INTRODUCTION: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD), characterized by abnormal movements during REM sleep, is a prodromal stage of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). While iRBD shows emerging brain changes, their impact on structural connectivity and network efficiency, and their predictive value, remain poorly characterized. METHODS: In this international prospective study, 198 polysomnography-confirmed iRBD patients and 174 controls underwent diffusion magnetic resonance imaging and were analyzed. Cutting-edge diffusion tractography and network-based statistics were applied to reconstruct individual connectomes and assess network properties predicting DLB or PD. RESULTS: Structural architecture was already disrupted in iRBD, with both reduced and compensatory increased connections. Global efficiency was decreased. Local efficiency in motor regions was altered and associated with early clinical symptoms. Altered local efficiency in the supramarginal gyrus predicted DLB only. DISCUSSION: Early disruption of brain architecture in iRBD predicts progression to synucleinopathy-related dementia, offering a novel potential prognostic biomarker. HIGHLIGHTS: Isolated rapid eye movement sleep behavior disorder (iRBD) patients show significant alterations in inter-regional structural connectivity. Global efficiency is reduced in iRBD compared to controls. Areas with increased local efficiency contribute to decreased global efficiency. Altered network efficiency is associated with emerging Parkinsonian features. Higher supramarginal efficiency predicts dementia with Lewy bodies in iRBD.
- Keywords
- dementia with Lewy bodies, diffusion magnetic resonance imaging, graph theory, parasomnias, sleep, structural connectivity, synucleinopathies,
- MeSH
- Lewy Body Disease * diagnostic imaging physiopathology MeSH
- Diffusion Magnetic Resonance Imaging MeSH
- Connectome MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain * diagnostic imaging pathology MeSH
- Nerve Net * diagnostic imaging MeSH
- Parkinson Disease diagnostic imaging physiopathology MeSH
- Polysomnography MeSH
- REM Sleep Behavior Disorder * diagnostic imaging physiopathology pathology MeSH
- Prospective Studies MeSH
- Aged MeSH
- Diffusion Tensor Imaging MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Accelerated epigenetic aging has been associated with changes in cognition. However, due to the lack of neuroimaging epigenetics studies, it is still unclear whether accelerated epigenetic. Aging in young adulthood might underlie the relationship between altered brain dynamics and cognitive functioning. We conducted neuroimaging epigenetics follow-up of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort in young adulthood and tested the possible mediatory role of accelerated epigenetic aging in the relationship between dynamic functional connectivity (DFC) and worse cognition. A total of 240 young adults (51% men; 28-30 years, all of European ancestry) participated in the neuroimaging epigenetics follow-up. Buccal swabs were collected to assess DNA methylation and calculate epigenetic aging using Horvath's epigenetic clock. Full-scale IQ was assessed using the Wechsler adult intelligence scale (WAIS). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired using a 3T Siemens Prisma MRI scanner, and DFC was assessed using mixture factor analysis, revealing information about the coverage of different DFC states. In women (but not men), lower coverage of DFC state 4 and thus lower frequency of epochs with high connectivity within the default mode network and between default mode, fronto-parietal, and visual networks was associated with lower full-scale IQ (AdjR2 = 0.05, std. beta = 0.245, p = 0.008). This relationship was mediated by accelerated epigenetic aging (ab = 7.660, SE = 4.829, 95% CI [0.473, 19.264]). In women, accelerated epigenetic aging in young adulthood mediates the relationship between altered brain dynamics and cognitive functioning. Prevention of cognitive decline should target women already in young adulthood.
- Keywords
- Horvath's epigenetic clock, dynamic functional connectivity (DFC), epigenetic aging, full‐scale IQ, mixed factor analysis (MFA), sex differences,
- MeSH
- Default Mode Network * diagnostic imaging physiology MeSH
- Adult MeSH
- Epigenesis, Genetic * physiology MeSH
- Intelligence * physiology MeSH
- Cognition * physiology MeSH
- Connectome * MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Magnetic Resonance Imaging MeSH
- DNA Methylation MeSH
- Young Adult MeSH
- Brain * diagnostic imaging physiology MeSH
- Nerve Net * diagnostic imaging physiology MeSH
- Aging * physiology genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Schizophrenia is a psychiatric disorder with heterogeneous clinical manifestations and complex aetiology. Notably, the triple-network model proposes an interesting framework for investigating abnormal neurocircuit activity at rest in schizophrenia. The present study on 30 chronic schizophrenia individuals and 30 controls aimed to explore the differences in EEG resting state effective connectivity within a triple-network model using source-localization-based Directed Transfer Function. Our findings revealed multiband effective connectivity disturbances within default mode (DMN), central executive (CEN), and salience (SN) networks in schizophrenia. The most significant difference was manifested in a global DMN hyperconnectivity, accompanied by low-band hyperconnectivity and high-band hypoconnectivity in CEN, along with the aberrant information flows in SN. In conclusion, our study presents novel insights into schizophrenia neuropathology, with a particular emphasis on the reversed directionality in information flows between hubs of SN, DMN, and CEN. This may be suggested as a promising biomarker of schizophrenia.
- Keywords
- Central executive network, Default mode network, EEG, Effective connectivity, Resting-state, Schizophrenia,
- MeSH
- Default Mode Network * physiopathology MeSH
- Adult MeSH
- Electroencephalography MeSH
- Connectome * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Nerve Net * physiopathology diagnostic imaging MeSH
- Schizophrenia * physiopathology diagnostic imaging MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Evidence suggests that brain-computer interface (BCI)-based rehabilitation strategies show promise in overcoming the limited recovery potential in the chronic phase of stroke. However, the specific mechanisms driving motor function improvements are not fully understood. OBJECTIVE: We aimed at elucidating the potential functional brain connectivity changes induced by BCI training in participants with chronic stroke. METHODS: A longitudinal crossover design was employed with two groups of participants over the span of 4 weeks to allow for within-subject (n = 21) and cross-group comparisons. Group 1 (n = 11) underwent a 6-day motor imagery-based BCI training during the second week, whereas Group 2 (n = 10) received the same training during the third week. Before and after each week, both groups underwent resting state functional MRI scans (4 for Group 1 and 5 for Group 2) to establish a baseline and monitor the effects of BCI training. RESULTS: Following BCI training, an increased functional connectivity was observed between the medial prefrontal cortex of the default mode network (DMN) and motor-related areas, including the premotor cortex, superior parietal cortex, SMA, and precuneus. Moreover, these changes were correlated with the increased motor function as confirmed with upper-extremity Fugl-Meyer assessment scores, measured before and after the training. CONCLUSIONS: Our findings suggest that BCI training can enhance brain connectivity, underlying the observed improvements in motor function. They provide a basis for developing novel rehabilitation approaches using non-invasive brain stimulation for targeting functionally relevant brain regions, thereby augmenting BCI-induced neuroplasticity and enhancing motor recovery.
- Keywords
- Brain-computer interface, Default mode network, Functional Connectivity, Neuroplasticity, Resting-state fMRI, Stroke,
- MeSH
- Stroke * physiopathology diagnostic imaging MeSH
- Chronic Disease MeSH
- Default Mode Network * physiopathology diagnostic imaging MeSH
- Adult MeSH
- Cross-Over Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Magnetic Resonance Imaging MeSH
- Brain * physiopathology diagnostic imaging MeSH
- Nerve Net * physiopathology diagnostic imaging MeSH
- Stroke Rehabilitation * methods MeSH
- Brain-Computer Interfaces * MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.
- Keywords
- Cortical folding, Graph theory, Magnetic resonance imaging, Morphological connectivity, Test-retest reliability,
- MeSH
- Depressive Disorder, Major pathology diagnostic imaging MeSH
- Adult MeSH
- Connectome methods MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Young Adult MeSH
- Cerebral Cortex * diagnostic imaging anatomy & histology MeSH
- Nerve Net * diagnostic imaging anatomy & histology MeSH
- Neural Pathways MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Recent fMRI resting-state findings show aberrant functional connectivity within somatomotor network (SMN) in schizophrenia. Moreover, functional connectivity aberrations of the motor system are often reported to be related to the severity of psychotic symptoms. Thus, it is important to validate those findings and confirm their relationship with psychopathology. Therefore, we decided to take an entirely data-driven approach in our fMRI resting-state study of 30 chronic schizophrenia outpatients and 30 matched control subjects. We used independent component analysis (ICA), dual regression, and seed-based connectivity analysis. We found reduced functional connectivity within SMN in schizophrenia patients compared to controls and SMN hypoconnectivity with the cerebellum in schizophrenia patients. The latter was strongly correlated with the severity of alogia, one of the main psychotic symptoms, i.e. poverty of speech and reduction in spontaneous speech,. Our results are consistent with the recent knowledge about the role of the cerebellum in cognitive functioning and its abnormalities in psychiatric disorders, e.g. schizophrenia. In conclusion, the presented results, for the first time clearly showed the involvement of the cerebellum hypoconnectivity with SMN in the persistence and severity of alogia symptoms in schizophrenia.
- Keywords
- Cerebellum, Negative symptoms, Schizophrenia, Somatomotor network, fMRI,
- MeSH
- Aphasia physiopathology diagnostic imaging etiology pathology MeSH
- Chronic Disease MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Cerebellum * diagnostic imaging physiopathology MeSH
- Nerve Net diagnostic imaging physiopathology MeSH
- Neural Pathways physiopathology diagnostic imaging MeSH
- Schizophrenia * diagnostic imaging physiopathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Brain imaging studies in complex regional pain syndrome (CRPS) have found mixed evidence for functional and structural changes in CRPS. In this cross-sectional study, we evaluated two patient cohorts from different centers and examined functional connectivity (rsFC) in 51 CRPS patients and 50 matched controls. rsFC was compared in predefined ROI pairs, but also in non-hypothesis driven analyses. Resting state (rs)fMRI changes in default mode network (DMN) and the degree rank order disruption index (kD) were additionally evaluated. Finally, imaging parameters were correlated with clinical severity and somatosensory function. Among predefined pairs, we found only weakly to moderately lower functional connectivity between the right nucleus accumbens and bilateral ventromedial prefrontal cortex in the infra-slow oscillations (ISO) band. The unconstrained ROI-to-ROI analysis revealed lower rsFC between the periaqueductal gray matter (PAG) and left anterior insula, and higher rsFC between the right sensorimotor thalamus and nucleus accumbens. In the correlation analysis, pain was positively associated with insulo-prefrontal rsFC, whereas sensorimotor thalamo-cortical rsFC was positively associated with tactile spatial resolution of the affected side. In contrast to previous reports, we found no group differences for kD or rsFC in the DMN, but detected overall lower data quality in patients. In summary, while some of the previous results were not replicated despite the larger sample size, novel findings from two independent cohorts point to potential down-regulated antinociceptive modulation by the PAG and increased connectivity within the reward system as pathophysiological mechanisms in CRPS. However, in light of the detected systematic differences in data quality between patients and healthy subjects, validity of rsFC abnormalities in CRPS should be carefully scrutinized in future replication studies.
- Keywords
- Biomarker, CRPS, Functional connectivity, Neuropathic pain, Resting-state fMRI,
- MeSH
- Default Mode Network diagnostic imaging physiopathology MeSH
- Adult MeSH
- Complex Regional Pain Syndromes * physiopathology diagnostic imaging MeSH
- Connectome methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Brain physiopathology diagnostic imaging MeSH
- Nerve Net physiopathology diagnostic imaging MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.
- Keywords
- Bipolar disorder, Functional connectivity, Major depressive disorder, Multivariate pattern analysis, Resting state,
- MeSH
- Bipolar Disorder * physiopathology diagnostic imaging MeSH
- Depressive Disorder, Major * physiopathology diagnostic imaging MeSH
- Adult MeSH
- Connectome methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain Mapping methods MeSH
- Brain physiopathology diagnostic imaging MeSH
- Multivariate Analysis MeSH
- Nerve Net diagnostic imaging physiopathology MeSH
- Neural Pathways physiopathology diagnostic imaging MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Brain activity during the resting state is widely used to examine brain organization, cognition and alterations in disease states. While it is known that neuromodulation and the state of alertness impact resting-state activity, neural mechanisms behind such modulation of resting-state activity are unknown. In this work, we used a computational model to demonstrate that change in excitability and recurrent connections, due to cholinergic modulation, impacts resting-state activity. The results of such modulation in the model match closely with experimental work on direct cholinergic modulation of Default Mode Network (DMN) in rodents. We further extended our study to the human connectome derived from diffusion-weighted MRI. In human resting-state simulations, an increase in cholinergic input resulted in a brain-wide reduction of functional connectivity. Furthermore, selective cholinergic modulation of DMN closely captured experimentally observed transitions between the baseline resting state and states with suppressed DMN fluctuations associated with attention to external tasks. Our study thus provides insight into potential neural mechanisms for the effects of cholinergic neuromodulation on resting-state activity and its dynamics.
- MeSH
- Acetylcholine metabolism MeSH
- Default Mode Network physiology diagnostic imaging MeSH
- Adult MeSH
- Connectome * MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Models, Neurological * MeSH
- Brain * physiology diagnostic imaging MeSH
- Nerve Net physiology diagnostic imaging MeSH
- Rest * physiology MeSH
- Computer Simulation MeSH
- Computational Biology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholine MeSH
Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.
- MeSH
- Adult MeSH
- Connectome * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Young Adult MeSH
- Brain pathology physiopathology MeSH
- Cerebral Cortex pathology physiopathology MeSH
- Nerve Net pathology physiopathology diagnostic imaging MeSH
- Neural Pathways physiopathology pathology MeSH
- Schizophrenia * pathology physiopathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH