Decreased Resting-state Functional Connectivity Research Articles

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis in 24,539 Individuals.

Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored. We conducted a whole-brain analysis on 24,539 adults aged 40 and above from the UK Biobank cohort. Subjects were categorized into individuals who use nicotine and who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging (rfMRI). We employed a network analysis method to assess the systematic effects of tobacco smoking on brain connectome by identifying subnetworks that show nicotine-use-related differences. Our analyses revealed two nicotine-use-related subnetworks with distinct network structure (permutation p-value < 0.001). In the first network, there is a significant decrease in resting-state functional connectivity (rsFC) between the basal ganglia regions (e.g., nucleus accumbens) and 73% of the remaining brain regions, emphasizing the central hub role of basal ganglia in addictive smoking behaviors. Additionally, a data-driven subnetwork mainly involving regions from frontal and occipital lobes, showed reduced rsFC among individuals who use nicotine. The results suggest significant alterations in the communication and coordination among the basal ganglia and the broader network of brain regions. The observed changes in rsFC indicate a widespread disruption in the connectivity patterns associated with nicotine use. This study identifies rsFC subnetworks related to chronic nicotine use through whole-brain connectome analysis. The findings confirm that widespread alterations in rsFC are centered around hub nodes within the basal ganglia, including bilateral nucleus accumbens, putamen, caudate, and globus pallidus. In addition, our analysis found a clique-forming subnetwork vulnerable to tobacco smoking consisting of regions from the visual, dorsal/ventral attention, and frontoparietal networks.

From convergence insufficiency to functional reorganization: Alongitudinal randomized controlled trial of treatment-induced connectivity plasticity.

Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting-state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office-based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task-related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms. A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one-hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting-state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t-tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group-level analysis for correlations with clinical measures. Paired t-test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)-SEF-Right (R)-V1, L-SEF-CV, R-SEF-R-PEF, R-SEF-L-V1, R-SEF-R-V1, R-SEF-CV, R-PEF-CV, L-V1-CV, R-V1-CV, and L-V1-R-V1. Significant correlations were observed between the RSFC strength of the R-SEF-R-PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05). OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants.

Behavioral Activation and Brain Network Changes in Depression.

Behavioral activation (BA) is a well-established method of evidence-based treatment for depression. There are clear links between the neural mechanisms underlying reward processing and BA treatment for depressive symptoms, including anhedonia; however, integrated interpretations of these two domains are lacking. Here we examine brain imaging studies involving BA treatments to investigate how changes in brain networks, including the reward networks, mediate the therapeutic effects of BA, and whether brain circuits are predictors of BA treatment responses. Increased activation of the prefrontal and subcortical regions associated with reward processing has been reported after BA treatment. Activation of these regions improves anhedonia. Conversely, some studies have found decreased activation of prefrontal regions after BA treatment in response to cognitive control stimuli in sad contexts, which indicates that the therapeutic mechanism of BA may involve disengagement from negative or sad contexts. Furthermore, the decrease in resting-state functional connectivity of the default-mode network after BA treatment appears to facilitate the ability to counteract depressive rumination, thereby promoting enjoyable and valuable activities. Conflicting results suggest that an intact neural response to rewards or defective reward functioning is predictive of the efficacy of BA treatments. Increasing the benefits of BA treatments requires identification of the unique individual characteristics determining which of these conflicting findings are relevant for the personalized treatment of each individual with depression.

Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis.

The present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS). PedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K-means clustering on cognitive scores. MRI metrics included brain T2-hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting-state (RS) functional connectivity (FC) were estimated. Three cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005). We identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.

Decreased resting-state functional connectivity and brain network abnormalities in the prefrontal cortex of elderly patients with Parkinson's disease accompanied by depressive symptoms.

This study aimed to explore the brain network characteristics in elderly patients with Parkinson's disease (PD) with depressive symptoms. Thirty elderly PD patients with depressive symptoms (PD-D) and 26 matched PD patients without depressive symptoms (PD-NOD) were recruited based on HAMD-24 with a cut-off of 7. The resting-state functional connectivity (RSFC) was conducted by 53-channel functional near-infrared spectroscopy (fNIRS). There were no statistically significant differences in MMSE scores, disease duration, Hoehn-Yahr stage, daily levodopa equivalent dose, and MDS-UPDRS III between the two groups. However, compared to the PD-NOD group, the PD-D group showed significantly higher MDS-UPDRS II, HAMA-14, and HAMD-24. The interhemispheric FC strength and the FC strength between the left dorsolateral prefrontal cortex (DLPFC-L) and the left frontal polar area (FPA-L) was significantly lower in the PD-D group (FDR p < 0.05). As for graph theoretic metrics, the PD-D group had significantly lower degree centrality (aDc) and node efficiency (aNe) in the DLPFC-L and the FPA-L (FDR, p < 0.05), as well as decreased global efficiency (aEg). Pearson correlation analysis indicated moderate negative correlations between HAMD-24 scores and the interhemispheric FC strength, FC between DLPFC-L and FPA-L, aEg, aDc in FPA-L, aNe in DLPFC-L and FPA-L. In conclusion, PD-D patients show decreased integration and efficiency in their brain networks. Furthermore, RSFC between DLPFC-L and FPA-L regions is negatively correlated with depressive symptoms. These findings propose that targeting DLPFC-L and FPA-L regions via non-invasive brain stimulation may be a potential intervention for alleviating depressive symptoms in elderly PD patients.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus

ObjectivesTo explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. MethodsSixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. ResultsPwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26–0.39, p = 0.01–0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). ConclusionsStructural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Resting state functional connectivity modifications in monoaminergic circuits underpin fatigue development in patients with multiple sclerosis.

Dysregulation of monoaminergic networks might have a role in the pathogenesis of fatigue in multiple sclerosis (MS). We investigated longitudinal changes of resting state (RS) functional connectivity (FC) in monoaminergic networks and their association with the development of fatigue in MS. Eighty-nine MS patients and 49 age- and sex-matched healthy controls (HC) underwent neurological, fatigue, and RS functional MRI assessment at baseline and after a median follow-up of 1.3 years (interquartile range = 1.01-2.01 years). Monoaminergic-related RS FC was estimated with an independent component analysis constrained to PET atlases for dopamine (DA), noradrenaline (NA), and serotonin (5-HT) transporters. At baseline, 24 (27%) MS patients were fatigued (F) and 65 were not fatigued (NF). Of these, 22 (34%) developed fatigue (DEV-FAT) at follow-up and 43 remained not fatigued (NO-FAT). At baseline, F-MS patients showed increased monoaminergic-related RS FC in the caudate nucleus vs NF-MS and in the hippocampal, postcentral, temporal, and occipital cortices vs NF-MS and HC. Moreover, F-MS patients exhibited decreased RS FC in the frontal cortex vs NF-MS and HC, and in the thalamus vs NF-MS. During the follow-up, no RS FC changes were observed in HC. NO-FAT patients showed limited DA-related RS FC modifications, whereas DEV-FAT MS patients showed increased DA-related RS FC in the left hippocampus, significant at time-by-group interaction analysis. In the NA-related network, NO-FAT patients showed decreased RS FC over time in the left superior frontal gyrus. This region showed increased RS FC in both DEV-FAT and F-MS patients; this divergent behavior was significant at time-by-group interaction analysis. Finally, DEV-FAT MS patients presented increased 5-HT-related RS FC in the angular and middle occipital gyri, while this latter region showed decreased 5-HT-related RS FC during the follow-up in F-MS patients. In MS patients, distinct patterns of alterations were observed in monoaminergic networks based on their fatigue status. Fatigue was closely linked to specific changes in the basal ganglia and hippocampal, superior frontal, and middle occipital cortices.

Functional and structural brain MRI changes associated with cognitive worsening in multiple sclerosis: a 3-year longitudinal study.

Heterogeneous processes may contribute to cognitive impairment in multiple sclerosis (MS). To apply a longitudinal multiparametric MRI approach to identify mechanisms associated with cognitive worsening in MS patients. 3T brain functional and structural MRI scans were acquired at baseline and after a median follow-up of 3.4years in 35 MS patients and 22 healthy controls (HC). Associations between cognitive worsening (reliable change index score < -1.25 at the Rao's battery) and longitudinal changes in regional T2-hyperintense white matter (WM) lesions, diffusion tensor microstructural WM damage, gray matter (GM) atrophy and resting state (RS) functional connectivity (FC) were explored. At follow-up, HC showed no clusters of significant microstructural WM damage progression, GM atrophy or changes in RS FC. At follow-up, 10 MS patients (29%) showed cognitive worsening. Compared to cognitively stable, cognitively worsened MS patients showed more severe GM atrophy of the right anterior cingulate cortex and bilateral supplementary motor area (p < 0.001). Cognitively worsened vs cognitively stable MS patients showed also decreased RS FC in the right hippocampus of the right working memory network and in the right insula of the default mode network. Increased RS FC in the left insula of the executive control network was found in the opposite comparison (p < 0.001). No significant regional accumulation of focal WM lesions nor microstructural WM abnormalities occurred in both patients' groups. GM atrophy progression in cognitively relevant brain regions combined with functional impoverishment in networks involved in cognitive functions may represent the substrates underlying cognitive worsening in MS.

Functional and Structural MRI Changes Associated With Cognitive Worsening in Multiple Sclerosis: A 3-Year Longitudinal Study (P11-3.003)

<h3>Objective:</h3> To apply a multiparametric MRI approach to identify mechanisms associated with cognitive worsening in multiple sclerosis (MS). <h3>Background:</h3> Heterogeneous processes may contribute to cognitive impairment in MS; however, its association with brain structural and functional MRI changes still need to be fully explored. <h3>Design/Methods:</h3> Brain dual-echo, 3D T1-weighted, diffusion-weighted imaging, and resting state (RS) functional MRI scans were acquired at baseline and after median follow up of 3.4 years in 35 MS patients and 22 healthy controls (HC). Associations between cognitive worsening at Rao’s battery and longitudinal changes in T2-hyperintense lesion location, WM microstructural damage, gray matter (GM) atrophy and RS functional connectivity (FC) were explored using tract-based spatial statistic, tensor-based morphometry and independent component analysis. <h3>Results:</h3> Fifteen (43%) MS patients were cognitively impaired at baseline and 10 (29%) showed cognitive deterioration at follow-up. At baseline, compared to HC, MS patients showed widespread WM damage and GM atrophy, and decreased RS FC in some clusters of executive control (ECN) and working memory networks (WMN). At follow-up, annualized volume loss of caudate nucleus was significantly higher in MS patients with vs without cognitive deterioration (−1.2% vs −0.2%, p&lt;0.05). No significant between-group differences in lesion location, WM microstructural changes or GM atrophy were found. Compared to stable MS patients, worsened patients showed decreased RS FC in right hippocampus of right WMN and in right insula of default mode network. In the opposite comparison, increased RS FC in left insula of ECN was found. <h3>Conclusions:</h3> While cognitively-stable MS patients showed increased RS FC in left insula, possibly reflecting a compensatory mechanism, cognitive deterioration in MS patients was associated with decreased RS FC in several functional brain networks, with limited GM atrophy progression. Our study suggests that, in MS patients already characterized by substantial structural damage, cognitive deterioration might be secondary to functional network collapse. <b>Disclosure:</b> Dr. Azzimonti has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Elisabetta Pagani has nothing to disclose. Olga Marchesi has nothing to disclose. Dr. Tedone has nothing to disclose. Carmen Vizzino has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Abnormal Thalamic Functional Connectivity Correlates With Cardiorespiratory Fitness and Physical Activity in Progressive Multiple Sclerosis (P12-8.011)

Abnormal Thalamic Functional Connectivity Correlates With Cardiorespiratory Fitness and Physical Activity in Progressive Multiple Sclerosis (P12-8.011)

Association of Brain Microstructure and Functional Connectivity With Cognitive Outcomes and Postnatal Growth Among Early School–Aged Children Born With Extremely Low Birth Weight

Postnatal growth may be associated with longitudinal brain development in children born preterm. To compare brain microstructure and functional connectivity strength with cognitive outcomes in association with postnatal growth among early school-aged children born preterm with extremely low birth weight. This single-center cohort study prospectively enrolled 38 children 6 to 8 years of age born preterm with extremely low birth weight: 21 with postnatal growth failure (PGF) and 17 without PGF. Children were enrolled, past records were retrospectively reviewed, and imaging data and cognitive assessments occurred from April 29, 2013, through February 14, 2017. Image processing and statistical analyses were conducted through November 2021. Postnatal growth failure in the early neonatal period. Diffusion tensor images and resting-state functional magnetic resonance images were analyzed. Cognitive skills were tested using the Wechsler Intelligence Scale; executive function was assessed based on a composite score calculated from the synthetic composite of the Children's Color Trails Test, STROOP Color and Word Test, and Wisconsin Card Sorting Test; attention function was evaluated using the Advanced Test of Attention (ATA); and the Hollingshead Four Factor Index of Social Status-Child was estimated. Twenty-one children born preterm with PGF (14 girls [66.7%]), 17 children born preterm without PGF (6 girls [35.3%]), and 44 children born full term (24 girls [54.5%]) were recruited. Attention function was less favorable in children with PGF than those without PGF (mean [SD] ATA score: children with PGF, 63.5 [9.4]; children without PGF, 55.7 [8.0]; P = .008). Significantly lower mean (SD) fractional anisotropy in the forceps major of the corpus callosum (0.498 [0.067] vs 0.558 [0.044] vs 0.570 [0.038]) and higher mean (SD) mean diffusivity in the left superior longitudinal fasciculus-parietal bundle (8.312 [0.318] vs 7.902 [0.455] vs 8.083 [0.393]; originally calculated as millimeter squared per second and rescaled 10 000 times as mean diffusivity × 10 000) were seen among children with PGF compared with children without PGF and controls, respectively. Decreased resting-state functional connectivity strength was observed in the children with PGF. The mean diffusivity of the forceps major of the corpus callosum significantly correlated with the attention measures (r = 0.225; P = .047). Functional connectivity strength between the left superior lateral occipital cortex and both superior parietal lobules correlated with cognitive outcomes of intelligence (right superior parietal lobule, r = 0.262; P = .02; and left superior parietal lobule, r = 0.286; P = .01) and executive function (right superior parietal lobule, r = 0.367; P = .002; and left superior parietal lobule, r = 0.324; P = .007). The ATA score was positively correlated with functional connectivity strength between the precuneus and anterior division of the cingulate gyrus (r = 0.225; P = .048); however, it was negatively correlated with functional connectivity strength between the posterior cingulate gyrus and both superior parietal lobules (the right superior parietal lobule [r = -0.269; P = .02] and the left superior parietal lobule [r = -0.338; P = .002]). This cohort study suggests that the forceps major of the corpus callosum and the superior parietal lobule were vulnerable regions in preterm infants. Preterm birth and suboptimal postnatal growth could have negative associations with brain maturation, including altered microstructure and functional connectivity. Postnatal growth may be associated with differences in long-term neurodevelopment among children born preterm.

Monoaminergic network abnormalities: a marker for multiple sclerosis-related fatigue and depression

ObjectiveTo investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on...

The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS.

Decreased resting-state functional connectivity of the habenula-cerebellar in a major depressive disorder.

BackgroundIn animal experiments, the habenula and septal nuclei are known as the key brain areas of depression. However, there are few magnetic resonance imaging (MRI) studies on the functional connectivity between these areas and the subcortical areas in humans with major depression. We aimed to investigate the difference in resting-state functional connectivity (RSFC) among the major regions of interest (ROI) in the subcortical areas, including both the habenula and septal nuclei.MethodsWe performed the seed-to-voxel analysis to investigate the RSFC between both the habenula and septal nucleus, as well as other subcortical regions. Furthermore, ROI-to-ROI analysis was performed among the combinations of ROI pairs in the subcortical areas.ResultsThe seed-to-voxel analysis showed a lower RSFC between the left habenula and the cerebellum in major depressive disorder (MDD) than in healthy controls (HCs). As a result of ROI-to-ROI analysis in subcortical areas, a total of 31 pairs of FCs in the MDD group showed a lower RSFC than in the HCs group.ConclusionThis study revealed a lower RSFC between the left habenula and cerebellum in patients with MDD and reduced RSFC among numerous subcortical areas. These new findings on the neural circuitry of MDD might contribute to an in-depth understanding of depression.

Decreased functional connectivity in patients with major depressive disorder and a history of childhood traumatization through experiences of abuse

BackgroundChildhood trauma (CT) increases vulnerability for the development of major depressive disorder (MDD). Alterations in resting-state functional connectivity (RSFC) have frequently been reported for MDD. These alterations may be much more prominent in depressive patients with a history of CT. The present study aims to compare RSFC in different brain networks of patients with MDD and CT (MDD+CT) vs. MDD and no CT compared to healthy controls. Methods45 patients (22 with CT) were compared to 23 age-and-gender-matched healthy control subjects. Demographic parameters, severity of MDD, severity of CT and comorbid anxiety disorders were assessed. For assessment of RSFC alterations, a seed-based approach within five well-established RSFC networks was used. ResultsCT in MDD patients predicts severity of comorbid anxiety. A significant decrease in in-between network RSFC-values of MDD patients compared to controls was found in the network pairs of default mode network (DMN) – dorsal attention network (DAN), ventral attention network (VAN) – DMN and DAN – affective network (AN). MDD+CT patients presented more aberrant RSFC than MDD-CT patients. MDD scores predicted the decrease in RSFC for MDD patients. Higher Childhood Trauma Questionnaire (CTQ) scores are linked to reduced functional connectivity (FC) between DMN – DAN. ConclusionsOur study shows reduced RSFC in MDD patients for DMN – DAN, VAN – DMN, DAN – AN and MDD+CT patients presented more aberrant RSFC so that we suspect CT to be a considerable factor in the etiology of MDD. Through dysregulated neural circuits, CT is likely to contribute to a distinct MDD pathophysiology.

Resting-State Brain Variability in Youth With Attention-Deficit/Hyperactivity Disorder.

In this study, we sought to determine the nature of the abnormality in resting-state default mode network (DMN) activation and explore its correlation with functional connectivity in attention-deficit/hyperactivity disorder (ADHD). We obtained resting-state functional magnetic resonance images of youth with ADHD and typically developing counterparts from the publicly available ADHD-200 database. We used data from Peking University (232 scans) and New York University (172 scans); the scan repetition time was 2 s for both data collection sites. We applied generalized estimating equations to estimate the variability of the averaged blood-oxygen-level-dependent (BOLD) time series extracted from the DMN at rest. We performed network-based statistics to determine the association between the observed differences in BOLD signal variability and altered functional connectivity. We analyzed data from 105 youth with ADHD (age: mean 12.17, standard deviation 2.31, median 12.25; 15.2% female, 84.8% male) and 140 typically developing youth (age: mean 11.99, standard deviation 2.28, median 11.85; 47.1% female, 52.9% male), who aged 7–17 years. The imaging data were cross-sectionally collected for each participant at one time point. We observed a greater number of significant BOLD signal changes and higher-order polynomial significant associations in youth with ADHD. Moreover, there were significant between-group differences in BOLD signal change after the first 140 s, which coincided with decreased resting-state functional connectivity within the DMN in youth with ADHD. Increased variability of neural signaling was intermittently observed in the brains of youth with ADHD at rest, thereby indicating their default mode state was more unstable than that of typically developing youth.

Markers of emotion regulation processes: A neuroimaging and behavioral study of reappraising abilities

Emotion regulation (ER) is a core element for individual well-being, and dysregulated emotional states are prominent in several mental disorders. Moreover, dispositional use of adaptive ER strategies, such as cognitive reappraisal, is usually associated to better psychological outcomes and less emotional problems. Thus, identifying markers of emotion dysregulation could serve as a key point for developing treatments against risks of psychopathological outcomes. Neuroimaging techniques could represent a useful tool within these aims, focusing on neurobiological markers of psychopathological illness. Given the well known gender differences in using ER strategies, we examined behavioral and neuroimaging patterns associated with dispositional use of reappraisal among a non-clinical female sample. We found that the individual predisposition to use cognitive reappraisal as an emotion regulation strategy was associated with decreased levels of dysregulation. From a neurobiological perspective, difficulties in using reappraisal were associated with decreased resting-state functional connectivity (rs-FC) between the Middle Temporal Gyrus and occipito-parietal regions. Moreover, rs-FC between prefrontal and occipito-parietal brain regions was negatively associated with emotion dysregulation levels. Microstructural anomalies across white matter tracts connecting temporal, parietal, and occipital brain regions were associated to difficulties in using reappraisal. Our findings suggest that specific behavioral and neurobiological substrates are linked to reappraising abilities. Furthermore, the ability to implement adaptive ER strategies could serve as protective factor against developing emotion dysregulation.

Functional connectivity alteration of the deprived auditory regions with cognitive networks in deaf and inattentive adolescents.

Adolescents with early profound deafness may present with distractibility and inattentiveness. The brain mechanisms underlying these attention impairments remain unclear. We performed resting-state functional magnetic resonance imaging to investigate the functional connectivity of the superior temporal and transverse temporal gyri in 25 inattentive adolescents with bilateral prelingual profound deafness, and compared the results with those of 27 age-matched normal controls. Pearson and Spearman's rho correlation analyses were used to investigate the correlations of altered functional connectivity with theclinical parameters, including the duration of hearing loss sign language, and hearing aid usage. Compared with normal controls, prelingual profound deafness demonstrated mainly decreased resting-state functional connectivity between the deprived auditory regions and several other brain functional networks, including the attention control, language comprehension, default-mode, and sensorimotor networks. Moreover, we also found enhanced resting-state functional connectivity between the deprived auditory cortex and salience network. These results indicate a negative impact of early hearing loss on the attentional and other high cognitive networks, and the use of sign language and hearing aids normalized the participants' connectivity between the primary auditory cortex and attention networks, which is crucial for the early intervention and clinical care of deaf adolescents.

Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices

BackgroundAlcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging. MethodsThis was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures. ResultsBoth craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 ± 0.8% vs. 10.6 ± 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex. ConclusionsWe provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.

Resting-state functional connectivity of the amygdala subregions in unmedicated patients with obsessive-compulsive disorder before and after cognitive behavioural therapy.

Background:Cognitive behavioural therapy (CBT) is considered an effective first-line treatment for obsessive–compulsive disorder (OCD). However, the neural basis of CBT for OCD has not yet been elucidated. The role of the amygdala in OCD and its functional coupling with the cerebral cortex have received increasing attention, and may provide new understanding of the neural basis of CBT for OCD.Methods:We acquired baseline resting-state functional MRI (fMRI) scans from 45 unmedicated patients with OCD and 40 healthy controls; we then acquired another wave of resting-state fMRI scans from the patients with OCD after 12 weeks of CBT. We performed seed-based resting-state functional connectivity analyses of the amygdala subregions to examine changes in patients with OCD as a result of CBT.Results:Compared to healthy controls, patients with OCD showed significantly increased resting-state functional connectivity at baseline between the left basolateral amygdala and the right middle frontal gyrus, and between the superficial amygdala and the right cuneus. In patients with OCD who responded to CBT, we found decreased resting-state functional connectivity after CBT between the amygdala subregions and the visual association cortices and increased resting-state functional connectivity between the amygdala subregions and the right inferior parietal lobe. Furthermore, these changes in resting-state functional connectivity were positively associated with changes in scores on the compulsion or obsession subscales of the Yale–Brown Obsessive–Compulsive Scale.Limitations:Because of the lack of a second scan for healthy controls after 12 weeks, our results may have been confounded by other variables.Conclusion:Our findings yield insights into the pathophysiology of OCD; they also reveal the potential neural changes elicited by CBT, and thus have implications for guiding effective treatment strategies with CBT for OCD.