Functional reorganization of intra‐ and internetwork connectivity in major depressive disorder after electroconvulsive therapy

Electroconvulsive therapy (ECT) is an effective and rapid treatment for major depressive disorder (MDD). However, the neurobiological underpinnings of ECT are still largely unknown. Recent studies have identified dysregulated brain networks in MDD. Therefore, we hypothesized that ECT may improve MDD symptoms through reorganizing these networks. To test this hypothesis, we used resting‐state functional connectivity to investigate changes to the intra‐ and internetwork architecture of five reproducible resting‐state networks: the default mode network (DMN), dorsal attention network (DAN), executive control network (CON), salience network (SAL), and sensory‐motor network. Twenty‐three MDD patients were assessed before and after ECT, along with 25 sex‐, age‐, and education‐matched healthy controls. At the network level, enhanced intranetwork connectivities were found in the CON in MDD patients after ECT. Furthermore, enhanced internetwork connectivities between the DMN and SAL, and between the CON and DMN, DAN, and SAL were also identified. At the nodal level, the posterior cingulate cortex had increased connections with the left posterior cerebellum, right posterior intraparietal sulcus (rpIPS), and right anterior prefrontal cortex. The rpIPS had increased connections with the medial PFC (mPFC) and left anterior cingulate cortex. The left lateral parietal had increased connections with the dorsal mPFC (dmPFC), left anterior prefrontal cortex, and right anterior cingulate cortex. The dmPFC had increased connection with the left anterolateral prefrontal cortex. Our findings indicate that enhanced interactions in intra‐ and internetworks may contribute to the ECT response in MDD patients. These findings provide novel and important insights into the neurobiological mechanisms underlying ECT.     

“临床治愈”抑郁症患者默认网络静息态功能连接研究

目的:结合静息态功能连接方法,探讨"临床治愈"抑郁症(remitted major depressive disorder,r MDD)患者默认网络(default mode network,DMN)功能连接的变化。方法:对22例经过住院治疗达到r MDD标准的患者(患者组)和22名相匹配正常对照组进行静息态功能磁共振扫描,以DMN公认的内侧前额叶(medial prefrontal cortex,m PFC)和后扣带回(posterior cingulate cortex,PCC)为种子点,通过种子点与全脑的功能连接分析,使用双样本t检验比较两组的功能连接差异。结果:与正常对照组比较,患者组m PFC与右侧角回(t=3.96,P0.01)、右侧旁扣带回(t=4.57,P0.01)、右侧额下回(t=4.25,P0.01)功能连接增加,与左侧前扣带回(t=-3.50,P0.01)、右侧PCC(t=-3.57,P0.01)功能连接降低;PCC与左侧枕中回(t=3.47,P0.01)、右侧枕中回(t=4.18,P0.01)功能连接增加。结论:r MDD患者DMN功能连接仍存在异常,可能与反刍症状及注意等认知偏向未完全改善有关。     

Aberrant Resting-State Functional Connectivity in the Default Mode Network in Pediatric Bipolar Disorder Patients with and without Psychotic Symptoms

Mood disorders/psychosis have been associated with dysfunctions in the default mode network(DMN).However,the relative contributions of DMN regions to state and trait disturbances in pediatric bipolar disorder(PBD)remain unclear.The aim of this study was to investigate the possible mechanisms of PBD through brain imaging and explore the influence of psychotic symptoms on functional alterations in PBD patients.Twenty-nine psychotic and 26 non-psychotic PBD patients,as well as 19 age-and sex-matched healthy controls underwent a restingstate functional MRI scan and the data were analyzed by independent component analysis.The DMN component from the fMRI data was extracted for each participant.Spearman's rank correlation analysis was performed between aberrant connectivity and clinical measurements.The results demonstrated that psychotic PBD was characterized by aberrant DMN connectivity in the anterior cingulate cortex/medial prefrontal cortex,bilateral caudate nucleus,bilateral angular gyri,and left middle temporal gyrus,while non-psychotic PBD was not,suggesting further impairment with the development of psychosis.In summary,we demonstrated unique impairment in DMN functional connectivity in the psychotic PBD group.These specific neuroanatomical abnormalities may shed light on the underlying pathophysiology and presentation of PBD.     

Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a ‘developmental-disconnection’ hypothesis of symptom development in this disorder.     

Retrosplenial cortex connectivity in schizophrenia

In this paper, we build on our previous analysis [Bluhm, R.L., Miller, J., Lanius, R.A., Osuch, E.A., Boksman, K., Neufeld, R.W.J., et al., 2007 Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophrenia Bulletin 33, 1004–1012] of resting state connectivity in schizophrenia by examining alterations in connectivity of the retrosplenial cortex. We have previously demonstrated altered connectivity of the posterior cingulate/precuneus, particularly with other regions of the “default network” (which includes the medial prefrontal cortex and bilateral lateral parietal cortex). It was hypothesized that the retrosplenial cortex would show aberrant patterns of connectivity with regions of the default network and regions associated with memory. Patients with schizophrenia (N = 17) and healthy controls (N = 17) underwent a 5.5-min resting functional magnetic resonance imaging scan. Lower correlations were observed in patients with schizophrenia than in healthy controls between the retrosplenial cortex and both the temporal lobe and regions of the default network. In patients with schizophrenia, activity in the retrosplenial cortex correlated negatively with activity in bilateral anterior cingulate gyrus/medial prefrontal cortex (BA 32/10), despite the fact that these regions, as part of the default network, were expected to show positive correlations in activity. Connectivity of the retrosplenial cortex was greater in patients with more positive symptoms with areas previously associated with hallucinations, particularly the left superior temporal gyrus. These results suggest that spontaneous activity in the retrosplenial cortex during rest is altered in patients with schizophrenia. These alterations may help to explain alterations in self-oriented processing in this patient population.     

Patterns of altered functional connectivity in mesial temporal lobe epilepsy

Purpose: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. Methods: We selected electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG‐fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated. Key Findings: In patients with right MTLE, group difference functional connectivity maps (RMTLE ? controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE ? controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. Significance: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.     

颞叶内侧癫癎海马功能连接的功能磁共振成像研究

目的研究颞叶内侧癫癎患者右侧海马与全脑,尤其是默认网络功能连接的关系,探讨颞叶内侧癫癎患者默认网络异常的机制及其形成的颞叶癫癎网络。方法23例颞叶内侧癫癎患者,采用静息功能连接的功能磁共振成像,选择右侧海马作为兴趣区,获得正常对照组和颞叶内侧癫癎组受试者的脑功能连接激活图,观察其右侧海马与全脑的功能连接。结果正常对照组受试者默认网络包括海马、后扣带回和（或）楔前叶、前扣带回和（或）前额叶内侧、角回及前颞叶。颞叶内侧癫癎组患者右侧海马与默认网络的正向功能连接明显减弱,与右侧额下回、颞上回及第一运动感觉皮质下部的正向功能连接增强;与前额叶背侧、顶间沟及第一运动感觉皮质上部的负向功能连接减弱。结论在颞叶内侧癫癎患者功能连接网络中,默认网络及部分正向功能连接网络受损,提示患者存在广泛的、与海马相关的生理功能丧失;与右侧额下回、颞上回及第一感觉运动皮质下部的功能连接增强则可能与颞叶癫癎网络有关。     

Aberrant Coupling Within and Across the Default Mode,Task-Positive,and Salience Network in Subjects at Risk for Psychosis

The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN), and possibly reflects competition between the processing of external and internal information, while the salience network (SN) is pivotal in regulating TPN and DMN activity. Because abnormal functional connectivity in these networks has been related to schizophrenia, we tested whether alterations are also evident in subjects at risk for psychosis. Resting-state functional magnetic resonance imaging was tested in 28 subjects with basic symptoms reporting subjective cognitive-perceptive symptoms; 19 with attenuated or brief, limited psychotic symptoms; and 29 matched healthy controls. We characterized spatial differences in connectivity patterns, as well as internetwork connectivity. Right anterior insula (rAI) was selected as seed region for identifying the SN; medioprefrontal cortex (MPFC) for the DMN and TPN. The 3 groups differed in connectivity patterns between the MPFC and right dorsolateral prefrontal cortex (rDLPFC), and between the rAI and posterior cingulate cortex (PCC). In particular, the typically observed antagonistic relationship in MPFC-rDLPFC, rAI-PCC, and internetwork connectivity of DMN-TPN was absent in both at-risk groups. Notably, those connectivity patterns were associated with symptoms related to reality distortions, whereas enhanced connectivity strengths of MPFC-rDLPFC and TPN-DMN were related to poor performance in cognitive functions. We propose that the loss of a TPN-DMN anticorrelation, accompanied by an aberrant spatial extent in the DMN, TPN, and SN in the psychosis risk state, reflects the confusion of internally and externally focused states and disturbance of cognition, as seen in psychotic disorders.Key words: resting-state fMRI, schizophrenia, anticorrelated networks, functional connectivity, central executive network, anterior insula, prodrome, intrinsic connectivity, brain     

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Neuropsychiatric syndromes are highly prevalent in Alzheimer's disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or “resting‐state” analysis, may help to clarify this issue. Using such approaches, alterations in the default‐mode and salience networks (SNs) have been described in Alzheimer's, although their relationship with specific symptoms remains unclear. We therefore carried out resting‐state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimer's patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default‐mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy. Hum Brain Mapp 35:1237–1246, 2014. © 2013 Wiley Periodicals, Inc.     

Disrupted default mode network connectivity in male adolescents with conduct disorder

Conduct disorder (CD) is a serious behavioral disorder of childhood and adolescence. The default mode network (DMN) is a brain network which supports self-referential cognitive processes and is typically deactivated during task performance. The aim of this study was to investigate DMN connectivity in male adolescents with pure CD compared to typically-developing controls. Eighteen male adolescents with CD and 18 sex-, age- and education-matched typically-developing (TD) participants were recruited. Current and lifetime psychiatric disorders were assessed using the Chinese version of the Schedule for Affective Disorder and Schizophrenia for School-Age Children-Present and Lifetime Version. Resting state functional magnetic resonance imaging (fMRI) data were obtained using a 3.0 T scanner. Independent components analysis (ICA) was used to investigate functional connectivity between the DMN and related brain regions. DMN activity was observed in medial prefrontal, posterior cingulate, and lateral parietal cortices, and extended to the brainstem. Adolescents with CD showed significantly reduced functional connectivity within the bilateral posterior cingulate cortex (PCC), bilateral precuneus and right superior temporal gyrus relative to TD controls. CD is associated with reduced functional connectivity within the DMN and between the DMN and other regions. These preliminary results suggest that deficits in DMN functional connectivity may serve as a biomarker of CD.     

Regional homogeneity changes in social anxiety disorder: a resting-state fMRI study

The previous task-based or resting perfusion studies in social anxiety disorder (SAD) patients have highlighted specific differences in brain response. Little is known about the changes in the local synchronization of spontaneous functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signals that occur in SAD during the resting state. We investigated altered neural activity in the resting state using a regional homogeneity (ReHo) analysis on 20 SAD and 20 healthy controls (HC). Compared with HC, SAD patients exhibited decreased coherence (ReHo) in the bilateral angular gyrus and the left medial prefrontal cortex within the default mode network (DMN), suggesting functional impairment of the perception of socially relevant emotional state and self-related mental representations; and also in the right dorsolateral prefrontal cortex and right inferior parietal gyrus within the central-executive network (CEN), reflecting the deficit of cognitive control of social anxiety. Significantly increased coherence (ReHo) was found in the left middle occipital gyrus, which would be consistent with their hypervigilance and hyperprosexia to the social communication even in the resting state. Our results might supply a novel way to look into neuro-pathophysiological mechanisms in SAD patients.     

Anatomical and functional connectivity in the default mode network of post‐traumatic stress disorder patients after civilian and military‐related trauma

Posttraumatic stress disorder (PTSD) is characterized by unwanted intrusive thoughts and hyperarousal at rest. As these core symptoms reflect disturbance in resting‐state mechanisms, we investigated the functional and anatomical involvement of the default mode network (DMN) in this disorder. The relation between symptomatology and trauma characteristics was considered. Twenty PTSD patients and 20 matched trauma‐exposed controls that were exposed to a similar traumatic event were recruited for this study. In each group, 10 patients were exposed to military trauma, and 10 to civilian trauma. PTSD, anxiety, and depression symptom severity were assessed. DMN maps were identified in resting‐state scans using independent component analysis. Regions of interest (medial prefrontal, precuneus, and bilateral inferior parietal) were defined and average z‐scores were extracted for use in the statistical analysis. The medial prefrontal and the precuneus regions were used for cingulum tractography whose integrity was measured and compared between groups. Similar functional and anatomical connectivity patterns were identified in the DMN of PTSD patients and trauma‐exposed controls. In the PTSD group, functional and anatomical connectivity parameters were strongly correlated with clinical measures, and there was evidence of coupling between the anatomical and functional properties. Type of trauma and time from trauma were found to modulate connectivity patterns. To conclude, anatomical and functional connectivity patterns are related to PTSD symptoms and trauma characteristics influence connectivity beyond clinical symptoms. Hum Brain Mapp 37:589–599, 2016. © 2015 Wiley Periodicals, Inc .     

Altered default mode network connectivity in Alzheimer's disease--a resting functional MRI and Bayesian network study

A number of functional magnetic resonance imaging (fMRI) studies reported the existence of default mode network (DMN) and its disruption due to the presence of a disease such as Alzheimer's disease (AD). In this investigation, first, we used the independent component analysis (ICA) technique to confirm the DMN difference between patients with AD and normal control (NC) reported in previous studies. Consistent with the previous studies, the decreased resting-state functional connectivity of DMN in AD was identified in posterior cingulated cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal cortex (IPC), inferior temporal cortex (ITC), and hippocampus (HC). Moreover, we introduced Bayesian network (BN) to study the effective connectivity of DMN and the difference between AD and NC. When compared the DMN effective connectivity in AD with the one in NC using a nonparametric random permutation test, we found that connections from left HC to left IPC, left ITC to right HC, right HC to left IPC, to MPFC and to PCC were all lost. In addition, in AD group, the connection directions between right HC and left HC, between left HC and left ITC, and between right IPC and right ITC were opposite to those in NC group. The connections of right HC to other regions, except left HC, within the BN were all statistically in-distinguishable from 0, suggesting an increased right hippocampal pathological and functional burden in AD. The altered effective connectivity in patients with AD may reveal more characteristics of the disease and may serve as a potential biomarker.     

Resting state and task‐induced deactivation: A methodological comparison in patients with schizophrenia and healthy controls

Changes in the default mode network (DMN) have been linked to multiple neurological disorders including schizophrenia. The anticorrelated relationship the DMN shares with task‐related networks permits the quantification of this network both during task (task‐induced deactivations: TID) and during periods of passive mental activity (extended rest). However, the effects of different methodologies (TID vs. extended rest) for quantifying the DMN in the same clinical population are currently not well understood. Moreover, several different analytic techniques, including independent component analyses (ICA) and seed‐based correlation analyses, exist for examining functional connectivity during extended resting states. The current study compared both methodologies and analytic techniques in a group of patients with schizophrenia (SP) and matched healthy controls. Results indicated that TID analyses, ICA, and seed‐based correlation all consistently identified the midline (anterior and posterior cingulate gyrus) and lateral parietal cortex as core regions of the DMN, as well as more variable involvement of temporal lobe structures. In addition, SP exhibited increased deactivation during task, as well as decreased functional connectivity with frontal regions and increased connectivity with posterior and subcortical areas during periods of extended rest. The increased posterior and reduced anterior connectivity may partially explain some of the cognitive dysfunction and clinical symptoms that are frequently associated with schizophrenia. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

The development of the intrinsic functional connectivity of default network subsystems from age 3 to 5

In recent years, research on human functional brain imaging using resting-state fMRI techniques has been increasingly prevalent. The term “default mode” was proposed to describe a baseline or default state of the brain during rest. Recent studies suggested that the default mode network (DMN) is comprised of two functionally distinct subsystems: a dorsal-medial prefrontal cortex (DMPFC) subsystem involved in self-oriented cognition (i.e., theory of mind) and a medial temporal lobe (MTL) subsystem engaged in memory and scene construction; both subsystems interact with the anterior medial prefrontal cortex (aMPFC) and posterior cingulate (PCC) as the core regions of DMN. The present study explored the development of DMN core regions and these two subsystems in both hemispheres from 3- to 5-year-old children. The analysis of the intrinsic activity showed strong developmental changes in both subsystems, and significant changes were specifically found in MTL subsystem, but not in DMPFC subsystem, implying distinct developmental trajectories for DMN subsystems. We found stronger interactions between the DMPFC and MTL subsystems in 5-year-olds, particularly in the left subsystems that support the development of environmental adaptation and relatively complex mental activities. These results also indicate that there is stronger right hemispheric lateralization at age 3, which then changes as bilateral development gradually increases through to age 5, suggesting in turn the hemispheric dominance in DMN subsystems changing with age. The present results provide primary evidence for the development of DMN subsystems in early life, which might be closely related to the development of social cognition in childhood.     

Aberrant Dependence of Default Mode/Central Executive Network Interactions on Anterior Insular Salience Network Activity in Schizophrenia

In schizophrenia, consistent structural and functional changes have been demonstrated for the insula including aberrant salience processing, which is critical for psychosis. Interactions within and across default mode and central executive network (DMN, CEN) are impaired in schizophrenia. The question arises whether these 2 types of changes are related. Recently, the anterior insula has been demonstrated to control DMN/CEN interactions. We hypothesized that aberrant insula and DMN/CEN activity in schizophrenia is associated with an impaired dependence of DMN/CEN interactions on anterior insular salience network (SN) activity. Eighteen patients with schizophrenia during psychosis and 20 healthy controls were studied by resting-state-fMRI and psychometric examination. High-model-order independent component analysis of fMRI data revealed spatiotemporal patterns of synchronized ongoing blood-oxygenation-level-dependent (BOLD) activity including SN, DMN, and CEN. Scores of functional and time-lagged connectivity across networks’ time courses were calculated. Connectivity scores and spatial network maps were compared between groups and related with patients’ hallucination and delusion severity. Spatial BOLD-synchronicity was altered in patients’ SN, DMN, and CEN, including decreased activity in the right anterior insula (rAI). Patients’ functional connectivity between DMN and CEN was increased and related with hallucinations severity. Importantly, patients’ time-lagged connectivity between SN and DMN/CEN was reduced, and decreased rAI activity of the SN was associated with both hallucinations and increased functional connectivity between DMN and CEN. Data provide evidence for an aberrant dependence of DMN/CEN interactions on anterior insular SN activity, linking impaired insula, DMN, CEN activity, and psychosis in schizophrenia.Key words: schizophrenia, psychosis, anterior insula, salience network, default mode network, central executive network     

Parietal memory network and default mode network in first‐episode drug‐naïve schizophrenia: Associations with auditory hallucination

Atypical spontaneous activities in resting‐state networks may play a role in auditory hallucinations (AHs), but networks relevant to AHs are not apparent. Given the debating role of the default mode network (DMN) in AHs, a parietal memory network (PMN) may better echo cognitive theories of AHs in schizophrenia, because PMN is spatially adjacent to the DMN and more relevant to memory processing or information integration. To examine whether PMN is more relevant to AHs than DMN, we characterized these intrinsic networks in AHs with 59 first‐episode, drug‐naïve schizophrenics (26 AH+ and 33 AH?) and 60 healthy participants in resting‐state fMRI. We separated the PMN, DMN, and auditory network (AN) using independent component analysis, and compared their functional connectivity across the three groups. We found that only AH+ patients displayed dysconnectivity in PMN, both AH+ and AH? patients exhibited dysfunctions of AN, but neither patient group showed abnormal connectivity within DMN. The connectivity of PMN significantly correlated with memory performance of the patients. Further region‐of‐interest analyses confirmed that the connectivity between the core regions of PMN, the left posterior cingulate gyrus and the left precuneus, was significantly lower only in the AH+ group. In exploratory correlation analysis, this functional connectivity metric significantly correlated with the severity of AH symptoms. The results implicate that compared to the DMN, the PMN is more relevant to the AH symptoms in schizophrenia, and further provides a more precise potential brain modulation target for the intervention of AH symptoms.     

Altered brain function in persistent postural perceptual dizziness: A study on resting state functional connectivity

This study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I–IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.     

Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest

The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia.Key words: unaffected siblings of schizophrenia patients, schizophrenia, cerebellum, functional connectivity, default-mode network     

Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study

Background

Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy.

Methods

We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, including regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects.

Results

Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and between medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnormalities along the MPFC–PCC and LIPL–RIPL pathways in patients with ADHD.

Limitations

Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings.

Conclusion

Adults with ADHD exhibit hyper- and hypoconnectivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.