Putamen volume predicts real‐time fMRI neurofeedback learning success across paradigms and neurofeedback target regions

Real‐time fMRI guided neurofeedback training has gained increasing interest as a noninvasive brain regulation technique with the potential to modulate functional brain alterations in therapeutic contexts. Individual variations in learning success and treatment response have been observed, yet the neural substrates underlying the learning of self‐regulation remain unclear. Against this background, we explored potential brain structural predictors for learning success with pooled data from three real‐time fMRI data sets. Our analysis revealed that gray matter volume of the right putamen could predict neurofeedback learning success across the three data sets (n = 66 in total). Importantly, the original studies employed different neurofeedback paradigms during which different brain regions were trained pointing to a general association with learning success independent of specific aspects of the experimental design. Given the role of the putamen in associative learning this finding may reflect an important role of instrumental learning processes and brain structural variations in associated brain regions for successful acquisition of fMRI neurofeedback‐guided self‐regulation.     

Brain network integration dynamics are associated with loss and recovery of consciousness induced by sevoflurane

The dynamic interplay of integration and segregation in the brain is at the core of leading theoretical accounts of consciousness. The human brain dynamically alternates between a sub‐state where integration predominates, and a predominantly segregated sub‐state, with different roles in supporting cognition and behaviour. Here, we combine graph theory and dynamic functional connectivity to compare resting‐state functional MRI data from healthy volunteers before, during, and after loss of responsiveness induced with different concentrations of the inhalational anaesthetic, sevoflurane. We show that dynamic states characterised by high brain integration are especially vulnerable to general anaesthesia, exhibiting attenuated complexity and diminished small‐world character. Crucially, these effects are reversed upon recovery, demonstrating their association with consciousness. Higher doses of sevoflurane (3% vol and burst‐suppression) also compromise the temporal balance of integration and segregation in the human brain. Additionally, we demonstrate that reduced anticorrelations between the brain''s default mode and executive control networks dynamically reconfigure depending on the brain''s state of integration or segregation. Taken together, our results demonstrate that the integrated sub‐state of brain connectivity is especially vulnerable to anaesthesia, in terms of both its complexity and information capacity, whose breakdown represents a generalisable biomarker of loss of consciousness and its recovery.     

Tele‐medicine and improvement of mental health problems in COVID‐19 pandemic: A systematic review

IntroductionTele‐medicine services have been developed in response to the COVID‐19 pandemic, which disrupts mental health services. The present study investigates the effectiveness of telephone‐delivered services for psychological disorders in the COVID‐19 pandemic.MethodsWe searched PubMed/Medline, Embase and Cochrane Controlled Register of Trials for relevant clinical studies up to February 1, 2022. Following terms were used: “severe acute respiratory syndrome”, “Coronavirus”, “Coronavirus infection”, “SARS‐CoV‐2”, “COVID‐19”, “mental disorder”, “mental health”, “mental health program”, “mental health service”, “psychiatric service”, “telemedicine”, “Telehealth”, “Tele‐health”, “Telecare”, “Mobile health”.ResultsTwelve relevant clinical articles were included in our study. Eight articles were parallel randomized controlled trials (RCTs), two were Quasi‐experimental, and one was a multicenter retrospective cohort study. A total of 1900 adults (18 years old or above that) were included. Online telecommunication methods like online apps and videoconference were the most common interventions. The most prevalent measured outcome was levels of anxiety and depression among participants. Eleven out of 12 articles showed a significant association between telemedicine and mental health improvement.ConclusionsThe included studies in the current systematic review reported the probable efficacy of telemedicine in improving mental health disorders during the COVID‐19 pandemic. But it is not possible to determine the best telecommunication method for each mental disorder in different populations and the preference of patients is still face to face therapy. So RCTs in different populations with previous mental disorders or chronic diseases are required to investigate the further telemedicine''s efficacy on managing mental problems.     

Updating the dual‐mechanism model for cross‐sensory attentional spreading: The influence of space‐based visual selective attention

Selective attention to visual stimuli can spread cross‐modally to task‐irrelevant auditory stimuli through either the stimulus‐driven binding mechanism or the representation‐driven priming mechanism. The stimulus‐driven attentional spreading occurs whenever a task‐irrelevant sound is delivered simultaneously with a spatially attended visual stimulus, whereas the representation‐driven attentional spreading occurs only when the object representation of the sound is congruent with that of the to‐be‐attended visual object. The current study recorded event‐related potentials in a space‐selective visual object‐recognition task to examine the exact roles of space‐based visual selective attention in both the stimulus‐driven and representation‐driven cross‐modal attentional spreading, which remain controversial in the literature. Our results yielded that the representation‐driven auditory Nd component (200–400 ms after sound onset) did not differ according to whether the peripheral visual representations of audiovisual target objects were spatially attended or not, but was decreased when the auditory representations of target objects were presented alone. In contrast, the stimulus‐driven auditory Nd component (200–300 ms) was decreased but still prominent when the peripheral visual constituents of audiovisual nontarget objects were spatially unattended. These findings demonstrate not only that the representation‐driven attentional spreading is independent of space‐based visual selective attention and benefits in an all‐or‐nothing manner from object‐based visual selection for actually presented visual representations of target objects, but also that although the stimulus‐driven attentional spreading is modulated by space‐based visual selective attention, attending to visual modality per se is more likely to be the endogenous determinant of the stimulus‐driven attentional spreading.     

Transcranial direct current stimulation for migraine: a systematic review and meta‐analysis of randomized controlled trials

BackgroundTranscranial direct current stimulation (tDCS) is a promising method for migraine treatment. In this study, we investigated the efficacy and safety of tDCS for migraine by conducting a systematic review and meta‐analysis of randomized controlled trials (RCTs).MethodsWe searched PubMed, EMBASE, Cochrane Library, and Web of Science up to December 02, 2021 for RCTs reporting tDCS for migraine treatment. Two authors independently evaluated the eligibility of the retrieved trials and extracted relevant data. Outcomes for the quantitative synthesis were reduction in migraine days per month and adverse events.ResultsEleven RCTs that included 425 patients with migraine were evaluated in the meta‐analysis. The efficacy and safety of anodal or cathodal stimulation targeting different brain areas, including primary motor cortex (M1), primary sensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and visual cortex (VC), were assessed in the RCTs enrolled. We found that tDCS with M1 and VC activation could reduce No. of migraine days per month in patients with migraine. Meanwhile, tDCS with VC inhibition could also reduce No. of migraine days per month in patients with migraine. However, there were no differences in the incidence of adverse events between the two groups.ConclusiontDCS activates M1 or activates/inhibits VC which could improve migraine symptoms. tDCS is an effective, preventive, and safe treatment for migraine.     

Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive–compulsive disorder

Recent evidence suggests that presupplementary motor area (pre‐SMA) and inferior frontal gyrus (IFG) play an important role in response inhibition. However, no study has investigated the relationship between these brain networks at resting‐state and response inhibition in obsessive–compulsive disorder (OCD). We performed resting‐state functional magnetic resonance imaging scans and then measured the response inhibition of 41 medication‐free OCD patients and 49 healthy control (HC) participants by using the stop‐signal task outside the scanner. We explored the differences between OCD and HC groups in the functional connectivity of pre‐SMA and IFG associated with the ability of motor response inhibition. OCD patients showed a longer stop‐signal reaction time (SSRT). Compared to HC, OCD patients exhibit different associations between the ability of motor response inhibition and the functional connectivity between pre‐SMA and IFG, inferior parietal lobule, dorsal anterior cingulate cortex, insula, and anterior prefrontal cortex. Additional analysis to investigate the functional connectivity difference from the seed ROIs to the whole brain voxels revealed that, compared to HC, OCD exhibited greater functional connectivity between pre‐SMA and IFG. Also, this functional connectivity was positively correlated with the SSRT score. These results provide additional insight into the characteristics of the resting‐state functional connectivity of the regions belonging to the cortico‐striato‐thalamo‐cortical circuit and the cingulo‐opercular salience network, underlying the impaired motor response inhibition of OCD. In particular, we emphasize the importance of altered functional connectivity between pre‐SMA and IFG for the pathophysiology of motor response inhibition in OCD.     

Mapping of whole‐cerebrum resting‐state networks using ultra‐high resolution acquisition protocols

Resting‐state functional magnetic resonance imaging (fMRI) has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 × 0.7 × 0.7 mm³, with only partial brain coverage. Therefore, this work aims to present a novel fMRI technique that was developed based on echo‐planar‐imaging with keyhole (EPIK) combined with repetition‐time‐external (TR‐external) EPI phase correction. Each technique has been previously shown to be effective in enhancing the spatial resolution of fMRI, and in this work, the combination of the two techniques into TR‐external EPIK provided a nominal spatial resolution of 0.51 × 0.51 × 1.00 mm³ (0.26 mm³ voxel) with whole‐cerebrum coverage. Here, the feasibility of using half‐millimetre in‐plane TR‐external EPIK for resting‐state fMRI was validated using 13 healthy subjects and the corresponding reproducible mapping of resting‐state networks was demonstrated. Furthermore, TR‐external EPIK enabled the identification of various resting‐state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high‐resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.     

Gamma‐band neural coupling during conceptual alignment

Conceptual alignment is a prerequisite for mutual understanding. However, little is known about the neurophysiological brain‐to‐brain underpinning during conceptual alignment for mutual understanding. Here, we recorded multi‐channel electroencephalogram (EEG) simultaneously from two participants in Experiment 1 and adopted the dual‐tACS techniques in Experiment 2 to investigate the underlying brain‐to‐brain EEG coupling during conceptual alignment and the possible enhancement effect. Our results showed that 1) higher phase‐locking value (PLV), a sensitive measure for quantifying neural coupling strength between EEG signals, at the gamma frequency band (28–40 Hz), was observed in the left temporoparietal site (left TP) area between successful versus unsuccessful conceptual alignment. The left TP gamma coupling strength correlated with the accuracy of conceptual alignment and differentiated whether subjects belonged to the SUCCESS or FAILURE groups in our study. 2) In‐phase gamma‐band transcranial alternating current stimulation (tACS) over the left TP area increased the accuracy of subjects in the SUCCESS group but not the FAILURE group. 3) The effect of perspective‐taking on the accuracy was mediated by the gamma coupling strength within the left TP area. Our results support the role of gamma‐band coupling between brains for interpersonal conceptual alignment. We provide dynamic interpersonal neurophysiological insights into the formation of successful communication.     

Efficacy and safety of 3‐n‐butylphthalide for the treatment of cognitive impairment: A systematic review and meta‐analysis

BackgroundCurrent evidence for the efficacy of pharmacological treatment in improving cognitive function is absent. Recent studies have reported that 3‐n‐butylphthalide (NBP) has a positive effect on improving cognitive impairment; however, its clinical efficacy and safety is unclear. Therefore, we conducted a meta‐analysis to assess its efficacy and safety for cognitive impairment.MethodsWe systematically searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases, and two reviewers independently screened and extracted the data from included studies. We synthesized the data using the Review Manager Software version 5.3.ResultsWe included six randomized clinical trials (RCTs), encompassing 851 patients with cognitive impairment. The results showed that NBP improved cognitive impairment. Specifically, the clinical efficacy was better than that in the control group, with better performance in improving the Mini‐Mental State Examination and the Montreal Cognitive Assessment scores, while decreasing the Alzheimer''s Disease Assessment Scale‐Cognitive subscale and the Clinician''s Interview‐Based Impression of Change plus caregiver input scores. There was no significant difference in the incidence of adverse events between both groups.ConclusionThe NBP is effective and safe in improving cognitive impairment; however, more high‐quality RCTs are needed to confirm these findings.     

Common abnormality of gray matter integrity in substance use disorder and obsessive‐compulsive disorder: A comparative voxel‐based meta‐analysis

The objective of the current study is to determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case‐control studies examining gray matter volume (GMV) alterations in substance use disorders (SUD) and obsessive‐compulsive disorder (OCD). Voxel‐based meta‐analysis within the individual disorders and conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta‐analytic coordinates and signed brain volumetric maps determining directed (reduced/increased) GMV alterations between the disorder groups and controls served as the primary outcome. The separate meta‐analysis demonstrated that SUD and OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Together the findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.     

The impact of COVID‐19 lockdown on brain metabolism

This study aims to evaluate the impact of French national lockdown of 55 days on brain metabolism of patients with neurological disorders. Whole‐brain voxel‐based PET analysis was used to correlate ¹⁸F‐FDG metabolism to the number of days after March 17, 2020 (in 95 patients; mean age: 54.3 years ± 15.7; 59 men), in comparison to the same period in 2019 before the SARS‐CoV‐2 outbreak (in 212 patients; mean age: 59.5 years ± 15.8; 114 men), and to the first 55 days of deconfinement (in 188 patients; mean age: 57.5 years ± 16.5; 93 men). Lockdown duration was negatively correlated to the metabolism of the sensory‐motor cortex with a prevailing effect on the left dominant pyramidal tract and on younger patients, also including the left amygdala, with only partial reversibility after 55 days of deconfinement. Weak overlap was found with the reported pattern of hypometabolism in long COVID (<9%). Restriction of physical activities, and possible related deconditioning, and social isolation may lead to functional disturbances of sensorimotor and emotional brain networks. Of note, this metabolic pattern seems distinct to those reported in long COVID. Further longitudinal studies with longer follow‐up are needed to evaluate clinical consequences and relationships on cognitive and mental health against functional deactivation hypothesis, and to extend these findings to healthy subjects in the context of lockdown.     

Hypoxic glioma‐derived extracellular vesicles harboring MicroRNA‐10b‐5p enhance M2 polarization of macrophages to promote the development of glioma

IntroductionThe delivery of biomolecules by tumor cell‐secreted extracellular vesicles (EVs) is linked to the development of glioma. Here, the present study was implemented to explore the functional significance of hypoxic glioma cell‐derived EVs carrying microRNA‐10b‐5 (miR‐10b‐5p) on glioma with the involvement of polarization of M2 macrophages.MethodsEVs were isolated from hypoxia‐stimulated glioma cells, and their role in polarization of M2 macrophages was studied by co‐culturing with macrophages. miR‐10b‐5p expression in glioma tissues, glioma‐derived EVs, and macrophages co‐cultured with EVs was characterized. Interaction among miR‐10b‐5p, NEDD4L, and PIK3CA was analyzed. The macrophages or glioma cells were transfected with overexpressing plasmid or shRNA to study the effects of miR‐10b‐5p/NEDD4L/PIK3CA on M2 macrophage polarization, and glioma cell proliferation, migration, and invasion in vitro and in vivo. ResultsPromotive role of hypoxia‐stimulated glioma‐derived EVs in macrophage M2 polarization was confirmed. Elevation of miR‐10b‐5p occurred in glioma tissues, glioma‐derived EVs and macrophages co‐cultured with EVs, and stimulated M2 polarization of macrophages. NEDD4L was a target gene of miR‐10b‐5p. Overexpression of NEDD4L could inhibit PI3K/AKT pathway through increase in ubiquitination and degradation of PIK3CA. Hypoxic glioma‐derived EVs harboring upregulated miR‐10b‐5p triggered an M2 phenotype in macrophages as well as enhanced aggressive tumor biology of glioma cells via inhibition of PIK3CA/PI3K/AKT pathway by targeting NEDD4L.ConclusionsIn summary, miR‐10b‐5p delivered by hypoxic glioma‐derived EVs accelerated macrophages M2 polarization to promote the progression of glioma via NEDD4L/PIK3CA/PI3K/AKT axis.     

Structural and functional brain alterations in anorexia nervosa:A multimodal meta‐analysis of neuroimaging studies

Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. Numerous voxel‐based morphometry (VBM) and resting‐state functional imaging studies have provided strong evidence of abnormal brain structure and intrinsic and functional activities in AN, but with inconsistent conclusions. Herein, a whole‐brain meta‐analysis was conducted on VBM (660 patients with AN, and 740 controls) and resting‐state functional imaging (425 patients with AN, and 461 controls) studies that measured differences in the gray matter volume (GMV) and intrinsic functional activity between patients with AN and healthy controls (HCs). Overall, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left middle occipital gyrus (extending to the left inferior parietal lobe). In resting‐state functional imaging studies, patients with AN displayed decreased resting‐state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting‐state functional activity in the right parahippocampal gyrus. This multimodal meta‐analysis identified reductions of gray matter and functional activity in the anterior and median cingulate in patients with AN, which contributes to further understanding of the pathophysiology of AN.     

New‐onset and persistent neurological and psychiatric sequelae of COVID‐19 compared to influenza: A retrospective cohort study in a large New York City healthcare network

ObjectivesNeurological and neuropsychiatric manifestations of post‐acute SARS‐CoV‐2 infection (neuro‐PASC) are common among COVID‐19 survivors, but it is unknown how neuro‐PASC differs from influenza‐related neuro‐sequelae. This study investigated the clinical characteristics of COVID‐19 patients with and without new‐onset neuro‐PASC, and of flu patients with similar symptoms.MethodsWe retrospectively screened 18,811 COVID‐19 patients and 5772 flu patients between January 2020 and June 2021 for the presence of new‐onset neuro‐sequelae that persisted at least 2 weeks past the date of COVID‐19 or flu diagnosis.ResultsWe observed 388 COVID‐19 patients with neuro‐PASC versus 149 flu patients with neuro‐sequelae. Common neuro‐PASC symptoms were anxiety (30%), depression (27%), dizziness (22%), altered mental status (17%), chronic headaches (17%), and nausea (11%). The average time to neuro‐PASC onset was 138 days, with hospitalized patients reporting earlier onset than non‐hospitalized patients. Neuro‐PASC was associated with female sex and older age (p < 0.05), but not race, ethnicity, most comorbidities, or COVID‐19 disease severity (p > 0.05). Compared to flu patients, COVID‐19 patients were older, exhibited higher incidence of altered mental status, developed symptoms more quickly, and were prescribed psychiatric drugs more often (p < 0.05).ConclusionsThis study provides additional insights into neuro‐PASC risk factors and differentiates between post‐COVID‐19 and post‐flu neuro‐sequelae.     

A deep learning based approach identifies regions more relevant than resting‐state networks to the prediction of general intelligence from resting‐state fMRI

Prediction of cognitive ability latent factors such as general intelligence from neuroimaging has elucidated questions pertaining to their neural origins. However, predicting general intelligence from functional connectivity limit hypotheses to that specific domain, being agnostic to time‐distributed features and dynamics. We used an ensemble of recurrent neural networks to circumvent this limitation, bypassing feature extraction, to predict general intelligence from resting‐state functional magnetic resonance imaging regional signals of a large sample (n = 873) of Human Connectome Project adult subjects. Ablating common resting‐state networks (RSNs) and measuring degradation in performance, we show that model reliance can be mostly explained by network size. Using our approach based on the temporal variance of saliencies, that is, gradients of outputs with regards to inputs, we identify a candidate set of networks that more reliably affect performance in the prediction of general intelligence than similarly sized RSNs. Our approach allows us to further test the effect of local alterations on data and the expected changes in derived metrics such as functional connectivity and instantaneous innovations.