Altered Connectivity Research Articles

Unveiling altered connectivity between cognitive networks and cerebellum in schizophrenia

Cognitive functioning is a crucial aspect in schizophrenia (SZ), and when altered it has devastating effects on patients' quality of life and treatment outcomes. Several studies suggested that they could result from altered communication between the cortex and cerebellum. However, the neural correlates underlying these impairments have not been identified. In this study, we investigated resting state functional connectivity (rsFC) in SZ patients, by considering the interactions between cortical networks supporting cognition and cerebellum. In addition, we investigated the relationship between SZ patients' rsFC and their symptoms.We used fMRI data from 74 SZ patients and 74 matched healthy controls (HC) downloaded from the publicly available database SchizConnect. We implemented a seed-based connectivity approach to identify altered functional connections between specific cortical networks and cerebellum. We considered ten commonly studied resting state networks, whose functioning encompasses specific cognitive functions, and the cerebellum, whose involvement in supporting cognition has been recently identified. We then explored the relationship between altered rsFC values and Positive and Negative Syndrome Scale (PANSS) scores.The SZ group showed increased connectivity values compared with HC group for cortical networks involved in attentive processes, which were also linked to PANSS items describing attention and language-related processing. We also showed decreased connectivity between cerebellar regions, and increased connectivity between them and attentive networks, suggesting the contribution of cerebellum to attentive and affective deficits.In conclusion, our findings highlighted the link between negative symptoms in SZ and altered connectivity within the cerebellum and between the same and cortical networks supporting cognition.

Altered white matter connectivity of ventral language networks in autism spectrum disorder: An automated fiber quantification analysis with multi-site datasets

Comprehension and pragmatic deficits are prevalent in autism spectrum disorder (ASD) and are potentially linked to altered connectivity in the ventral language networks. However, previous magnetic resonance imaging studies have not sufficiently explored the microstructural abnormalities in the ventral fiber tracts underlying comprehension dysfunction in ASD. Additionally, the precise locations of white matter (WM) changes in the long tracts of patients with ASD remain poorly understood. In the current study, we applied the automated fiber-tract quantification (AFQ) method to investigate the fine-grained WM properties of the ventral language pathway and their relationships with comprehension and symptom manifestation in ASD. The analysis included diffusion/T1 weighted imaging data of 83 individuals with ASD and 83 age-matched typically developing (TD) controls. Case-control comparisons were performed on the diffusion metrics of the ventral tracts at both the global and point-wise levels. We also explored correlations between diffusion metrics, comprehension performance, and ASD traits, and conducted subgroup analyses based on age range to examine developmental moderating effects. Individuals with ASD exhibited remarkable hypoconnectivity in the ventral tracts, particularly in the temporal portions of the left inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF). These WM abnormalities were associated with poor comprehension and more severe ASD symptoms. Furthermore, WM alterations in the ventral tract and their correlation with comprehension dysfunction were more prominent in younger children with ASD than in adolescents. These findings indicate that WM disruptions in the temporal portions of the left ILF/IFOF are most notable in ASD, potentially constituting the core neurological underpinnings of comprehension and communication deficits in autism. Moreover, impaired WM connectivity and comprehension ability in patients with ASD appear to improve with age.

W20 - Modular-Level Alterations in Functional Brain Connectivity Associated With Cannabis Use

W20 - Modular-Level Alterations in Functional Brain Connectivity Associated With Cannabis Use

Sex-specific alterations in functional connectivity and network topology in patients with degenerative cervical myelopathy

Patients with degenerative cervical myelopathy (DCM) experience structural and functional brain reorganization. However, few studies have investigated the influence of sex on cerebral alterations. The present study investigates the role of sex on brain functional connectivity (FC) and global network topology in DCM and healthy controls (HCs). The resting-state functional MRI data was acquired for 100 patients (58 males vs. 42 females). ROI-to-ROI FC and network topological features were characterized for each patient and HC. Group differences in FC and network topological features were examined. Compared to healthy counterparts, DCM males exhibited higher FC between vision-related brain regions, and cerebellum, brainstem, and thalamus, but lower FC between the intracalcarine cortex and frontal and somatosensory cortices, while DCM females demonstrated higher FC between the thalamus and cerebellar and sensorimotor regions, but lower FC between sensorimotor and visual regions. DCM males displayed higher FC within the cerebellum and between the posterior cingulate cortex (PCC) and vision-related regions, while DCM females displayed higher FC between frontal regions and the PCC, cerebellum, and visual regions. Additionally, DCM males displayed significantly greater intra-network connectivity and efficiency compared to healthy counterparts. Results from the present study imply sex-specific supraspinal functional alterations occur in patients with DCM.

Characteristics of the Structural Connectivity in Patients with Brain Injury and Chronic Health Symptoms: A Pilot Study.

Diffusion properties from diffusion tensor imaging (DTI) are exquisitely sensitive to white matter abnormalities incurred during traumatic brain injury (TBI), especially for those patients with chronic post-TBI symptoms such as headaches, dizziness, fatigue, etc. The evaluation of structural and functional connectivity using DTI has become a promising method for identifying subtle alterations in brain connectivity associated with TBI that are otherwise not visible with conventional imaging. This study assessed whether TBI patients with (n = 17) or without (n = 16) chronic symptoms (TBIcs/TBIncs) exhibit any changes in structural connectivity (SC) and mean fractional anisotropy (mFA) of intra- and inter-hemispheric connections when compared to a control group (CG) (n = 13). Reductions in SC and mFA were observed for TBIcs compared to CG, but not for TBIncs. More connections were found to have mFA reductions than SC reductions. On the whole, SC is dominated by ipsilateral connections for all the groups after the comparison of contralateral and ipsilateral connections. More contra-ipsi reductions of mFA were found for TBIcs than TBIncs compared to CG. These findings suggest that TBI patients with chronic symptoms not only demonstrate decreased global and regional mFA but also reduced structural network connectivity.

Alterations in electroencephalographic functional connectivity in individuals with major depressive disorder: a resting-state electroencephalogram study.

Major depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC). In this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4-8 Hz; alpha, 8-12 Hz; beta1, 12-16 Hz; beta2, 16-24 Hz; and beta3, 24-40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17). During the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked. Our study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression. The study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD.

Disrupted Brain Network Measures in Parkinson's Disease Patients with Severe Hyposmia and Cognitively Normal Ability.

Neuroscience has revolved around brain structural changes, functional activity, and connectivity alteration in Parkinson's Disease (PD); however, how the network topology organization becomes altered is still unclear, specifically in Parkinson's patients with severe hyposmia. In this study, we have examined the functional network topological alteration in patients affected by Parkinson's Disease with normal cognitive ability (ODN), Parkinson's Disease with severe hyposmia (ODP), and healthy controls (HCs) using resting-state functional magnetic resonance imaging (rsfMRI) data. We have analyzed brain topological organization using popular graph measures such as network segregation (clustering coefficient, modularity), network integration (participation coefficient, path length), small-worldness, efficiency, centrality, and assortativity. Then, we used a feature ranking approach based on the diagonal adaptation of neighborhood component analysis, aiming to determine a graph measure that is sensitive enough to distinguish between these three different groups. We noted significantly lower segregation and local efficiency and small-worldness in ODP compared to ODN and HCs. On the contrary, we did not find differences in network integration in ODP compared to ODN and HCs, which indicates that the brain network becomes fragmented in ODP. At the brain network level, a progressive increase in the DMN (Default Mode Network) was observed from healthy controls to ODN to ODP, and a continuous decrease in the cingulo-opercular network was observed from healthy controls to ODN to ODP. Further, the feature ranking approach has shown that the whole-brain clustering coefficient and small-worldness are sensitive measures to classify ODP vs. ODN, as well as HCs. Looking at the brain regional network segregation, we have found that the cerebellum and limbic, fronto-parietal, and occipital lobes have higher ODP reductions than ODN and HCs. Our results suggest network topological measures, specifically whole-brain segregation and small-worldness decreases. At the network level, an increase in DMN and a decrease in the cingulo-opercular network could be used as biomarkers to characterize ODN and ODP.

Convergent functional change of frontoparietal network in obsessive-compulsive disorder: a voxel-based meta-analysis.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness with complex clinical manifestations. Cognitive dysfunction may underlie OC symptoms. The frontoparietal network (FPN) is a key region involved in cognitive control. However, the findings of impaired FPN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the FPN in OCD. PubMed, Web of Science, Scopus, and EBSCOhost were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies exploring dysfunction in the FPN of OCD patients using three indicators: the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo) and functional connectivity (FC). We compared all patients with OCD and control group in a primary analysis, and divided the studies by medication in secondary meta-analyses with the activation likelihood estimation (ALE) algorithm. A total of 31 eligible studies with 1359 OCD patients (756 men) and 1360 healthy controls (733 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of FPN, mainly in the left dorsolateral prefrontal cortex (DLPFC, BA9), left inferior frontal gyrus (IFG, BA47), left superior temporal gyrus (STG, BA38), right posterior cingulate cortex (PCC, BA29), right inferior parietal lobule (IPL, BA40) and bilateral caudate. Additionally, altered connectivity within- and between-FPN were observed in the bilateral DLPFC, right cingulate gyrus and right thalamus. The secondary analyses showed improved convergence relative to the primary analysis. OCD patients showed dysfunction FPN, including impaired local important nodal brain regions and hypoconnectivity within the FPN (mainly in the bilateral DLPFC), during the resting state. Moreover, FPN appears to interact with the salience network (SN) and default mode network (DMN) through pivotal brain regions. Consistent with the hypothesis of fronto-striatal circuit dysfunction, especially in the dorsal cognitive circuit, these findings provide strong evidence for integrating two pathophysiological models of OCD.

Changes of brain functional network in Alzheimer’s disease and frontotemporal dementia: a graph-theoretic analysis

BackgroundAlzheimer’s disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias, presenting with similar clinical features that challenge accurate diagnosis. Despite extensive research, the underlying pathophysiological mechanisms remain unclear, and effective treatments are limited. This study aims to investigate the alterations in brain network connectivity associated with AD and FTD to enhance our understanding of their pathophysiology and establish a scientific foundation for their diagnosis and treatment.MethodsWe analyzed preprocessed electroencephalogram (EEG) data from the OpenNeuro public dataset, comprising 36 patients with AD, 23 patients with FTD, and 29 healthy controls (HC). Participants were in a resting state with eyes closed. We estimated the average functional connectivity using the Phase Lag Index (PLI) for lower frequencies (delta and theta) and the Amplitude Envelope Correlation with leakage correction (AEC-c) for higher frequencies (alpha, beta, and gamma). Graph theory was applied to calculate topological parameters, including mean node degree, clustering coefficient, characteristic path length, global and local efficiency. A permutation test was then utilized to assess changes in brain network connectivity in AD and FTD based on these parameters.ResultsBoth AD and FTD patients showed increased mean PLI values in the theta frequency band, along with increases in average node degree, clustering coefficient, global efficiency, and local efficiency. Conversely, mean AEC-c values in the alpha frequency band were notably diminished, which was accompanied by decreases average node degree, clustering coefficient, global efficiency, and local efficiency. Furthermore, AD patients in the occipital region showed an increase in theta band node degree and decreased alpha band clustering coefficient and local efficiency, a pattern not observed in FTD.ConclusionsOur findings reveal distinct abnormalities in the functional network topology and connectivity in AD and FTD, which may contribute to a better understanding of the pathophysiological mechanisms of these diseases. Specifically, patients with AD demonstrated a more widespread change in functional connectivity, while those with FTD retained connectivity in the occipital lobe. These observations could provide valuable insights for developing electrophysiological markers to differentiate between the two diseases.

Aberrant baseline brain activity and disrupted functional connectivity in patients with vascular cognitive impairment due to cerebral small vessel disease.

This study aims to examine the alterations in aberrant brain activity and network connectivity between individuals with mild and major vascular cognitive impairment (VCI). A total of 114 patients with cerebral small vessel disease (CSVD) were included in this study, comprising 61 individuals with mild VCI (mean age, 55.7 ± 6.9 years; male, 42.6%) and 53 cases with major VCI (mean age, 57.6 ± 5.5 years; male, 58.5%). Additionally, 53 age-, gender-, and education-matched healthy subjects were recruited as normal controls (NC) (mean age, 54.9 ± 7.9 years; male, 52.9%). All participants underwent neuropsychological assessments and magnetic resonance imaging scans. One-way analysis of variance was used to compare fractional amplitude of low-frequency fluctuation (fALFF) values among the three groups. Two-sample t-tests were conducted to assess functional connectivity matrices between different groups for each connection. Moreover, mediation analyses were performed to explore the mediating effect of aberrant brain activity on the relationship between cognitive impairment and CSVD total burden. VCI patients exhibited aberrant brain activity in regions such as the right thalamus (THA_R), right cuneus (CUN_R), left postcentral gyrus (PoCG_L), right postcentral gyrus (PoCG_R), right median cingulate, paracingulate gyri (PCG_R), and left precuneus (PCUN_L). Reduced positive functional connectivity was predominantly observed among nodes including PCUN_L, CUN_R, PoCG_L, PoCG_R, right posterior cingulate (PCG_R), and left occipital gyrus (IOG_L) in VCI patients. The aberrant baseline brain activity and disrupted brain network were more pronounced with worsening cognitive function. Increased fALFF values in THA_R, CUN_R, and PoCG_L mediated cognitive impairment in CSVD patients. Abnormal brain activities in THA_R, CUN_R, and PoCG_L, along with their associated abnormal functional connections, play a significant role in VCI. The study revealed a progressive increase in aberrant brain activity and network connectivity with advancing stages of VCI.

Association between the functional connectivity of ventral tegmental area-prefrontal network and pure apathy in Parkinson's disease: a cross-sectional study.

Apathy, characterized by diminished goal-directed behaviors, frequently occurs in patients with Parkinson's disease (PD). The dopamine-releasing neurons of the ventral tegmental area (VTA) have been closely related to this behavioral disruption and project widely to the corticolimbic areas, yet their functional and structural connectivity in regard to other brain regions remain unknown in patients with PD and pure apathy (PD-PA). This study thus aimed to characterize the alterations of functional connectivity (FC) of the VTA and white matter structural connectivity in PD-PA. In this study, 29 patients with PD-PA, 37 with PD but not pure apathy (PD-NPA), and 28 matched healthy controls (HCs) underwent T1-weighted, resting state functional magnetic resonance imaging, and diffusion tensor imaging scans. Patients of this cross-sectional retrospective study were consecutively recruited from The First Affiliated Hospital of Nanjing Medical University between April 2017 and October 2021. Meanwhile, HCs were consecutively recruited from the local community and the Health Examination Center of our hospital. An analysis of covariance and a general linear model were respectively conducted to investigate the functional and structural connectivity among three groups. The tract-based spatial statistics (TBSS) approach was used to investigate the white matter structural connectivity. Patients with PD-PA showed reduced FC of the VTA with the left medial superior frontal gyrus (SFGmed) when compared to the patients with PD-NPA [t=-3.67; voxel-level P<0.001; cluster-level family-wise error-corrected P (PFWE)<0.05]. Relative to the HCs, patients with PD-PA demonstrated reduced FC of the VTA with the left SFGmed (t=-4.98; voxel-level P<0.001; cluster-level PFWE<0.05), right orbital superior frontal gyrus (SFGorb) (t=-5.08; voxel-level P<0.001; cluster-level PFWE<0.05), and right middle frontal gyrus (MFG) (t=-5.08; voxel-level P<0.001; cluster-level PFWE<0.05). Moreover, the reductions in VTA FC with the left SFGmed were associated with severe apathy symptoms in patients with PD-PA (r=-0.600; P=0.003). However, a TBSS approach did not reveal any significant differences in fiber tracts between the three groups. This study identified reduced FC within the mesocortical network (VTA-SFGmed) of patients with PD-PA. These findings may provide valuable information for administering neuromodulation therapies in the alleviation of apathy symptoms in those with PD.

Cross-Frequency Coupling as a Biomarker for Early Stroke Recovery

Background The application of neuroimaging-based biomarkers in stroke has enriched our understanding of post-stroke recovery mechanisms, including alterations in functional connectivity based on synchronous oscillatory activity across various cortical regions. Phase-amplitude coupling, a type of cross-frequency coupling, may provide additional mechanistic insight. Objective To determine how the phase of prefrontal cortex delta (1-3 Hz) oscillatory activity mediates the amplitude of motor cortex beta (13-20 Hz) oscillations in individual’s early post-stroke. Methods Participants admitted to an inpatient rehabilitation facility completed resting and task-based EEG recordings and motor assessments around the time of admission and discharge along with structural neuroimaging. Unimpaired controls completed EEG procedures during a single visit. Mixed-effects linear models were performed to assess within- and between-group differences in delta-beta prefrontomotor coupling. Associations between coupling and motor status and injury were also determined. Results Thirty individuals with stroke and 17 unimpaired controls participated. Coupling was greater during task versus rest conditions for all participants. Though coupling during affected extremity task performance decreased during hospitalization, coupling remained elevated at discharge compared to controls. Greater baseline coupling was associated with better motor status at admission and discharge and positively related to motor recovery. Coupling demonstrated both positive and negative associations with injury involving measures of lesion volume and overlap injury to anterior thalamic radiation, respectively. Conclusions This work highlights the utility of prefrontomotor cross-frequency coupling as a potential motor status and recovery biomarker in stroke. The frequency- and region-specific neurocircuitry featured in this work may also facilitate novel treatment strategies in stroke.

Altered thalamus functional connectivity in patients with acute unilateral vestibulopathy: a resting-state fMRI study.

Acute unilateral vestibulopathy (AUVP) is the second leading cause of peripheral vestibular vertigo. Full recovery of AUVP is related to sufficient central vestibular compensation. It has been confirmed that the vestibular nucleus and vestibular cortex are involved in the process of vestibular compensatory in AUVP patients. However, few studies have focused on the functional compensation of thalamus in patients with AUVP. This study aimed to explore the alterations of resting-state functional connectivity (FC) focused on thalamus using functional magnetic resonance imaging (fMRI) in AUVP patients. Data of 3D-T1 and resting-state fMRI were collected from 40 AUVP patients and 35 healthy controls (HC). Seeds-based (bilateral thalamus) FC was analyzed to investigate the changes in FC between the two groups. Furthermore, we evaluated the associations between altered thalamus FC and clinical features in AUVP patients using Pearson's partial correlation. Compared with HC, AUVP patients showed decreased FC between bilateral thalamus and left insula. We also observed decreased FC between right thalamus and left supramarginal gyrus. Additionally, we found increased FC between left thalamus and right postcentral gyrus (PCG), as well as increased FC between right thalamus and regions of bilateral PCG, right middle frontal gyrus and right middle occipital gyrus in AUVP patients. Furthermore, the FC between left thalamus and left insula was negatively correlated with values of canal paresis in patients with AUVP (p = 0.010, r = -0.434). Our results provided first evidence for the decreased thalamo-vestibular cortex pathway, as well as increased thalamo-somatosensory and thalamo-visual cortex pathway in AUVP patients. These findings help us better understand the underlying mechanisms of central dynamic compensatory following an acute unilateral peripheral vestibular damage.

Altered Corticobrainstem Connectivity during Spontaneous Fluctuations in Pain Intensity in Painful Trigeminal Neuropathy.

Chronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN). Since this brainstem circuit is modulated by higher brain input, we sought to determine which cortical sites might be influencing this brainstem network during spontaneous fluctuations in pain intensity. Over 12 min, we recorded the ongoing pain intensity in 24 PTN participants and classified them as fluctuating (n = 13) or stable (n = 11). Using a PAG seed, we identified connections between the PAG and emotional-affective sites such as the hippocampal and posterior cingulate cortices, the sensory-discriminative posterior insula, and cognitive-affective sites such as the dorsolateral prefrontal (dlPFC) and subgenual anterior cingulate cortices that were altered dependent on spontaneous high and low pain intensity. Additionally, sliding-window functional connectivity analysis revealed that the dlPFC-PAG connection anticorrelated with perceived pain intensity over the entire 12 min period. These findings reveal cortical systems underlying moment-to-moment changes in perceived pain in PTN, which likely cause dysregulation in the brainstem circuits previously identified, and consequently alter the appraisal of pain across time.

Exploring functional and structural connectivity disruptions in spinocerebellar ataxia type 3: Insights from gradient analysis.

Spinocerebellar Ataxia Type 3 (SCA3) is a rare genetic ataxia that impacts the entire brain and is characterized as a neurodegenerative disorder affecting the neural network. This study explores how alterations in the functional hierarchy, connectivity, and structural changes within specific brain regions significantly contribute to the heterogeneity of symptom manifestations in patients with SCA3. We prospectively recruited 51 patients with SCA3 and 59 age-and sex-matched healthy controls. All participants underwent comprehensive multimodal neuroimaging and clinical assessments. In SCA3 patients, an innovative approach utilizing gradients in resting-state functional connectivity (FC) was employed to examine atypical patterns of hierarchical processing topology from sensorimotor to supramodal regions in the cerebellum and cerebrum. Coupling analyses of abnormal FC and structural connectivity among regions of interest (ROIs) in the brain were also performed to characterize connectivity alterations. Additionally, relationships between quantitative ROI values and clinical variables were explored. Patients with SCA3 exhibited either compression or expansion within the primary sensorimotor-to-supramodal gradient through four distinct calculation methods, along with disruptions in FC and structural connectivity coupling. A comprehensive correlation was identified between the altered gradients and the clinical manifestations observed in patients. Notably, altered fractional anisotropy values were not significantly correlated with clinical variables. Abnormal gradients and connectivity in the cerebellar and cerebral cortices in SCA3 patients may contribute to disrupted motor-to-supramodal functions. Moreover, these findings support the potential utility of FCG analysis as a biomarker for diagnosing SCA3 and assessing treatment efficacy.

Altered Physiological, Affective, and Functional Connectivity Responses to Acute Stress in Patients With Alcohol Use Disorder

BackgroundThere is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The current study examined physiological and affective responses to stress and functional connectivity in AUD. MethodsSalivary cortisol samples, pulse rate, and affect ratings were collected on 2 days from 34 individuals with moderate or severe AUD during early abstinence and 34 control participants. On one of the days, stress was induced, and on the other day, a nonstressful control task was performed. Following the intervention, participants underwent functional magnetic resonance imaging to assess functional connectivity, with a focus on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress. ResultsFor pulse rate and cortisol, stress responses were blunted in AUD, whereas the affective response was stronger. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior default mode network, cerebellum, and midcingulate cortex and of the posterior default mode network seed with the striatum and thalamus. ConclusionsThe results suggest a dissociation between subjectively experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies.

IPSC-Derived Astrocytes and Neurons Replicate Brain Gene Expression, Epigenetic, Cell Morphology and Connectivity Alterations Found in Autism.

We used iPSC-derived neurons and astrocytes of patients with autism vs. controls (5/group) to examine whether they replicate the postmortem brain expression/epigenetic alterations of autism. Additionally, DNA methylation of 10 postmortem brain samples (5/group) was analyzed for genes affected in PSC-derived cells. We found hyperexpression of TGFB1, TGFB2, IL6 and IFI16 and decreased expression of HAP1, SIRT1, NURR1, RELN, GPX1, EN2, SLC1A2 and SLC1A3 in the astrocytes of patients with autism, along with DNA hypomethylation of TGFB2, IL6, TNFA and EN2 gene promoters and a decrease in HAP1 promoter 5-hydroxymethylation in the astrocytes of patients with autism. In neurons, HAP1 and IL6 expression trended alike. While HAP1 promoter was hypermethylated in neurons, IFI16 and SLC1A3 promoters were hypomethylated and TGFB2 exhibited increased promoter 5-hydroxymethlation. We also found a reduction in neuronal arborization, spine size, growth rate, and migration, but increased astrocyte size and a reduced growth rate in autism. In postmortem brain samples, we found DNA hypomethylation of TGFB2 and IFI16 promoter regions, but DNA hypermethylation of HAP1 and SLC1A2 promoters in autism. Autism-associated expression/epigenetic alterations in iPSC-derived cells replicated those reported in the literature, making them appropriate surrogates to study disease pathogenesis or patient-specific therapeutics.

Stage-dependent differential impact of network communication on cognitive function across the continuum of cognitive decline in Parkinson's disease

ObjectiveOur objective was to explore the patterns of resting-state network (RSN) connectivity alterations and investigate how the influences of individual-level network connections on cognition varied across clinical stages without assuming a constant relationship. Methods108 PD patients with continuum of cognitive decline (PD-NC = 46, PD-MCI = 43, PDD = 19) and 34 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological tests. Independent component analysis (ICA) and graph theory analyses (GTA) were employed to explore RSN connection changes. Additionally, stage-dependent differential impact of network communication on cognitive performance were examined using sparse varying coefficient modeling. ResultsCompared to HCs, the dorsal attention network (DAN) and dorsal sensorimotor network (dSMN) were central networks with decreased connections in PD-NC and PD-MCI stage, while the lateral visual network (LVN) emerged as a central network in patients with dementia. Additionally, connectivity of the cerebellum network (CBN) increased in the PD-NC and PD-MCI stages. GTA demonstrated decreased nodal metrics for DAN and dSMN, coupled with an increase for CBN. Moreover, the degree centrality (DC) values of DAN and dSMN exhibited a stage-dependent differential impact on cognitive performance across the continuum of cognitive decline. ConclusionOur findings suggest that across the progression of cognitive impairment, the LVN gradually transitions into a core node with reduced connectivity, while the enhancement of connections in CBN diminishes. Furthermore, the non-linear relationship between the DC values of RSNs and cognitive decline indicates the potential for tailored interventions targeting specific stages.

Altered functional connectivity subserving expressed emotion environments in schizophrenia: An fNIRS study

Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates among individuals with schizophrenia (SZ). In our previous work (Wang et al., 2023), we conducted the first feasibility study of using functional near-infrared spectroscopy (fNIRS) with our developed EE stimuli to examine cortical hemodynamics in SZ. To better understand the neural mechanisms underlying EE environmental factors in SZ, we extended our investigation by employing functional connectivity (FC) analysis with a graph theory approach to fNIRS signals. Relative to healthy controls (N=40), individuals with SZ (N=37) exhibited altered connectivity across the medial prefrontal cortex (mPFC), left ventrolateral prefrontal cortex (vlPFC), and left superior temporal gyrus (STG) while exposed to EE environments. Notably, while individuals with SZ were exposed to high-EE environments, (i) reduced connectivity was observed in these brain regions and (ii) the left vlPFC-STG coupling was found to be associated with the negative symptom severity. Taken together, our FC findings suggest individuals with SZ experience a more extensive disruption in neural functioning and coordination, particularly indicating an increased susceptibility to high-EE environments. This further supports the potential utility of integrating fNIRS with the created EE stimuli for assessing EE environmental influences, paving the way for more targeted therapeutic interventions.

Parasite prevalence is determined by infection state- and risk-dependent dispersal of the host.

The spread of parasites and the emergence of disease are currently threatening global biodiversity and human welfare. To address this threat, we need to better understand those factors that determine parasite persistence and prevalence. It is known that dispersal is central to the spatial dynamics of host-parasite systems. Yet past studies have typically assumed that dispersal is a species-level constant, despite a growing body of empirical evidence that dispersal varies with ecological context, including the risk of infection and aspects of host state such as infection status (parasite-dependent dispersal; PDD). Here, we develop a metapopulation model to understand how different forms of PDD shape the prevalence of a directly transmitted parasite. We show that increasing host dispersal rate can increase, decrease or cause a non-monotonic change in regional parasite prevalence, depending on the type of PDD and characteristics of the host-parasite system (transmission rate, virulence, and dispersal mortality). This result contrasts with previous studies with parasite-independent dispersal which concluded that prevalence increases with host dispersal rate. We argue that accounting for host dispersal responses to parasites is necessary for a complete understanding of host-parasite dynamics and for predicting how parasite prevalence will respond to changes such as human alteration of landscape connectivity. This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.