Towards precision functional brain network mapping in Parkinson’s disease

State-dependent modulation of functional connectivity in early blind individuals

Stroke causes direct structural damage to local brain networks and indirect functional damage to distant brain regions. Neuroplasticity after stroke involves molecular changes within perilesional tissue that can be influenced by regions functionally connected to the site of injury. Spontaneous functional recovery can be enhanced by rehabilitative strategies, which provides experience-driven cell signaling in the brain that enhances plasticity. Functional neuroimaging in humans and rodents has shown that spontaneous recovery of sensorimotor function after stroke is associated with changes in resting-state functional connectivity (RS-FC) within and across brain networks. At the molecular level, GABAergic inhibitory interneurons can modulate brain plasticity in peri-infarct and remote brain regions. Among this cell-type, a decrease in parvalbumin (PV)-immunoreactivity has been associated with improved behavioral outcome. Subjecting rodents to multisensory stimulation through exposure to an enriched environment (EE) enhances brain plasticity and recovery of function after stroke. Yet, how multisensory stimulation relates to RS-FC has not been determined. In this study, we investigated the effect of EE on recovery of RS-FC and behavior in mice after stroke, and if EE-related changes in RS-FC were associated with levels of PV-expressing neurons. Photothrombotic stroke was induced in the sensorimotor cortex. Beginning 2 days after stroke, mice were housed in either standard environment (STD) or EE for 12 days. Housing in EE significantly improved lost tactile-proprioceptive function compared to mice housed in STD environment. RS-FC in the mouse was measured by optical intrinsic signal imaging 14 days after stroke or sham surgery. Stroke induced a marked reduction in RS-FC within several perilesional and remote brain regions. EE partially restored interhemispheric homotopic RS-FC between spared motor regions, particularly posterior secondary motor. Compared to mice housed in STD cages, EE exposure lead to increased RS-FC between posterior secondary motor regions and contralesional posterior parietal and retrosplenial regions. The increased regional RS-FC observed in EE mice after stroke was significantly correlated with decreased PV-immunoreactivity in the contralesional posterior motor region. In conclusion, experimental stroke and subsequent housing in EE induces dynamic changes in RS-FC in the mouse brain. Multisensory stimulation associated with EE enhances RS-FC among distinct brain regions relevant for recovery of sensorimotor function and controlled movements that may involve PV/GABA interneurons. Our results indicate that targeting neural circuitry involving spared motor regions across hemispheres by neuromodulation and multimodal sensory stimulation could improve rehabilitation after stroke.

Altered Resting-State Functional Connectivity in Internet Gaming Disorder: Convergent Evidence and Independent Validation.

Anticorrelated resting-state functional connectivity in awake rat brain

Recurrent episodes in major depressive disorder (MDD) are common but the neuroimaging features predictive of recurrence are not established. Participants in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study who achieved remission after 12 weeks of treatment withcognitive behavior therapy, duloxetine, or escitalopram were prospectively monitored for up to 21 months for recurrence. Neuroimaging markers predictive of recurrence were identified from week 12 functional magnetic resonance imaging scans by analyzing whole-brain resting state functional connectivity (RSFC) using seeds for four brain networks that are altered in MDD. Neuroimaging correlates of established clinical predictors of recurrence, including the magnitude of depressive (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) symptom severity at time of remission, and a comorbid anxiety disorder were examined for their similarity to the neuroimaging predictors of recurrence. Of the 344 patients randomized in PReDICT, 61 achieved remission and had usable scans for analysis, 9 of whom experienced recurrence during follow-up. Recurrence was predicted by: 1) increased RSFC between subcallosal cingulate cortex (SCC) and right anterior insula, 2) decreased RSFC between SCC and bilateral primary visual cortex, and 3) decreased RSFC between insula and bilateral caudate. Week 12 depression and anxiety scores were negatively correlated with RSFC strength between executive control and default mode networks, but they were not correlated with the three RSFC patterns predicting recurrence. We conclude that altered RSFC in SCC and anterior insula networks are prospective risk factors associated with MDD recurrence, reflecting additional sources of risk beyond clinical measures.

BackgroundCognitive Reserve (CR) refers to the brain’s ability to maintain optimal cognitive function despite damage or pathology. The neural implementation of CR is a major research focus, and resting‐state functional connectivity (RSFC) has emerged as a promising imaging correlate of CR. We assessed RSFC as a function of two different proxy measures of CR and further assessed the impact of these brain networks on longitudinal cognitive performance in a sample of cognitively unimpaired (CU) individuals at risk of Alzheimer’s disease (AD).MethodAnalyses were conducted in 328 CU individuals from the ALFA cohort (mean age = 60.8, SD = 4.74) with available CSF Aß, p‐tau, resting‐state fMRI and longitudinal cognitive assessment (average follow‐up time = 3.35 years, SD = 0.53). CSF Aß42 and Aß40 were assessed with the exploratory NeuroToolKit, while p‐tau181 was measured with the Elecsys® Phospho‐Tau (181P) CSF immunoassay (both Roche Diagnostics International Ltd). We examined the impact of years of education (YOE) and global score of the Cognitive Reserve Questionnaire (CRQ) on the RSFC amongst 246 brain regions of the Brainnetome atlas using the CONN toolbox, selecting a cluster threshold of p<0.005, and adjusting or the effects of age, sex, and APOE status.ResultOf the entire sample, 38.4% had positive CSF Aß42/40 markers. YOE was related to an increased RSFC between regions of the salience network and the anterior default‐mode network (DMN). Increased negative RSFC was found as a function of YOE between primary visual areas and regions of the executive control as well as dorsal attention (Fig. 1). In models adjusted by CSF biomarkers, the increased RSFC between the anterior DMN and salience regions predicted better PACC score over time and further modulated the association between CSF Aß42/40 and longitudinal PACC (Fig. 2). CRQ score was associated with a decreased RSFC between the posterior DMN and inferior temporal areas. These patterns of reduced RSFC significantly mediated the impact of CSF Aß42/40 on longitudinal memory performance (Fig.3).ConclusionRSFC may provide insights into the mechanisms relating CR and cognitive resilience in preclinical AD. Further, the expression of RSFC patterns may serve as an outcome in intervention studies aiming to boost CR.

Large-scale network dysfunction in the acute state compared to the remitted state of bipolar disorder: A meta-analysis of resting-state functional connectivity.

Resting-state functional connectivity in prefrontal cortex investigated by functional near-infrared spectroscopy: A longitudinal and cross-sectional study

Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD. Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD. Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up. Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson’s disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD. Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h per day, 6 days per week) of enriched rehabilitation (ER) or conventional rehabilitation (CR). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed general motor function using the Unified PD Rating Scale-part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI). Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER. Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG).

Considerable advances in the role of oxytocin (OT) effect on behavior and the brain network have been made, but the effect of OT on the association between inter-individual differences in functional connectivity (FC) and behavior is elusive. Here, by using a face-perception task and multiple connectome-based predictive models, we aimed to (1) determine whether OT could enhance the association among behavioral performance, resting-state FC (rsFC), and task-state FC (tsFC) and (2) if so, explore the role of OT in enhancing this triangular association. We found that in the OT group, the prediction performance of using rsFC or tsFC to predict task behavior was higher than that of the PL group. Additionally, the correlation coefficient between rsFC and tsFC was substantially higher in the OT group than in the PL group. The strength of these associations could be partly explained by OT altering the brain's FCs related to social cognition and face perception in both the resting and task states, mainly in brain regions such as the limbic system, prefrontal cortex, temporal poles, and temporoparietal junction. Taken together, these results provide novel evidence and a corresponding mechanism for how neuropeptides cause increased associations among inter-individual differences across different levels (e.g., behavior and large-scale brain networks in both resting and task-state), and may inspire future research on the role of neuropeptides in the cross levels association of both clinical and nonclinical use.

Developmental sex differences in resting state functional connectivity of amygdala sub-regions

The gut-brain axis represents a sophisticated bidirectional communication network connecting the gastrointestinal tract and central nervous system through neural, endocrine, and immune pathways. Insulin-like growth factors (IGFs), particularly IGF-1 and IGF-2, function as pivotal mediators within this communication framework. These polypeptide growth factors regulate intestinal barrier integrity, microbiota homeostasis, neurogenesis, and synaptic plasticity mechanisms. Clinical evidence from 1989 to 2024 demonstrates that gut microbiota-derived short-chain fatty acids enhance IGF-1 production through novel molecular mechanisms. This narrative review examines IGF roles in gut-brain communication and evaluates therapeutic potential for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and depression, as well as inflammatory bowel disorders. Current clinical trials investigating IGF-based interventions show preliminary promising results, though studies remain limited in scope and patient numbers. Key therapeutic challenges include delivery mechanisms across biological barriers, oncogenic safety concerns related to cell proliferation, and substantial individual variability in treatment responses. Future directions emphasize development of tissue-specific IGF modulators, microbiome-targeted interventions, and precision medicine approaches utilizing advanced biomarkers. Understanding IGF-mediated gut-brain communication presents therapeutic opportunities for complex pathological conditions simultaneously affecting gastrointestinal and neurological systems.

Resting-state functional connectivity as a marker of disease progression in Parkinson's disease: A longitudinal MEG study.

Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.