Brain-derived subgroups of bipolar II depression associate with inflammation and choroid plexus morphology.

AIM: Elevated inflammation and larger choroid plexus (ChP) volume has been previously identified in mood disorders. Connections between inflammation, ChP, and clinical symptoms in bipolar II depression (BDII-D) are unclear. Data-driven clustering based on neuroanatomical phenotypes may help to elucidate neurobiological associations in BDII-D. METHODS: Inflammatory cytokines, clinical symptoms, and neuroanatomical features were assessed in 150 BDII-D patients. Sixty-eight cortical surface area (SA) and 19 subcortical volumes were extracted using FreeSurfer. The ChP volume was segmented manually using 3D Slicer. Regularized canonical correlation analysis was used to identify significantly correlated components between cortical SA and subcortical volumes (excluding the ChP), followed by k-means clustering to define brain-derived subgroups of BDII-D. Low-grade inflammation was derived by averaging the standardized z scores of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α), which were computed to create a composite z-value score. Partial Pearson correlations followed by multiple comparison correction were conducted to explore associations between inflammation, clinical symptoms, and ChP volume. RESULTS: Subgroup I demonstrated smaller subcortical volume and cortical SA, higher inflammation, and larger ChP volume compared with subgroup II. Greater ChP volume was associated with a higher low-grade inflammation (mean r = 0.289, q = 0.003), CRP (mean r = 0.249, q = 0.007), IL-6 (left r = 0.200, q = 0.03), and TNF-α (right r = 0.226, q = 0.01), while greater IL-1ß was significantly associated with severe depressive symptoms in BDII-D (r = 0.218, q = 0.045). CONCLUSIONS: Neuroanatomically-derived subgroups of BDII-D differed in their inflammation levels and ChP volume. These findings suggest an important role of elevated peripheral inflammation and larger ChP in BDII-D.

Modular organization of functional brain networks in patients with degenerative cervical myelopathy.

Previous studies have indicated that brain functional plasticity and reorganization in patients with degenerative cervical myelopathy (DCM). However, the effects of cervical cord compression on the functional integration and separation between and/or within modules remain unclear. This study aimed to address these questions using graph theory. Functional MRI was conducted on 46 DCM patients and 35 healthy controls (HCs). The intra- and inter-modular connectivity properties of the whole-brain functional network and nodal topological properties were then calculated using theoretical graph analysis. The difference in categorical variables between groups was compared using a chi-squared test, while that between continuous variables was evaluated using a two-sample t-test. Correlation analysis was conducted between modular connectivity properties and clinical parameters. Modules interaction analyses showed that the DCM group had significantly greater inter-module connections than the HCs group (DMN-FPN: t = 2.38, p = 0.02); inversely, the DCM group had significantly lower intra-module connections than the HCs group (SMN: t = - 2.13, p = 0.036). Compared to HCs, DCM patients exhibited higher nodal topological properties in the default-mode network and frontal-parietal network. In contrast, DCM patients exhibited lower nodal topological properties in the sensorimotor network. The Japanese Orthopedic Association (JOA) score was positively correlated with inter-module connections (r = 0.330, FDR p = 0.029) but not correlated with intra-module connections. This study reported alterations in modular connections and nodal centralities in DCM patients. Decreased nodal topological properties and intra-modular connection in the sensory-motor regions may indicate sensory-motor dysfunction. Additionally, increased nodal topological properties and inter-modular connection in the default mode network and frontal-parietal network may serve as a compensatory mechanism for sensory-motor dysfunction in DCM patients. This could provide an implicative neural basis to better understand alterations in brain networks and the patterns of changes in brain plasticity in DCM patients.

Abnormal intrinsic brain functional network dynamics in patients with cervical spondylotic myelopathy.

The specific topological changes in dynamic functional networks and their role in cervical spondylotic myelopathy (CSM) brain function reorganization remain unclear. This study aimed to investigate the dynamic functional connection (dFC) of patients with CSM, focusing on the temporal characteristics of the functional connection state patterns and the variability of network topological organization. Eighty-eight patients with CSM and 77 healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. We applied the sliding time window analysis method and K-means clustering analysis to capture the dFC variability patterns of the two groups. The graph-theoretical approach was used to investigate the variance in the topological organization of whole-brain functional networks. All participants showed four types of dynamic functional connection states. The mean dwell time in state 2 was significantly different between the two groups. Particularly, the mean dwell time in state 2 was significantly longer in the CSM group than in the healthy control group. Among the four states, switching of relative brain networks mainly included the executive control network (ECN), salience network (SN), default mode network (DMN), language network (LN), visual network (VN), auditory network (AN), precuneus network (PN), and sensorimotor network (SMN). Additionally, the topological properties of the dynamic network were variable in patients with CSM. Dynamic functional connection states may offer new insights into intrinsic functional activities in CSM brain networks. The variance of topological organization may suggest instability of the brain networks in patients with CSM.

The Correlation between Functional Connectivity of the Primary Somatosensory Cortex and Cervical Spinal Cord Microstructural Injury in Patients with Cervical Spondylotic Myelopathy.

OBJECTIVES: To explore functional connectivity reorganization of the primary somatosensory cortex, the chronic microstructure damage of the cervical spinal cord, and their relationship in cervical spondylotic myelopathy (CSM) patients. METHODS: Thirty-three patients with CSM and 23 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. Six subregions (including leg, back, chest, hand, finger and face) of bilateral primary somatosensory cortex (S1) were selected for seed-based whole-brain functional connectivity (FC). Then, we calculated the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the cervical spinal cord. Correlation analysis was conducted between FC values of brain regions and DTI parameters of cervical spinal cord (ADC, FA), and their relationship with each other and clinical parameters. RESULTS: Compared with the HC group, the CSM group showed decreased FC between areas of the left S1hand, the left S1leg, the right S1chest, and the right S1leg with brain regions. The mean FA values of the cervical spinal cord in CSM patients were positively correlated with JOA scores. Especially, the FApos values of bilateral posterior funiculus were positively correlated with JOA scores. The ADC and FA values of bilateral posterior funiculus in the cervical spinal cord were also positively correlated with the FC values. CONCLUSIONS: There was synchronization between chronic cervical spinal cord microstructural injury and cerebral cortex sensory function compensatory recombination. DTI parameters of the posterior cervical spinal cord could objectively reflect the degree of cerebral cortex sensory function impairment to a certain extent.

Disruption of human brain connectivity networks in patients with cervical spondylotic myelopathy.

BACKGROUND: Brain functional plasticity and reorganization in patients with cervical spondylotic myelopathy (CSM) is increasingly being explored and validated. However, specific topological alterations in functional networks and their role in CSM brain functional reorganization remain unclear. This study investigates the topological architecture of intrinsic brain functional networks in CSM patients using graph theory. METHODS: Functional MRI was conducted on 67 CSM patients and 60 healthy controls (HCs). The topological organization of the whole-brain functional network was then calculated using theoretical graph analysis. The difference in categorical variables between groups was compared using a chi-squared test, while that between continuous variables was evaluated using a two-sample t-test. Nonparametric permutation tests were used to compare network measures between the two groups. RESULTS: Small-world architecture in functional brain networks were identified in both CSM patients and HCs. Compared with HCs, CSM patients showed a decreased area under the curve (AUC) of the characteristic path length (FDR q=0.040), clustering coefficient (FDR q=0.037), and normalized characteristic path length (FDR q=0.038) of the network. In contrast, there was an increased AUC of normalized clustering coefficient (FDR q=0.014), small-worldness (FDR q=0.009), and global network efficiency (FDR q=0.027) of the network. In local brain regions, nodal topological properties revealed group differences which were predominantly in the default-mode network (DMN), left postcentral gyrus, bilateral putamen, lingual gyrus, and posterior cingulate gyrus. CONCLUSIONS: This study reported altered functional topological organization in CSM patients. Decreased nodal centralities in the visual cortex and sensory-motor regions may indicate sensory-motor dysfunction and blurred vision. Furthermore, increased nodal centralities in the cerebellum may be compensatory for sensory-motor dysfunction in CSM, while the increased DMN may indicate increased psychological processing in CSM patients.

Altered Functional Connectivity Density in Young Survivors of Acute Lymphoblastic Leukemia Using Resting-State fMRI.

OBJECTIVE: Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients. METHODS: Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients. RESULTS: The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A. CONCLUSION: Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.