Seed-based Connectivity Analysis Research Articles

Intrinsic differences in insular circuits moderate the negative association betweennicotine dependence andcingulate-striatal connectivity strength.

The development of brain-based biomarkers to assess nicotine dependence severity and treatment efficacy are essential to improve the current marginally effective treatment outcomes. Cross-sectional resting state functional connectivity (rsFC) studies in humans identified a circuit between the dorsal anterior cingulate cortex and the ventral striatum that negatively correlated with increased nicotine dependence severity but was unaffected by acute nicotine administration, suggesting a trait marker of addiction. However, whether this trait circuit dysregulation is predispositional to or resultant from nicotine dependence is unclear. Using a rat model of nicotine dependence with longitudinal fMRI measurements, we assessed the relationship between ACC-striatal rsFC and nicotine dependence severity. Data-driven modularity-based parcellation of the rat medial prefrontal cortex (mPFC) combined with seed-based connectivity analysis with the striatum recapitulated the cingulate-striatum relationship observed in humans. Furthermore, the relationship between cingulate-striatal brain circuits and nicotine dependence severity as indexed by the intensity of precipitated withdrawal, was fully statistically moderated by a predispositional insular-frontal cortical functional circuit. These data suggest that the identified trans-species ACC-striatal circuit relationship with nicotine dependence severity is dysregulated following chronic nicotine administration-induced dependence and may be biased by individual differences in predispositional insula-based striatal-frontal circuits, highlighting the circuit's potential as a biomarker of dependence severity.

Alterations in Amygdala Connectivity in Internet Addiction Disorder

Recent studies have revealed structural and functional abnormalities in amygdala due to Internet addiction (IA) associated with emotional disturbance. However, the role of amygdala connectivity that is responsible for emotion-cognition interactions is largely unknown in IA. This study aims to explore the amygdala connectivity abnormalities in IA. The functional and structural connectivity of bilateral amygdala were examined using seed-based connectivity analysis, and the structural integrity on white mater tracts passing through amygdala was also examined. Additionally, a correlation analysis was performed to investigate the relationship between brain connectivity and duration of IA. We found that IA subjects had decreased negative functional connectivity (FC) between amygdala and dorsolateral prefrontal cortex (DLPFC), and had increased negative FC between amygdala and precuneus and superior occipital gyrus (SOG). While IA subjects had decreased positive FC between amygdala and anterior cingulate cortex (ACC), and had increased positive FC between amygdala and thalamus. The FC between left amygdala and right DLPFC had significant correlation with duration of IA. The structural connectivity and integrity between amygdala and ACC were also decreased in IA subjects. These findings indicate that the amygdala connectivity is altered in IA subjects. The altered FC of amygdala-DLPFC is associated with duration of IA.

Resting-State Functional Connectivity of the Thalamus in Complete Spinal Cord Injury

Background. Neuroimaging studies of spinal cord injury (SCI) have mostly examined the functional organization of the cortex, with only limited focus on the subcortical substrates of the injury. However, thalamus is an important modulator and sensory relay that requires investigation at a subnuclei level to gain insight into the neuroplasticity following SCI. Objective. To use resting-state functional magnetic resonance imaging to examine the functional connectivity (FC) of thalamic subnuclei in complete SCI patients. Methods. A seed-based connectivity analysis was applied for 3 thalamic subnuclei: pulvinar, mediodorsal, and ventrolateral nucleus in each hemisphere. A nonparametric 2-sample t test with permutations was applied for each of the 6 thalamic seeds to compute FC differences between 22 healthy controls and 19 complete SCI patients with paraplegia. Results. Connectivity analysis showed a decrease in the FC of the bilateral mediodorsal nucleus with right superior temporal gyrus and anterior cingulate cortex in the SCI group. Similarly, the left ventrolateral nucleus exhibited decreased FC with left superior temporal gyrus in SCI group. In contrast, left pulvinar nucleus demonstrated an increase in FC with left inferior frontal gyrus and left inferior parietal lobule in SCI group. Our findings also indicate a negative relationship between postinjury durations and thalamic FC to regions of sensorimotor and visual cortices, where longer postinjury durations (~12 months) is associated with higher negative connectivity between these regions. Conclusion. This study provides evidence for reorganization in the thalamocortical connections known to be involved in multisensory integration and affective processing, with possible implications in the generation of sensory abnormalities after SCI.

Altered functional connectivity during evaluation of self-relevance in women with borderline personality disorder

Self-relevant functional abnormalities and identity disorders constitute the core psychopathological components in borderline personality disorder (BPD). Evidence suggests that appraising the relevance of environmental information to the self may be altered in BPD. However, only a few studies have examined self-relevance (SR) in BPD, and the neural correlates of SR processing has not yet been investigated in this patient group. The current study sought to evaluate brain activation differences between female patients with BPD and healthy controls during SR processing. A task-based fMRI paradigm was applied to evaluate SR processing in 23 female patients with BPD and 23 matched healthy controls. Participants were presented with a set of short sentences and were instructed to rate the stimuli. The differences in fMRI signals between SR rating (task of interest) and valence rating (control task) were examined. During SR rating, participants showed elevated activations of the cortical midline structures (CMS), known to be involved in the processing of self-related stimuli. Furthermore, we observed an elevated activation of the supplementary motor area (SMA) and the regions belonging to the mirror neuron system (MNS). Using whole-brain, seed-based connectivity analysis on the task-based fMRI data, we studied connectivity of networks anchored to the main CMS regions. We found a discrepancy in the connectivity pattern between patients and controls regarding connectivity of the CMS regions with the basal ganglia-thalamus complex. These observations have two main implications: First, they confirm the involvement of the CMS in SR evaluations of our stimuli and add evidence about the involvement of an extended network including the MNS and the SMA in this task. Second, the functional connectivity profile observed in BPD provides evidence for an altered functional interplay between the CMS and the brain regions involved in salience detection and reward evaluation, including the basal ganglia and the thalamus.

Aberrant patterns of default-mode network functional connectivity associated with metabolic syndrome: A resting-state study.

IntroductionMetabolic syndrome (MetS) is a clustering of three or more cardiovascular risk factors (RF), including hypertension, obesity, high cholesterol, or hyperglycemia. MetS and its component RFs are more prevalent in older age, and can be accompanied by alterations in brain structure. Studies have shown altered functional connectivity (FC) in samples with individual RFs as well as in clinical populations that are at higher risk to develop MetS. These studies have indicated that the default mode network (DMN) may be particularly vulnerable, yet little is known about the overall impact of MetS on FC in this network.MethodsIn this study, we evaluated the integrity of FC to the DMN in participants with MetS relative to non‐MetS individuals. Using a seed‐based connectivity analysis approach, resting‐state functional MRI (fMRI) data were analyzed, and the FC measures among the DMN seed (isthmus of the cingulate) and rest of the brain voxels were estimated.ResultsParticipants with MetS demonstrated reduced positive connectivity between the DMN seed and left superior frontal regions, and reduced negative connectivity between the DMN seed and left superior parietal, left postcentral, right precentral, right superior temporal and right superior parietal regions, after accounting for age‐ and sex‐effects.ConclusionsOur results suggest that MetS is associated with alterations in FC between the DMN and other regions of the brain. Furthermore, these results indicate that the overall burden of vascular RFs associated with MetS may, in part, contribute to the pathophysiology underlying aberrant FC in the DMN.

Fronto-parietal and temporal brain dysfunction in depression: A fMRI investigation of auditory mismatch processing.

Mismatch responses reflect neural mechanisms of early cognitive processing in the auditory domain. Disturbances of these mechanisms on multiple levels of neural processing may contribute to clinical symptoms in major depression (MD). A functional magnetic resonance imaging (fMRI) study was conducted to identify neurobiological foundations of altered mismatch processing in MD. Twenty-five patients with major depression and 25 matched healthy individuals completed an auditory mismatch paradigm optimized for fMRI. Brain activity during mismatch processing was compared between groups. Moreover, seed-based connectivity analyses investigated depression-specific brain networks. In patients, mismatch processing was associated with reduced activation in the right auditory cortex as well as in a fronto-parietal attention network. Moreover, functional coupling between the right auditory cortex and frontal areas was reduced in patients. Seed-to voxel analysis on the whole-brain level revealed reduced connectivity between the auditory cortex and the thalamus as well as posterior cingulate. The present study indicates deficits in sensory processing on the level of the auditory cortex in depression. Hyposensitivity in a fronto-parietal network presumably reflects altered attention mechanisms in depression. The observed impairments may contribute to psychopathology by reducing the ability of the affected individuals to orient attention toward important environmental cues.

Altered functional connectivity of dentate nucleus in parkinsonian and cerebellar variants of multiple system atrophy.

The cerebellum is known to influence cerebral cortical activity via cerebello-thalamo-cortical (CTC) circuits and thereby may be implicated in the pathophysiology of multiple system atrophy (MSA). As the aim of this study, we investigated the abnormalities of corticocerebellar functional connectivity (FC) in patients with two variants of MSA. Resting-state functional magnetic resonance imaging (rs-fMRI) studies were obtained from 55 patients with MSA, including Parkinsonian (MSAp, n = 29) and cerebellar (MSAc, n = 26) variants. We also examined a similar number of healthy controls (HC, n = 51). Seed-based connectivity analysis was performed to assess alterations in CTC circuits. Relations between FC and clinical scores were assessed as well. Compared with the HC group, diminished FC was evident from bilateral dentate nucleus (DN) to motor cortex, bilateral basal ganglia, right cerebellum, default mode network (DMN), and limbic system in patients with MSAc. Patients with MSAp (vs HC subjects) showed less FC from left DN to right putamen, DMN, and limbic systems. Reduced FC was also demonstrated from left DN to DMN in patients with MSAc (vs MSAp), as well as from right DN to right cerebellum, DMN, basal ganglia, motor cortex, and limbic systems. In addition, the extent of FC from right DN to right cerebellum negatively correlated with Unified Parkinson's Disease Rating Scale-III scores in patients with MSA, while showing a positive association with Montreal Cognitive Assessment scores. The FC of DN was similarly altered in patients with MSAc and MSAp, although right cerebellar and motor cortical changes were more widespread in the MSAc group. There may be differing mechanisms of cerebellar functional activity responsible for motor and cognitive impairment, which should be further investigated.

Seed-Based Connectivity Analysis of Resting-State fMRI in Patients with Brain Tumors: A Feasibility Study

In this study, we present our experience using resting-state functional magnetic resonance imaging (rs-fMRI) in preoperative planning. We performed group analysis to demonstrate the effects of brain tumor on resting-state networks (RSNs). Thirty patients with supratentorial gliomas were included in the study. Preoperative rs-fMRI and structural magnetic resonance imaging were performed in all cases. The rs-fMRI was preprocessed (realignment, slice time correction, coregistration to structural images, normalization, and smoothing). The structural images were segmented and normalized. Band filtering and denoising were applied to the functional images. Connectivity analysis was performed using seed-based connectivity analysis (SCA) at single subject level and group level. Correlation algorism has been used with r > 0.5. RSNs could be detected in all patients. They showed similarity to the results of the task-based fMRI, when task-based fMRI was feasible. Detection of the networks was also possible in patients with neurologic deficits, in whom task-based fMRI was not possible. We could use SCA in patients under anesthesia. High-level networks (default mode, salience, and dorsal attention networks) were detectable but showed a wide spectrum of spatial alterations and component disconnections. rs-fMRI is a feasible method for extended brain mapping. Diverse RSNs could be detected in patients with brain tumors and could be applied in preoperative planning. SCA was a robust and direct approach for data analysis and could answer specific clinically relevant questions. However, further studies are needed to validate the technique and its clinical impact.

The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer\u2019s disease

In Alzheimer’s disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNFVal66Met) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNFVal66Met an important modulating factor of cognitive impairment in AD. However, the effect of BDNFVal66Met on functional networks that may underlie cognitive impairment in AD is poorly understood. Using a cross-validation approach, we first explored in subjects with autosomal dominant AD (ADAD) from the Dominantly Inherited Alzheimer Network (DIAN) the effect of BDNFVal66Met on resting-state fMRI assessed functional networks. In seed-based connectivity analysis of six major large-scale networks, we found a stronger decrease of hippocampus (seed) to medial-frontal connectivity in the BDNFVal66Met carriers compared to BDNFVal homozogytes. BDNFVal66Met was not associated with connectivity in any other networks. Next, we tested whether the finding of more pronounced decrease in hippocampal-medial-frontal connectivity in BDNFVal66Met could be also found in elderly subjects with sporadically occurring Aβ, including a group with subjective cognitive decline (N = 149, FACEHBI study) and a group ranging from preclinical to AD dementia (N = 114, DELCODE study). In both of these independently recruited groups, BDNFVal66Met was associated with a stronger effect of more abnormal Aβ-levels (assessed by biofluid-assay or amyloid-PET) on hippocampal-medial-frontal connectivity decreases, controlled for hippocampus volume and other confounds. Lower hippocampal-medial-frontal connectivity was associated with lower global cognitive performance in the DIAN and DELCODE studies. Together these results suggest that BDNFVal66Met is selectively associated with a higher vulnerability of hippocampus-frontal connectivity to primary AD pathology, resulting in greater AD-related cognitive impairment.

Whole-brain functional connectivity during script-driven aggression in borderline personality disorder

ObjectiveIntense anger and anger-related aggression are frequently reported by patients with borderline personality disorders (BPD). Recent results suggest that anger-related aggression and its control is associated with a complex interplay of different neural systems in BPD. To further investigate this, we complement standard activation and seed-based connectivity analyses by examining whole-brain changes in functional connectivity during anger and reactive aggression in BPD. MethodsWe reanalyzed functional MRI data from 33 women with BPD, all of them fulfilling BPD criterion 8, “anger proneness”, according to DSM-IV, and 30 healthy women. Subjects performed a script-driven imagery task consisting of four phases: baseline, anger-induction by a narrative of interpersonal rejection, a narrative of directing physical aggression towards others, and relaxation. We used a data-driven, spatially constrained spectral clustering approach to parcellate the brain into 200 regions. For each script-phase and subject, we computed the full connectivity matrix using wavelet coefficient correlations in the 0.05–0.10 Hz range. We calculated the individual increase in connectivity from baseline to the anger-induction and physical aggression phases by subtracting the corresponding connectivity matrices per subject, as well as the increase and decrease from the anger-induction to the aggression phase. We then applied permutation-based sampling to determine a combined threshold on the strength of individual connections and the size of the discovered networks for these difference matrices. ResultsWe discovered a single, large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. This network consisted of regions in the anterior and posterior cingulate cortex, precuneus, dorsomedial prefrontal cortex, superior and middle temporal gyrus, hippocampus, insula, ventrolateral and dorsolateral prefrontal cortex, superior parietal lobe, thalamus, precentral and postcentral gyrus, caudate, pallidum, cerebellum, middle occipital lobe, lingual gyrus, calcarine sulcus, and fusiform gyrus. Hub regions with highest node centrality were found in the right caudate and left thalamus. We found no significant differences for the increase of connectivity from baseline to anger-induction, as well as for the increase or decrease from the anger-induction to the aggression phase. ConclusionsWe identified a large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. The regions constituting this network belong to four previously described functional networks: The frontoparietal cognitive control network, the extended default mode network, the visual system, and the motor system. This stronger increase in connectivity between regions of different functional brain systems associated with cognitive control of behavior, socio-affective and self-referential thinking, as well as salience processing and emotion regulation, visual perception, and action is mediated via hubs in the thalamus and caudate, i.e., core components of the thalamocorticostriatal motor loop essential for action selection and initiation. These findings suggest increased interaction of prefrontal cognitive control processes with thalamocorticostriatal action-selection processes in female patients with BPD during the processing of aggressive action impulses, which are facilitated by states of high emotional salience and associated processes of self-referential and social processing, and ineffective emotion regulation.

Aberrant functional connectivity profiles of brain regions associated with salience and reward processing in female patients with borderline personality disorder.

Recent resting-state functional connectivity studies have shown significant group differences in several networks between patients suffering from borderline personality disorder (BPD) and healthy controls. However, reliable and consistent findings have not been reported yet. Several methodological factors might be responsible for the discrepant findings, including the heterogeneity of patient samples in terms of symptom severity. In the current study, we combined investigations of the whole-brain resting-state functional connectivity patterns of BPD patients with seed-based connectivity measures and then computed the correlation of connectivity measures with borderline symptom severity. Correlation-based connectivity analysis was performed on resting-state functional magnetic resonance imaging (fMRI) data from 26 female BPD patients and 26 healthy controls. Increased intrinsic connectivity was found in clusters involving part of the caudate nucleus and the left insula in the patient group, indicating greater integration of each region. Further seed-based connectivity analyses revealed that with the caudate seed, the patient data exhibited an increased resting-state functional connectivity in the bilateral ventral striatum and the midline prefrontal regions extending to the ACC, a network associated with reward processing. The left insula seed showed significantly increased connectivity with the bilateral fronto-orbital/insula, the inferior parietal lobule and the mid-cingulate cortex, a network involved in attention and salience encoding, in the patient population. Moreover, symptom severity, as assessed with the BSL-95 outside the scanner, was negatively correlated with the coupling of the insula and the striatum in the BPD group. Overall, an increased functional connectivity within two large-scale circuitries underlying reward and salience processing was evident in patients, as compared to healthy participants. When correlated with borderline symptom severity, a reduced connectivity between key regions belonging to the reward system and salience network was observed in the patients. These findings may be helpful for facilitating further understanding of the potential mechanisms underlying the BPD pathophysiology and thereby delineate potential treatment targets.

Changes in Functional Connectivity Following Treatment With Emotion Regulation Therapy.

Emotion regulation therapy (ERT) is an efficacious treatment for distress disorders (i.e., depression and anxiety), predicated on a conceptual model wherein difficult to treat distress arises from intense emotionality (e.g., neuroticism, dispositional negativity) and is prolonged by negative self-referentiality (e.g., worry, rumination). Individuals with distress disorders exhibit disruptions in two corresponding brain networks including the salience network (SN) reflecting emotion/motivation and the default mode network (DMN) reflecting self-referentiality. Using resting-state functional connectivity (rsFC) analyses, seeded with primary regions in each of these networks, we investigated whether ERT was associated with theoretically consistent changes across nodes of these networks and whether these changes related to improvements in clinical outcomes. This study examined 21 generalized anxiety disorder (GAD) patients [with and without major depressive disorder (MDD)] drawn from a larger intervention trial (Renna et al., 2018a), who completed resting state fMRI scans before and after receiving 16 sessions of ERT. We utilized seed-based connectivity analysis with seeds in the posterior cingulate cortex (PCC), right anterior insula, and right posterior insula, to investigate whether ERT was associated with changes in connectivity of nodes of the DMN and SN networks to regions across the brain. Findings revealed statistically significant treatment linked changes in both the DMN and SN network nodes, and these changes were associated with clinical improvement corresponding to medium effect sizes. The results are discussed in light of a nuanced understanding of the role of connectivity changes in GAD and MDD, and begin to provide neural network support for the hypothesized treatment model predicated by ERT.

Intrinsic oscillations of auditory networks in schizophrenia and bipolar disorder

Objective: Several types of evidence have shown that auditory networks are dysfunctional in schizophrenia (Sch) and bipolar disorders (BD). Auditory cortices show abnormalities in hallucinations or during remission. This study aimed to assess resting-state connectivity of auditory cortices in Sch and BD. Method: Patients with BD-1 (n=28), BD-2 (n=21), Sch (n=30), and healthy controls (HC, n=30) were enrolled into the study. A 3 Tesla whole-body magnetic resonance imaging (MRI) system with a 32-channel phase-array head coil was used to acquire the MRI data. T1-weighted anatomical and gradient-echo based Echoplanar Imaging sequences were used. MATLAB and Freesurfer software packages were used for data analyses. Connectivity alterations within the auditory network guided our further seed-based connectivity analysis. Results: The left angular gyrus volume was decreased in Sch and BD-2 groups. The supramarginal gyrus had hyperconnectivity with the medial prefrontal cortices and decreased connectivity with the medial superior temporal gyrus (STG) in the BD-1 and BD-2 groups. The left superior temporal sulcus (STS) had increased connectivity with the bilateral posterior cingulate cortex in BD-1 and BD-2 and increased connectivity with the dorsal prefrontal cortices in the Sch group. The STS had increased connectivity with the medial STG in the BD-1 and Sch groups, whereas connectivity decreased in the BD-2 group. Conclusion: These findings suggest that functional connectivity of resting-state networks are altered in BD and Sch. Auditory network alterations may predispose to dysfunctional auditory information processing. Further studies are needed to determine the relationship between symptoms and auditory network dysfunction.

Altered default mode network connectivity in adolescents with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.

Similarities and differences in cerebellar grey matter volume and disrupted functional connectivity in idiopathic Parkinson's disease and multiple system atrophy

ObjectiveThis study investigated the potential differences in changes to cerebellar grey matter volume (GMV) and functional connectivity (FC) and the association between them, which might elucidate cerebellar function in multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). MethodsResting-state functional magnetic resonance imaging and three-dimensional T1 scans were obtained from 38 IPD, 62 MSA, and 59 healthy controls (HC). Seed-based connectivity analysis and voxel-based morphometry analysis were performed to assess the changes of cerebellar FC and GMV between the patient groups. ResultDecreased cerebellar GMV was found in the motor cerebellum in both patient groups relative to HC, and broader reduction of GMV was observed in both cognitive and motor cerebellum in MSA compared with IPD and HC. Compared with IPD, the MSA group exhibited decreased FC between bilateral dentate nucleus (DN) and default mode network (DMN). Decreased intracerebellar FC was observed in both patient groups relative to HC. Cerebellar GMV was positively correlated with FC of intracerebellum and DN-DMN in MSA. Motor/cognitive scores were associated with DN-DMN FC, with considerable cerebellar GMV loss in MSA patients. ConclusionCerebellar GMV loss and cerebellar FC alterations showed similarities in IPD and MSA, along with more widespread changes to GMV in motor and cognitive cerebellum and altered DN-DMN FC in MSA. Further research is needed to better describe the alterations of cerebellar GMV in the cognitive cerebellum and association between cerebellar GMV and intracerebellar FC during the early stages of MSA and IPD.

Disrupted Cerebellar Connectivity With the Central Executive Network and the Default-Mode Network in Unmedicated Bipolar II Disorder.

Objective: Bipolar disorder (BD) is a common psychiatric disease. Although structural and functional abnormalities of the cerebellum in BD patients have been reported by recent neuroimaging studies, the cerebellar-cerebral functional connectivity (FC) has not yet been examined. The present study aims to investigate the FC between the cerebellum and cerebrum, particularly the central executive network (CEN) and the default-mode network (DMN) in bipolar II disorder (BD II).Methods: Ninety-four patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging. Seed-based connectivity analyses were performed using cerebellar seeds previously identified as being involved in the CEN (bilateral Crus Ia) and DMN (bilateral Crus Ib).Results: Compared with HCs, BD II depression patients appeared decreased FC in the right Crus Ia-left dorsal lateral prefrontal cortex (dlPFC) and -left anterior cingulate cortex (ACC), the right Crus Ib-left medial prefrontal cortex (mPFC), -left middle temporal gyrus (MTG), and -left inferior temporal gyrus (ITG). No altered FC between the left Crus Ia or Crus Ib and the cerebral regions was found.Conclusions: Patients with BD II depression showed disrupted FC between the cerebellum and the CEN (mainly in the left dlPFC and ACC) and DMN (mainly in the left mPFC and temporal lobe), suggesting the significant role of the cerebellum-CEN and -DMN connectivity in the pathogenesis of BD.

Involvement of the Precuneus/Posterior Cingulate Cortex Is Significant for the Development of Alzheimer's Disease: A PET (THK5351, PiB) and Resting fMRI Study.

Background: Imaging studies in Alzheimer’s disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls.Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls.Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC.Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

Altered resting-state cerebellar-cerebral functional connectivity in obsessive-compulsive disorder.

The role of the cerebellum in obsessive-compulsive disorder (OCD) has drawn increasing attention. However, the functional connectivity between the cerebellum and the cerebral cortex has not been investigated in OCD, nor has the relationship between such functional connectivity and clinical symptoms. A total of 27 patients with OCD and 21 healthy controls (HCs) matched on age, sex and education underwent magnetic resonance imaging (MRI). Seed-based connectivity analyses were performed to examine differences in cerebellar-cerebral connectivity in patients with OCD compared with HCs. Associations between functional connectivity and clinical features in OCD were analyzed. Compared with HCs, OCD patients showed significantly decreased cerebellar-cerebral functional connectivity in executive control and emotion processing networks. Within the OCD group, decreased functional connectivity in an executive network spanning the right cerebellar Crus I and the inferior parietal lobule was positively correlated with symptom severity, and decreased connectivity in an emotion processing network spanning the left cerebellar lobule VI and the lingual gyrus was negatively correlated with illness duration. Altered functional connectivity between the cerebellum and cerebral networks involved in cognitive-affective processing in patients with OCD provides further evidence for the involvement of the cerebellum in the pathophysiology of OCD, and is consistent with impairment in executive control and emotion regulation in this condition.

Functional Disconnectivity during Inter-Task Resting State in Dementia with Lewy Bodies

Aims: Limited research has been done on the functional connectivity in visuoperceptual regions in dementia with Lewy bodies (DLB) patients. This study aimed to investigate the functional connectivity differences between a task condition and an inter-task resting state condition within a visuoperceptual paradigm, in DLB patients compared with Alzheimer disease (AD) patients and healthy elderly control subjects. Methods: Twenty-six DLB, 29 AD, and 22 healthy subjects underwent a detailed clinical and neuropsychological examination along with a functional MRI during the different conditions of a visuoperceptual paradigm. Functional images were analyzed using group-level spatial independent component analysis and seed-based connectivity analyses. Results: While the DLB patients scored well and did not differ from the control and AD groups in terms of functional activity and connectivity during the task conditions, they showed decreased functional connectivity in visuoperceptual regions during the resting state condition, along with a temporal impairment of the default-mode network activity. Functional connectivity disturbances were also found within two attentional-executive networks and between these networks and visuoperceptual regions. Conclusion: We found a specific functional profile in the switching between task and resting state conditions in DLB patients. This result could help better characterize functional impairments in DLB and their contribution to several core symptoms of this pathology such as visual hallucinations and cognitive fluctuations.

Task-positive and task-negative networks in major depressive disorder: A combined fMRI and EEG study

BackgroundThe study of intrinsic connectivity networks, i.e., sets of brain regions that show a high degree of interconnectedness even in the absence of a task, showed that major depressive disorder (MDD) patients demonstrate an increased connectivity within the default mode network (DMN), which is active in a resting state and is implicated in self-referential processing, and a decreased connectivity in task-positive networks (TPNs), which increase their activity in attention tasks. Cortical localization of this ‘dominance’ of the DMN over the TPN in MDD patients is not fully understood. Besides, this effect has been investigated using fMRI and its electrophysiological underpinning is not known. MethodIn this study, we tested the dominance hypothesis using seed-based connectivity analysis of resting-state fMRI and EEG data obtained in 41 MDD patients and 23 controls. ResultsIn MDD patients, as compared to controls, insula, pallidum/putamen, amygdala, and left dorso- and ventrolateral prefrontal cortex are more strongly connected with DMN than with TPN seeds. In EEG, all significant effects were obtained in the delta frequency band. LimitationsfMRI and EEG data were not obtained simultaneously during the same session. ConclusionsIn MDD patients, major emotion and attention regulation circuits are more strongly connected with DMN than with TPN implying they are more prepared to respond to internally generated self-related thoughts than to environmental challenges.