Inferior Frontal Orbital Gyrus Research Articles

Brain network centrality and connectivity are associated with clinical subtypes and disease progression in Parkinson's disease.

To investigate brain network centrality and connectivity alterations in different Parkinson's disease (PD) clinical subtypes using resting-state functional magnetic resonance imaging (RS-fMRI), and to explore the correlation between baseline connectivity changes and the clinical progression. Ninety-two PD patients were enrolled at baseline, alongside 38 age- and sex-matched healthy controls. Of these, 85 PD patients underwent longitudinal assessments with a mean of 2.75 ± 0.59 years. Two-step cluster analysis integrating comprehensive motor and non-motor manifestations was performed to define PD subtypes. Degree centrality (DC) and secondary seed-based functional connectivity (FC) were applied to identify brain network centrality and connectivity changes among groups. Regression analysis was used to explore the correlation between baseline connectivity changes and clinical progression. Cluster analysis identified two main PD subtypes: mild PD and moderate PD. Two different subtypes within the mild PD were further identified: mild motor-predominant PD and mild-diffuse PD. Accordingly, the disrupted DC and seed-based FC in the left inferior frontal orbital gyrus and left superior occipital gyrus were severe in moderate PD. The DC and seed-based FC alterations in the right gyrus rectus and right postcentral gyrus were more severe in mild-diffuse PD than in mild motor-predominant PD. Moreover, disrupted DC were associated with clinical manifestations at baseline in patients with PD and predicted motor aspects progression over time. Our study suggested that brain network centrality and connectivity changes were different among PD subtypes. RS-fMRI holds promise to provide an objective assessment of subtype-related connectivity changes and predict disease progression in PD.

Dynamical alterations of brain function and gut microbiome in weight loss.

Intermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis. In this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples. Our results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes. There was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

Links among genetic variants and hierarchical brain structural and functional networks for antidepressant treatment: A multivariate study

BackgroundAntidepressant treatment effects are strongly heritable and have substantial effects on brain function and structure, but the underlying mechanisms are still poorly understood. In this research, we aimed to evaluate the factors of single nucleotide polymorphisms (SNPs) and hierarchical brain structural and functional networks that were associated with antidepressant treatment. Moreover, we further explored the correlations and mediation pattern among “brain structure-brain function-gene” in major depressive disorder (MDD). MethodsWe analysed 405 SNPs and rich club/feeder/local connections of hierarchical structural and functional networks with three-way parallel independent component analysis in 179 MDD patients. The group-discriminative independent components of the three modalities between responders and non-responders of antidepressant treatment were identified. Pearson correlations and mediation analysis were further utilized to investigate the associations among SNPs and connections of the structural and functional networks. ResultsNotably, correlations with antidepressant treatment outcomes were found in structural, functional and SNP modalities simultaneously. The features of group-discriminative independent components included the shared feeder connections of hub regions with the inferior frontal orbital gyrus and amygdala in structural and functional modalities and genes enriched in circadian rhythmic processes and dopaminergic synapse pathways. The structural feeder network displayed close correlations with SNPs and the functional feeder network. Furthermore, the structural feeder network could mediate the association between SNPs and the functional feeder network, implying that genetic variants might influence brain function by affecting brain structure in MDD. ConclusionsThese findings provide potential biomarkers for antidepressant therapy and provide a better grasp of the associations among SNPs and hierarchical structural and functional networks in MDD.

Abnormal Voxel-Based Degree Centrality in Patients With Postpartum Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

Postpartum depression (PPD) is a major public health concern with significant consequences for mothers, their children, and their families. However, less is known about its underlying neuropathological mechanisms. The voxel-based degree centrality (DC) analysis approach provides a new perspective for exploring the intrinsic dysconnectivity pattern of whole-brain functional networks of PPD. Twenty-nine patients with PPD and thirty healthy postpartum women were enrolled and received resting-state functional magnetic resonance imaging (fMRI) scans in the fourth week after delivery. DC image, clinical symptom correlation, and seed-based functional connectivity (FC) analyses were performed to reveal the abnormalities of the whole-brain functional network in PPD. Compared with healthy controls (HCs), patients with PPD exhibited significantly increased DC in the right hippocampus (HIP.R) and left inferior frontal orbital gyrus (ORBinf.L). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the above two brain regions is all over 0.7. In the seed-based FC analyses, the PPD showed significantly decreased FC between the HIP.R and right middle frontal gyrus (MFG.R), between the HIP.R and left median cingulate and paracingulate gyri (DCG.L), and between the ORBinf.L and the left fusiform (FFG.L) compared with HCs. The PPD showed significantly increased FC between the ORBinf.L and the right superior frontal gyrus, medial (SFGmed.R) compared with HCs. Mean FC between the HIP.R and DCG.L positively correlated with EDPS scores in the PPD group. This study provided evidence of aberrant DC and FC within brain regions in patients with PPD, which was associated with the default mode network (DMN) and limbic system (LIN). Identification of these above-altered brain areas may help physicians to better understand neural circuitry dysfunction in PPD.

Aberrant interhemispheric functional connectivity and cerebral blood flow in vascular dementia (VD) and non‐amyloid mild cognitive impairment (NamyMCI)

AbstractBackgroundPrevious studies have demonstrated that functional connectivity and relative cerebral blood flow were altered in patients suffered from Alzheimer’s disease (AD) and Mild cognitive impairment (MCI). However, the application on vascular dementia (VD) and non‐amyloid mild cognitive impairment (VMCI) are still unclear.Method65 participants (18 healthy controls HC, 16 AD, 18 NamyMCI, 13 vascular dementia (VD)) were recruited, from the university hospital memory clinic, to undergo MRI scanning. All participants underwent structural MRI, resting state functional MRI (rs‐fMRI) scanning and pseudo continuous arterial spin labelling (pCASL) with post‐labelling delay time at 2000ms in the same session. Voxel Mirrored Homotopic Connectivity (VMHC) was calculated based on the method used by Kelly et al., 2011 [1] and Zuo et al., 2010 [2]. The analysis of pCASL images performed using ASL‐MRICloud by Li et al., 2017 [3]. White matter hypointensities on T1‐weighted 3D anatomical images of each individual was calculated using FreeSurfer image analysis suite 6.0. Group differences in VMHC, absolute CBF and relative CBF were determined by performing whole brain voxel‐wise ANCOVA analysis on subject‐specific VMHC maps, absolute CBF maps and relative CBF maps respectively, with age, gender and GM volume as covariates. To identify the significant associations between IFC and CBF, a voxel‐wise correlation analysis was conducted using the DPABI v 4.0.ResultBoth IFC and CBF were reduced in AD group. However there is no significant relationship found in correlation analysis. For NamyMCI group, negative correlation were found in precuneus, cuneus, calcarine, superior frontal gyrus and insula. For VD, positive correlation was found in superior frontal gyrus, inferior frontal orbital gyrus, rolandic operculum and superior temporal gyrus. Also, the T1 white matter hypointensity volume was significantly larger than that of the other groups (p<0.001).ConclusionIFC reduction in AD was independent to CBF reduction, probably related amyloid deposition. For NamyMCI, negative correlation suggested that CBF increases to compensate the attenuated IFC to maintain daily functions. For VD, CBF reduction relates positively with IFC, suggested the CBF reduction is one of the factors contributed to IFC reduction in VD.

Amplitude of Low-Frequency Fluctuation in Multiple Frequency Bands in Tension-Type Headache Patients: A Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: Tension-type headache (TTH), the most prevalent primary headache disorder, imposes an enormous burden on the people of the world. The quest to ease suffering from this neurological disorder has sustained research interest. The present study aimed at evaluating the amplitude of low-frequency oscillations (LFOs) of the brain in multiple frequency bands in patients with TTH.Methods: To address this question, 63 participants were enrolled in the study, including 32 TTH patients and 31 healthy controls (HCs). For all the participants, amplitude of low-frequency fluctuation (ALFF) was measured in six frequency bands (conventional frequency bands, 0.01–0.08 Hz; slow-2, 0.198–0.25 Hz; slow-3, 0.073–0.198 Hz; slow-4, 0.027–0.073 Hz; slow-5, 0.01–0.027 Hz; and slow-6, 0–0.01 Hz), and the differences between TTH patients and HCs were examined. To explore the relationship between the altered ALFF brain regions in the six frequency bands and the Visual Analog Scale (VAS) score in the TTH patients, Pearson’s correlation analysis was performed.Results: In all the six frequency bands, a decreased ALFF value was detected, and regions showing reduced ALFF values were mostly located in the middle frontal gyrus and superior gyrus. A frequency-dependent alternating characterization of intrinsic brain activity was found in the left caudate nucleus in the slow-2 band of 0.198–0.25 Hz and in the right inferior frontal orbital gyrus in the slow-5 band of 0.01–0.027 Hz. For the correlation results, both the left anterior cingulate and paracingulate gyri and right superior parietal gyrus showed a positive correlation with the VAS score in the slow-4 frequency band of 0.027–0.073 Hz.Conclusion: The ALFF alterations in the brain regions of TTH patients are involved in pain processing. The altered LFOs in the multiple regions may help promote the understanding of the pathophysiology of TTH. These observations could also allow the future treatment of TTH to be more directional and targeted and could promote the development of TTH treatment.

Abnormal Degree Centrality in White Matter Hyperintensities: A Resting-State Functional Magnetic Resonance Imaging Study.

Background: White matter hyperintensities (WMHs) are a common occurrence with aging and are associated with cognitive impairment. However, the neurobiological mechanisms of WMHs remain poorly understood. Functional magnetic resonance imaging (fMRI) is a prominent tool that helps in non-invasive examinations and is increasingly used to diagnose neuropsychiatric diseases. Degree centrality (DC) is a common and reliable index in fMRI, which counts the number of direct connections for a given voxel in a network and reflects the functional connectivity within brain networks. We explored the underlying mechanism of cognitive impairment in WMHs from the perspective of DC.Methods: A total of 104 patients with WMHs and 37 matched healthy controls (HCs) were enrolled in the current study. All participants underwent individual and overall cognitive function tests and resting-state fMRI (rs-fMRI). WMHs were divided into three groups (39 mild WMHs, 37 moderate WMHs, and 28 severe WMHs) according to their Fazekas scores, and the abnormal DC values in the WMHs and HCs groups were analyzed.Results: There was a significant difference in the right inferior frontal orbital gyrus and left superior parietal gyrus between the WMHs and HCs groups. The functional connectivity between the right inferior frontal orbital gyrus and left inferior temporal gyrus, left superior parietal gyrus, and left parietal inferior gyrus was also different in the WMHs group.Conclusion: The change in DC value may be one of the underlying mechanisms of cognitive impairment in individuals with WMHs, which provides us with a new approach to delaying cognitive impairment in WMHs.

Spatial Expression Pattern of ZNF391 Gene in the Brains of Patients With Schizophrenia, Bipolar Disorders or Major Depressive Disorder Identifies New Cross-Disorder Biotypes: A Trans-Diagnostic, Top-Down Approach.

The results generated from large psychiatric genomic consortia show us some new vantage points to understand the pathophysiology of psychiatric disorders. We explored the potential of integrating the transcription output of the core gene underlying the commonality of psychiatric disorders with a clustering algorithm to redefine psychiatric disorders. Our results showed that an extended MHC region was associated with the common factor of schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) at the level of genomic significance, with rs7746199 (P = 4.905e-08), a cis-eQTL to the gene ZNF391, pinpointed as a potential causal variant driving the signals in the region. Gene expression pattern of ZNF391 in the brain led to the emergence of 3 biotypes, independent of disorder. The 3 biotypes performed significantly differently in working memory and demonstrated different gray matter volumes in the right inferior frontal orbital gyrus (RIFOG), with a partial causal pathway arising from ZNF391 to RIFOG to working memory. Our study illustrates the potential of a trans-diagnostic, top-down approach in understanding the commonality of psychiatric disorders.

Observing Plasticity of the Auditory System: Volumetric Decreases Along with Increased Functional Connectivity in Aspiring Professional Musicians.

Playing music relies on several sensory systems and the motor system, and poses strong demands on control processes, hence, offering an excellent model to study how experience can mold brain structure and function. Although most studies on neural correlates of music expertise rely on cross-sectional comparisons, here we compared within-person changes over time in aspiring professionals intensely preparing for an entrance exam at a University of the Arts to skilled amateur musicians not preparing for a music exam. In the group of aspiring professionals, we observed gray-matter volume decrements in left planum polare, posterior insula, and left inferior frontal orbital gyrus over a period of about 6 months that were absent among the amateur musicians. At the same time, the left planum polare, the largest cluster of structural change, showed increasing functional connectivity with left and right auditory cortex, left precentral gyrus, left supplementary motor cortex, left and right postcentral gyrus, and left cingulate cortex, all regions previously identified to relate to music expertise. In line with the expansion–renormalization pattern of brain plasticity (Wenger et al., 2017a. Expansion and renormalization of human brain structure during skill acquisition. Trends Cogn Sci. 21:930–939.), the aspiring professionals might have been in the selection and refinement period of plastic change.

Atrophy of right inferior frontal orbital gyrus and frontoparietal functional connectivity abnormality in depressed suicide attempters.

Although structural and functional brain abnormalities have been observed in depressed suicide attempters (DS), structural deficits and functional impairments together with their relationship in DS remain unclear. To clarify this issue, we aimed to examine the differences in gray matter (GM) alteration, corresponding functional connectivity (FC) change, and their relationship between DS and depressed non-suicide attempters (NDS). Sixty-eight DS, 119 NDS and 103 healthy controls were enrolled and subjected to magnetic resonance imaging scans. The patients were evaluated using the 17-item Hamilton Rating Scale for Depression (HRSD) and Nurses' Global Assessment of Suicide Risk (NGASR) scale. Both voxel-based morphometry and resting-state FC analyses were performed based on functional and structural imaging data. Compared with NDS, the DS group showed reduced GM volume in the right inferior frontal orbital gyrus (IFOG) and left caudate (CAU) but increased GM volume in the left calcarine fissure, weaker negative right IFOG-left rectus gyrus (REG) FC, and weaker positive right IFOG-left inferior parietal lobule (IPL) FC. In DS, the GM volume of the right IFOG and left CAU was negatively correlated with NGASR and HRSD scores, respectively; the right IFOG-left IPL FC was negatively correlated with cognitive factor scores; and the GM volume of the right IFOG was positively correlated with IFOG-REG and IFOG-IPL FC. Our findings indicate that structural deficit with its related functional alterations in brain circuits converged in right IFOG centralized pathways and may play a central role in suicidal behaviors in depression.

Ischemic Stroke in Pontine and Corona Radiata: Location Specific Impairment of Neural Network Investigated With Resting State fMRI.

Objective: This study aims to investigate location-specific functional remodeling following ischemic stroke in pons and corona radiata.Methods: This study was approved by the local Institutional Review Board. Written consent was obtained from each of the participants prior to the MRI examination. Thirty six subjects with first ever acute ischemic stroke in pons (PS, n = 15, aged 62.8 ± 11.01 years) or corona radiata (CRS, n = 21, aged 59.33 ± 13.84 years) as well as 30 age and sex matched healthy controls (HC, n = 30, aged 60 ± 6.43 years) were examined with resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and degree centrality (DC) were calculated using a voxel-based approach. Intergroup differences in ReHo and DC were explored using a permutation test with a threshold-free cluster enhancement (PT TFCE, number of permutations = 1,000, family-wise error rate (FWER) < 0.05).Results: ReHo and DC alterations were identified in distributed anatomies for both PS and CRS groups. DC mainly increased in the bilateral anterior and posterior cingulate cortex, the inferior frontal-orbital gyrus, and decreased in the bilateral cuneus, calcarine, and the precuneus, while ReHo mainly decreased in the precentral and the postcentral gyri, inferior parietal lobules, precuneus, posterior cingulate cortex, and the superior occipital gyrus. PS and CRS groups were not significantly different in ReHo or DC (FWER > 0.05).Conclusions: Focal ischemic stroke in pons or corona radiata leads to extensive alterations in the functional network centrality. IS-induced network remodeling is more anatomy-specific than pathway-specific, which may underpin the clinicotopographical profiles during the disease dynamic. Approaches targeting neural pathway and functional connectivity may shed light on a better characterization and management innovation of ischemic stroke.

Abnormal Alterations of Regional Spontaneous Neuronal Activity in Inferior Frontal Orbital Gyrus and Corresponding Brain Circuit Alterations: A Resting-State fMRI Study in Somatic Depression.

Background: Major depressive disorders often involve somatic symptoms and have been found to have fundamental differences from non-somatic depression (NSD). However, the neural basis of this type of somatic depression (SD) is unclear. The aim of this study is to use the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses to examine the abnormal, regional, spontaneous, neuronal activity and the corresponding brain circuits in SD patients. Methods: 35 SD patients, 25 NSD patients, and 27 matched healthy controls were selected to complete this study. The ALFF and seed-based FC analyses were employed, and the Pearson correlation was determined to observe possible clinical relevance. Results: Compared with NSD, the SD group showed a significant ALFF increase in the right inferior temporal gyrus; a significant ALFF decrease in left hippocampus, right inferior frontal orbital gyrus and left thalamus; and a significant decrease in the FC value between the right inferior frontal orbital gyrus and the left inferior parietal cortex (p < 0.05, corrected). Within the SD group, the mean ALFF value of the right inferior frontal orbital gyrus was associated with the anxiety factor scores (r = –0.431, p = 0.010, corrected). Conclusions: Our findings suggest that abnormal differences in the regional spontaneous neuronal activity of the right inferior frontal orbital gyrus were associated with dysfunction patterns of the corresponding brain circuits during rest in SD patients, including the limbic-cortical systems and the default mode network. This may be an important aspect of the underlying mechanisms for pathogenesis of SD at the neural level.

Epigenetic Changes of FKBP5 as a Link Connecting Genetic and Environmental Risk Factors with Structural and Functional Brain Changes in Major Depression.

The gene for the glucocorticoid receptor regulator FK506 binding protein 5 (FKBP5) plays a role for risk, response to treatment, and changes in brain areas in major depressive disorder (MDD). Chronic stress is associated with lower methylation of FKBP5. Our aim was to investigate whether methylation of FKBP5 reflected exposure to childhood adversity in MDD and controls and whether it was associated with structure and function of emotional processing regions. FKBP5 intron 7 GR response element region methylation and rs1360780 allelic status were assessed from whole blood in 56 MDD adults and 50 controls. Using magnetic resonance imaging, we assessed gray matter concentration of selected areas and their function during valence recognition of emotional images. Childhood adversity was investigated using the Childhood Trauma Questionnaire. In MDD patients carrying the high-risk T allele of rs1360780, lower methylation of FKBP5 was predicted by childhood adversity (F=4.95, p=0.04). In all participants, lower FKBP5 intron methylation levels were associated with reduced gray matter concentration in the inferior frontal orbital gyrus bilaterally (Wald chi-square=11.93, pFDR<0.01) and, in MDD, with its bilaterally higher activation during valence recognition (Wald chi-square=5.58, p=0.02). Activation of this region, regardless of side, was found to be lower in MDD compared to controls (Wald chi-square=3.88, p=0.049) and to be inversely correlated with depression severity (Wald chi-square=4.65, p=0.03). Our findings support the hypothesis that, in genetically predisposed individuals carrying a high-risk variant of the gene, childhood maltreatment might induce demethylation of FKBP5. This is in turn associated with structural and functional changes in the inferior frontal orbital gyrus, a relevant area for the clinical symptoms of MDD.

Resting Brain Activity Related to Dispositional Mindfulness: a PET Study

Mindfulness denotes a state of consciousness characterized by receptive attention to and awareness of present events and experiences. As a personality trait, it constitutes the ability to become aware of mental activities such as sensations, images, feelings, and thoughts, and to disengage from judgment, conditioned emotions, and their cognitive processing or automatic inhibition. Default brain activity reflects the stream of consciousness and sense of self at rest. Analysis of brain activity at rest in persons with mindfulness propensity may help to elucidate the neurophysiological basis of this important mental trait. The sample consisted of 32 persons—23 with mental disorders and 9 healthy controls. Dispositional mindfulness (DM) was operationalized by Mindful Attention Awareness Scale (MAAS). Brain activity at rest with eyes closed was assessed by fluorodeoxyglucose positron emission tomography (F-18-FDG PET). After adjustment for depression, anxiety, age and years of education, resting glucose metabolism in superior parietal lobule and left precuneus/Brodmann area (BA) 7 was positively associated with DM. Activity of the left inferior frontal orbital gyrus (BA 47) and bilateral anterior thalamus were inversely associated with DM. DM appears to be associated with increased metabolic activity in some core area of the default mode network (DMN) and areas connected to the DMN, such as BA 7, hosting sense of self functions. Hypometabolism on the other hand was found in some nodes connected to the DMN, such as left inferior frontal orbital gyrus and bilateral thalamus, commonly related to functions of memory retrieval, decision making, or outward attention.

Lesion-symptom mapping of a complex figure copy task: A large-scale PCA study of the BCoS trial.

Complex figure copying is a commonly used neuropsychological test. Here we explored the neural basis of the factors underlying complex figure copying (CFC), using data from the Birmingham Cognitive Screen (BCoS) in a large group of sub-acute, ischemic stroke patients (239). We computed two analyses: in the first we assessed the contribution of co-morbid deficits (i.e. in gesture processing, object use, visual neglect, pictures naming and sustained attention) to the lesions associated with CFC. In a second analysis a Principle Component Analysis (PCA) was used to isolate different underlying task components and to link to clinical neuroimaging scans. A voxel-based morphometry (VBM) analysis showed that poor CFC performance was associated with lesions to bi-lateral thalamus, lingual, right fusiform and right inferior parietal cortices (rIPC). The latter association with the posterior parietal cortex was diminished after controlling for neglect. Follow up analysis showed the neglect partially mediated the correlation of CFC and rIPC. The PCA revealed three main underlying components: (1) a component associated with high-level motor control common to different measures of apraxia and linked to the left postcentral gyrus, the right thalamus and middle frontal gyrus; (2) a visuo-motor transformation component unique to the CFC and associated with lesions to the posterior occipital and sensory cortices; (3) a component associated with multistep object use tasks which was correlated with lesions to the left inferior frontal orbital gyrus, the right fusiform and cerebellum. Using clinical symptoms, cognitive profiles and lesion mapping we showed that beyond visual perception, CFC performance is supported by three functional networks: one for high-level motor control, a visuo-motor transformation component, and multistep object use network.