parietal lobule, and stable LGI in left lingual gyrus. LGI was also examined in a previously defined neurophenotype of boys with ASD and disproportionate megalencephaly. At 3 years-of-age, this subgroup exhibited increased LGI in right dorsomedial prefrontal cortex, cingulate cortex, and paracentral cortex, and left cingulate cortex and superior frontal gyrus relative to TD boys and increased LGI in right paracentral lobule and parahippocampal gyrus, and left precentral gyrus compared with boys with ASD and normal brain size. In summary, this study identified alterations in the pattern and development of LGI during early childhood in ASD. Distinct patterns of alterations in subgroups of boys with ASD suggests that multiple neurophenotypes exist and boys with ASD and disproportionate megalencephaly should be evaluated separately.

Connectome-Based Biomarkers Predict Subclinical Depression and Identify Abnormal Brain Connections With the Lateral Habenula and Thalamus.

Abstract: Subclinical depression (SD) has been considered as the precursor to major depressive disorder. Accurate prediction of SD and identification of its etiological origin are urgent. Bursts within the lateral habenula (LHb) drive depression in rats, but whether dysfunctional LHb is associated with SD in human is unknown. Here we develop connectome-based biomarkers which predict SD and identify dysfunctional brain regions and connections. T1 weighted images and resting-state functional MRI (fMRI) data were collected from 34 subjects with SD and 40 healthy controls (HCs). After the brain is parcellated into 48 brain regions (246 subregions) using the human Brainnetome Atlas, the functional network of each participant is constructed by calculating the correlation coefficient for the time series of fMRI signals of each pair of subregions. Initial candidates of abnormal connections are identified by the two-sample t-test and input into Support Vector Machine models as features. A total of 24 anatomical-region-based models, 231 sliding-window-based models, and 100 random-selection-based models are built. The performance of these models is estimated through leave-one-out cross-validation and evaluated by measures of accuracy, sensitivity, confusion matrix, receiver operating characteristic curve, and the area under the curve (AUC). After confirming the region with the highest accuracy, subregions within the thalamus and connections associated with subregions of LHb are compared. It is found that five prediction models using connections of the thalamus, posterior superior temporal sulcus, cingulate gyrus, superior parietal lobule, and superior frontal gyrus achieve an accuracy >0.9 and an AUC >0.93. Among 90 abnormal connections associated with the thalamus, the subregion of the right posterior parietal thalamus where LHb is located has the most connections (n = 18), the left subregion only has 3 connections. In SD group, 10 subregions in the thalamus have significantly different node degrees with those in the HC group, while 8 subregions have lower degrees ( p < 0.01), including the one with LHb. These results implicate abnormal brain connections associated with the thalamus and LHb to be associated with SD. Integration of these connections by machine learning can provide connectome-based biomarkers to accurately diagnose SD.

Brain Networks Underlying Eye’s Pupil Dynamics

Abstract: Phasic changes in eye's pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.

Dissociating motor–speech from lexico-semantic systems in the left frontal lobe: insight from a series of 17 awake intraoperative mappings in glioma patients

Abstract: Functional brain mapping during awake surgery procedures is the gold standard technique in the management of left frontal lobe tumors. Nevertheless, a unified picture of the language subsystems encountered during left frontal lobe mapping is still lacking. We retrospectively analyzed the 49 cortical and the 33 axonal sites of functional language mapping performed in 17 patients operated for a left frontal lobe glioma under awake conditions. Sites were tagged on the postoperative MRI, based on anatomical landmarks and intraoperative photography. All MRIs and tags were then registered in the MNI template. Speech disturbances related to motor functions (speech arrest—with or without superior limb arrest—, stuttering, and vocalization) were grouped together as “motor–speech” responses. Anomias, semantic paraphasia, perseverations, and PPTT errors were classified as “lexico-semantic” responses. MNI-registered axonal sites were used as seed for computing disconnectome maps from a tractogram atlas of ten healthy individuals, as implemented in the BCB toolkit. The cortical distribution of lexico-semantic responses appeared to be located anteriorly (pars triangularis of the inferior frontal gyrus and posterior end of the middle and superior frontal gyrus) compared to motor–speech responses (lower end of the precentral gyrus and pars opercularis). Within the white matter, motor–speech responses and lexico-semantic responses overlapped on the trajectory of the aslant and fronto-striatal tracts, but the lexico-semantic sites were located more anteriorly (mean Y coordinate on the MNI system was 21.2 mm for lexico-semantic sites and 14.3 mm for the motor–speech sites; Wilcoxon test: W = 60.5, p = 0.03). Moreover, disconnectome maps evidenced a clear distinction between the two subsystems: posterior fronto-striatal and frontal aslant tracts, corpus callosum and cortico-spinal tract were related to the motor–speech sites, whereas anterior frontal aslant tract, inferior-fronto-occipital fasciculus (IFOF) and anterior thalamic radiations were related to the lexico-semantic sites. Hence, we evidenced distinct anatomical substrates for the motor–speech and lexico-semantic systems. Regarding the aslant/fronto-striatal system, an anterior to posterior gradient was found, with a lexico-semantic role for the anterior part and a motor–speech involvement for the posterior part. For tumors abutting the precentral sulcus, posterior boundaries of the resection are made of motor–speech sites, meaning that the anteriorly located lexico-semantic system is no more functional, as a result of network reorganization by plasticity.

Central nervous system involvement in late-onset Pompe disease: clues from neuroimaging and neuropsychological analysis.

Abstract: Background and purpose Late-onset Pompe disease (LOPD) is a rare, multisystem disorder that is well established to mainly impair skeletal muscle function. Systematic studies exploring brain functions in LOPD are lacking. The aim of this study was to detect morphological and functional brain alterations as well as neuropsychological impairment in LOPD. Methods We studied 21 patients (10 male, mean age 49 ± 18.4 years) with defined diagnosis of LOPD, divided into two groups: one with pre-symptomatic hyperCKemia with no muscle weakness and the second with limb-girdle muscle weakness. All patients underwent 3T magnetic resonance imaging (MRI) to obtain morphological/angiographic evaluation as well as normalized cortical brain volume and resting-state functional MRI. Fazekas score was applied to quantify white matter lesions, whereas Smoker's criteria were used to examine dolichoectasia. A complete neuropsychological assessment was performed. Results The MRI data showed that 12/21 patients (57%) demonstrated signs of cerebral vasculopathy, with a Fazekas score >2 in 67%. According to Smoker's criteria, 11/21 patients (52%) had a dolichoectasia of the vertebrobasilar system; an intracranial aneurysm was detected in 3/21 patients (14%). Resting-state functional MRI demonstrated significantly decreased brain connectivity in the salience network with a more relevant reduction in the bilateral middle and superior frontal gyrus. Gray matter atrophy correlated with age and disease duration. A mild impairment in executive functions was also identified. Conclusions In this LOPD cohort the results showed morphological and functional brain alterations with mild neuropsychological dysfunction, mainly in the limb-girdle muscle weakness group. Cerebrovascular alterations seemed to be not related to common risk factors, suggesting a major role of enzymatic deficiency in the pathogenesis of brain abnormalities.

Anodal tDCS affects neuromodulatory effects of the norepinephrine system on superior frontal theta activity during response inhibition.

Abstract: Medial and superior frontal theta oscillations are important for response inhibition. The norepinephrine (NE) system has been shown to modulate these oscillations possibly via gain control mechanisms, which depend on the modulation of neuron membrane potentials. Because the latter are also modulated by tDCS, the interrelation of tDCS and NE effects on superior frontal theta band activity needs investigation. We test the hypothesis that anodal tDCS affects modulatory effects of the NE system on theta band activity during inhibitory control in superior frontal regions. Using EEG beamforming, theta band activity in the superior frontal gyrus (SFG) was integrated (correlated) with the pupil diameter data as an indirect index of NE activity. In a within-subject design, healthy participants completed a response inhibition task in two sessions in which they received 2 mA anodal tDCS over the vertex, or sham stimulation. There were no behavioral effects of anodal tDCS. Yet, tDCS affected correlations between SFG theta band activity time course and the pupil diameter time course. Correlations were evident after sham stimulation (r = .701; p < .004), but absent after anodal tDCS. The observed power of this dissociation was above 95%. The data suggest that anodal tDCS may eliminate neuromodulatory effects, likely of the NE system, on theta band activity during response inhibition in a structure of the response inhibition network. The NE system and tDCS seem to target similar mechanisms important for cognitive control in the prefrontal cortex. The results provide a hint why tDCS often fails to induce overt behavioral effects and shows that neurobiological systems, which may exert similar effects as tDCS on neural processes should closely be monitored in tDCS experiments.

The Association Between Distinct Frontal Brain Volumes and Behavioral Symptoms in Mild Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

Abstract: Our aim was to investigate the association between behavioral symptoms of agitation, disinhibition, irritability, elation, and aberrant motor behavior to frontal brain volumes in a cohort with various neurodegenerative diseases. A total of 121 patients with mild cognitive impairment (MCI, n = 58), Alzheimer's disease (AD, n = 45) and behavioral variant frontotemporal dementia (bvFTD, n = 18) were evaluated with a Neuropsychiatric Inventory (NPI). A T1-weighted MRI scan was acquired for each participant and quantified with a multi-atlas segmentation method. The volumetric MRI measures of the frontal lobes were associated with neuropsychiatric symptom scores with a linear model. In the regression model, we included CDR score and TMT B time as covariates to account for cognitive and executive functions. The brain volumes were corrected for age, gender and head size. The total behavioral symptom score of the five symptoms of interest was negatively associated with the volume of the subcallosal area (β = −0.32, p = 0.002). High disinhibition scores were associated with reduced volume in the gyrus rectus (β = −0.30, p = 0.002), medial frontal cortex (β = −0.30, p = 0.002), superior frontal gyrus (β = −0.28, p = 0.003), inferior frontal gyrus (β = −0.28, p = 0.005) and subcallosal area (β = −0.28, p = 0.005). Elation scores were associated with reduced volumes of the medial orbital gyrus (β = −0.30, p = 0.002) and inferior frontal gyrus (β = −0.28, p = 0.004). Aberrant motor behavior was associated with atrophy of frontal pole (β = −0.29, p = 0.005) and the subcallosal area (β = −0.39, p < 0.001). No significant associations with frontal brain volumes were found for agitation and irritability. We conclude that the subcallosal area may be common neuroanatomical area for behavioral symptoms in neurodegenerative diseases, and it appears to be independent of disease etiology.

Reduced Cortical Thickness in Schizophrenia and Schizotypal Disorder.

Abstract: Schizotypal disorder is characterized by odd behavior and attenuated forms of schizophrenic features without the manifestation of overt and sustained psychoses. Past studies suggest that schizotypal disorder shares biological and psychological commonalties with schizophrenia. Structural magnetic resonance imaging (MRI) studies have demonstrated both common and distinct regional gray matter changes between schizophrenia and schizotypal disorder. However, no study has compared cortical thickness, which is thought to be a specific indicator of cortical atrophy, between schizophrenia and schizotypal disorder. The subjects consisted of 102 schizophrenia and 46 schizotypal disorder patients who met the International Classification of Diseases, 10th edition criteria and 79 gender- and age-matched healthy controls. Each participant underwent a T1-weighted 3-D MRI scan using a 1.5-Tesla scanner. Cortical thickness was estimated using FreeSurfer. Consistent with previous studies, schizophrenia patients exhibited wide-spread cortical thinning predominantly in the frontal and temporal regions as compared with healthy subjects. Patients with schizotypal disorder had a significantly reduced cortical thickness in the left fusiform and parahippocampal gyri, right medial superior frontal gyrus, right inferior frontal gyrus, and right medial orbitofrontal cortex as compared with healthy controls. Schizophrenia patients had thinner cortices in the left precentral and paracentral gyri than those with schizotypal disorder. Common cortical thinning patterns observed in schizophrenia and schizotypal disorder patients may be associated with vulnerability to psychosis. Our results also suggest that distinct cortical changes in schizophrenia and schizotypal disorder may be associated with the differences in the manifestation of clinical symptoms among these disorders.

Multimodal Brain Changes in First-Episode Mania: A Voxel-Based Morphometry, Functional Magnetic Resonance Imaging, and Connectivity Study.

Abstract: Background: Brain structural and functional changes in bipolar disorder (BD) are well-established findings, but it is uncertain whether these changes are already present in first episode mania (FEM). Methods: We compared 31 FEM subjects, with 31 healthy individuals matched for age, sex, and premorbid IQ. Whole-brain voxel-wise morphometry, functional magnetic resonance imaging during the n-back task, and a functional connectivity analysis were performed. Results: There were no volumetric differences between the 2 groups. During the 2-back task, FEM patients did not perform differently from controls and activated similar regions, but they showed less deactivation in the ventromedial prefrontal cortex (vmPFC), the anterior hub of the default mode network (DMN). They showed preserved functional connectivity between the vmPFC and other regions of the DMN, but increased connectivity with the superior frontal gyrus. Conclusions: The absence of volumetric changes in FEM patients suggests that these changes could be related to progression of the illness. On the other hand, the failure of deactivation of the anterior hub of the DMN is present from the onset of the illness and may represent a core pathophysiological feature of BD.

Increased Functional Connectivity of the Angular Gyrus During Imagined Music Performance.

Abstract: The angular gyrus (AG) is a hub of several networks that are involved in various functions, including attention, self-processing, semantic information processing, emotion regulation, and mentalizing. Since these functions are required in music performance, it is likely that the AG plays a role in music performance. Considering that these functions emerge as network properties, this study analyzed the functional connectivity of the AG during the imagined music performance task and the resting condition. Our hypothesis was that the functional connectivity of the AG is modulated by imagined music performance. In the resting condition, the AG had connections with the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and precuneus as well as the superior and inferior frontal gyri and with the temporal cortex. Compared with the resting condition, imagined music performance increased the functional connectivity of the AG with the superior frontal gyrus (SFG), mPFC, precuneus, PCC, hippocampal/parahippocampal gyrus (H/PHG), and amygdala. The anterior cingulate cortex (ACC) and superior temporal gyrus (STG) were newly engaged or added to the AG network during the task. In contrast, the supplementary motor area (SMA), sensorimotor areas, and occipital regions, which were anti-correlated with the AG in the resting condition, were disengaged during the task. These results lead to the conclusion that the functional connectivity of the AG is modulated by imagined music performance, which suggests that the AG plays a role in imagined music performance.

Altered Spatial and Temporal Brain Connectivity in the Salience Network of Sensorineural Hearing Loss and Tinnitus

Abstract: Sensorineural hearing loss (SNHL), sometimes accompanied with tinnitus, is associated with dysfunctions within and outside the classical auditory pathway. The salience network, which is anchored in bilateral anterior insula and dorsal anterior cingulate cortex, has been implicated in sensory integration. Partial auditory deprivation could alter the characteristics of the salience network and other related brain areas, thereby contributing to hearing impairments-induced neuropsychiatric symptoms. To test this hypothesis, we performed fMRI scanning and neuropsychological tests on 32 subjects with long-term bilateral hearing impairment and 30 well-matched Controls. Non-directional functional connectivity and directional Granger causality analysis were used to identify aberrant spatial and temporal patterns of connections targeting bilateral anterior insula and dorsal anterior cingulate cortex. We found that the left anterior insula showed decreased connectivity with right precentral gyrus and superior frontal gyrus. The connections between the dorsal anterior cingulate cortex and middle frontal gyrus, superior parietal gyrus and supplementary motor area (SMA) were also reduced. Relative to Controls, SNHL patients showed abnormal effective connectivity of the salience network, including inferior temporal gyrus, cerebellum lobule VI, lobule VIII, precentral gyrus, middle frontal gyrus and SMA. Furthermore, correlation analysis demonstrated that some of these atypical connectivity measures were correlated with performance of neuropsychiatric tests. These findings suggest that the inefficient modulation of the salience network might contribute to the neural basis of SNHL and tinnitus, as well as associated cognition and emotion deficits.

Different Contexts in the Oddball Paradigm Induce Distinct Brain Networks in Generating the P300.

Abstract: Despite the P300 event-related potential (ERP) differences between distinct stimulus sequences, the effect of stimulus sequence on the brain network is still left unveiled. To uncover the corresponding effect of stimulus sequence, we thus investigated the differences of functional brain networks, when a target (T) or standard (S) stimulus was presented preceding another T as background context. Results of this study demonstrated that, when an S was first presented preceding a T (i.e., ST sequence), the P300 experiencing large amplitude was evoked by the T, along with strong network architecture. In contrast, if a T was presented in advance [i.e., target-to-target (TT) sequence], decreased P300 amplitude and attenuated network efficiency were demonstrated. Additionally, decreased activations in regions, such as inferior frontal gyrus and superior frontal gyrus were also revealed in TT sequence. Particularly, the effect of stimulus sequence on P300 network could be quantitatively measured by brain network properties, the increase in network efficiency corresponded to large P300 amplitude evoked in P300 task.

Identification of brain regions associated with working memory deficit in schizophrenia

Abstract: Background: Schizophrenia, a severe psychological disorder, shows symptoms such as hallucinations and delusions. In addition, patients with schizophrenia often exhibit a deficit in working memory which adversely impacts the attentiveness and the behavioral characteristics of a person. Although several clinical efforts have already been made to study working memory deficit in schizophrenia, in this paper, we investigate the applicability of a machine learning approach for identification of the brain regions that get affected by schizophrenia leading to the dysfunction of the working memory. Methods: We propose a novel scheme for identification of the affected brain regions from functional magnetic resonance imaging data by deploying group independent component analysis in conjunction with feature extraction based on statistical measures, followed by sequential forward feature selection. The features that show highest accuracy during the classification between healthy and schizophrenia subjects are selected. Results: This study reveals several brain regions like cerebellum, inferior temporal gyrus, superior temporal gyrus, superior frontal gyrus, insula, and amygdala that have been reported in the existing literature, thus validating the proposed approach. We are also able to identify some functional changes in the brain regions, such as Heschl gyrus and the vermian area, which have not been reported in the literature involving working memory studies amongst schizophrenia patients. Conclusions: As our study confirms the results obtained in earlier studies, in addition to pointing out some brain regions not reported in earlier studies, the findings are likely to serve as a cue for clinical investigation, leading to better medical intervention.

Resting state functional connectivity of networks associated with reward and habit in anorexia nervosa.

Abstract: Neurobiological disturbances associated with reward and/or habit learning are theorized to maintain symptoms of anorexia nervosa (AN). Although research has investigated responses in brain regions associated with reward and habit to disorder-specific cues (e.g., food) and presumed rewards (e.g., money), little is known about the functional organization of the circuits underlying these constructs independent of stimulus. This study aimed to provide initial data on the synchrony of networks associated with reward and habit in AN by comparing resting-state functional connectivity (RSFC) patterns between AN and healthy control (HC) participants in these circuits and delineating how these patterns relate to symptoms. Using theoretically selected seeds in the nucleus accumbens (NAcc), ventral caudate, and dorsal caudate, reflecting a continuum from reward- to habit- oriented regions, RSFC patterns were compared between AN restricting subtype (n = 19) and HC (n = 19) participants (cluster threshold: p < .01). Exploratory correlations between RSFC z-scores and Eating Disorder Examination (EDE) scores, BMI, and illness duration were conducted. The AN group demonstrated lower RSFC between the NAcc and superior frontal gyrus, between the ventral caudate and frontal and posterior regions, and between the dorsal caudate and frontal, temporal, and posterior regions. In the AN group, lower NAcc- superior frontal gyrus RSFC correlated with greater EDE Global scores (r = −.58, CI: −.83, −.13). These resting-state synchrony disruptions of the ventral and dorsal frontostriatal circuits, considered in context of the broader literature, support the utility of further investigating possible reward and habit disturbances supporting symptoms in AN.

Abnormal resting-state cerebral-limbic functional connectivity in bipolar depression and unipolar depression.

Abstract: Distinctive patterns of functional connectivity (FC) abnormalities in neural circuitry has been reported in patients with bipolar depression (BD) and unipolar depression (UD). However, it is unclear that whether this distinct functional connectivity patterns are diagnosis specific between BD and UD. This study aimed to compare patterns of functional connectivity among BD, UD and healthy controls (HC) and determine the distinct functional connectivity patterns which can differentiate BD from UD. Totally 23 BD, 22 UD, and 24 HC were recruited to undergo resting-state fMRI scanning. FC between each pair of brain regions was calculated and compared among the three groups, the associations of FC with depressive symptom were also analyzed. Both patient groups showed significantly decreased cerebral-limbic FC located between the default mode network [posterior cingulated gyrus (PCG) and precuneus] and limbic regions (hippocampus, amygdala and thalamus) than HC. Moreover, the BD group exhibited more decreased FC mainly in the cortical regions (middle temporal gyrus, PCG, medial superior frontal gyrus, inferior occipital gyrus and superior temporal gyrus), but the UD group is more associated with limbic alterations. These decreased FCs were negatively correlated with HAMD scores in both BD and UD patients. BD and UD patients demonstrate different patterns of abnormal cerebral-limbic FC, reflected by decreased FC within cerebral cortex and limbic regions in BD and UD, respectively. The distinct FC abnormal pattern of the cerebral-limbic circuit might be applied as biomarkers to differentiate these two depressive patient groups.

Alzheimer\'s patient brain myeloid cells exhibit enhanced aging and unique transcriptional activation

Abstract: Gene expression changes in brain microglia from mouse models of Alzheimer’s disease (AD) are highly characterized and reflect specific myeloid cell activation states that could modulate AD risk or progression. While some groups have produced valuable expression profiles for human brain cells1–4, the cellular clarity with which we now view transcriptional responses in mouse AD models has not yet been realized for human AD tissues due to limited availability of fresh tissue samples and technological hurdles of recovering transcriptomic data with cell-type resolution from frozen samples. We developed a novel method for isolating multiple cell types from frozen post-mortem specimens of superior frontal gyrus for RNA-Seq and identified 66 genes differentially expressed between AD and control subjects in the myeloid cell compartment. Myeloid cells sorted from fusiform gyrus of the same subjects showed similar changes, and whole tissue RNA analyses further corroborated our findings. The changes we observed did not resemble the “damage-associated microglia” (DAM) profile described in mouse AD models5, or other known activation states from other disease models. Instead, roughly half of the changes were consistent with an “enhanced human aging” phenotype, whereas the other half, including the AD risk gene APOE, were altered in AD myeloid cells but not differentially expressed with age. We refer to this novel profile in human Alzheimer’s microglia/myeloid cells as the HAM signature. These results, which can be browsed at research-pub.gene.com/BrainMyeloidLandscape/reviewVersion, highlight considerable differences between myeloid activation in mouse models and human disease, and provide a genome-wide picture of brain myeloid activation in human AD.