Aberrant Brain Activity Research Articles

Aberrant Intraregional Brain Activity and Functional Connectivity in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.

Background and PurposeThe appearance and aggravation of diarrhea-predominant irritable bowel syndrome (IBS-D) have proven to be closely related to psychosocial factors. We aimed to measure altered spontaneous brain activity and functional connectivity (FC) in patients with IBS-D using resting-state functional magnetic resonance imaging (RS-fMRI) and to analyze the relationship between these parameters and emotional symptoms.MethodsThirty-six adult IBS-D patients and thirty-six demographic-matched healthy controls (HCs) underwent RS-fMRI scans. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of the two groups were compared. The abnormal regions were selected as the regions of interest to compare whole-brain seed-based FC between the groups. The relationships between RS-fMRI data and mood and gastrointestinal symptoms were analyzed using correlation and mediation analyses.ResultsCompared with HCs, IBS-D patients showed increased ALFF in the right cerebellum posterior lobe, the right lingual gyrus/calcarine, the right postcentral gyrus, the right superior frontal gyrus (SFG), and middle frontal gyrus (MFG), with decreased ALFF in the right inferior parietal lobule, the right striatum, the right anterior cingulated cortex, the right insula, the right hippocampus, the right thalamus, the right midbrain, and the left precuneus. IBS-D patients showed increased ReHo in the bilateral lingual gyrus/calcarine, the bilateral SFG, the right MFG, and the right postcentral gyrus, with decreased ReHo in the orbital part of the left inferior frontal gyrus and the right supplementary motor area. Patients showed enhanced FC between the left precuneus and the bilateral orbitofrontal cortex (OFC). There was a positive correlation between increased ALFF values in the right midbrain and anxiety-depression symptoms in IBS-D patients, and the mediating effect of gastrointestinal symptoms indirectly caused this correlation.ConclusionIBS-D patients had dysregulated spontaneous activity and FC in regions related to pain regulation and emotional arousal involved in prefrontal–limbic–midbrain circuit and somatosensory processing. The development of mood disorders in IBS-D patients may be partly related to the dysfunction of components in the dopamine pathway (especially the midbrain, OFC) due to visceral pain.

Neuronal correlates underlying the role of the zinc sensing receptor (GPR39) in passive-coping behaviour

The Zn2+ receptor GPR39 is proposed to be involved in the pathophysiology of depression. GPR39 knockout (KO) animals show depressive- and anxiety-like behaviour, and resistance to conventional monoamine-based antidepressants. However, it is unclear as to which brain regions are involved in the pro-depressive phenotype of GPR39KO mice and the resistance to monoamine-targeting antidepressant treatment. Our current study confirmed previous results, showing that mice lacking GPR39 display enhanced passive coping-like behaviour compared with their wild-type controls. Furthermore, this study shows for the first time that GPR39KO displayed aberrant challenge-induced neuronal activity in key brain regions associated with passive coping behaviour. Imipramine induced only a marginal reduction in the enhanced passive coping behaviour in GPR39KO mice, which was associated with attenuation of the hyperactive prefrontal cortex. Similarly, the aberrant activity within the amygdalar subregions was normalized following imipramine treatment in the GPR39KO mice, indicating that imipramine mediates these effects independently of GPR39 in the prefrontal cortex and amygdala. However, imipramine failed to modulate the aberrant brain activity in other brain regions, such as the anterior CA3 and the dentate gyrus, in GPR39KO mice. Normalization of aberrant activity in these areas has been shown previously to accompany successful behavioural effects of antidepressants. Taken together, our data suggest that monoamine-based antidepressants such as imipramine exert their action via GPR39-dependent and -independent pathways. Failure to modulate passive-coping related aberrant activity in important brain areas of the depression circuitry is proposed to mediate/contribute to the greatly reduced antidepressant action of monoamine-based antidepressants in GPR39KO mice.

Error-Related Brain Activity in Patients With Obsessive-Compulsive Disorder and Unaffected First-Degree Relatives: Evidence for Protective Patterns

BackgroundIndicators of increased error monitoring are associated with obsessive-compulsive disorder (OCD), as shown in electroencephalography and functional magnetic resonance imaging studies. As most studies used strictly controlled samples (excluding comorbidity and medication), it remains open whether these findings extend to naturalistic settings. Thus, we assessed error-related brain activity in a large, naturalistic OCD sample. We also explored which activity patterns might qualify as vulnerability endophenotypes or protective factors for the disorder. To this aim, a sample of unaffected first-degree relatives of patients with OCD was also included. MethodsParticipants (84 patients with OCD, 99 healthy control participants, and 37 unaffected first-degree relatives of patients with OCD) completed a flanker task while blood oxygen level–dependent responses were measured with functional magnetic resonance imaging. Aberrant error-related brain activity in patients and relatives was identified. ResultsPatients with OCD showed increased error-related activity in the supplementary motor area and within the default mode network, specifically in the precuneus and postcentral gyrus. Unaffected first-degree relatives showed increased error-related activity in the bilateral inferior frontal gyrus. ConclusionsIncreased supplementary motor area and default mode network activity in patients with OCD replicates previous studies and might indicate excessive error signals and increased self-referential error processing. Increased activity of the inferior frontal gyrus in relatives may reflect increased inhibition. Impaired response inhibition in OCD has been demonstrated in several studies and might contribute to impairments in suppressing compulsive actions. Thus, increased inferior frontal gyrus activity in the unaffected relatives of patients with OCD may have contributed to protection from symptom development.

Neurobiological antecedents of multisite pain in children.

Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnerable to developing chronic pain later in life. We examined structural and functional brain magnetic resonance imaging metrics in a subset of children from the first 2 assessments of the Adolescent Brain and Cognitive Development Study. Children (aged 9-10) who were pain free at baseline and then developed multisite pain 1 year later (n = 115) were matched to control children who were pain free at both timepoints (n = 230). We analyzed brain structure (cortical thickness and gray matter volume) and function (spontaneous neural activity and functional connectivity). Results were deemed significant at the cluster level P < 0.05 false discovery rate corrected for multiple comparisons. At baseline, children who subsequently developed multisite pain had increased neural activity in superior parietal /primary somatosensory and motor cortices and decreased activity in the medial prefrontal cortex. They also exhibited stronger functional connectivity between the salience network, somatosensory, and default mode network regions. No significant differences in the brain structure were observed. Increased neural activity and functional connectivity between brain regions, consistent to that seen in adults with chronic pain, exist in children before developing multisite pain. These findings may represent a neural vulnerability to developing future chronic pain.

Reduced prefrontal activity and suicidal behaviour in early schizophrenia

IntroductionApproximately, 15- 26% of patients with first-episode psychosis, including schizophrenia, are likely to have attempted suicide by their first treatment contact. Studies of suicidal behavior outside of schizophrenia have indicated grey matter volume loss in the prefrontal and orbitofrontal cortex, and aberrant brain activity in relation to emotional recognition and dysfunction.ObjectivesThis study aimed to investigate the functional neural correlates of suicidal behavior in early schizophrenia.MethodsfMRI faces task was conducted (fearful face versus neutral face) in 8 participants with first-episode schizophrenia together with standardised scales including PANSS and SBQ-R. fMRI activation was compared using a two-sample t-test in participants with low and high suicidal behavior. Extent threshold is 0 voxels and significance level p&lt;0.001 (FWE corrected). Processing of images was carried out using SPM12 and Matlab.Results8 participants were recruited; 5 males and 3 females, mean age of 26.5. Results suggest that participants with higher suicidal behaviour showed reduced activation on the anterior-cingulate gyrus and medial frontal gyrus, which are parts of PFC, (p= .005). There was also a significant difference in task response accuracy, where, participants with high suicidal behaviour made more accurate responses compared to low group (t (3) = 3.65, p = .035).ConclusionsThis is an exploratory study, investigated the differences in brain activity in patients with schizophrenia who are at risk of completed suicide and, therefore might provide new insights into the underlying mechanisms. Further work should address how PFC activity changes with risk over time and its potential utility as a biomarker in suicide.

Theory of Mind impairments in early course schizophrenia: An fMRI study

Theory of Mind (ToM) refers to the ability to perceive others’ mental states. Lower ToM has often been associated with poorer functional outcomes in schizophrenia, making it an important treatment target. However, little is known about the underlying neural mechanisms associated with ToM impairments in early course schizophrenia. This study aimed to validate the False Belief task to measure ToM in schizophrenia and to identify aberrant brain activity associated with impairments. 36 individuals with early course schizophrenia and 17 controls were administered the Hinting Task and performed a functional magnetic resonance imaging (fMRI) False Belief task. Between-group differences were examined in a priori regions of interest (ROIs) known to be associated with ToM tasks: medial prefrontal cortex, ventral medial prefrontal cortex, and both the left and right temporal parietal junction (TPJ). We observed a significant positive association between Hinting Task performance and False Belief accuracy, validating the False Belief task as a measure of ToM. Compared to controls, individuals with schizophrenia exhibited reduced brain activation in all four ROIs during the fMRI False Belief task. Furthermore, task-related activations in bilateral TPJs were shown to be positively associated with ToM abilities regardless of diagnosis. Individuals with schizophrenia with lower performance on the False Belief task showed significant reductions in task-related activation in the bilateral TPJ compared to controls, while reductions were not significant for those with higher performance. Our findings suggest that lower neural activity in the bilateral TPJ are associated with ToM impairments observed in individuals with early course schizophrenia.

Altered brain functional network dynamics in obsessive-compulsive disorder.

Obsessive–compulsive disorder (OCD) is a debilitating and disabling neuropsychiatric disorder, whose neurobiological basis remains unclear. Although traditional static resting‐state magnetic resonance imaging (rfMRI) studies have found aberrant functional connectivity (FC) in OCD, alterations in whole‐brain FC and topological properties in the context of brain dynamics remain relatively unexplored. The rfMRI data of 29 patients with OCD and 40 healthy controls were analyzed using group independent component analysis to obtain independent components (ICs) and a sliding‐window approach to generate dynamic functional connectivity (dFC) matrices. dFC patterns were clustered into three reoccurring states, and state transition metrics were obtained. Then, graph‐theory methods were applied to dFC matrices to calculate the variability of network topological organization. The occurrence of a state (State 1) with the highest modularity index and lowest mean FC between networks was increased significantly in OCD, and the fractional time in brain State 1 was positively correlated with anxiety level in patients. State 1 was characterized by having positive connections within default mode (DMN) and salience networks (SAN), and negative coupling between the two networks. Additionally, ICs belonging to DMN and SAN showed lower temporal variability of nodal degree centrality and efficiency in patients, which was related to longer illness duration and higher current obsession ratings. Our results provide evidence of clinically relevant aberrant dynamic brain activity in OCD. Increased functional segregation among networks and impaired functional flexibility in connections among brain regions in DMN and SAN may play important roles in the neuropathology of OCD.

Effects of Transcranial Direct Current Stimulation (tDCS) in the Normalization of Brain Activation in Patients with Neuropsychiatric Disorders: A Systematic Review of Neurophysiological and Neuroimaging Studies.

Background People with neuropsychiatric disorders have been found to have abnormal brain activity, which is associated with the persistent functional impairment found in these patients. Recently, transcranial direct current stimulation (tDCS) has been shown to normalize this pathological brain activity, although the results are inconsistent. Objective We explored whether tDCS alters and normalizes brain activity among patients with neuropsychiatric disorders. Moreover, we examined whether these changes in brain activity are clinically relevant, as evidenced by brain-behavior correlations. Methods A systematic review was conducted according to PRISMA guidelines. Randomized controlled trials that studied the effects of tDCS on brain activity by comparing experimental and sham control groups using either electrophysiological or neuroimaging methods were included. Results With convergent evidence from 16 neurophysiological/neuroimaging studies, active tDCS was shown to be able to induce changes in brain activation patterns in people with neuropsychiatric disorders. Importantly, anodal tDCS appeared to normalize aberrant brain activation in patients with schizophrenia and substance abuse, and the effect was selectively correlated with reaction times, task-specific accuracy performance, and some symptom severity measures. Limitations and Conclusions. Due to the inherent heterogeneity in brain activity measurements for tDCS studies among people with neuropsychiatric disorders, no meta-analysis was conducted. We recommend that future studies investigate the effect of repeated cathodal tDCS on brain activity. We suggest to clinicians that the prescription of 1-2 mA anodal stimulation for patients with schizophrenia may be a promising treatment to alleviate positive symptoms. This systematic review is registered with registration number CRD42020183608.

Tinnitus and auditory cortex: using adapted functional near-infrared spectroscopy to measure resting-state functional connectivity.

ObjectiveTinnitus, phantom sound perception, arises from aberrant brain activity within auditory cortex. In tinnitus animal models, auditory cortex neurons show increased spontaneous firing and neural synchrony. In humans, similar hyperactivation in auditory cortex has been displayed with functional near-infrared spectroscopy (fNIRS). Resting-state functional connectivity (RSFC) or increased connectivity between brain regions has also been shown in tinnitus using fNIRS. However, current fNIRS technology utilizes infrared (IR)-sources and IR-detectors placed on the scalp that restricts (~3 cm depth IR penetration) signal capture to outer cerebral cortex due to skin and skull bone. To overcome this limitation, in this proof of concept study, we adapted fNIRS probes to fit in the external auditory canal (EAC) to physically place IR-probes deeper within the skull thereby extracting neural signals from deeper auditory cortex.MethodsTwenty adults with tinnitus and 20 nontinnitus controls listened to periods of silence and broadband noise before and after 5 min of silence to calculate RSFC. Concurrent scalp probes over auditory cortex and an adapted probe placed in the right EAC were utilized.ResultsFor standard probes, left and right auditory cortex in tinnitus showed increased RSFC to each other and to other nonauditory cortices. Interestingly, adapted fNIRS probes showed trends toward increased RSFC.ConclusionWhile many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.

Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy.

Mitochondria are major sources of reactive oxygen species (ROS) within the cell and are especially vulnerable to oxidative stress. Oxidative damage to mitochondria results in disrupted mitochondrial function and cell death signaling, finally triggering diverse pathologies such as epilepsy, a common neurological disease characterized with aberrant electrical brain activity. Antioxidants are considered as promising neuroprotective strategies for epileptic condition via combating the deleterious effects of excessive ROS production in mitochondria. In this review, we provide a brief discussion of the role of mitochondrial oxidative stress in the pathophysiology of epilepsy and evidences that support neuroprotective roles of antioxidants targeting mitochondrial oxidative stress including mitochondria-targeted antioxidants, polyphenols, vitamins, thiols, and nuclear factor E2-related factor 2 (Nrf2) activators in epilepsy. We point out these antioxidative compounds as effectively protective approaches for improving prognosis. In addition, we specially propose that these antioxidants exert neuroprotection against epileptic impairment possibly by modulating cell death interactions, notably autophagy-apoptosis, and autophagy-ferroptosis crosstalk.

Working memory training restores aberrant brain activity in adult attention-deficit hyperactivity disorder.

The development of treatments for attention impairments is hampered by limited knowledge about the malleability of underlying neural functions. We conducted the first randomized controlled trial to determine the modulations of brain activity associated with working memory (WM) training in adults with attention‐deficit hyperactivity disorder (ADHD). At baseline, we assessed the aberrant functional brain activity in the n‐back WM task by comparing 44 adults with ADHD with 18 healthy controls using fMRI. Participants with ADHD were then randomized to train on an adaptive dual n‐back task or an active control task. We tested whether WM training elicits redistribution of brain activity as observed in healthy controls, and whether it might further restore aberrant activity related to ADHD. As expected, activity in areas of the default‐mode (DMN), salience (SN), sensory‐motor (SMN), frontoparietal (FPN), and subcortical (SCN) networks was decreased in participants with ADHD at pretest as compared with healthy controls, especially when the cognitive load was high. WM training modulated widespread FPN and SN areas, restoring some of the aberrant activity. Training effects were mainly observed as decreased brain activity during the trained task and increased activity during the untrained task, suggesting different neural mechanisms for trained and transfer tasks.

Aberrant Awake Spontaneous Brain Activity in Obstructive Sleep Apnea: A Review Focused on Resting-State EEG and Resting-State fMRI.

As one of the most common sleep-related respiratory disorders, obstructive sleep apnea (OSA) is characterized by excessive snoring, repetitive apnea, arousal, sleep fragmentation, and intermittent nocturnal hypoxemia. Focused on the resting-state brain imaging techniques, we reviewed the OSA-related resting-state electroencephalogram and resting-state functional magnetic resonance imaging (rsfMRI) studies. Compared with the healthy control group, patients with OSA presented increased frontal and central δ/θ powers during resting-state wakefulness, and their slow-wave activity showed a positive correlation with apnea–hypopnea index. For rsfMRI, the prefrontal cortex and insula may be the vital regions for OSA and are strongly related to the severity of the disease. Meanwhile, some large-scale brain networks, such as the default-mode network, salience network, and central executive network, play pivotal roles in the pathology of OSA. We then discussed the contribution of resting-state brain imaging as an evaluation approach for disease interventions. Finally, we briefly introduced the effects of OSA-related physiological and mental diseases and discussed some future research directions from the perspective of resting-state brain imaging.

The effect of vagal nerve stimulation on hippocampal-thalamic functional connectivity in epilepsy patients

BackgroundVagal nerve stimulation (VNS) is widely used as an auxiliary treatment for patients with intractable epilepsy. Up to now, the therapeutic mechanisms remain elusive, and no surgical prediction criteria has been proposed. MethodsIn this study, the resting-state functional magnetic resonance imaging (rs-fMRI) was chosen to explore aberrant intrinsic brain activity and functional connections in 14 epilepsy patients with VNS stimulators between March 2019 and April 2019. Seven patients who ≥ 50 % seizure reduction was defined as responders, and seven non-responders. All patients had got rs-fMRI scan before and after operation. The hippocampal - thalamic connections (hippocampal and thalamus as regions of interest) were detected to evaluate the diversity in all 14 patients and seven responders with stimulation at 0, 0.5, 1.0, and 1.5 mA. The hippocampal-thalamic connections before operation were also examined between responders and non-responders. ResultsThe preoperative left hippocampal - left thalamic connections and left hippocampal - right thalamic connections in responders were lower than those in non-responders (p < 0.05). While, there was no significant difference in hippocampal - thalamic connections in all epilepsy patients or responders with different current intensities (p > 0.05). ConclusionsVNS may be more suitable for patients with lower left hippocampal - left thalamic connections and/or left hippocampal - right thalamic connections. The current intensity ≤ 1.5 mA and stimulation time ≤ 3 months may not cause significant changes in hippocampal-thalamic functional connectivity.

Neuronal correlates of spider phobia in a combined fNIRS-EEG study

Specific phobia is associated with aberrant brain activation in confrontation paradigms with phobic stimuli. In previous EEG research enhanced event-related potentials (ERPs) in the late-positive potential (LPP) window have been observed. Further, studies with functional near-infrared spectroscopy (fNIRS) and fMRI suggest that spider phobia is associated with enhanced activation within cortical and subcortical areas. In the current study we investigated the neuronal correlates of spider phobia in a combined fNIRS–EEG study. To this end, 37 spider phobic patients (PP) and 32 healthy controls (HC) underwent a symptom provocation paradigm during which subjects watched video clips of spiders and domestic animals (confrontation phase) after being primed on the content of the video (anticipation phase). Simultaneously, fNIRS, EEG, electromyography (EMG), electrocardiography and behavioral measures were assessed. Results showed increased LPP amplitudes, increased hemodynamic responses in the cognitive control network, and increased EMG activity and heart rate during spider conditions in PP in comparison to HC. Furthermore, in behavioral ratings PP showed higher emotional distress and avoidance. Behavioral ratings, fNIRS and EEG data showed positive correlations on a between-subject as well as on a within-subject level. Our results merge the existing data on neurophysiological correlates of phobic stimulus processing in hemodynamic and electrophysiological research and extend those of static visual material (pictures) to dynamic visual material (videos).

Dorsolateral prefrontal cortex and amygdala function during cognitive reappraisal predicts weight restoration and emotion regulation impairment in anorexia nervosa.

Although deficits in affective processing are a core component of anorexia nervosa (AN), we lack a detailed characterization of the neurobiological underpinnings of emotion regulation impairment in AN. Moreover, it remains unclear whether these neural correlates scale with clinical outcomes. We investigated the neural correlates of negative emotion regulation in a sample of young women receiving day-hospital treatment for AN (n = 21) and healthy controls (n = 21). We aimed to determine whether aberrant brain activation patterns during emotion regulation predicted weight gain following treatment in AN patients and were linked to AN severity. To achieve this, participants completed a cognitive reappraisal paradigm during functional magnetic resonance imaging. Skin conductance response, as well as subjective distress ratings, were recorded to corroborate task engagement. Compared to controls, patients with AN showed reduced activation in the dorsolateral prefrontal cortex (dlPFC) during cognitive reappraisal [pFWE<0.05, threshold-free cluster enhancement (TFCE) corrected]. Importantly, psycho-physiological interaction analysis revealed reduced functional connectivity between the dlPFC and the amygdala in AN patients during emotion regulation (pFWE<0.05, TFCE corrected), and dlPFC-amygdala uncoupling was associated with emotion regulation deficits (r = -0.511, p = 0.018) and eating disorder severity (r = -0.565, p = .008) in the AN group. Finally, dlPFC activity positively correlated with increases in body mass index (r = 0.471, p = 0.042) and in body fat mass percentage (r = 0.605, p = 0.008) following 12 weeks of treatment. Taken together, our findings indicate that individuals with AN present altered fronto-amygdalar response during cognitive reappraisal and that this response may serve as a predictor of response to treatment and be linked to clinical severity.

Persistent Differences in Brain Structure in Developmental Dyscalculia: A Longitudinal Morphometry Study.

Developmental dyscalculia (DD) is a learning disability affecting the acquisition of numerical-arithmetical skills. Affected people show persistent deficits in number processing, which are associated with aberrant brain activation and structure. Reduced gray matter has been reported in DD for the parietal cortex including the intraparietal sulcus (IPS), but also the frontal and occipito-temporal cortex. Furthermore, dyscalculics show white matter differences for instance in the inferior (ILF) and superior longitudinal fasciculus (SLF). However, the longitudinal development of these structural differences is unknown. Therefore, our goal was to investigate the developmental trajectory of gray and white matter in children with and without DD. In this longitudinal study, neuropsychological measures and T1-weighted structural images were collected twice with an interval of 4 years from 13 children with DD (8.2–10.4 years) and 10 typically developing (TD) children (8.0–10.4 years). Voxel-wise estimation of gray and white matter volumes was assessed using voxel-based morphometry for longitudinal data. The present findings reveal for the first time that DD children show persistently reduced gray and white matter volumes over development. Reduced gray matter was found in the bilateral inferior parietal lobes including the IPS, supramarginal gyri, left precuneus, cuneus, right superior occipital gyrus, bilateral inferior and middle temporal gyri, and insula. White matter volumes were reduced in the bilateral ILF and SLF, inferior fronto-occipital fasciculus (IFOF), corticospinal tracts, and right anterior thalamic radiation (ATR). Behaviorally, children with DD performed significantly worse in various numerical tasks at baseline and follow-up, corroborating persistent deficits in number processing. The present results are in line with the literature showing that children with DD have reduced gray and white matter volumes in the numerical network. Our study further sheds light on the trajectory of brain development, revealing that these known structural differences in the long association fibers and the adjacent regions of the temporal- and frontoparietal cortex persist in dyscalculic children from childhood into adolescence. In conclusion, our results underscore that DD is a persistent learning disorder accompanied by deficits in number processing and reduced gray and white matter volumes in number related brain areas.

Designing a Successful Neurofeedback Training for Children with Autism Spectrum Disorder

Abstract. The goal of this article was to highlight important issues that have to be considered when designing an electroencephalography (EEG)-based neurofeedback training for children with Autism Spectrum Disorder and to provide practical advice for a successful implementation. Autism is a heterogeneous and complex disorder, which leads to a broad and varied profile of symptoms as well as to huge individual differences between the affected children. This is why the neurofeedback training protocol has to be individually designed based on the specific symptoms as well as in consideration of the existing theories about aberrant brain activity, and why it then needs to be evaluated empirically. Furthermore, neurofeedback training has to be optimized individually regarding the specific control signal, feedback and practical implementations in order to lead to the desired improvements.

Abnormalities of intrinsic regional brain activity in first-episode and chronic schizophrenia: a meta-analysis of resting-state functional MRI

Resting-state functional MRI (fMRI) studies have provided much evidence for abnormal intrinsic brain activity in schizophrenia, but results have been inconsistent. We conducted a meta-analysis of whole-brain, resting-state fMRI studies that explored differences in amplitude of low-frequency fluctuation (ALFF) between people with schizophrenia (including first episode and chronic) and healthy controls. A systematic literature search identified 24 studies comparing a total of 1249 people with schizophrenia and 1179 healthy controls. Overall, patients with schizophrenia displayed decreased ALFF in the bilateral postcentral gyrus, bilateral precuneus, left inferior parietal gyri and right occipital lobe, and increased ALFF in the right putamen, right inferior frontal gyrus, left inferior temporal gyrus and right anterior cingulate cortex. In the subgroup analysis, patients with first-episode schizophrenia demonstrated decreased ALFF in the bilateral inferior parietal gyri, right precuneus and left medial prefrontal cortex, and increased ALFF in the bilateral putamen and bilateral occipital gyrus. Patients with chronic schizophrenia showed decreased ALFF in the bilateral postcentral gyrus, left precuneus and right occipital gyrus, and increased ALFF in the bilateral inferior frontal gyri, bilateral superior frontal gyrus, left amygdala, left inferior temporal gyrus, right anterior cingulate cortex and left insula. The small sample size of our subgroup analysis, predominantly Asian samples, processing steps and publication bias could have limited the accuracy of the results. Our comprehensive meta-analysis suggests that findings of aberrant regional intrinsic brain activity during the initial stages of schizophrenia, and much more widespread damage with the progression of disease, may contribute to our understanding of the progressive pathophysiology of schizophrenia.

Abnormal Spontaneous Neural Activity of the Central Auditory System Changes the Functional Connectivity in the Tinnitus Brain: A Resting-State Functional MRI Study.

ObjectiveAn abnormal state of the central auditory system (CAS) likely plays a large role in the occurrence of phantom sound of tinnitus. Various tinnitus studies using resting-state functional MRI (RS-fMRI) have reported aberrant spontaneous brain activity in the non-auditory system and altered functional connectivity between the CAS and non-auditory system. This study aimed to investigate abnormal functional connections between the aberrant spontaneous activity in the CAS and the whole brain in tinnitus patients, compared to healthy controls (HC) using RS-fMRI.Materials and MethodsRS-fMRI from 16 right-ear tinnitus patients with normal hearing (TNHs) and 15 HC individuals was collected, and the time series were extracted from different clusters of a CAS template, supplied by the Anatomy Toolbox of the Statistical Parametric Mapping software. These data were used to derive the smoothed mean amplitude of low-frequency fluctuation (smALFF) values and calculate the relationship between such values and the corresponding clinical data. In addition, clusters in the CAS identified by the smALFF maps were set as seed regions for calculating and comparing the brain-wide connectivity between TNH and HC.ResultsWe identified the different clusters located in the left higher auditory cortex (HAC) and the right inferior colliculus (IC) from the smALFF maps that contained increased (HAC) and decreased (IC) activity when the TNH group was compared to the HC group, respectively. The value of increased smALFF cluster in the HAC was positively correlated with the tinnitus score, but the decreased smALFF cluster in the IC was not correlated with any clinical characters of tinnitus. The TNH group displayed increased connectivity, compared to the HC group, in brain regions that encompassed the left IC, bilateral Heschl gyrus, bilateral supplementary motor area, right insula, bilateral superior temporal gyrus, right middle temporal gyrus, left hippocampus, left amygdala, and right supramarginal gyrus.ConclusionTinnitus may be linked to abnormal spontaneous activity in the HAC, which can arise from the neural plasticity induced from the increased functional connectivity between the auditory network, cerebellum, and limbic system.

Common and Distinct Patterns of Intrinsic Brain Activity Alterations in Major Depression and Bipolar Disorder: Voxel-Based Meta-Analysis

Background: Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded been consistent. Methods: A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) were conducted. Findings: MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC)), bilateral insula and decreased ALFF in the bilateral cerebellum, precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus (IFG), insula, and right SFG, superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum, ACC, and STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus (PCC), and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Interpretation: MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies. Funding Statement: The study was supported by grants from the National Natural Science Foundation of China (81971597, 81671670, 81801685, and 81501456); National Natural Science Foundation of Guangdong Province, China (2018A030310003); Project in Basic Research and Applied Basic Research in General Colleges and Universities of Guangdong, China (2018KZDXM009); Planned Science and Technology Project of Guangzhou, China (20160402007 and 201604020184). Declaration of Interests: The authors declare that they have no conflict of interests. Ethical Approval Statement: Not required.