Resting-state Neuroimaging Studies Research Articles

State Changes During Resting-State (Magneto)encephalographic Studies: The Effect of Drowsiness on Spectral, Connectivity, and Network Analyses.

BackgroundA common problem in resting-state neuroimaging studies is that subjects become drowsy or fall asleep. Although this could drastically affect neurophysiological measurements, such as magnetoencephalography (MEG), its specific impact remains understudied. We aimed to systematically investigate how often drowsiness is present during resting-state MEG recordings, and how the state changes alter quantitative estimates of oscillatory activity, functional connectivity, and network topology.MethodsAbout 8-min MEG recordings of 19 healthy subjects, split into ~13-s epochs, were scored for the presence of eyes-open (EO), alert eyes-closed (A-EC), or drowsy eyes-closed (D-EC) states. After projection to source-space, results of spectral, functional connectivity, and network analyses in 6 canonical frequency bands were compared between these states on a global and regional levels. Functional connectivity was analyzed using the phase lag index (PLI) and corrected amplitude envelope correlation (AECc), and network topology was analyzed using the minimum spanning tree (MST).ResultsDrowsiness was present in >55% of all epochs that did not fulfill the AASM criteria for sleep. There were clear differences in spectral results between the states (A-EC vs. D-EC) and conditions (EO vs. A-EC). The influence of state and condition was far less pronounced for connectivity analyses, with only minimal differences between D-EC and EO in the AECc in the delta band. There were no effects of drowsiness on any of the MST measures.ConclusionsDrowsiness during eyes-closed resting-state MEG recordings is present in the majority of epochs, despite the instructions to stay awake. This has considerable influence on spectral properties, but much less so on functional connectivity and network topology. These findings are important for interpreting the results of EEG/MEG studies using spectral analyses in neurological disease, where recordings should be evaluated for the presence of drowsiness. For connectivity analyses or studies on network topology, this seems of far less importance.

Investigating cerebellar neural function in schizophrenia using delay eyeblink conditioning: A pilot fMRI study

There is accruing evidence of cerebellar abnormalities in individuals with schizophrenia as measured by performance on a variety of tasks believed to be dependent on cerebellar integrity, including delay eyeblink conditioning. There is also evidence of cerebellar dysfunction on a neural level in schizophrenia from both task-based and resting state neuroimaging studies, however few studies have examined cerebellar neural function while the cerebellum is directly recruited in individuals with schizophrenia. In the current pilot study, we examined neural activity during an explicitly cerebellar task in individuals with schizophrenia or schizoaffective disorder and non-psychiatric controls. Participants underwent delay eyeblink conditioning during fMRI. Results indicated eyeblink conditioning impairment in patients as evidenced by a group by time interaction for conditioned responses. A significant cluster of cerebellar activation was present in controls but not patients during the first half of conditioning; there were no significant differences in activation between groups. An ROI analysis focused on the cerebellum in patients revealed two significant clusters that were inversely associated with negative symptom severity. These results are broadly consistent with the theory of cognitive dysmetria, wherein cerebellar abnormalities are theorized to contribute to motor as well as cognitive and affective disturbances in schizophrenia.

Reduced spatiotemporal brain dynamics are associated with increased depressive symptoms after a relationship breakup

Depressive symptoms following a stressful life event, such as a relationship breakup, are common, and constitute a potent risk factor for the onset of a major depressive episode. Resting-state neuroimaging studies have increasingly identified abnormal whole-brain communication in patients with depression, but it is currently unclear whether depressive symptoms in individuals without a clinical diagnosis have reliable neural underpinnings. We investigated to what extent the severity of depressive symptoms in a non-clinical sample was associated with imbalances in the complex dynamics of the brain during rest. To this end, a novel intrinsic ignition approach was applied to resting-state neuroimaging data from sixty-nine participants with varying degrees of depressive symptoms following a relationship breakup. Ignition-based measures of integration, hierarchy, and metastability were calculated for each participant, revealing a negative correlation between these measures and depressive ratings. We found that the severity of depressive symptoms was associated with deficits in the brain’s capacity to globally integrate and process information over time. Furthermore, we found that increased depressive symptoms were associated with reduced spatial diversity (i.e., hierarchy) and reduced temporal variability (i.e., metastability) in the functional organization of the brain. These findings suggest the merit of investigating constrained dynamical complexity as it is sensitive to the level of depressive symptoms even in a non-clinical sample.

Abnormalities of regional homogeneity and its correlation with clinical symptoms in Naïve patients with first-episode schizophrenia.

Several resting-state neuroimaging studies have indicated abnormal regional homogeneity (ReHo) in chronic schizophrenia; however, little work has been conducted to investigate naïve patients with first-episode schizophrenia (FES). Even less investigated is the association between ReHo measures and clinical symptom severity in naïve patients with FES. The current study evaluated ReHo alterations in whole brain, and assessed the correlations between ReHo measures and clinical variables in naïve patients with FES. Forty-four naïve patients with FES and 26 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Group-level analysis was utilized to analyze the ReHo differences between FES and HC in a voxel-by-voxel manner. Severity of symptoms was evaluated using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). The correlation between the severity of symptoms and ReHo map was examined in patients using voxel-wise correlation analyses within brain areas that showed a significant ReHo alteration in patients compared with controls. Compared with the healthy control group, the FES group showed a significant decrease in ReHo values in the left medial frontal gyrus (MFG), right precentral gyrus, left superior temporal gyrus (STG), left left middle temporal gyrus (MTG), left thalamus, and significant increase in ReHo values in the left MFG, left inferior parietal lobule (IPL), left precuneus, and right lentiform nucleus (LN). In addition, the correlation analysis showed the PANSS total score negatively correlated with ReHo in the right precentral gyrus and positively correlated with ReHo in the left thalamus, the positive factor positively correlated with ReHo in the right thalamus, the disorganized/concrete factor positively correlated with ReHo in left posterior cingulate gyrus (PCG), the excited factor positively correlated with ReHo in the left precuneus, and the depressed factor negatively correlated with ReHo in the right postcentral gyrus and positively correlated with ReHo in the right thalamus. Our results indicate that widespread ReHo abnormalities occurred in an early stage of schizophrenic onset, suggesting a potential neural basis for the pathogenesis and symptomatology of schizophrenia.

Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis.

Purpose: The neural mechanisms that give rise to the phantom sound of tinnitus have not been fully elucidated. Neuroimaging studies have revealed abnormalities in resting-state activity that could represent the neural signature of tinnitus, but there is considerable heterogeneity in the data. To address this issue, we conducted a meta-analysis of published neuroimaging studies aimed at identifying a common core of resting-state brain abnormalities in tinnitus patients.Methods: A systematic search was conducted for whole-brain resting-state neuroimaging studies with SPECT, PET and functional MRI that compared chronic tinnitus patients with healthy controls. The authors searched PubMed, Science Direct, Web of Knowledge and Embase databases for neuroimaging studies on tinnitus published up to September 2016. From each study, coordinates were extracted from clusters with significant differences between tinnitus subjects and controls. Meta-analysis was performed using the activation likelihood estimation (ALE) method.Results: Data were included from nine resting-state neuroimaging studies that reported a total of 51 distinct foci. The meta-analysis identified consistent regions of increased resting-state brain activity in tinnitus patients relative to controls that included, bilaterally, the insula, middle temporal gyrus (MTG), inferior frontal gyrus (IFG), parahippocampal gyrus, cerebellum posterior lobe and right superior frontal gyrus. Moreover, decreased brain activity was only observed in the left cuneus and right thalamus.Conclusions: The current meta-analysis is, to our knowledge, the first to demonstrate a characteristic pattern of resting-state brain abnormalities that may serve as neuroimaging markers and contribute to the understanding of neuropathophysiological mechanisms for chronic tinnitus.

Abnormal interhemispheric resting-state functional connectivity in primary open-angle glaucoma.

Glaucoma is the second leading cause of blindness and it has been the topic of massive studies to explore the underlying mechanisms of the disease. Resting-state neuroimaging studies have been widely applied to investigate the functional damage of the brain, but little is known about the alterations of the interhemispheric resting-state functional connectivity (RSFC) in patients with primary open-angle glaucoma (POAG). In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to explore the interhemispheric RSFC of the brain in POAG patients. The result showed decreased VMHC in the precuneus and the occipital lobe including calcarine and cuneus, as well as increased VMHC in the lingual gyrus, insula, supramarginal gyrus, and frontal gyrus. Meanwhile, we found the mean VMHC in precuneus was negatively correlated (r=-0.551, P=0.041) with Cup-to-disk Ratio. Significant differences between POAG patients and normal controls reveal the altered brain regions and the functional damage, strengthening the understanding of the primary open-angle glaucoma.

Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings

BackgroundSeveral resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. Methods27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. ResultsWe observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus. ConclusionsThis abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia.

Resting-state neuroimaging studies: a new way of identifying differences and similarities among the anxiety disorders?

This review examines recent functional neuroimaging research of resting-state regional connectivity between brain regions in anxiety disorders. Studies compiled in the PubMed- National Center for Biotechnology Information database targeting resting-state functional connectivity in anxiety disorders were reviewed. Diagnoses included posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), panic disorder (PD), and specific phobia (SP). Alterations to network connectivity were demonstrated in PTSD, GAD, SAD, OCD, and PD in several resting-state investigations. Differences from control subjects were primarily observed in the default mode network within PTSD, SAD, and OCD. Alterations within the salience network were observed primarily in PTSD, GAD, and SAD. Alterations in corticostriatal networks were uniquely observed in OCD. Finally, alterations within somatosensory networks were observed in SAD and PD investigations. Resting-state studies involving SPs as a primary diagnosis (with or without comorbidities) were not generated during the literature search. The emerging use of resting-state paradigms may be an effective method for understanding associations between anxiety disorders. Targeted studies of PD and SPs, meta-analyses of the studies conducted to date, and studies of the impact of specific comorbid presentations, are recommended future research directions.

La dysrégulation émotionnelle est-elle une des composantes du trouble déficit d’attention/hyperactivité ?

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents. It is characterized by age-inappropriate inattention/impulsiveness and/or hyperactivity symptoms. ADHD shows a high comorbidity with oppositional defiant disorder (ODD), a disorder that features symptoms of emotional lability. Due to this comorbidity, emotional lability was long considered a secondary consequence of ADHD, which could arise under the influence of environmental factors such as inefficient parenting practices, as part of an ODD diagnosis. In this model of heterotypic continuity, emotional lability was considered not to play any causal role regarding ADHD symptomatology. As opposed to this view, it is now well established that a large number of children with ADHD and without any comorbid disorder exhibit symptoms of emotional lability. Furthermore, recent studies have found that negative emotionality accounts for significant unique variance in ADHD symptom severity, along with motor-perceptual and executive function deficits. Barkley proposed that ADHD is characterized by deficits of executive functions, and that a deficiency in the executive control of emotions is a necessary component of ADHD. According to this theory, the extent to which an individual with ADHD displays a deficiency in behavioral inhibition is the extent to which he or she will automatically display an equivalent degree of deficiency in emotional inhibition. However, not all children with ADHD exhibit symptoms of emotional lability, and studies have found that the association between emotional lability and ADHD was not mediated by executive function or motivational deficits. Task-based and resting state neuroimaging studies have disclosed an altered effective connectivity between regions dedicated to emotional regulation in children with ADHD when compared to typically developing children, notably between the amygdala, the prefrontal cortex, the hippocampus and the ventral striatum. Morphological alterations of the amygdala have also been reported in previous structural studies in children with ADHD. Emotional lability can result from different neurobiological mechanisms. In particular, bottom-up and top-down processes can be opposed. Bottom-up related emotional dysregulation involves an increased emotional reactivity, and is thought to be linked to the automatic evaluative activity of the amygdala. Top-down mechanisms are associated with the regulation of such activity, and rely on a prefrontal network including the lateral prefrontal cortex, the anterior cingulate cortex and the orbitofrontal cortex. Since various neuropsychological impairments and alterations in multiple brain networks have been implicated in the etiology of ADHD, contemporary models emphasize its neuropsychological heterogeneity. It is therefore likely that some but not all children with ADHD will exhibit neurobiological alterations in circuits dedicated to emotional regulation, possibly at different levels. Future research will have to identify the different causal pathways and to decide whether emotional lability represents a criterion to subtype ADHD diagnoses. Emotional dysregulation is now known to play a causal role regarding ADHD symptomatology. Along with executive functioning, reaction time variability and potentially delay aversion, emotional dysregulation should therefore be included in future theoretical models of ADHD, as well as in clinical practice when identifying the major impairments in this diagnostic group and when deciding therapeutic strategies.

Characterization of individuals with chronic pain: phenotyping approaches used in MAPP

Pain is a complex perception affecting one’s state of consciousness, functional status, and quality of life. Clinically, pain intensity is often the only facet of pain that is assessed; but two large research networks (i.e., the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) [1] and the Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) [2]) have characterized pain in accordance with broader pain concepts. MAPP was designed to characterize individuals with urologic chronic pelvic pain syndromes (UCPPS) which consisted of diagnoses such as interstitial cystitis, bladder pain syndrome, chronic prostatitis, and chronic pelvic pain syndrome. Characterization of the sample of n=1039 individuals occurred at multiple sites and at multiple levels of analysis including: biomarkers, self-report questionnaires, quantitative sensory testing (QST), functional neurobiological studies, and structured and resting state neuroimaging studies. A comprehensive assessment occurred at baseline followed longitudinally by biweekly or bimonthly internet questionnaires and more extensive in-clinic visits at 24 and 48 weeks following baseline [3]. The self-report methods covered both urologic-specific and non-urological domains relevant to chronic pain which are consistent with the bio-psycho-social model of pain. Urological domains included urological diagnostics, symptoms and impact, sexual functioning, self-esteem, and social relationships. Non-urological-specific self-assessment included clinical pain, functional status, mood, co-morbid conditions, personality, attitudes/ beliefs, and early life trauma. Biological specimens linked to clinical data included cheek swabs and plasma, as well as urine for exploration of infectious etiology. Also linked to the clinical data was quantitative sensory testing (QST) which helped to characterize individuals with respect to pain threshold, and neuroimaging studies providing structural, functional and network connectivity data corresponding to central pain processing and modulation. Ultimately, the goal of such extensive phenotyping will be to identify subgroups of individuals with UCPPS who have distinct underlying pathophysiology to which more optimal treatment approaches can be aligned thus offering the potential for improved disease management and improved patient care.

P-790 - Neural correlates of frustration in depressed patients and healthy controls: an fMRI study

Depressed patients demonstrate low frustration tolerance which increases the risk of suicide and causes difficulties in social adaptation. Resting-state neuroimaging studies revealed abnormalities in “default-mode” network in Major Depressive Disorder (MDD). To our knowledge, functional network responsible for frustration has not been investigated in depressed subjects previously. To investigate functional responses to frustration in MDD subjects and healthy controls (HCs). 15 subjects with MDD and 15 HCs underwent 10-min fMRI scanning. We used modified Stroop-test to investigate subjects’ responses to frustration. There were two sessions: during the first one the subject had to determine the color of the text by pressing corresponding button while scanning; the second one was a “frustrative” part when the subject had to respond within a short period of time. We modified this interval so that it was almost impossible to respond correctly and keep within the allotted time. The subject was being informed on its performance during the test. Independent component analysis was used to isolate the frustration network in each subject. Group maps of the response network were compared. A within-group analysis was performed in the MDD group to explore effects of depression scores on functional connectivity. We revealed differences in limbic functional connectivity patterns during the test perfomance in MDD in comparison to HCs. The findings suggest that low frustration tolerance in depressed patients can be explained by the impaired function of stress-response brain network and reveal perspectives for future research on depression and suicide risk.

Déterminants de la non prise en charge diagnostiqueet thérapeutique des personnes à risque d'infection par le virus de l'hépatite C (VHC), consultant dans les réseaux de soins spécialisés: étude GYMKHANA

Le trouble déficit d’attention/hyperactivité (TDA/H) est le trouble neurodéveloppemental le plus fréquent chez l’enfant et l’adolescent. Son diagnostic repose sur trois ensembles de symptômes : inattention, impulsivité et hyperactivité ; mais des études mobilisant des méthodologies variées mettent également en évidence des symptômes de labilité émotionnelle chez les patients présentant un TDA/H. Ces symptômes ne sont pas seulement une conséquence secondaire de déficits des fonctions exécutives : la dysrégulation émotionnelle semble être une composante indépendante du trouble, contribuant de manière significative à sa symptomatologie. Les modèles étiopathogéniques actuels reflètent l’hétérogénéité clinique du TDA/H, en identifiant de multiples voies cérébrales pouvant sous-tendre un même ensemble de symptômes. Aux côtés des atteintes des voies fronto-corticales impliquées dans les déficits des fonctions exécutives, des études de neuro-imagerie récentes reportent des altérations fonctionnelles des voies fronto-limbiques impliquées dans la régulation émotionnelle chez des patients présentant un TDA/H. Cet ensemble de données récentes nous éloigne d’une conception purement cognitive du trouble, et est donc d’une grande importance pour la pratique clinique.Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents. It is characterized by age-inappropriate inattention/impulsiveness and/or hyperactivity symptoms. ADHD shows a high comorbidity with oppositional defiant disorder (ODD), a disorder that features symptoms of emotional lability. Due to this comorbidity, emotional lability was long considered a secondary consequence of ADHD, which could arise under the influence of environmental factors such as inefficient parenting practices, as part of an ODD diagnosis. In this model of heterotypic continuity, emotional lability was considered not to play any causal role regarding ADHD symptomatology.As opposed to this view, it is now well established that a large number of children with ADHD and without any comorbid disorder exhibit symptoms of emotional lability. Furthermore, recent studies have found that negative emotionality accounts for significant unique variance in ADHD symptom severity, along with motor-perceptual and executive function deficits. Barkley proposed that ADHD is characterized by deficits of executive functions, and that a deficiency in the executive control of emotions is a necessary component of ADHD. According to this theory, the extent to which an individual with ADHD displays a deficiency in behavioral inhibition is the extent to which he or she will automatically display an equivalent degree of deficiency in emotional inhibition. However, not all children with ADHD exhibit symptoms of emotional lability, and studies have found that the association between emotional lability and ADHD was not mediated by executive function or motivational deficits. Task-based and resting state neuroimaging studies have disclosed an altered effective connectivity between regions dedicated to emotional regulation in children with ADHD when compared to typically developing children, notably between the amygdala, the prefrontal cortex, the hippocampus and the ventral striatum. Morphological alterations of the amygdala have also been reported in previous structural studies in children with ADHD.Emotional lability can result from different neurobiological mechanisms. In particular, bottom-up and top-down processes can be opposed. Bottom-up related emotional dysregulation involves an increased emotional reactivity, and is thought to be linked to the automatic evaluative activity of the amygdala. Top-down mechanisms are associated with the regulation of such activity, and rely on a prefrontal network including the lateral prefrontal cortex, the anterior cingulate cortex and the orbitofrontal cortex. Since various neuropsychological impairments and alterations in multiple brain networks have been implicated in the etiology of ADHD, contemporary models emphasize its neuropsychological heterogeneity. It is therefore likely that some but not all children with ADHD will exhibit neurobiological alterations in circuits dedicated to emotional regulation, possibly at different levels. Future research will have to identify the different causal pathways and to decide whether emotional lability represents a criterion to subtype ADHD diagnoses.Emotional dysregulation is now known to play a causal role regarding ADHD symptomatology. Along with executive functioning, reaction time variability and potentially delay aversion, emotional dysregulation should therefore be included in future theoretical models of ADHD, as well as in clinical practice when identifying the major impairments in this diagnostic group and when deciding therapeutic strategies.