Most recent paper

Front Neurosci. 2024 Oct 30;18:1397234. doi: 10.3389/fnins.2024.1397234. eCollection 2024.

ABSTRACT

BACKGROUND: Mindfulness training has been shown to promote positive mental health outcomes and related changes in neural networks such as the default mode network, which has a central node in the posterior cingulate cortex (PCC). Previous work from our group reported on the impact of a novel, neurofeedback augmented mindfulness training (NAMT) task on regulation of PCC hemodynamic activity in typically developing adolescents. The present pilot study aimed to expand on this finding by examining the pre-post changes of the NAMT task on resting-state functional connectivity of the PCC.

METHODS: Thirty-one typically developing adolescents (14.77 ± 1.23 years; 45% female) underwent a resting-state functional magnetic resonance imaging scan both before and after completing the NAMT task. A linear mixed effects model was used to assess for changes in functional connectivity of the PCC across the two resting-state runs.

RESULTS: Data did not support the hypothesized decrease in connectivity between the PCC seed and other DMN regions from pre- to post-NAMT task. However, we observed a significant increase in functional connectivity between the PCC and a cluster encompassing the left hippocampus and amygdala following completion of the NAMT task (run 1 Fisher's Z = 0.16; run 2 Fisher's Z = 0.26).

CONCLUSION: Although preliminary, this finding suggests NAMT has the potential to strengthen connectivity between default mode and salience regions. We speculate that such changed connectivity may facilitate enhanced self-referential and emotional processing in adolescents.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT04053582.

PMID:39539491 | PMC:PMC11558881 | DOI:10.3389/fnins.2024.1397234

CNS Neurosci Ther. 2024 Nov;30(11):e70087. doi: 10.1111/cns.70087.

ABSTRACT

STUDY OBJECTIVES: Sleep deprivation (SD) is prevalent in our increasingly round-the-clock society. Optimal countermeasures such as ample recovery sleep are often unfeasible, and brief naps, while helpful, do not fully restore cognitive performance following SD. Thus, we propose that targeted interventions, such as repetitive transcranial magnetic stimulation (rTMS), may enhance cognitive performance recovery post-SD.

METHODS: We recruited 50 participants for two SD experiments. In the first experiment, participants performed a psychomotor vigilance task (PVT) under three conditions: normal sleep (resting wakefulness), after 24 h of SD, and following a subsequent 30-min nap. We analyzed dynamic changes in PVT outcomes and cerebral responses across conditions to identify the optimal stimulation target. Experiment 2 adopted the same protocol except that, after the nap, 10-Hz, sham-controlled, individualized rTMS was administrated. Then, an analysis of variance was conducted to investigate the ability of stimulation to improve the PVT reaction times.

RESULTS: Through task-related functional magnetic resonance imaging, we identified cerebral responses within the right middle frontal gyrus (MFG) as the optimal stimulation target. Subsequent application of individualized 10-Hz rTMS over the right MFG attenuated SD-induced deterioration of vigilance.

CONCLUSION: Our findings suggest that combining a brief nap with individualized rTMS can significantly aid the recovery of vigilance following SD. This approach, through modulating neural activity within functional brain networks, is a promising strategy to counteract the cognitive effects of SD.

PMID:39539093 | PMC:PMC11561304 | DOI:10.1111/cns.70087

Neuroimage Clin. 2024 Nov 2;44:103696. doi: 10.1016/j.nicl.2024.103696. Online ahead of print.

ABSTRACT

BACKGROUND: Working memory (WM) deficits are among the most prominent cognitive impairments in attention deficit hyperactivity disorder (ADHD). While functional connectivity is a prevailing approach in brain imaging of ADHD, alterations in WM-related functional brain networks and their malleability by cognitive training are not well known. We examined whole-brain functional connectivity differences between adults with and without ADHD during n-back WM tasks and rest at pretest, as well as the effects of WM training on functional and structural brain connectivity in the ADHD group.

METHODS: Forty-two adults with ADHD and 36 neurotypical controls performed visuospatial and verbal n-back tasks during functional magnetic resonance imaging (fMRI). In addition, seven-minute resting state fMRI data and diffusion-weighted MR images were collected from all participants. The adults with ADHD continued into a 5-week randomized controlled WM training trial (experimental group training on a dual n-back task, n = 21; active control group training on Bejeweled II video game, n = 21), followed by a posttraining MRI. Brain connectivity was examined with Network-Based Statistic.

RESULTS: At the pretest, adults with ADHD had decreased functional connectivity compared with the neurotypical controls during both n-back tasks in networks encompassing fronto-parietal, temporal, occipital, cerebellar, and subcortical brain regions. Furthermore, WM-related connectivity in widespread networks was associated with performance accuracy in a continuous performance test. Regarding resting state connectivity, no group differences or associations with task performance were observed. WM training did not modulate functional or structural connectivity compared with the active controls.

CONCLUSION: Our results indicate large-scale abnormalities in functional brain networks underlying deficits in verbal and visuospatial WM commonly faced in ADHD. Training-induced plasticity in these networks may be limited.

PMID:39536524 | DOI:10.1016/j.nicl.2024.103696

J Cogn Neurosci. 2024 Nov 9:1-30. doi: 10.1162/jocn_a_02278. Online ahead of print.

ABSTRACT

The dual-stream model of speech processing describes a cortical network involved in speech processing. However, it is not yet known if the dual-stream model represents actual intrinsic functional brain networks. Furthermore, it is unclear how disruptions after a stroke to the functional connectivity of the dual-stream model's regions are related to speech production and comprehension impairments seen in aphasia. To address these questions, in the present study, we examined two independent resting-state fMRI data sets: (1) 28 neurotypical matched controls and (2) 28 chronic left-hemisphere stroke survivors collected at another site. We successfully identified an intrinsic functional network among the dual-stream model's regions in the control group using functional connectivity. We then used both standard functional connectivity analyses and graph theory approaches to determine how this connectivity may predict performance on clinical aphasia assessments. Our findings provide evidence that the dual-stream model of speech processing is an intrinsic network as measured via resting-state MRI and that functional connectivity of the hub nodes of the dual-stream network defined by graph theory methods, but not overall average network connectivity, is weaker in the stroke group than in the control participants. In addition, the functional connectivity of the hub nodes predicted linguistic impairments on clinical assessments. In particular, the relative strength of connectivity of the right hemisphere's homologues of the left dorsal stream hubs to the left dorsal hubs, versus to the right ventral stream hubs, is a particularly strong predictor of poststroke aphasia severity and symptomology.

PMID:39536158 | DOI:10.1162/jocn_a_02278

Front Hum Neurosci. 2024 Oct 29;18:1453638. doi: 10.3389/fnhum.2024.1453638. eCollection 2024.

ABSTRACT

BACKGROUND: Temporal interference (TI) stimulation, an innovative non-invasive brain stimulation approach, has the potential to activate neurons in deep brain regions. However, the dynamic mechanisms underlying its neuromodulatory effects are not fully understood. This study aims to investigate the effects of TI stimulation on dynamic functional connectivity (dFC) in the motor cortex.

METHODS: 40 healthy adults underwent both TI and tDCS in a double-blind, randomized crossover design, with sessions separated by at least 48 h. The total stimulation intensity of TI is 4 mA, with each channel's intensity set at 2 mA and a 20 Hz frequency difference (2 kHz and 2.02 kHz). The tDCS stimulation intensity is 2 mA. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before, during, and after stimulation. dFC was calculated using the left primary motor cortex (M1) as the region of interest (ROI) and analyzed using a sliding time-window method. A two-way repeated measures ANOVA (group × time) was conducted to evaluate the effects of TI and tDCS on changes in dFC.

RESULTS: For CV of dFC, significant main effects of stimulation type (P = 0.004) and time (P < 0.001) were observed. TI showed lower CV of dFC than tDCS in the left postcentral gyrus (P < 0.001). TI-T2 displayed lower CV of dFC than TI-T1 in the left precentral gyrus (P < 0.001). For mean dFC, a significant main effect of time was found (P < 0.001). TI-T2 showed higher mean dFC than tDCS-T2 in the left postcentral gyrus (P = 0.018). Within-group comparisons revealed significant differences between time points in both TI and tDCS groups, primarily in the left precentral and postcentral gyri (all P < 0.001). Results were consistent across different window sizes.

CONCLUSION: 20 Hz TI stimulation altered dFC in the primary motor cortex, leading to a significant decreasing variability and increasing mean connectivity strength in dFC. This outcome indicates that the 20 Hz TI frequency interacted with the motor cortex's natural resonance.

PMID:39534013 | PMC:PMC11554487 | DOI:10.3389/fnhum.2024.1453638

Int J Clin Health Psychol. 2024 Oct-Dec;24(4):100517. doi: 10.1016/j.ijchp.2024.100517. Epub 2024 Oct 30.

ABSTRACT

BACKGROUND/OBJECTIVE: Research on the ontogenetic development of brain networks using resting state has shown to be useful for understanding age-associated changes in brain connectivity. This work aimed to analyze the relationship between brain connectivity, age and intelligence.

METHODS: A sample of 26 children and adolescents between 6 and 18 years of both sexes underwent a resting-state functional magnetic resonance imaging study. We estimated the values of fractional Amplitude low-frequency fluctuations (fALFF) and the values of Regional homogeneity (ReHo) in a voxelwise analysis to later correlate them with age and intelligence quotient (IQ).

RESULTS: No significant correlations were found with IQ, but it was found that the fALFF values of the left precentral cortex (premotor cortex and supplementary motor area), as well as the ReHo values of the medial frontal gyrus, and the precentral cortex of the left hemisphere, correlate with age. Conclusions: Hubs related to various "task positive" networks closely related to cognitive functioning would present a development more related to age and relatively independent of individual differences in intelligence. These findings suggest that the premotor cortex and supplementary motor cortex could be a cortical hub that develops earlier than previously reported and that it would be more related to age than to intelligence level.

PMID:39533988 | PMC:PMC11555343 | DOI:10.1016/j.ijchp.2024.100517

Hum Brain Mapp. 2024 Nov;45(16):e70076. doi: 10.1002/hbm.70076.

ABSTRACT

Perfusion changes in white matter (WM) lesions and normal-appearing brain regions play an important pathophysiological role in multiple sclerosis (MS). However, most perfusion imaging methods require exogenous contrast agents, the repeated use of which is discouraged. Using resting-state functional MRI (rs-fMRI), we aimed to investigate differences in perfusion between white matter lesions and normal-appearing brain regions in MS and healthy participants. A total of 41 MS patients and 41 age- and sex-matched healthy participants received rs-fMRI, from which measures of cerebral hemodynamics and oxygenation were extracted and compared across brain regions and study groups using within- and between-group nonparametric tests, linear mixed models, and robust multiple linear regression. We found longer blood arrival times and lower blood volumes in lesions than in normal-appearing WM. Higher blood volumes were found in MS patients' deep WM lesions compared to healthy participants, and blood arrival time was more delayed in MS patients' deep WM lesions than in healthy participants. Delayed blood arrival time in the cortical grey matter was associated with greater cognitive impairment in MS patients. Perfusion imaging using rs-fMRI is useful for WM lesion characterization. rs-fMRI-based blood arrival times and volumes are associated with cognitive function.

PMID:39535849 | PMC:PMC11558553 | DOI:10.1002/hbm.70076

Asian J Psychiatr. 2024 Nov 4;102:104303. doi: 10.1016/j.ajp.2024.104303. Online ahead of print.

ABSTRACT

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) studies have shown altered brain activity in major depressive disorder (MDD) and schizophrenia (SZ). Despite differing diagnoses, SZ and MDD share similar features. However, functional brain activity similarities and differences between SZ and MDD remain unclear.

METHODS: Participants with MDD, SZ, and normal controls (n=36 each) underwent resting-state fMRI scans. Amplitude of low-frequency fluctuations (ALFF) was used to analyze the preprocessed rs-fMRI data. One-way ANOVAs and post hoc analyses compared ALFF values in different brain regions. Pearson correlation analysis examined associations with clinical symptoms.

RESULTS: Comparison among the three groups revealed significant differences in ALFF values within the left superior parietal cortex (L-SPC) and bilateral striatum. Through pairwise comparisons, patients with SZ but not patients with MDD were found to exhibit increased striatum ALFF values relative to NC individuals, but decreased in MDD. Meanwhile, L-SPC ALFF values were significantly increased in patients with SZ relative to both normal control individuals and patients with MDD, while no differences in these values were observed between the normal control and MDD groups. The Pearson correlation analyses showed significant positive correlations between ALFF in the striatum and PANSS positive score, but no significant correlation with other symptom severity in SZ and MDD.

CONCLUSION: These findings support the hypothesis of alterations in brain functional activity as a fundamental component of the pathogenesis of MDD and SZ. The observed differences in functional brain activity in the superior parietal cortex and striatum between MDD and SZ provide a neuroimaging basis that can contribute to the differential diagnosis of these debilitating conditions.

PMID:39531911 | DOI:10.1016/j.ajp.2024.104303

Brain Connect. 2024 Nov 12. doi: 10.1089/brain.2023.0087. Online ahead of print.

ABSTRACT

Introduction: The influence of the cerebellum in poststroke aphasia recovery is poorly understood. Despite the right cerebellum being identified as a critical region involved in both language and cognitive functions, little is known about functional connections between the cerebellum and bilateral cortical hemispheres following stroke. This study investigated the relationship between chronic poststroke naming deficits and cerebello-cerebral resting-state functional connectivity (FC). Methods: Twenty-five cognitively normal participants and 42 participants with chronic poststroke aphasia underwent resting-state functional magnetic resonance imaging. Participants with aphasia also underwent language assessment. We conducted regions of interest (ROI)-to-ROI analyses to investigate the FC between the right cerebellar Crus I/II (seed ROI; Cereb1r/Cereb2r) and bilateral cortical language regions and compared these results to cognitively normal controls. Single-subject connectivity parameters were extracted and used as independent variables in a stepwise multiple linear regression model associating Boston Naming Test (BNT) score with FC measures. Results: FC analyses demonstrated correlations between the right cerebellar Crus I/II and both left and right cortical regions for both cognitively normal controls and stroke participants. Additionally, aphasia severity and lesion load had an effect on the cerebello-cerebral network connectivity in participants with aphasia. In a stepwise multiple linear regression, controlling for aphasia severity, time poststroke and lesion load, FC between the right Cereb2-left Cereb1 (standardized beta [std B]= -0.255, p < 0.004), right Cereb2-right anterior MTG (std B = 0.259, p < 0.004), and the right Cereb2-left anterior STG (std B = -0.208, p < 0.018) were significant predictors of BNT score. The overall model fit was R2 = 0.786 (p = 0.001). Conclusion: Functional connections between the right cerebellum and residual bilateral cerebral hemisphere regions may play a role in predicting naming ability in poststroke aphasia.

PMID:39531223 | DOI:10.1089/brain.2023.0087

Trials. 2024 Nov 11;25(1):752. doi: 10.1186/s13063-024-08606-8.

ABSTRACT

BACKGROUND: The therapeutic use of intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (LDLPFC) is a relatively new but promising treatment option for depression. There is a need for more knowledge on the mechanisms involved in its antidepressant effects.

METHODS: This is a single-centre, prospective, randomized, double-blind, placebo-controlled trial with two arms, iTBS and sham iTBS. Adult outpatients with unipolar major depressive disorder of at least moderate severity will undergo cognitive assessment with an N-back task (0-back and 2-back), functional and structural magnetic resonance imaging and assessment of depression severity before and after brain stimulation. Neuronavigated iTBS or sham stimulation will be targeted at the LDPFC once a day for 10 consecutive workdays. ITBS will be delivered with the parameters 120% of resting motor threshold, triplet 50 Hz bursts repeated at 5 Hz; 2 s on and 8 s off, 600 pulses per session with a total duration of 3 min 9 s. The severity of depression will be measured with the Montogomery Aasberg Depression Rating Scale and the Beck Depression Inventory - second edition. In the iTBS group relative to sham, we expect significant antidepressant effects and improved N-back performance, associated with increased integrity in white matter tracts functionally connected with the LDLPFC and emotion regulation areas within the rostral anterior cingulate cortices, alongside potential increases in cortical thickness in these regions. On functional imaging, we expect to observe increased brain activity in the LDPFC during the performance of the N-back condition with higher cognitive load (2-back) in the iTBS group relative to sham.

DISCUSSION: iTBS is a promising, time-efficient, and considered a safe treatment option for depression according to existing evidence. This trial aims to assess the neurocognitive impact of a 2-week, once-daily iTBS compared to sham iTBS, targeting the LDLPFC in depressed adult outpatients. The study investigates the relationships between changes in cerebral measures and cognitive performance on an N-back task in relation to the antidepressant effect following iTBS. This trial delves into the neurocognitive mechanisms of iTBS in depression, potentially offering novel scientific insights into its treatment effects and mechanisms of action.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06534684. Retrospectively registered on August 1st 2024.

PMID:39529199 | PMC:PMC11555895 | DOI:10.1186/s13063-024-08606-8

Neuroscience. 2024 Oct 17:S0306-4522(24)00537-2. doi: 10.1016/j.neuroscience.2024.10.026. Online ahead of print.

ABSTRACT

The aim of this study was to investigate alterations in the resting-state brain functional network characteristics of lifelong premature ejaculation (PE) patients using surface-based degree centrality (DC), and to analyze the correlation between these alterations and clinical symptoms in PE patients. The study included individuals with lifelong PE (patient group, n = 36) and a control group matched by age and education level (control group, n = 22). Resting-state functional magnetic resonance imaging (fMRI) scans were performed on all participants. Surface-based degree centrality analysis was conducted and the differences between the two groups were compared using t-tests. Further, the DC values of brain regions showing significant differences were correlated with clinical symptoms. Compared to the control group, the patient group exhibited significantly reduced degree centrality (DC) values in the left precuneus and significantly increased DC values in the right supplementary motor area (SMA). Furthermore, intravaginal ejaculatory latency time (IELT) and Chinese Index of Premature Ejaculation (CIPE) values were positively correlated with left precuneus DC values and negatively correlated with right SMA DC values. Patients with primary lifelong ejaculation demonstrate abnormalities in key brain network nodes and their connections with relevant brain regions, which are strongly associate with clinical symptoms. These findings enhance our understanding of the neuronal pathological changes in PE patients.

PMID:39426708 | DOI:10.1016/j.neuroscience.2024.10.026

Mol Psychiatry. 2024 Oct 18. doi: 10.1038/s41380-024-02779-z. Online ahead of print.

ABSTRACT

Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (AppNL-G-F/hMapt), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923/ALX001) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment.

PMID:39424929 | DOI:10.1038/s41380-024-02779-z

Sci Rep. 2024 Oct 18;14(1):24473. doi: 10.1038/s41598-024-74282-y.

ABSTRACT

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by deficits in attention, hyperactivity, and/or impulsivity. Resting-state functional connectivity analysis has emerged as a promising approach for ADHD classification using resting-state functional magnetic resonance imaging (rs-fMRI), although with limited accuracy. Recent studies have highlighted dynamic changes in functional connectivity patterns among ADHD children. In this study, we introduce Skip-Vote-Net, a novel deep learning-based network designed for classifying ADHD from typically developing children (TDC) by leveraging dynamic connectivity analysis on rs-fMRI data collected from 222 participants included in the NYU dataset within the ADHD-200 database. Initially, for each subject, functional connectivity matrices were constructed from overlapping segments using Pearson's correlation between mean time series of 116 regions of interest defined by the Automated Anatomical Labeling (AAL) 116 atlas. Skip-Vote-Net was then developed, employing a majority voting mechanism to classify ADHD/TDC children, as well as distinguishing between the two main subtypes: the inattentive subtype (ADHDI) and the predominantly combined subtype (ADHDC). The proposed method was evaluated across four classification scenarios: (1) two-class classification of ADHD from TD children using balanced data, (2) two-class classification between ADHD and TD children using unbalanced data, (3) two-class classification between ADHDI and ADHDC, and (4) three-class classification among ADHDI, ADHDC, and TD children. Using Skip-Vote-Net, we achieved mean classification accuracies of 97% ± 1.87 and 97.7% ± 2.2 for the balanced and unbalanced classification cases, respectively. Furthermore, the mean classification accuracy for discriminating between ADHDI and ADHDC reached 99.4% ± 1.21. Finally, the proposed method demonstrated an average accuracy of 98.86% ± 1.03 in classifying ADHDI, ADHDC, and TD children collectively. Our findings highlight the superior performance of Skip-Vote-Net over existing methods in the classification of ADHD, showcasing its potential as an effective diagnostic tool for identifying ADHD subtypes and distinguishing ADHD from typically developing children.

PMID:39424632 | DOI:10.1038/s41598-024-74282-y

Neuroimage. 2024 Oct 16:120886. doi: 10.1016/j.neuroimage.2024.120886. Online ahead of print.

ABSTRACT

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.

PMID:39424016 | DOI:10.1016/j.neuroimage.2024.120886

Clin Transl Med. 2024 Oct;14(10):e70055. doi: 10.1002/ctm2.70055.

ABSTRACT

BACKGROUND: Huntington's disease (HD) is marked by irreversible loss of neuronal function for which currently no availability for disease-modifying treatment exists. Advances in the understanding of disease progression can aid biomarker development, which in turn can accelerate therapeutic discovery.

METHODS: We characterised the progression of altered dynamics of whole-brain network states in the zQ175DN mouse model of HD using a dynamic functional connectivity (FC) approach to resting-state fMRI and identified quasi-periodic patterns (QPPs) of brain activity constituting the most prominent resting-state networks.

RESULTS: The occurrence of the normative QPPs, as observed in healthy controls, was reduced in the HD model as the phenotype progressed. This uncovered progressive cessation of synchronous brain activity with phenotypic progression, which is not observed with the conventional static FC approaches. To better understand the potential underlying cause of the observed changes in these brain states, we further assessed how mutant huntingtin (mHTT) protein deposition affects astrocytes and pericytes - one of the most important effectors of neurovascular coupling, along phenotypic progression. Increased cell-type dependent mHTT deposition was observed at the age of onset of motor anomalies, in the caudate putamen, somatosensory and motor cortex, regions that are prominently involved in HD pathology as seen in humans.

CONCLUSION: Our findings provide meaningful insights into the development and progression of altered functional brain dynamics in this HD model and open new avenues in assessing the dynamics of whole brain states, through QPPs, in clinical HD research.

HIGHLIGHTS: Hyperactivity in the LCN-linked regions within short QPPs observed before motor impairment onset. DMLN QPP presents a progressive decrease in DMLN activity and occurrence along HD-like phenotype development. Breakdown of the LCN DMLN state flux at motor onset leads to a subsequent absence of the LCN DMLN QPP at an advanced HD-like stage.

PMID:39422700 | DOI:10.1002/ctm2.70055

Imaging Neurosci (Camb). 2024;2:10.1162/imag_a_00258. doi: 10.1162/imag_a_00258. Epub 2024 Aug 12.

ABSTRACT

The auditory system comprises multiple subcortical brain structures that process and refine incoming acoustic signals along the primary auditory pathway. Due to technical limitations of imaging small structures deep inside the brain, most of our knowledge of the subcortical auditory system is based on research in animal models using invasive methodologies. Advances in ultrahigh-field functional magnetic resonance imaging (fMRI) acquisition have enabled novel noninvasive investigations of the human auditory subcortex, including fundamental features of auditory representation such as tonotopy and periodotopy. However, functional connectivity across subcortical networks is still underexplored in humans, with ongoing development of related methods. Traditionally, functional connectivity is estimated from fMRI data with full correlation matrices. However, partial correlations reveal the relationship between two regions after removing the effects of all other regions, reflecting more direct connectivity. Partial correlation analysis is particularly promising in the ascending auditory system, where sensory information is passed in an obligatory manner, from nucleus to nucleus up the primary auditory pathway, providing redundant but also increasingly abstract representations of auditory stimuli. While most existing methods for learning conditional dependency structures based on partial correlations assume independently and identically Gaussian distributed data, fMRI data exhibit significant deviations from Gaussianity as well as high-temporal autocorrelation. In this paper, we developed an autoregressive matrix-Gaussian copula graphical model (ARMGCGM) approach to estimate the partial correlations and thereby infer the functional connectivity patterns within the auditory system while appropriately accounting for autocorrelations between successive fMRI scans. Our results show strong positive partial correlations between successive structures in the primary auditory pathway on each side (left and right), including between auditory midbrain and thalamus, and between primary and associative auditory cortex. These results are highly stable when splitting the data in halves according to the acquisition schemes and computing partial correlations separately for each half of the data, as well as across cross-validation folds. In contrast, full correlation-based analysis identified a rich network of interconnectivity that was not specific to adjacent nodes along the pathway. Overall, our results demonstrate that unique functional connectivity patterns along the auditory pathway are recoverable using novel connectivity approaches and that our connectivity methods are reliable across multiple acquisitions.

PMID:39421593 | PMC:PMC11485223 | DOI:10.1162/imag_a_00258

J Transl Med. 2024 Oct 17;22(1):945. doi: 10.1186/s12967-024-05757-9.

ABSTRACT

BACKGROUND: Although numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA).

METHODS: Demographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors.

RESULTS: LSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05).

CONCLUSION: These findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/ .

PMID:39420319 | DOI:10.1186/s12967-024-05757-9

Neuroimage. 2024 Oct 15:120887. doi: 10.1016/j.neuroimage.2024.120887. Online ahead of print.

ABSTRACT

Current models of brain networks may potentially be improved by integrating our knowledge of structural connections, within and between circuits, with metrics of functional interactions between network nodes. The former may be obtained from diffusion MRI of white matter (WM), while the latter may be derived by measuring correlations between resting state BOLD signals from pairs of gray matter (GM) regions. From inspection of diffusion MRI data, it is clear that each WM voxel within a 3D image array may be traversed by multiple WM structural tracts, each of which connects a pair of GM nodes. We hypothesized that by appropriately weighting and then integrating the functional connectivity of each such connected pair, the overall engagement of any WM voxel in brain functions could be evaluated. This model introduces a structural constraint to earlier studies of WM engagement and addresses some limitations of previous efforts to relate structure and function. Using concepts derived from graph theory, we obtained spatial maps of WM engagement which highlight WM regions critical for efficient communications across the brain. The distributions of WM engagement are highly reproducible across subjects and depict a notable interdependence between the distribution of GM activities and the detailed organization of WM. Additionally, we provide evidence that the engagement varies over time and shows significant differences between genders. These findings suggest the potential of WM engagement as a measure of the integrity of normal brain functions and as a biomarker for neurological and cognitive disorders.

PMID:39419426 | DOI:10.1016/j.neuroimage.2024.120887

Brain Behav. 2024 Oct;14(10):e70106. doi: 10.1002/brb3.70106.

ABSTRACT

OBJECTIVE: Chronic kidney disease (CKD) is increasingly recognized as a risk factor for alterations in brain function. However, detecting early-stage symptoms and structural changes remains challenging, potentially leading to delayed treatment. In our study, we aimed to investigate spontaneous brain activity changes in CKD patients using resting-state functional magnetic resonance imaging (fMRI). Additionally, we explored the correlation between common biomarkers reflecting CKD severity and brain activity.

METHODS: We recruited a cohort of 22 non-dialysis-dependent CKD patients and 22 controls for resting-state fMRI scans. Amplitude of low-frequency fluctuations (ALFFs) and regional homogeneity (ReHo) were calculated to evaluate brain activity. Regression analysis was conducted to explore the correlations between biomarkers reflecting the severity of CKD and brain activity.

RESULTS: CKD patients exhibited reduced z-scored ALFF (zALFF) and mean ALFF (mALFF) in the bilateral putamen, right caudate nucleus, left anterior cingulate, and right precuneus. Changes in bilateral putamen were also found in smCohe-ReHo and szCohe-ReHo analyses. Urine albumin-to-creatinine ratio (UACR), urine protein-to-creatinine ratio (UPCR), and serum albumin levels were associated with attenuated putamen activity.

CONCLUSION: Non-dialysis-dependent CKD patients had changes in zALFF, mALFF, smCohe-ReHo, and szCohe-ReHo values in specific brain regions, especially bilateral putamen. UACR, UPCR, and serum albumin levels are associated with putamen activity attenuation in rs-fMRI.

PMID:39417474 | DOI:10.1002/brb3.70106

Ther Adv Ophthalmol. 2024 Oct 15;16:25158414241280201. doi: 10.1177/25158414241280201. eCollection 2024 Jan-Dec.

ABSTRACT

BACKGROUND: Charles Bonnet syndrome (CBS) is a condition in which people with vision loss experience complex visual hallucinations. These complex visual hallucinations may be caused by increased excitability in the visual cortex that are present in some people with vision loss but not others.

OBJECTIVES: We aimed to evaluate the association between γ-aminobutyric acid (GABA) in the visual cortex and CBS. We also tested the relationship among visually evoked responses, functional connectivity, and CBS.

DESIGN: This is a prospective, case-controlled, cross-sectional observational study.

METHODS: We applied 3-Tesla magnetic resonance spectroscopy, as well as task-based and resting state (RS) connectivity functional magnetic resonance imaging in six participants with CBS and six controls without CBS. GABA+ was measured in the early visual cortex (EVC) and in the lateral occipital cortex (LOC). Participants also completed visual acuity and cognitive tests, and the North-East Visual Hallucinations Interview.

RESULTS: The two groups were well-matched for age, gender, visual acuity and cognitive scores. There was no difference in GABA+ levels between groups in the visual cortex. Most participants showed the expected blood oxygenation level dependent (BOLD) activation to images of objects and the phase-scrambled control. Using a fixed effects analysis, we found that BOLD activation was greater in participants with CBS compared to controls. Analysis of RS connectivity with LOC and EVC showed little difference between groups. A fixed effects analysis showed a correlation between the extent of functional connectivity with LOC and hallucination strength.

CONCLUSION: Overall, our results provide no strong evidence for an association between GABAergic inhibition in the visual cortex and CBS. We only found subtle differences in visual function and connectivity between groups. These findings suggest that the neurochemistry and visual connectivity for people with Charles Bonnet hallucinations are comparable to a sight loss population. Differences between groups may emerge when investigating subtle and transient changes that occur at the time of visual hallucinations.

PMID:39416975 | PMC:PMC11481065 | DOI:10.1177/25158414241280201