Voxel-wise Functional Connectivity Analysis Research Articles

Characteristics of locus coeruleus functional connectivity network in patients with comorbid migraine and insomnia

BackgroundMigraine and insomnia are prevalent conditions that often co-occur, each exacerbating the other and substantially impacting the quality of life. The locus coeruleus (LC), a brainstem region responsible for norepinephrine synthesis, participates in pain modulation, sleep/wake cycles, and emotional regulation, rendering it a potential nexus in the comorbidity of migraine and insomnia. Disruptions in the LC-noradrenergic system have been hypothesized to contribute to the comorbidities of migraine and insomnia, although neuroimaging evidence in humans remains scarce. In this study, we aimed to investigate the intrinsic functional connectivity (FC) network of the LC in patients with comorbid migraine and subjective chronic insomnia and patients with migraine with no insomnia (MnI) using resting-state functional magnetic resonance imaging (rs-fMRI) and seed-based FC analyses.MethodsIn this cross-sectional study, 30 patients with comorbid migraine and chronic insomnia (MI), 30 patients with MnI, and 30 healthy controls (HCs) were enrolled. Participants underwent neuropsychological testing and rs-fMRI. The LC-FC network was constructed using seed-based voxel-wise FC analysis. To identify group differences in LC-FC networks, voxel-wise covariance analysis was conducted with sex and age as covariates. Subsequently, a partial correlation analysis was conducted to probe the clinical relevance of aberrant LC-FC in patients with MI and MnI.ResultsExcept for the insomnia score, no other significant difference was detected in demographic characteristics and behavioral performance between the MI and MnI groups. Compared with HCs, patients with MI exhibited altered LC-FC in several brain regions, including the dorsomedial prefrontal cortex (DMPFC), anterior cerebellum, dorsolateral prefrontal cortex (DLPFC), thalamus, and parahippocampal gyrus (PHG). Lower FC between the LC and DLPFC was associated with greater insomnia severity, whereas higher FC between the LC and DMPFC was linked to longer migraine attack duration in the MI group.ConclusionOur findings reveal the presence of aberrant LC-FC networks in patients with MI, providing neuroimaging evidence of the interplay between these conditions. The identified LC-FC alterations may serve as potential targets for therapeutic interventions and highlight the importance of considering the LC-noradrenergic system in the management of MI.

Flow augmentation therapies preserve brain network integrity and hemodynamics in a canine permanent occlusion model

The acute phase of ischemic stroke presents a critical window for therapeutic intervention, where novel approaches such as hyper-acute cerebral flow augmentation offer promising avenues for neuroprotection. In this study, we investigated the effects of two such therapies, NEH (a combination of norepinephrine and hydralazine) and Sanguinate (pegylated bovine carboxyhemoglobin), on resting-state functional connectivity, global mean signal (GMS), and blood oxygen level-dependent (BOLD) time lag in a pre-clinical canine model of stroke via permanent occlusion of the middle cerebral artery (total of n = 40 IACUC-approved mongrel canines randomly split into control/natural history and two treatment groups). Utilizing group independent component analysis (ICA), we identified and examined the integrity of sensorimotor and visual networks both pre- and post-occlusion, across treatment and control groups. Our results demonstrated that while the control group exhibited significant disruptions in these networks following stroke, the treatment groups showed remarkable preservation of network integrity. Voxel-wise functional connectivity analysis revealed less pronounced alterations in the treatment groups, suggesting maintained neural connections. Notably, the treatments stabilized GMS, with only minimal reductions observed post-occlusion compared to significant decreases in the control group. Furthermore, BOLD time-lag unity plots indicated that NEH and Sanguinate maintained consistent hemodynamic response timing, as evidenced by tighter clustering around the line of unity, suggesting a potential neuroprotective effect. These findings were underscored by robust statistical analyses, including paired T-tests and Mann–Whitney U tests, which confirmed the significance of the connectivity changes observed. The correlation of BOLD time-lag variations with neuroimaging functional biomarkers highlighted the impact of stroke and the efficacy of early therapeutic interventions. Our study supports the further study of flow augmentation therapies such as NEH and Sanguinate in stroke treatment protocols and suggests flow augmentation therapies should be further explored in an effort to improve patient outcomes.

Recent-onset and persistent tinnitus: Uncovering the differences in brain activities using resting-state functional magnetic resonance imaging technologies.

This study aimed to investigate the differences in intra-regional brain activity and inter-regional functional connectivity between patients with recent-onset tinnitus (ROT) and persistent tinnitus (PT) using resting-state functional magnetic resonance imaging (rs-fMRI), including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and voxel-wise functional connectivity (FC). We acquired rs-fMRI scans from 82 patients (25 without recent-onset tinnitus, 28 with persistent tinnitus, and 29 healthy controls). Age, sex, and years of education were matched across the three groups. We performed ALFF, ReHo, and voxel-wise FC analyses for all patients. Compared with the control group, participants with ROT and PT manifested significantly reduced ALFF and ReHo activity within the left and right dorsolateral superior frontal gyrus (SFG) and gyrus rectus (GR). Additional voxel-wise FC revealed decreased connectivity between the dorsolateral SFG (left and right) and the right superior parietal gyrus (SPG), right middle frontal gyrus (MFG), and left medial superior frontal gyrus (mSFG) within these two groups. Significant differences were observed between the ROT and PT groups, with the ROT group demonstrating reduced FC. Our data suggest that patients with PT have more difficulty monitoring external stimuli and reorienting attention than patients with ROT. In addition, patients who perceive higher levels of disruption from tinnitus are more likely to develop persistent and debilitating tinnitus once the tinnitus lasts longer than six months. Therefore, we strongly recommend that clinicians implement effective tinnitus management strategies in patients with ROT as soon as possible.

Functional Coupling between the Fronto-Parietal Network and Default Mode Network Is Associated with Balanced Time Perspective.

Balanced time perspective refers to the ability to flexibly switch between different temporal foci in an adaptive manner according to the current context. Functional connectivity within the default mode network (DMN) has been suggested to support balanced time perspective. The coupling between the DMN and fronto-parietal network (FPN) may drive many important expressions of internally directed cognition. However, it remains unclear whether balanced time perspective is supported by the interaction between the FPN and DMN. To examine these issues, we recruited 91 participants (52 males with mean age of 19.6, and 39 females with mean age of 20.0) to undergo resting-state brain imaging scan and to complete a questionnaire measuring balanced time perspective. Seed-based voxel-wise functional connectivity analyses implicated midline DMN regions including the anterior medial prefrontal cortex (amPFC) and posterior cingulate cortex (PCC) along with the anterior cingulate cortex (ACC), precuneus, and cerebellum in supporting a balanced time perspective. More importantly, functional connectivity between the right amPFC and right dorsal lateral prefrontal cortex (DLPFC) in the FPN was found to associate with balanced time perspective. Our findings suggest the importance of coordinated brain activity in supporting a balanced time perspective.

Altered functional connectivity of cerebellar dentate nucleus in peak-dose dyskinesia in Parkinson's disease.

The cerebellum is associated with the emergence of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD), yet the neural mechanism remains obscure. Our aim was to ascertain the role of functional connectivity (FC) patterns of the cerebellar dentate nucleus (DN) in the pathogenesis of peak-dose dyskinesia in PD. Twenty-three peak-dose dyskinetic PD patients, 27 non-dyskinetic PD patients, and 36 healthy controls (HCs) were enrolled and underwent T1-weighted and resting-state functional magnetic resonance imaging (rs-fMRI) scans after dopaminergic medication intake. We selected left and right DN as the regions of interest and then employed voxel-wise FC analysis and voxel-based morphometry analysis (VBM). The correlations between the altered FC pattern and clinical scores were also examined. Finally, receiver operating characteristic (ROC) curve analysis was performed to assess the potential of DN FC measures as a feature of peak-dose dyskinesia in PD. Dyskinetic PD patients showed excessively increased FC between the left DN and right putamen compared with the non-dyskinetic. When compared with controls, dyskinetic PD patients mainly exhibited increased FC between left DN and bilateral putamen, left paracentral lobule, right postcentral gyrus, and supplementary motor area. Additionally, non-dyskinetic PD patients displayed increased FC between left DN and left precentral gyrus and right paracentral lobule compared with controls. Meanwhile, increased FC between DN (left/right) and ipsilateral cerebellum lobule VIII was observed in both PD subgroups. However, no corresponding alteration in gray matter volume (GMV) was found. Further, a positive correlation between the z-FC values of left DN-right putamen and the Unified Dyskinesia Rating Scale (UDysRS) was confirmed in dyskinetic PD patients. Notably, ROC curve analyses revealed that the z-FC values of left DN-right putamen could be a potential neuroimaging feature identifying dyskinetic PD patients. Our findings demonstrated that the excessively strengthened connectivity of DN-putamen might contribute to the pathophysiological mechanisms of peak-dose dyskinesia in PD.

Functional connectivity of the hippocampus in predicting early antidepressant efficacy in patients with major depressive disorder

BakgroudThe hippocampus is involved in the pathophysiology of major depressive disorder (MDD), and its structure and function have been reported to be related to the antidepressant response. This study aimed to identify relationships between hippocampal functional connectivity (FC) and early improvement in patients with MDD and to further explore the ability of hippocampal FC to predict early efficacy. MethodsThirty-six patients with nonpsychotic MDD were recruited and underwent resting-state functional magnetic resonance imaging scans at baseline. After two weeks of treatment with escitalopram, patients were divided into subgroups with early improved depression (EID, n= 19) and nonimproved depression (NID, n=17) . A voxelwise FC analysis was performed with the bilateral hippocampus as seeds, two-sample t-tests were used to compare hippocampal FC between groups. Receiver operating characteristic (ROC) curves were constructed to determine the best FC measures and optimal threshold for differentiating EID from END. ResultsThe EID group showed significantly higher FC between the left hippocampus and left inferior frontal gyrus and precuneus than the END group. And the left hippocampal FC of these two regions were positively correlated with the reduction ratio of the depressive symptom scores. The ROC curve analysis revealed that summed FC scores for these two regions exhibited the highest area under the curve, with a sensitivity of 0.947 and specificity of 0.882 at a summed score of 0.14. LimitationsThe sample used in this study was relatively small. ConclusionsThese findings demonstrated that FC of the left hippocampus can predict early efficacy of antidepressant.

Resting cerebral oxygen metabolism exhibits archetypal network features.

Standard magnetic resonance imaging approaches offer high‐resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low‐frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual‐echo, pseudocontinuous arterial spin labeling, and blood‐oxygen‐level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain‐wide, CMRO2 low‐frequency fluctuations were subjected to graph‐based and voxel‐wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2 fluctuations exhibited complex, small‐world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel‐wise CMRO2 connectivity also exhibited spatial patterns consistent with four targeted resting‐state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital‐visual). These are the first findings to support the use of calibration‐derived CMRO2 low‐frequency fluctuations for detecting brain‐wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration‐derived oxygen metabolism signals for examining the intrinsic organization of the human brain.

Self-reported experiences of discrimination in older black adults are associated with insula functional connectivity.

Self-reported experiences of discrimination are associated with a number of negative health outcomes. However, the neurobiological correlates of discrimination remain elusive. Recent neuroimaging work suggests that the amygdala is sensitive to forms of social adversity and the insula is involved in assessments of trust. We hypothesized that functional connectivity (FC) of these brain regions may be associated with discrimination in older Black adults. One-hundred and twenty-four nondemented older Black adults participating in the Minority Aging Research Study or the Clinical Core study of the Rush Alzheimer's Disease Center completed a measure of self-reported experiences of discrimination and a 3T MRI brain scan including structural T1 and resting-state fMRI EPIBOLD sequences. The right and left amygdala and insula regions were anatomically delineated as ROIs according to the Harvard-Oxford Brain Atlas and whole-brain voxelwise FC analyses were conducted using default parameters in the CONN toolbox. In regression analyses controlling for demographics and global cognition, self-reported experiences of discrimination were associated with greater FC between the left insula and the bilateral intracalcarine cortex, weaker FC between the left insula and the left dorsolateral prefrontal cortex, and weaker FC between the right insula and the left supplementary motor area. Amygdala analyses yielded no significant findings. Greater self-reported experiences of discrimination are associated with differential insula functional connectivity in older adults. More specifically, results suggest that discrimination is associated with differential connectivity of a key region (the insula) involved in trust perception.

Individual differences in local functional brain connectivity affect TMS effects on behavior

Behavioral effects of transcranial magnetic stimulation (TMS) often show substantial differences between subjects. One factor that might contribute to these inter-individual differences is the interaction of current brain states with the effects of local brain network perturbation. The aim of the current study was to identify brain regions whose connectivity before and following right parietal perturbation affects individual behavioral effects during a visuospatial target detection task. 20 subjects participated in an fMRI experiment where their brain hemodynamic response was measured during resting state, and then during a visuospatial target detection task following 1 Hz rTMS and sham stimulation. To select a parsimonious set of associated brain regions, an elastic net analysis was used in combination with a whole-brain voxel-wise functional connectivity analysis. TMS-induced changes in accuracy were significantly correlated with the pattern of functional connectivity during the task state following TMS. The functional connectivity of the left superior temporal, angular, and precentral gyri was identified as key explanatory variable for the individual behavioral TMS effects. Our results suggest that the brain must reach an appropriate state in which right parietal TMS can induce improvements in visual target detection. The ability to reach this state appears to vary between individuals.

Altered putamen and cerebellum connectivity among different subtypes of Parkinson's disease.

ObjectiveImpairment of basal ganglia (BG)‐thalamo‐cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.MethodsA total of 16 patients with tremor‐dominant (TD) PD, 23 patients with postural instability and gait difficulty‐dominant (PIGD) PD, and 31 HC that underwent functional magnetic resonance imaging were observed. Voxel‐wise FC analysis was performed by computing correlation between bilateral putamen and other voxels within the brain. Correlation analysis was performed between FC strength and clinical symptoms.ResultsCompared with PIGD group, TD group showed increased FC between left putamen and right cerebellum lobule VI and cerebellum crus I, then we compared the cerebellum FC difference among the three groups. The cerebellum lobule VI FC difference was mainly involved in motor related cortex, and the cerebellum crus I FC difference was related to cognition areas. While compared with HC, TD and PIGD groups both had significant FC difference brain areas correlated with motor and cognition symptoms. The connectively of putamen and right cerebellum lobules VI and I showed positive correlation with tremor and Montreal Cognitive Assessment degree of scores, respectively. The connectivity of putamen and sensorimotor cortex had negative correlation with PIGD scores.ConclusionsThe altered connectivity of BG‐cortical circuit in patients with PD was related to PIGD symptoms. Motor and cognitive impairments declined slower in patients with TD PD, which may be related to increased functional connectivity between putamen and cerebellum.

Methamphetamine acutely alters frontostriatal resting state functional connectivity in healthy young adults.

Chronic use of methamphetamine impairs frontostriatal structure and function, which may result in increased incentive-motivational responses to drug cues and decreased regulation of drug-seeking behavior. However, less is known regarding how the drug affects these circuits after acute administration. The current study examined the effects of a single dose of methamphetamine on resting state frontostriatal functional connectivity in healthy volunteers. Participants (n=22, 12 female) completed two sessions in which they received methamphetamine (20mg) and placebo before a resting state scan during functional magnetic resonance imaging. Participants also provided self-report measures of euphoria and stimulation at regular intervals. We conducted seed-based voxelwise functional connectivity analyses using three bilateral striatal seed regions: nucleus accumbens (NAcc), caudate, and putamen and compared connectivity following methamphetamine versus placebo administration. Additionally, we conducted correlational analyses to assess if drug-induced changes in functional connectivity were related to changes in subjective response. Methamphetamine increased NAcc functional connectivity with medial frontal regions (ie, orbitofrontal cortex, medial frontal gyrus, and superior frontal gyrus) and decreased NAcc functional connectivity with subgenual anterior cingulate cortex (ACC). Methamphetamine also increased functional connectivity between putamen and left inferior frontal gyrus (IFG), and individuals who displayed greater drug-induced increase in connectivity reported less euphoria and stimulation. These findings provide important information regarding the effects of methamphetamine on brain function in nonaddicted individuals. Further studies will reveal whether such effects contribute to the abuse potential of the drug and whether they are related to the frontostriatal impairments observed after chronic methamphetamine use.

Genetic contribution of catechol-O-methyltransferase in dorsolateral prefrontal cortex functional changes in the first episode schizophrenia.

Catechol-O-methyltransferase (COMT) gene variants have been reported to be implicated in the pathogenesis of psychotic symptoms in schizophrenia, especially in negative symptoms. These symptoms including apathy, blunted affect, social withdrawal and motor retardation. Neuroimaging studies suggested that negative symptoms appear to be associated with impaired activities of the prefrontal cortex in particular the dorsolateral prefrontal cortex (DLPFC). Given that the COMT gene is highly expressed in the DLPFC, it is poorly understood whether the disease state and COMT val158met polymorphisms have main and interactive effect on the resting state functional connectivity (RSFC) of DLPFC-related pathways. To this end, fifty-five first episode schizophrenia (FES) and fifty-three healthy controls were genotyped using blood samples and underwent magnetic resonance imaging scanning. Seed-based voxel wise functional connectivity analysis was performed by placing bilateral pairs of seeds with DLPFC in area 46 defined by Brodmann's atlas. A two-ways ANCOVA model was performed with val158met genotypes and disease state as the between subjects factors. Significant disease × COMT interactive effect was found mainly in the left DLPFC with the left anterior cingulate cortex, right precuneus, right superior parietal gyrus, which were overlapped with disease main effect. And these RSFC had positive correlations with affective blunting scores in FES patients with val homozygotes, but not with met carriers. Our results showed that the disease and the genotypes in COMT gene have significant interactive effect on RSFC of DLPFC and provided evidence for a disease-dependent pattern of gene action.

Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: Preliminary results

Biomarkers of inflammation, including inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), are reliably increased in a subset of patients with depression, anxiety disorders and post-traumatic stress disorder (PTSD). Administration of innate immune stimuli to laboratory subjects and the associated release of inflammatory cytokines has been shown to affect brain regions involved in fear, anxiety and emotional processing such as the amygdala. However, the role of inflammation in altered circuitry involving amygdala and other brain regions and its subsequent contribution to symptom severity in depression, anxiety disorders and PTSD is only beginning to be explored. Herein, medically-stable, currently unmedicated outpatients with a primary diagnosis of major depressive disorder (MDD; n = 48) underwent resting-state functional MRI (rfMRI) to determine whether altered connectivity between the amygdala and whole brain was observed in a subset of patients with high inflammation and symptoms of anxiety. Whole-brain, voxel-wise functional connectivity analysis of the right and left amygdala as a function of inflammation (plasma CRP concentrations) revealed that increased CRP predicted decreased functional connectivity between right amygdala and left ventromedial prefrontal cortex (vmPFC) (corrected p < 0.05). Amygdala-vmPFC connectivity was, in turn, negatively correlated with symptoms of anxiety (r = −0.33, df = 46, p = 0.022). In exploratory analyses, relationships between low amygdala-vmPFC connectivity and high anxiety were only observed in patients with a secondary diagnosis of an anxiety disorder or PTSD (r = −0.54 to −0.87, p < 0.05). More work is needed to understand the role of inflammation and its effects on amygdala-vmPFC circuitry and symptoms of anxiety in MDD patients with comorbid anxiety disorders or PTSD.

Functional Connectivity Changes in Systemic Lupus Erythematosus: A Resting-State Study.

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

Increased Alcohol Seeking in Mice Lacking Gpr88 Involves Dysfunctional Mesocorticolimbic Networks

BackgoundAlcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively sought for prevention and treatment. The orphan G protein–coupled receptor GPR88 is enriched in mesocorticolimbic pathways, and Gpr88 knockout mice show hyperactivity and risk-taking behavior, but a potential role for this receptor in drug abuse has not been examined. MethodsWe tested Gpr88 knockout mice for alcohol-drinking and -seeking behaviors. To gain system-level understanding of their alcohol endophenotype, we also analyzed whole-brain functional connectivity in naïve mice using resting-state functional magnetic resonance imaging. ResultsGpr88 knockout mice showed increased voluntary alcohol drinking at both moderate and excessive levels, with intact alcohol sedation and metabolism. Mutant mice also showed increased operant responding and motivation for alcohol, while food and chocolate operant self-administration were unchanged. Alcohol place conditioning and alcohol-induced dopamine release in the nucleus accumbens were decreased, suggesting reduced alcohol reward in mutant mice that may partly explain enhanced alcohol drinking. Seed-based voxelwise functional connectivity analysis revealed significant remodeling of mesocorticolimbic centers, whose hallmark was predominant weakening of prefrontal cortex, ventral tegmental area, and amygdala connectional patterns. Also, effective connectivity from the ventral tegmental area to the nucleus accumbens and amygdala was reduced. ConclusionsGpr88 deletion disrupts executive, reward, and emotional networks in a configuration that reduces alcohol reward and promotes alcohol seeking and drinking. The functional connectivity signature is reminiscent of alterations observed in individuals at risk for AUD. The Gpr88 gene, therefore, may represent a vulnerability/resilience factor for AUD, and a potential drug target for AUD treatment.

Local and Extensive Neuroplasticity in Carpal Tunnel Syndrome: A Resting-State fMRI Study

Carpal tunnel syndrome (CTS) is a most common peripheral nerve entrapment neuropathy characterized by sensorimotor deficits in median nerve innervated digits. Block-design task-related functional magnetic resonance imaging (fMRI) studies have been used to investigate CTS-related neuroplasticity in the primary somatosensory cortices. However, considering the persistence of digital paresthesia syndrome caused by median nerve entrapment, spontaneous neuronal activity might provide a better understanding of CTS-related neuroplasticity, which remains unexplored. The present study aimed to investigate both local and extensive spontaneous neuronal activities with resting-state fMRI. A total of 28 bilateral CTS patients and 24 normal controls were recruited, and metrics, including amplitude of low-frequency fluctuation (ALFF) and voxel-wise functional connectivity (FC), were used to explore synaptic activity at different spatial scales. Correlations with clinical measures were further investigated by linear regression. Decreased amplitudes of low-frequency fluctuation were observed in the bilateral primary sensory cortex (SI) and secondary sensory cortex (SII) in CTS patients (AlphaSim corrected P < .05). This was found to be negatively related to the sensory thresholds of corresponding median nerve innervated fingers. In the voxel-wise FC analysis, with predefined seed regions of interest in the bilateral SI and primary motor cortex, we observed decreased interhemispheric and increased intrahemispheric FC. Additionally, both interhemispheric and intrahemispheric FC were found to be significantly correlated with the mean ALFF.

Amygdala Atrophy and Its Functional Disconnection with the Cortico-Striatal-Pallidal-Thalamic Circuit in Major Depressive Disorder in Females.

BackgroundMajor depressive disorder (MDD) is approximately twice as common in females than males. Furthermore, female patients with MDD tend to manifest comorbid anxiety. Few studies have explored the potential anatomical and functional brain changes associated with MDD in females. Therefore, the purpose of the present study was to investigate the anatomical and functional changes underlying MDD in females, especially within the context of comorbid anxiety.MethodsIn this study, we recruited antidepressant-free females with MDD (N = 35) and healthy female controls (HC; N = 23). The severity of depression and anxiety were evaluated by the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Structural and resting-state functional images were acquired on a Siemens 3.0 Tesla scanner. We compared the structural volumetric differences between patients and HC with voxel-based morphometry (VBM) analyses. Seed-based voxel-wise correlative analyses were used to identify abnormal functional connectivity. Regions with structural deficits showed a significant correlation between gray matter (GM) volume and clinical variables that were selected as seeds. Furthermore, voxel-wise functional connectivity analyses were applied to identify the abnormal connectivity relevant to seed in the MDD group.ResultsDecreased GM volume in patients was observed in the insula, putamen, amygdala, lingual gyrus, and cerebellum. The right amygdala was selected as a seed to perform connectivity analyses, since its GM volume exhibited a significant correlation with the clinical anxiety scores. We detected regions with disrupted connectivity relevant to seed primarily within the cortico-striatal-pallidal-thalamic circuit.ConclusionsAmygdaloid atrophy, as well as decreased functional connectivity between the amygdala and the cortico-striatal-pallidal-thalamic circuit, appears to play a role in female MDD, especially in relation to comorbid anxiety.

Gray Matter Loss and Related Functional Connectivity Alterations in A Chinese Family With Benign Adult Familial Myoclonic Epilepsy.

Benign adult familial myoclonic epilepsy (BAFME) is a non-progressive monogenic epilepsy syndrome. So far, the structural and functional brain reorganizations in BAFME remain uncharacterized. This study aims to investigate gray matter atrophy and related functional connectivity alterations in patients with BAFME using magnetic resonance imaging (MRI).Eleven BAFME patients from a Chinese pedigree and 15 matched healthy controls were enrolled in the study. Optimized voxel-based morphometric and resting-state functional MRI approaches were performed to measure gray matter atrophy and related functional connectivity, respectively. The Trail-Making Test-part A and part B, Digit Symbol Test (DST), and Verbal Fluency Test (VFT) were carried out to evaluate attention and executive functions.The BAFME patients exhibited significant gray matter loss in the right hippocampus, right temporal pole, left orbitofrontal cortex, and left dorsolateral prefrontal cortex. With these regions selected as seeds, the voxel-wise functional connectivity analysis revealed that the right hippocampus showed significantly enhanced connectivity with the right inferior parietal lobule, bilateral middle cingulate cortex, left precuneus, and left precentral gyrus. Moreover, the BAFME patients showed significant lower scores in DST and VFT tests compared with the healthy controls. The gray matter densities of the right hippocampus, right temporal pole, and left orbitofrontal cortex were significantly positively correlated with the DST scores. In addition, the gray matter density of the right temporal pole was significantly positively correlated with the VFT scores, and the gray matter density of the right hippocampus was significantly negatively correlated with the duration of illness in the patients.The current study demonstrates gray matter loss and related functional connectivity alterations in the BAFME patients, perhaps underlying deficits in attention and executive functions in the BAFME.

Altered corticostriatal functional connectivity in individuals with high social anhedonia.

Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia. Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect. Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression. Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.

Voxel-Wise Functional Connectomics Using Arterial Spin Labeling Functional Magnetic Resonance Imaging: The Role of Denoising.

The objective of this study was to investigate voxel-wise functional connectomics using arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI). Since ASL signal has an intrinsically low signal-to-noise ratio (SNR), the role of denoising is evaluated; in particular, a novel denoising method, dual-tree complex wavelet transform (DT-CWT) combined with the nonlocal means (NLM) algorithm is implemented and evaluated. Simulations were conducted to evaluate the performance of the proposed method in denoising images and in detecting functional networks from noisy data (including the accuracy and sensitivity of detection). In addition, denoising was applied to in vivo ASL datasets, followed by network analysis using graph theoretical approaches. Efficiencies cost was used to evaluate the performance of denoising in detecting functional networks from in vivo ASL fMRI data. Simulations showed that denoising is effective in detecting voxel-wise functional networks from low SNR data and/or from data with small total number of time points. The capability of denoised voxel-wise functional connectivity analysis was also demonstrated with in vivo data. We concluded that denoising is important for voxel-wise functional connectivity using ASL fMRI and that the proposed DT-CWT-NLM method should be a useful ASL preprocessing step.