Altered Resting-state Functional Connectivity Research Articles

Evaluating migraine with typical aura with neuroimaging.

To provide an up-to-date narrative literature review of imaging in migraine with typical aura, as a means to understand better migraine subtypes and aura biology. Characterizing subtypes of migraine with typical aura and appreciating possible biological differences between migraine with and without aura, are important to understanding the neurobiology of aura and trying to advance personalized therapeutics in this area through imaging biomarkers. One means of doing this over recent years has been the use of increasingly advanced neuroimaging techniques. We conducted a literature review of neuroimaging studies in migraine with aura, using a PubMed search for terms 'imaging migraine', 'aura imaging', 'migraine with aura imaging', 'migraine functional imaging' and 'migraine structural imaging'. We collated the findings of the main studies, excluding small case reports and series with n < 6, and have summarized these and their implications for better understanding of aura mechanisms. Aura is likely mediated by widespread brain dysfunction in areas involving, but not limited to, visual cortex, somatosensory and insular cortex, and thalamus. Higher brain excitability in response to sensory stimulation and altered resting-state functional connectivity in migraine sufferers with aura could have a genetic component. Pure visual aura compared to visual aura with other sensory or speech symptoms as well, may involve different functional reorganization of brain networks and additional mitochondrial dysfunction mediating more aura symptoms. There is a suggestion of at least some distinct neurobiological differences between migraine with and without aura, despite the shared phenotypic similarity in headache and other migraine-associated symptoms. It is clear from the vast majority of aura phenotypes being visual that there is a particular predisposition of the occipital cortex to aura mechanisms. Why this is the case, along with the relationships between cortical spreading depression and headache, and the reasons why aura does not consistently present in affected individuals, are all important research questions for the future.

Neuroplasticity Following Stroke from a Functional Laterality Perspective: A fNIRS Study.

To explore alterations of resting-state functional connectivity (rsFC) in sensorimotor cortex following strokes with left or right hemiplegia considering the lateralization and neuroplasticity. Seventy-three resting-state functional near-infrared spectroscopy (fNIRS) files were selected, including 26 from left hemiplegia (LH), 21 from right hemiplegia (RH) and 26 from normal controls (NC) group. Whole-brain analyses matching the Pearson correlation were used for rsFC calculations. For right-handed normal controls, rsFC of motor components (M1 and M2) in the left hemisphere displayed a prominent intensity in comparison with the right hemisphere (p < 0.05), while for stroke groups, this asymmetry has disappeared. Additionally, RH rather than LH showed stronger rsFC between left S1 and left M1 in contrast to normal controls (p < 0.05), which correlated inversely with motor function (r = -0.53, p < 0.05). Regarding M1, rsFC within ipsi-lesioned M1 has a negative correlation with motor function of the affected limb (r = -0.60 for the RH group and -0.43 for the LH group, p < 0.05). The rsFC within contra-lesioned M1 that innervates the normal side was weakened compared with that of normal controls (p < 0.05). Stronger rsFC of motor components in left hemisphere was confirmed by rs-fNIRS as the "secret of dominance" for the first time, while post-stroke hemiplegia broke this cortical asymmetry. Meanwhile, a statistically strengthened rsFC between left S1 and M1 only in right-hemiplegia group may act as a compensation for the impairment of the dominant side. This research has implications for brain-computer interfaces synchronizing sensory feedback with motor performance and transcranial magnetic regulation for cortical excitability to induce cortical plasticity.

Discovering functional connectivity features characterizing multiple sclerosis phenotypes using explainable artificial intelligence.

Multiple sclerosis (MS) is a neurological condition characterized by severe structural brain damage and by functional reorganization of the main brain networks that try to limit the clinical consequences of structural burden. Resting-state (RS) functional connectivity (FC) abnormalities found in this condition were shown to be variable across different MS phases, according to the severity of clinical manifestations. The article describes a system exploiting machine learning on RS FC matrices to discriminate different MS phenotypes and to identify relevant functional connections for MS stage characterization. To this end, the system exploits some mathematical properties of covariance-based RS FC representation, which can be described by a Riemannian manifold. The classification performance of the proposed framework was significantly above the chance level for all MS phenotypes. Moreover, the proposed system was successful in identifying relevant RS FC alterations contributing to an accurate phenotype classification.

Effects of a probiotic add-on treatment on fronto-limbic brain structure, function, and perfusion in depression: Secondary neuroimaging findings of a randomized controlled trial

BackgroundProbiotics are suggested to improve depressive symptoms via the microbiota-gut-brain axis. We have recently shown a beneficial clinical effect of probiotic supplementation in patients with depression. Their underlying neural mechanisms remain unknown. MethodsA multimodal neuroimaging approach including diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling was used to investigate the effects of a four-weeks probiotic supplementation on fronto-limbic brain structure, function, and perfusion and whether these effects were related to symptom changes. ResultsThirty-two patients completed both imaging assessments (18 placebo and 14 probiotics group). Probiotics maintained mean diffusivity in the left uncinate fasciculus, stabilized it in the right uncinate fasciculus, and altered resting-state functional connectivity (rsFC) between limbic structures and the temporal pole to a cluster in the precuneus. Moreover, a cluster in the left superior parietal lobule showed altered rsFC to the subcallosal cortex, the left orbitofrontal cortex, and limbic structures after probiotics. In the probiotics group, structural and functional changes were partly related to decreases in depressive symptoms. LimitationsThis study has a rather small sample size. An additional follow-up MRI session would be interesting for seeing clearer changes in the relevant brain regions as clinical effects were strongest in the follow-up. ConclusionProbiotic supplementation is suggested to prevent neuronal degeneration along the uncinate fasciculus and alter fronto-limbic rsFC, effects that are partly related to the improvement of depressive symptoms. Elucidating the neural mechanisms underlying probiotics' clinical effects on depression provide potential targets for the development of more precise probiotic treatments.

Resting state functional connectivity differentiation of neuropathic and nociceptive pain in individuals with chronic spinal cord injury

Many individuals with spinal cord injury live with debilitating chronic pain that may be neuropathic, nociceptive, or a combination of both in nature. Identification of brain regions demonstrating altered connectivity associated with the type and severity of pain experience may elucidate underlying mechanisms, as well as treatment targets. Resting state and sensorimotor task-based magnetic resonance imaging data were collected in 37 individuals with chronic spinal cord injury. Seed-based correlations were utilized to identify resting state functional connectivity of regions with established roles in pain processing: the primary motor and somatosensory cortices, cingulate, insula, hippocampus, parahippocampal gyri, thalamus, amygdala, caudate, putamen, and periaqueductal gray matter. Resting state functional connectivity alterations and task-based activation associated with individuals’ pain type and intensity ratings on the International Spinal Cord Injury Basic Pain Dataset (0–10 scale) were evaluated. We found that intralimbic and limbostriatal resting state connectivity alterations are uniquely associated with neuropathic pain severity, whereas thalamocortical and thalamolimbic connectivity alterations are associated specifically with nociceptive pain severity. The joint effect and contrast of both pain types were associated with altered limbocortical connectivity. No significant differences in task-based activation were identified. These findings suggest that the experience of pain in individuals with spinal cord injury may be associated with unique alterations in resting state functional connectivity dependent upon pain type.

Altered whole-brain resting-state functional connectivity and brain network topology in typhoon-related post-traumatic stress disorder.

Altered resting-state functional connectivity has been found in patients with post-traumatic stress disorder (PTSD). However, the alteration of resting-state functional connectivity at whole-brain level in typhoon-traumatized individuals with PTSD remains largely unknown. To investigate changes in whole-brain resting-state functional connectivity and brain network topology in typhoon-traumatized subjects with and without PTSD. Cross-sectional study. Twenty-seven patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC) underwent resting-state functional MRI scanning. The whole brain resting-state functional connectivity network was constructed based on the automated anatomical labeling atlas. The graph theory method was used to analyze the topological properties of the large-scale resting-state functional connectivity network. Whole-brain resting-state functional connectivity and the topological network property were compared by analyzing the variance. There was no significant difference in the area under the curve of γ, λ, σ, global efficiency, and local efficiency among the three groups. The PTSD group showed increased dorsal cingulate cortex (dACC) resting-state functional connectivity with the postcentral gyrus (PoCG) and paracentral lobe and increased nodal betweenness centrality in the precuneus relative to both control groups. Compared with the PTSD and HC groups, the TEC group showed increased resting-state functional connectivity between the hippocampus and PoCG and increased connectivity strength in the putamen. In addition, compared with the HC group, both the PTSD and TEC groups showed increased connectivity strength and nodal efficiency in the insula. Aberrant resting-state functional connectivity and topology were found in all trauma-exposed individuals. These findings broaden our knowledge of the neuropathological mechanisms of PTSD.

The Common Neural Mechanism of Somatic Symptoms of Depression and Anxiety Disorders: A Resting-State Functional Magnetic Resonance Imaging Study

Introduction: Somatic symptoms often occur as a manifestation of depression and anxiety. The subgenual anterior cingulate cortex (sgACC) has been shown to be closely related to both depression and anxiety and plays an important role in somatic symptoms. However, little is known regarding whether the abnormal function of the sgACC contributes to the common somatic symptoms of depression and anxiety. Methods: Resting-state functional connectivity (RSFC) analysis based on the seed of the sgACC was investigated in 23 major depressive disorder (MDD) patients with somatic symptoms, 20 generalized anxiety disorder (GAD) patients with somatic symptoms, and 22 demographically matched healthy controls (HCs). The severity of depression, anxiety, and somatic symptoms was assessed using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the 15-item somatic symptom severity scale from the Patient Health Questionnaire (PHQ-15), respectively. An analysis of covariance analysis (ANCOVA) was conducted to determine RSFC alterations among GAD, MDD, and HC groups with age, gender, and head motion as covariates. Correlation analyses were conducted between the RSFC of the sgACC and PHQ-15. Results: The significantly different RSFC of right sgACC among the three groups was found in right STG, left cerebellum, and right postcentral. Post hoc analysis indicated that both MDD and GAD patients showed a decreased RSFC between the right sgACC and right STG than HCs, and both were negatively correlated with the PHQ-15 scores. Conclusion: The abnormally decreased RSFC of the sgACC and STG may be the underlying common mechanisms of depression and anxiety combined with somatic symptoms.

Distal neuropathic pain in HIV is associated with functional connectivity patterns in default mode and salience networks.

HIV-associated distal neuropathic pain (DNP) is one of the most prevalent, disabling, and treatment-resistant complications of HIV, but its biological underpinnings are incompletely understood. While data specific to mechanisms underlying HIV DNP are scarce, functional neuroimaging of chronic pain more broadly implicates the role of altered resting-state functional connectivity within and between salience network (SN) and default mode network (DMN) regions. However, it remains unclear the extent to which HIV DNP is associated with similar alterations in connectivity. The current study aimed to bridge this gap in the literature through examination of resting-state functional connectivity patterns within SN and DMN regions among people with HIV (PWH) with and without DNP. Resting state functional magnetic resonance imaging (rs-fMRI) scans were completed among 62 PWH with HIV-associated peripheral neuropathy, of whom 27 reported current DNP and 35 did not. Using subgrouping group iterative multiple estimation, we compared connectivity patterns in those with current DNP to those without. We observed weaker connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) and stronger connectivity between the anterior cingulate cortex (ACC) and thalamus among those reporting DNP. Overall, these findings implicate altered within DMN (i.e., MPFC-PCC) and within SN (i.e., ACC-thalamus) connectivity as potential manifestations of adaptation to pain from neuropathy and/or mechanisms underlying the development/maintenance of DNP. Findings are discussed in the context of differential brain response to pain (i.e., mind wandering, pain aversion, pain facilitation/inhibition) and therapeutic implications.

Acute tryptophan depletion balances altered resting-state functional connectivity of the salience network in female patients recovered from anorexia nervosa.

Background:It has been suggested that individuals predisposed to or recovered from anorexia nervosa experience a hyperserotonergic state associated with anxiety that might be mitigated by restricted food intake, because diminished levels of the tryptophan precursor lower the central availability of serotonin (5-HT). At the neural level, the salience network is a system of functionally connected brain regions; it has been closely associated with 5-HT functioning and mental disorders (including anorexia nervosa). The aim of the present study was to investigate the effect on the salience network of a temporary dietary manipulation of 5-HT synthesis in patients with anorexia nervosa.Methods:In this double-blind crossover study, we obtained data on resting-state functional connectivity from 22 weight-recovered female patients with a history of anorexia nervosa, and 22 age-matched female healthy controls. The study procedure included acute tryptophan depletion (a dietary intervention that lowers the central 5-HT synthesis rate) and a sham condition.Results:We identified an interaction of group and experimental condition in resting-state functional connectivity between the salience network and the orbitofrontal cortex extending to the frontal pole (F1,42 = 12.52; pFWE = 0.026). Further analysis revealed increased resting-state functional connectivity during acute tryptophan depletion in patients recovered from anorexia nervosa, resembling that of healthy controls during the sham condition (T42 = −0.66; p = 0.51).Limitations:The effect of acute tryptophan depletion on the central availability of 5-HT can be judged only indirectly using plasma ratios of tryptophan to large neutral amino acids. Moreover, the definition of anorexia nervosa recovery varies widely across studies, limiting comparability.Conclusion:Taken together, our findings support the notion of 5-HT dysregulation in anorexia nervosa and indicate that reduced 5-HT synthesis and availability during acute tryptophan depletion (and possibly with food restriction) may balance hyperserotonergic functioning and the associated resting-state functional connectivity of the salience network.

Altered resting-state functional connectivity of the dorsal anterior cingulate cortex with intrinsic brain networks in male problematic smartphone users

The excessive use of smartphones is associated with various medical complications and mental health problems. However, existing research findings on neurobiological mechanisms behind problematic smartphone use are limited. In this study, we investigated functional connectivity in problematic smartphone users, focusing on the default mode network (DMN) and attentional networks. We hypothesized that problematic smartphone users would have alterations in functional connectivity between the DMN and attentional networks and that such alterations would correlate with the severity of problematic smartphone use. This study included 30 problematic smartphone users and 35 non-problematic smartphone users. We carried out group independent component analysis (group ICA) to decompose resting-state functional magnetic resonance imaging (fMRI) data into distinct networks. We examined functional connectivity using seed-to-seed analysis and identified the nodes of networks in group ICA, which we used as region of interest. We identified greater functional connectivity of the dorsal anterior cingulate cortex (dACC) with the ventral attention network (VAN) and with the DMN in problematic smartphone users. In seed-to-seed analysis, problematic smartphone users showed atypical dACC-VAN functional connectivity which correlated with the smartphone addiction proneness scale total scores. Our resting-state fMRI study found greater functional connectivity between the dACC and attentional networks in problematic smartphone users. Our findings suggest that increased bottom-up and interoceptive attentional processing might play an important role in problematic smartphone use.

Alteration of resting-state functional connectivity network properties in patients with social anxiety disorder after virtual reality-based self-training.

Social anxiety disorder (SAD) is a mental disorder characterized by excessive anxiety in social situations. This study aimed to examine the alteration of resting-state functional connectivity in SAD patients related to the virtual reality-based self-training (VRS) which enables exposure to social situations in a controlled environment. Fifty-two SAD patients were randomly assigned to the experimental group who received the VRS, or the control group who did not. Self-report questionnaires and resting-state functional magnetic resonance imaging (fMRI) were performed to assess clinical symptoms and analyze the resting-state network properties, respectively. Significant decrease in social anxiety and an increase in self-esteem was found in the experimental group. From the resting-state fMRI analysis, alteration of local network properties in the left dorsolateral prefrontal gyrus (-10.0%, p = 0.025), left inferior frontal gyrus (-32.3%, p = 0.044), left insula (-17.2%, p = 0.046), left Heschl's gyrus (-21.2%, p = 0.011), bilateral inferior temporal gyrus (right: +122.6%, p = 0.045; left:−46.7%, p = 0.015), and right calcarine sulcus (+17.0%, p = 0.010) were found in the experimental group. Average shortest path length (+8.3%, p = 0.008) and network efficiency (-7.6%, p = 0.011) are found to be altered from the global network property analysis. In addition, the experimental group displayed more positive and more negative changes in the correlation trend of average shortest path length (p = 0.004) and global network efficiency (p = 0.014) with the severity of social anxiety, respectively. These results suggest potential effectiveness of the VRS, which is possibly related to the change of aberrant processing and control of visual and auditory linguistic stimuli and the adaptive change in rumination pattern.

Alterations in resting-state functional connectivity associated to the age-related decline in time-based prospective memory.

Time-based prospective memory (TBPM) is defined as the ability to remember to perform intended actions at a specific time in the future. TBPM is impaired in aging, and this decline has been associated with white-matter alterations within the superior fronto-occipital fasciculus. In the present study, we used resting-state functional magnetic resonance imaging from 22 healthy young (26 ± 5.2years) and 23 older (63 ± 6.1years) participants to investigate how age-related alterations in resting-state functional connectivity are related to TBPM performance, and whether these alterations are associated with the white-matter disruptions we have previously observed with diffusion tensor imaging. Whole-brain analyses revealed lower resting-state functional connectivity in older participants compared with younger ones, which in turn correlated with TBPM performance. These correlations were mainly located in the salience network and the parietal part of the frontoparietal network. Our findings suggest that resting-state functional connectivity alterations contribute to the age-related decline in TBPM.

Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT.

Probiotics can alter brain function via the gut–brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut–brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut–brain communication and hence brain function.

Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

The role of basal ganglia network in neural plasticity in neuromyelitis optica spectrum disorder with myelitis

ObjectivesTo explore the alternation of the brain baseline activity in neuromyelitis optica spectrum disorder (NMOSD) patients after myelitis, and characterize the representation of the neural plasticity process. MethodsClinical evaluation and resting-state fMRI were obtained from 20 NMOSD patients with myelitis and 20 healthy controls, matched in gender and age. Resting-state networks (RSNs) were identified through independent component analysis (ICA), and functional connectivity (FC) intra-RSNs and between region-of-interest (ROI) seed to whole-brain voxels were analyzed. Between-group comparisons and correlations with motor performance were also assessed. ResultsA total of 14 main functional RSNs were identified. Group comparison of intra-network FCs revealed that FC strengths increased in basal ganglia network (BGN) and left frontoparietal network, decreased in sensorimotor network and default mode network in NMOSD. Better motor performance was found closely correlated with higher FC of BGN. Additionally, remarkably increased FC between caudate in BGN with cerebellum, frontal lobe and parietal lobe was discovered in further ROI-based whole-brain voxels FC analysis. ConclusionsNMOSD patients presented wide brain resting-state functional connectivity alterations after myelitis, and BGN might be highly active in the process of neural plasticity in chronic stage of NMOSD. Besides, understanding neural plasticity representation, especially that in NMOSD patients after myelitis, might have important applications in monitoring and designing rehabilitative approaches.

Altered resting-state functional connectivity in hiPSCs-derived neuronal networks from schizophrenia patients.

Schizophrenia (SZ) is a severe mental disorder that arises from abnormal neurodevelopment, caused by genetic and environmental factors. SZ often involves distortions in reality perception and it is widely associated with alterations in brain connectivity. In the present work, we used Human Induced Pluripotent Stem Cells (hiPSCs)-derived neuronal cultures to study neural communicational dynamics during early development in SZ. We conducted gene and protein expression profiling, calcium imaging recordings, and applied a mathematical model to quantify the dynamism of functional connectivity (FC) in hiPSCs-derived neuronal networks. Along the neurodifferentiation process, SZ networks displayed altered gene expression of the glutamate receptor-related proteins HOMER1 and GRIN1 compared to healthy control (HC) networks, suggesting a possible tendency to develop hyperexcitability. Resting-state FC in neuronal networks derived from HC and SZ patients emerged as a dynamic phenomenon exhibiting connectivity configurations reoccurring in time (hub states). Compared to HC, SZ networks were less thorough in exploring different FC configurations, changed configurations less often, presented a reduced repertoire of hub states and spent longer uninterrupted time intervals in this less diverse universe of hubs. Our results suggest that alterations in the communicational dynamics of SZ emerging neuronal networks might contribute to the previously described brain FC anomalies in SZ patients, by compromising the ability of their neuronal networks for rapid and efficient reorganization through different activity patterns.

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.

First Trimester Dexamethasone Treatment Is Not Associated With Alteration in Resting-state Connectivity at Adolescent or Adult Age.

ContextPrenatal treatment with dexamethasone (DEX) has been used to prevent virilization in females at risk of congenital adrenal hyperplasia (CAH). Both affected and unaffected girls, as well boys, are treated until the genotype and sex of the fetus is known (gestational weeks 10-12). After that, only affected girls are treated until term. Exposure to a high synthetic glucocorticoid dosage may alter the developmental trajectory of the brain, with alterations in resting-state functional connectivity of the brain at adult age.ObjectiveTo investigate resting-state functional connectivity in subjects at risk of having CAH, exposed to DEX treatment during the first trimester of fetal life, both in the whole brain and in 3 regions of interest (amygdala, hippocampus, and superior frontal gyrus).Design, Setting, and ParticipantsEighteen participants (8 females) at risk of having CAH, exposed to DEX treatment, and 38 controls (24 females), age range 16 to 26 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. We used 2 different approaches: an exploratory whole-brain analysis and seed-based analysis. For seed-based analysis, we chose 3 different brain regions (amygdala, hippocampus, and superior frontal gyrus) based on our previous findings and literature evidence.ResultsWe did not observe any differences in functional connectivity during rest, either in the whole brain nor in seed-based connectivity analyses at this adolescent and young adult age.ConclusionsOur results are reassuring; however, future studies on larger samples and with more sensitive methodologies are needed to confirm these findings.

Altered resting-state functional connectivity within corticostriatal and subcortical-striatal circuits in chronic pain

Brain corticostriatal circuits are important for understanding chronic pain and highly relevant to motivation and cognitive processes. It has been demonstrated that in patients with chronic back pain, altered nucleus accumbens (NAcc)—medial prefrontal cortex (MPFC) circuit fMRI-based activity is predictive of patient outcome. We evaluated the NAcc-MPFC circuit in patients with another chronic pain condition, fibromyalgia, to extend these important findings. First, we compared fMRI-based NAcc-MPFC resting-state functional connectivity in patients with fibromyalgia (N = 32) vs. healthy controls (N = 37). Compared to controls, the NAcc-MPFC circuit’s connectivity was significantly reduced in fibromyalgia. In addition, within the fibromyalgia group, NAcc-MPFC connectivity was significantly correlated with trait anxiety. Our expanded connectivity analysis of the NAcc to subcortical brain regions showed reduced connectivity of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in fibromyalgia. Lastly, in an exploratory analysis comparing our fibromyalgia and healthy control cohorts to a separate publicly available dataset from patients with chronic back pain, we identified reduced NAcc-MPFC connectivity across both the patient groups with unique alterations in NAcc-mesolimbic connectivity. Together, expanding upon prior observed alterations in brain corticostriatal circuits, our results provide novel evidence of altered corticostriatal and mesolimbic circuits in chronic pain.

Altered resting-state functional connectivity of insula in children with primary nocturnal enuresis.

ObjectivePrimary nocturnal enuresis (PNE) is a common developmental condition in school-aged children. The objective is to better understand the pathophysiology of PNE by using insula-centered resting-state functional connectivity (rsFC).MethodsWe recruited 66 right-handed participants in our analysis, 33 with PNE and 33 healthy control (HC) children without enuresis matched for gender and age. Functional and structural MRI data were obtained from all the children. Seed-based rsFC was used to examine differences in insular functional connectivity between the PNE and HC groups. Correlation analyses were carried out to explore the relationship between abnormal insula-centered functional connectivity and clinical characteristics in the PNE group.ResultsCompared with HC children, the children with PNE demonstrated decreased left and right insular rsFC with the right medial superior frontal gyrus (SFG). In addition, the bilateral dorsal anterior insula (dAI) seeds also indicated the reduced rsFC with right medial SFG. Furthermore, the right posterior insula (PI) seed showed the weaker rsFC with the right medial SFG, while the left PI seed displayed the weaker rsFC with the right SFG. No statistically significant correlations were detected between aberrant insular rsFC and clinical variables (e.g., micturition desire awakening, bed-wetting frequency, and bladder volume) in results without global signal regression (GSR) in the PNE group. However, before and after setting age as a covariate, significant and positive correlations between bladder volume and the rsFC of the left dAI with right medial SFG and the rsFC of the right PI with right medial SFG were found in results with GSR in the PNE group.ConclusionTo the best of our knowledge, this study explored the rsFC patterns of the insula in children with PNE for the first time. These results uncovered the abnormal rsFC of the insula with the medial prefrontal cortex without and with GSR in the PNE group, suggesting that dysconnectivity of the salience network (SN)-default mode network (DMN) may involve in the underlying pathophysiology of children with PNE. However, the inconsistent associations between bladder volume and dysconnectivity of the SN-DMN in results without and with GSR need further studies.