State fMRI Research Articles

Resting state functional magnetic resonance imaging in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hemopoietic stem cell transplantation

BACKGROUND: Multiple sclerosis is a chronic autoimmune disease characterized by multifocal foci of demyelination in the central nervous system, usually affecting people of working age. The disease causes damage to the blood-brain barrier, the development of multifocal inflammation, destruction of the myelin sheath of axons and various degrees of damage. It is clinically manifested by restriction of motor activity, visual acuity, as well as other symptoms leading to loss of performance and disability of the patient. AIM: determination of changes in the functional connectivity of brain neural networks in patients with multiple sclerosis before and after high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation by performing functional magnetic resonance imaging at rest. MATERIALS AND METHODS: The data of functional magnetic resonance imaging of patients with multiple sclerosis were analyzed in dynamics before and after the use of high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation. The study involved 25 patients with a verified diagnosis of multiple sclerosis. Each underwent complex magnetic resonance imaging at two time points (before and after high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation) with a difference of 12 months, which included structural magnetic resonance imaging - in order to exclude the presence of pathological foci in the brain (in addition to foci of multiple sclerosis) and functional magnetic resonance imaging.-resonance imaging at rest — to assess functional connectivity. Also, according to the method generally accepted in classical neurology, a clinical neurological examination was performed. RESULTS: At the stage of comparing data on the two groups obtained using functional magnetic resonance imaging at rest, changes in functional activity were detected in various parts of the brain, presumably responsible for clinical differences in the studied groups. CONCLUSION: Currently, the links between brain structures and morphological changes that cause cognitive impairment in multiple sclerosis are being studied. To predict the progression of the disease, the development of biomarkers, including those based on functional magnetic resonance imaging, is required. Evaluating changes in the functional connectivity of brain neural networks can help personalize therapeutic and rehabilitation approaches.

Resting-state brain activation patterns and network topology distinguish human sign and goal trackers

The “Sign-tracker/Goal-tracker” (ST/GT) is an animal model of individual differences in learning and motivational processes attributable to distinctive conditioned responses to environmental cues. While GT rats value the reward-predictive cue as a mere predictor, ST rats attribute it with incentive salience, engaging in aberrant reward-seeking behaviors that mirror those of impulse control disorders. Given its potential clinical value, the present study aimed to map such model onto humans and investigated resting state functional magnetic resonance imaging correlates of individuals categorized as more disposed to sign-tracking or goal-tracking behavior. To do so, eye-tracking was used during a translationally informed Pavlovian paradigm to classify humans as STs (n = 36) GTs (n = 35) or as Intermediates (n = 33), depending on their eye-gaze towards the reward-predictive cue or the reward location. Using connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in STs, and dominant cortical involvement in GTs. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Altered functional connectivity within the primary visual networks and neurotransmitter activity in male smokers: A group ICA study

Smoking puts patients at high risk for cognitive and psychiatric disorders. The aim of this study was to explore the effects of nicotine use on primary visual network (PVN) and its association with neurotransmitters. A total of 59 tobacco use disorder (TUD) patients and 51 healthy controls (HC) participated in this study and underwent resting state functional magnetic resonance imaging scans. Functional connectivity (FC) within the network was explored using independent component analysis. In addition, the spatial correlations of PVN changes with neurotransmitters and their correlations with clinical characteristics of patients were evaluated using the JuSpace toolbox and SPSS. We found reduced FC within the PVN in patients with TUD compared with HC. In terms of relevant analysis, there is a spatial correlation between FC changes in the patient's PVN and a higher distribution of dopamine receptor and gamma-aminobutyric acid receptor. This study revealed changes in the FC and neurotransmitters of the PVN in patients with TUD, expanding the potential neural mechanisms underlying sensory perception and psychiatric disorders.

Distinct connectivity patterns in bipolar and unipolar depression: a functional connectivity multivariate pattern analysis study

BackgroundPatients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD.MethodologyIn a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls.ResultsFC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG.ConclusionsDifferences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.

Single-dose psilocybin alters resting state functional networks in patients with body dysmorphic disorder

Body dysmorphic disorder (BDD) is a severe psychiatric condition characterized by preoccupation with perceived flaws in one's appearance, which the individual views as defective or ugly. Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, has emerged as a potential therapeutic agent for depression and other psychiatric disorders. This study aimed to identify subacute neural changes predicting symptomatic response to psilocybin treatment in adults with BDD. Eight adults with moderate-to-severe nondelusional BDD were administered a single oral 25 mg dose of psilocybin, accompanied by psychological support, and underwent resting state functional magnetic resonance imaging assessments 1 day before and 1 day after the dosing. Both a region of interest (ROI)-to-ROI analysis and multivariate pattern analysis (MVPA) were used to identify changes in resting state functional connectivity (rsFC) at day 1 after dosing that predicted treatment response at week 1, measured by change in Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDD-YBOCS) score. All participants completed the dosing and follow-up assessments over 12 weeks. BDD-YBOCS scores decreased at week 1 and week 12 after dosing (p<0.001 for both). MVPA revealed a significant increase in rsFC within the Executive Control Network (ECN) at day 1. Increased rsFC within the ECN (dlPFC – Superior Parietal Lobule [FPL]), between the ECN and Default Mode Network (dlPFC – Precuneus), and between the ECN and the Salience Network (dlPFC – insula) were predictive of improvement in BDD symptoms at week 1. These findings are the first report of subacute brain effects of psilocybin in patients with BDD. Given the small sample size and uncontrolled design of the study, larger controlled studies are necessary to validate these observations. Clinical Trials Registration: Clinicaltrials.gov ID: NCT04656301

Whole brain causal functional connectivity analysis of noise-induced deafness based on resting state-functional magnetic resonance imaging

Objective: To investigate the changes of directional connections of auditory and non-auditory in patients with noise-induced deafness (NID) by degree centrality (DC) and Granger causality analysis (GCA), and to explore the mode of brain function remodeling after NID. Methods: In October 2023, a total of 58 patients diagnosed with NID by the Occupational Diseases Department of Yantaishan Hospital of Yantai from 2014 to 2022 were collected as case group (NID group), and 42 healthy volunteers matched by gender, age and education level were selected as the control group (HC group). Resting state-functional magnetic resonance imaging (Rs-fMRI) was perfomed and PC analysis was performed. The brain regions with statistically significant differences in DC values between groups and the bilateral Heschl regions were extracted as regions of interest (ROI) for voxel-based whole brain GCA and correlation analysis. Results: Compared with HC group, the SOG.L DC value of NID group was lower, the connectivity values of SFGdor.L to SOG.L was increased, the connectivity value of PCL.L to SOG.L was decreased, the connectivity values of ORBmid.L, PCG.R and CUN. L/R to HES.L were increased, the connectivity value of SFGdor.L to HES.L was decreased, the connectivity value of HES.L to PCUN.L was decreased, the connectivity values of ORBsup.L and PCG.R to HES.R were increased, the connectivity value of HES.R to CUN.L was decreased (P voxel level<0.01, P cluster level<0.05). The connectivity value of PCL.L to SOG.L was negatively correlated with the weighted value of the better whisper frequency (P<0.05) . Conclusion: The NID patients have abnormal directional connectivity activity in multiple brain regions, such as auditory vision, executive control, somatosensory movement, and default mode network. It is suggested that hearing loss may cause complex neural remodeling between auditory and non-auditory centers.

Divergent pattern of functional connectivity within the dorsal attention network differentiates schizophrenia and bipolar disorder patients.

Schizophrenia (SZ) and bipolar disorder (BD) share common clinical features, symptoms, and neurocognitive deficits, which results in common misdiagnosis. Recently, it has been suggested that alterations within brain networks associated with perceptual organization yield potential to distinguish SZ and BD individuals. The aim of our study was to evaluate whether functional connectivity (FC) of the dorsal attention network (DAN) may differentiate both conditions. The study involved 90 participants: 30 remitted SZ patients, 30 euthymic BD patients, and 30 healthy controls (HC). Resting state functional magnetic resonance imaging was used to compare the groups in terms of the FC within the core nodes of the DAN involving frontal eye fields (FEF) and intraparietal sulcus (IPS). BD patients presented weaker inter-hemispheric FC between right and left FEF than HC. While SZ did not differ from HC in terms of inter-FEF connectivity, they presented increased inter- and intra-hemispheric FC between FEF and IPS. When compared with BD, SZ patients showed increased FC between right FEF and other nodes of the network (bilateral IPS and left FEF). We have shown that altered resting state FC within DAN differentiates BD, SZ, and HC groups. Divergent pattern of FC within DAN, consisting of hypoconnectivity in BD and hyperconnectivity in SZ, might yield a candidate biomarker for differential diagnosis between both conditions. More highly powered studies are needed to confirm these possibilities.

Local brain abnormalities in emotional disorders: Evidence from resting state fMRI studies.

Emotional disorders inflict an enormous burden on society. Research on brain abnormalities implicated in emotional disorders has witnessed great progress over the past decades. Using cross-sectional and longitudinal designs, resting state functional magnetic resonance imaging (rs-fMRI) and its analytic approaches have been applied to characterize the local properties of patients with emotional disorders. Additionally, brain activity alterations of emotional disorders have shown frequency-specific. Despite the gains in understanding the roles of brain abnormalities in emotional disorders, the limitation of the small sample size needs to be highlighted. Lastly, we proposed that evidence from the positive psychology research stream presents it as a viable discipline, whose suggestions could be developed in future emotional disorders research. Such interdisciplinary research may produce novel treatments and intervention options. This article is categorized under: Psychology > Brain Function and Dysfunction.

Brain topology underlying executive functions across the lifespan: focus on the default mode network.

While traditional neuroimaging approaches to the study of executive functions (EFs) have typically employed task-evoked paradigms, resting state studies are gaining popularity as a tool for investigating inter-individual variability in the functional connectome and its relationship to cognitive performance outside of the scanner. Using resting state functional magnetic resonance imaging data from the Human Connectome Project Lifespan database, the present study capitalized on graph theory to chart cross-sectional variations in the intrinsic functional organization of the frontoparietal (FPN) and the default mode (DMN) networks in 500 healthy individuals (from 10 to 100 years of age), to investigate the neural underpinnings of EFs across the lifespan. Topological properties of both the FPN and DMN were associated with EF performance but not with a control task of picture naming, providing specificity in support for a tight link between neuro-functional and cognitive-behavioral efficiency within the EF domain. The topological organization of the DMN, however, appeared more sensitive to age-related changes relative to that of the FPN. The DMN matures earlier in life than the FPN and it ıs more susceptible to neurodegenerative changes. Because its activity is stronger in conditions of resting state, the DMN might be easier to measure in noncompliant populations and in those at the extremes of the life-span curve, namely very young or elder participants. Here, we argue that the study of its functional architecture in relation to higher order cognition across the lifespan might, thus, be of greater interest compared with what has been traditionally thought.

Expression of microRNA induced by postoperative delirium-like behavior is associated with long-term default mode network disruption: Sequencing and a secondary analysis of resting-state fMRI data.

Resting state functional magnetic resonance imaging (rs-fMRI) has been widely used in studying default mode network (DMN) changes in postoperative delirium (POD). Reproducibility and interpretability of the analyzing results remain insufficiently studied. Delirium-like behavior was induced by tibial fixation surgery under isoflurane anesthesia. Firstly, we evaluated delirium-like behavior and inflammatory responses in hippocampus and systemic level. Then the expressions of microRNA (miRNA) and target gene were sequenced and validated. Afterwards the functional connectivity (FC) in DMN was analyzed. Finally, results were correlated with DMN changes. POD-like behavior caused significant changes of miR-34b-5p, miR-328-5p, and miR-3505 in miRNA level and Nos1, Tubb3, and Gys1 in the gene level. The FC in left and right hippocampus (L-Hip and R-Hip) and right auditory cortex (R-AC) was found significantly changed. Significant correlations were found in FCL-Hip/R-AC and FCR-Hip/R-AC for miR-34b-5p and miR-3505, as well as Nos1 and Tubb3. For miR-328-5p, no significant correlations were found. Our study demonstrates that POD-like behavior induced significant miRNA and gene expression changes were associated with hippocampus related long-term FC disruption in DMN. The results increased reproducibility and interpretability for standardized rs-fMRI data analysis, as well as providing potential targets for postoperative delirium treatment.

Structural and functional connectivity in relation to executive functions in antipsychotic-naïve patients with first episode schizophrenia

Patients with schizophrenia exhibit structural and functional dysconnectivity but the relationship to the well-documented cognitive impairments is less clear. This study investigates associations between structural and functional connectivity and executive functions in antipsychotic-naïve patients experiencing schizophrenia. Sixty-four patients with schizophrenia and 95 matched controls underwent cognitive testing, diffusion weighted imaging and resting state functional magnetic resonance imaging. In the primary analyses, groupwise interactions between structural connectivity as measured by fixel-based analyses and executive functions were investigated using multivariate linear regression analyses. For significant structural connections, secondary analyses examined whether functional connectivity and associations with executive functions also differed for the two groups. In group comparisons, patients exhibited cognitive impairments across all executive functions compared to controls (p < 0.001), but no group difference were observed in the fixel-based measures. Primary analyses revealed a groupwise interaction between planning abilities and fixel-based measures in the left anterior thalamic radiation (p = 0.004), as well as interactions between cognitive flexibility and fixel-based measures in the isthmus of corpus callosum and cingulum (p = 0.049). Secondary analyses revealed increased functional connectivity between grey matter regions connected by the left anterior thalamic radiation (left thalamus with pars opercularis p = 0.018, and pars orbitalis p = 0.003) in patients compared to controls. Moreover, a groupwise interaction was observed between cognitive flexibility and functional connectivity between contralateral regions connected by the isthmus (precuneus p = 0.028, postcentral p = 0.012), all p-values corrected for multiple comparisons. We conclude that structural and functional connectivity appear to associate with executive functions differently in antipsychotic-naïve patients with schizophrenia compared to controls.

Is there a relationship between resting state connectivity within large-scale functional networks and implicit motor learning impairments in schizophrenia and bipolar disorder?

The aim of this exploratory study is to evaluate whether implicit motor learning impairments observed in schizophrenia (SZ) and bipolar disorder (BD) are associated with the resting state functional connectivity (rs-FC) within large-scale functional networks. The study involved 30 BD patients, 30 SZ patients and 30 healthy controls (HC). Implicit motor learning was evaluated with the use of serial reaction time task (SRTT). Prior to the training patients underwent resting state functional magnetic resonance imaging (rsfMRI) examination. We have measured rs-FC within salience network (SAN), default mode network (DMN), frontoparietal network (FPN), sensorimotor network (SMN), limbic network (LN) and visual network (VIN) and their associations with implicit motor learning indices. rs-FC within SAN, DMN, FPN, SMN, LN and VIN reveal no significant association with implicit motor learning indices. BD, SZ and HC groups did not differ in terms of rs-FC within abovementioned networks. We have shown that in the studied groups SRTT performance could not be predicted by rs-FC within the major large-scale functional networks, i.e., SMN, FPN, VIN, LN, SAN and DMN. The observation of the independence of implicit motor learning from the initial activity of these systems is important for proper understanding of neuronal underpinnings of this process and planning further neuroimaging research on this topic.

Hub disruption in HIV disease and cocaine use: A connectomics analysis of brain function

BackgroundCocaine use (CU) is prevalent in people with HIV (PWH). Both conditions are linked to changes in cognitive functioning and neural network topology. The current study utilizes graph theory to investigate functional connectomics associated with HIV and CU, focusing on disruption of densely connected nodes called hubs. MethodsResting state functional magnetic resonance imaging (fMRI) from 206 adults (ages 22–55 years) were analyzed. A HIV x CU factorial design was implemented with participants in four groups: HIV+CU (n= 41), HIV only (n= 88), CU only (n= 36), and controls (n= 41). Functional connectomes were constructed, and thresholded graph metrics were calculated. Network centrality metrics – betweenness centrality (BC), participation coefficient (PC), and within module degree (WD) – were quantified into hub disruption indices (HDI). For each index, a 2×2 ANCOVA was performed controlling for education. ResultsParticipants were 68 % male and 74 % African-American with a mean age of 44.4 years. HIV and CU were associated with hub disruption in all three indices. Interactions were significant for HDI-PC and HDI-WD, such that HIV disease was associated with greater hub disruption among participants without CU, but not among participants with CU. Overall, lower global cognitive functioning was associated with greater hub disruption on all three indices. ConclusionsWidespread hub disruption was evident in HIV disease and CU, highlighting topological reorganization in both diseases with neurocognitive effects. Hub-related measures inform functional connectivity disruptions in HIV disease and CU, particularly with respect to changes in network topology throughout the connectome.

Subclinical brain manifestations of repeated mild traumatic brain injury are changed by chronic exposure to sleep loss, caffeine, and sleep aids

IntroductionAfter mild traumatic brain injury (mTBI), the brain is labile for weeks and months and vulnerable to repeated concussions. During this time, patients are exposed to everyday circumstances that, in themselves, affect brain metabolism and blood flow and neural processing. How commonplace activities interact with the injured brain is unknown. The present study in an animal model investigated the extent to which three commonly experienced exposures—daily caffeine usage, chronic sleep loss, and chronic sleep aid medication—affect the injured brain in the chronic phase. MethodsSubclinical trauma by repeated mTBIs was produced by our head rotational acceleration injury model, which causes brain injury consistent with the mechanism of concussion in humans. Forty-eight hours after a third mTBI, chronic administrations of caffeine, sleep restriction, or zolpidem (sedative hypnotic) began and were continued for 70 days. On Days 30 and 60 post injury, resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were performed. ResultsChronic caffeine, sleep restriction, and zolpidem each changed the subclinical brain characteristics of mTBI at both 30 and 60 days post injury, detected by different MRI modalities. Each treatment caused microstructural alterations in DTI metrics in the insular cortex and retrosplenial cortex compared with mTBI, but also uniquely affected other gray and white matter regions. Zolpidem administration affected the largest number of individual structures in mTBI at both 30 and 60 days, and not necessarily toward normalization (sham treatment). Chronic sleep restriction changed local functional connectivity at 30 days in diametrical opposition to chronic caffeine ingestion, and both treatment outcomes were different from sham, mTBI-only and zolpidem comparisons. The results indicate that commonly encountered exposures modify subclinical brain activity and structure long after healing is expected to be complete. ConclusionsChanges in activity and structure detected by fMRI are widely understood to reflect changes in the functions of the affected region which conceivably underlie mTBI neuropathology and symptomatology in the chronic phase after injury.

Neuroimaging correlates of Alzheimer's disease biomarker concentrations in a racially diverse high-risk cohort of middle-aged adults.

In this study, we investigated biomarkers in a midlife, racially diverse, at-risk cohort to facilitate early identification and intervention. We examined neuroimaging measures, including resting state functional magnetic resonance imaging (fMRI), white matter hyperintensity vo (WMH), and hippocampal volumes, alongside cerebrospinal fluid (CSF) markers. Our data set included 76 cognitively unimpaired, middle-aged, Black Americans (N=29, F/M=17/12) and Non-Hispanic White (N=47, F/M=27/20) individuals. We compared cerebrospinal fluid phosphorylated tau141 and amyloid beta (Aβ)42 to fMRI default mode network (DMN) subnetwork connectivity, WMH volumes, and hippocampal volumes. Results revealed a significant race × Aβ42 interaction in Black Americans: lower Aβ42 was associated with reduced DMN connectivity and increased WMH volumes regions but not in non-Hispanic White individuals. Our findings suggest that precuneus DMN connectivity and temporal WMHs may be linked to Alzheimer's disease risk pathology during middle age, particularly in Black Americans. Cerebrospinal fluid (CSF) amyloid beta (Aβ)42 relates to precuneus functional connectivity in Black, but not White, Americans. Higher white matter hyperintensity volume relates to lower CSF Aβ42 in Black Americans. Precuneus may be a hub for early Alzheimer's disease pathology changes detected by functional connectivity.

Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption.

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing. Although the high comorbidity of cigarette smoking with drinking behaviors may collectively affect brain activity, there could be independent effects of smoking in alcohol use disorder that impact brain function and behavior. We hypothesized that smoking status, independent of alcohol use, would be associated with aberrations of nucleus accumbens functional connectivity to brain regions that facilitate reward processing, salience attribution, and inhibitory control. Resting state functional magnetic resonance imaging data from thirty-one nonsmokers and nineteen smoking individuals were analyzed using seed-based correlations of the bilateral accumbens with all other brain voxels. Statistical models accounted for drinks consumed per week. The smoking group demonstrated significantly higher functional connectivity between the left accumbens and the bilateral insula and anterior cingulate cortex, as well as hyperconnectivity between the right accumbens and the insula. Confirmatory analyses using the insula and cingulate clusters generated from the original analysis as seed regions reproduced the hyperconnectivity in smokers between the bilateral insular regions and the accumbens. In conclusion, smoking status had distinct effects on neural activity; hyperconnectivity between the accumbens and insula in smokers may reflect enhanced encoding of the reinforcing effects of smoking and greater orientation toward smoking-associated stimuli.

Constraint Induced Movement Therapy Confers only a Transient Behavioral Benefit but Enduring Functional Circuit-Level Changes after Experimental TBI.

Although the behavioral outcome of Constraint-Induced Movement Therapy (CIMT) is well known, and that a combination of CIMT and arm use training potentiates the effect, there has been limited study of the brain circuits involved that respond to therapy. An understanding of CIMT from a brain network level would be useful for guiding the duration of effective therapy, the type of training regime to potentiate the outcome, as well as brain regional targets that might be amenable for direct neuromodulation. Here we investigated the effect of CIMT therapy alone unconfounded by additional rehabilitation training in order to determine the impact of intervention at the circuit level. Adult rats were injured by controlled cortical impact injury and studied before and then after 2wks of CIMT or noCIMT at 1-3wks post-injury using a combination of forelimb behavioral tasks and task-based and resting state functional magnetic resonance imaging at 3 and 7wks post-injury and compared to sham rats. There was no difference in behavior or functional imaging between CIMT and noCIMT after injury before intervention so that data are unlikely to be confounded by differences in injury severity. CIMT produced only a transient reduction in limb deficits compared to noCIMT immediately after the intervention, but no difference thereafter. However, CIMT resulted in a persistent reduction in contralesional limb-evoked activation and a corresponding ipsilesional cortical plasticity compared to noCIMT that endured 4wks after intervention. This was associated with a significant amelioration of intra and inter-hemispheric connectivity present in the noCIMT group at 7wks post-injury.

Fusing multi-scale functional connectivity patterns via Multi-Branch Vision Transformer (MB-ViT) for macaque brain age prediction

Brain age (BA) is defined as a measure of brain maturity and could help characterize both the typical brain development and neuropsychiatric disorders in mammals. Various biological phenotypes have been successfully applied to predict BA of human using chronological age (CA) as label. However, whether the BA of macaque, one of the most important animal models, can also be reliably predicted is largely unknown. To address this question, we propose a novel deep learning model called Multi-Branch Vision Transformer (MB-ViT) to fuse multi-scale (i.e., from coarse-grained to fine-grained) brain functional connectivity (FC) patterns derived from resting state functional magnetic resonance imaging (rs-fMRI) data to predict BA of macaques. The discriminative functional connections and the related brain regions contributing to the prediction are further identified based on Gradient-weighted Class Activation Mapping (Grad-CAM) method. Our proposed model successfully predicts BA of 450 normal rhesus macaques from the publicly available PRIMatE Data Exchange (PRIME-DE) dataset with lower mean absolute error (MAE) and mean square error (MSE) as well as higher Pearson's correlation coefficient (PCC) and coefficient of determination (R2) compared to other baseline models. The correlation between the predicted BA and CA reaches as high as 0.82 of our proposed method. Furthermore, our analysis reveals that the functional connections predominantly contributing to the prediction results are situated in the primary motor cortex (M1), visual cortex, area v23 in the posterior cingulate cortex, and dysgranular temporal pole. In summary, our proposed deep learning model provides an effective tool to accurately predict BA of primates (macaque in this study), and lays a solid foundation for future studies of age-related brain diseases in those animal models.

Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?

BackgroundInflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. MethodsWe used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. ResultsWe found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. ConclusionsThus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression.