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Frontiers in Integrative Neuroscience 2021Delusions are marked, fixed beliefs that are incongruent with reality. Delusions, with comorbid hallucinations, are a hallmark of certain psychotic disorders (e.g.,...
Delusions are marked, fixed beliefs that are incongruent with reality. Delusions, with comorbid hallucinations, are a hallmark of certain psychotic disorders (e.g., schizophrenia). Delusions can present transdiagnostically, in neurodegenerative (e.g., Alzheimer's disease and fronto-temporal dementia), nervous system disorders (e.g., Parkinson's disease) and across other psychiatric disorders (e.g., bipolar disorder). The burden of delusions is severe and understanding the heterogeneity of delusions may delineate a more valid nosology of not only psychiatric disorders but also neurodegenerative and nervous system disorders. We systematically reviewed structural neuroimaging studies reporting on delusions in four disorder types [schizophrenia (SZ), bipolar disorder (BP), Alzheimer's disease (AD), and Parkinson's disease (PD)] to provide a comprehensive overview of neural changes and clinical presentations associated with delusions. Twenty-eight eligible studies were identified. This review found delusions were most associated with gray matter reductions in the dorsolateral prefrontal cortex (SZ, BP, and AD), left claustrum (SZ and AD), hippocampus (SZ and AD), insula (SZ, BP, and AD), amygdala (SZ and BP), thalamus (SZ and AD), superior temporal gyrus (SZ, BP, and AD), and middle frontal gyrus (SZ, BP, AD, and PD). However, there was a great deal of variability in the findings of each disorder. There is some support for the current dopaminergic hypothesis of psychosis, but we also propose new hypotheses related to the belief formation network and cognitive biases. We also propose a standardization of assessments to aid future transdiagnostic study approaches. Future studies should explore the neural and biological underpinnings of delusions to hopefully, inform future treatment.
PubMed: 35140591
DOI: 10.3389/fnint.2021.726321 -
Frontiers in Neurology 2021Theta burst stimulation (TBS), a type of patterned repetitive transcranial magnetic stimulation (rTMS), has several advantages, such as short time of single treatment...
Theta burst stimulation (TBS), a type of patterned repetitive transcranial magnetic stimulation (rTMS), has several advantages, such as short time of single treatment and low stimulation intensity compared with traditional rTMS. Since the efficacy of TBS on the symptoms of Parkinson's disease (PD) was inconsistent among different studies, we systematically searched these studies and quantitatively analyzed the therapeutic effect of TBS for patients with PD. We followed the recommended PRISMA guidelines for systematic reviews. Studies from PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov from January 1, 2005 of each database to September 30, 2021 were analyzed. We also manually retrieved studies of reference. Eight eligible studies with 189 participants (received real TBS and/or sham TBS) were included. This metaanalysis found that TBS did not significantly improve Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score in the "on" medicine state (SMD = -0.06; 95% CI, -0.37 to 0.25; = 0.69; = 0%), while, it brought significant improvement of UPDRS-III scores in the "off" medicine state (SMD = -0.37; 95% CI, -0.65 to -0.09; < 0.01; = 19%). Subgroup analysis found that merely continuous TBS (cTBS) over the supplementary motor area (SMA) brought significant improvement of UPDRS-III score (SMD = -0.63; 95% CI, -1.02 to -0.25; < 0.01). TBS had insignificant effectiveness for upper limb movement disorder both in the "on" and "off" medicine status (SMD = -0.07; 95% CI, -0.36 to 0.22; = 0.64; = 0%; SMD = -0.21; 95% CI, -0.57 to 0.15; = 0.26; = 0%; respectively). TBS significantly improved slowing of gait in the "off" medicine status (SMD = -0.37; 95% CI, -0.71 to -0.03; = 0.03; = 0%). Subgroup analysis suggested that only intermittent TBS (iTBS) over the primary motor cortex (M1) + dorsolateral prefrontal cortex (DLPFC) had significant difference (SMD = -0.57; 95% CI, -1.13 to -0.01; = 0.04). Additionally, iTBS over the M1+ DLPFC had a short-term (within 2 weeks) therapeutic effect on PD depression (MD = -2.93; 95% CI, -5.52 to -0.33; = 0.03). Our study demonstrated that cTBS over the SMA could significantly improve the UPDRS-III score for PD patients in the "off," not in the "on," medicine state. TBS could not bring significant improvement of upper limb movement dysfunction. ITBS over the M1+DLPFC could significantly improve the slowing of gait in the "off" medicine status. Additionally, iTBS over the M1+DLPFC has a short-term (within 2 weeks) therapeutic effect on PD depression. Further RCTs of a large sample, and excellent design are needed to confirm our conclusions.
PubMed: 35095722
DOI: 10.3389/fneur.2021.762100 -
Transcranial Direct Current Stimulation on Parkinson's Disease: Systematic Review and Meta-Analysis.Frontiers in Neurology 2021Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available...
Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD. Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms. A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were included. Ten studies ( = 236) were included in meta-analysis and 25 studies ( = 405) in qualitative synthesis. The most frequently stimulated targets were dorsolateral prefrontal cortex and primary motor cortex. No significant effect was found among single targets on motor outcomes: Unified Parkinson's Disease Rating Scale (UPDRS) III - motor aspects (MD = -0.98%, 95% CI = -10.03 to 8.07, = 0.83, = 0%), UPDRS IV - dyskinesias (MD = -0.89%, CI 95% = -3.82 to 2.03, = 0.55, = 0%) and motor fluctuations (MD = -0.67%, CI 95% = -2.45 to 1.11, = 0.46, = 0%), timed up and go - gait (MD = 0.14%, CI 95% = -0.72 to 0.99, = 0.75, = 0%), Berg Balance Scale - balance (MD = 0.73%, CI 95% = -1.01 to 2.47, = 0.41, = 0%). There was no significant effect of single vs. multiple targets in: UPDRS III - motor aspects (MD = 2.05%, CI 95% = -1.96 to 6.06, = 0.32, = 0%) and gait (SMD = -0.05%, 95% CI = -0.28 to 0.17, = 0.64, = 0%). Simple univariate meta-regression analysis between treatment dosage and effect size revealed that number of sessions (estimate = -1.7, SE = 1.51, z-score = -1.18, = 0.2, IC = -4.75 to 1.17) and cumulative time (estimate = -0.07, SE = 0.07, z-score = -0.99, = 0.31, IC = -0.21 to 0.07) had no significant association. There was no significant tDCS alone short-term effect on motor function, balance, gait, dyskinesias or motor fluctuations in Parkinson's disease, regardless of brain area or targets stimulated.
PubMed: 35082749
DOI: 10.3389/fneur.2021.794784 -
The International Journal of... Jun 2022The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first, to our knowledge, systematic review of functional...
BACKGROUND
The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first, to our knowledge, systematic review of functional neuroimaging correlates of placebo response in adults with anxiety/depressive disorders.
METHODS
We systematically searched a large set of databases up to February 2021 based on a pre-registered protocol (PROSPERO CRD42019156911). We extracted neuroimaging data related to clinical improvement following placebo or related to placebo mechanisms. We did not perform a meta-analysis due to the small number of included studies and significant heterogeneity in study design and outcome measures.
RESULTS
We found 12 relevant studies for depressive disorders and 4 for anxiety disorders. Activity in the ventral striatum, rostral anterior cingulate cortex and other default mode network regions, orbitofrontal cortex, and dorsolateral prefrontal cortex correlated with placebo antidepressant responses. Activity in regions of the default mode network, including posterior cingulate cortex, was associated with placebo anxiolysis. There was also evidence for possible involvement of the endogenous opioid, dopamine, and serotonin systems in placebo antidepressant and anxiolytic effects.
CONCLUSIONS
Several brain regions and molecular systems may be involved in these placebo effects. Further adequately powered studies exploring causality and controlling for confounders are required.
Topics: Adult; Antidepressive Agents; Anxiety Disorders; Functional Neuroimaging; Humans; Neuroimaging; Placebo Effect
PubMed: 35078210
DOI: 10.1093/ijnp/pyac009 -
Journal of Affective Disorders Apr 2022Background We evaluated the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD), and ranked the relative... (Meta-Analysis)
Meta-Analysis Review
Background We evaluated the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD), and ranked the relative efficacy of different stimulation protocols. Methods We performed a search for randomised, sham-controlled trials of rTMS for OCD. The primary analysis included both a pairwise meta-analysis and a series of frequentist network meta-analyses (NMA) of OCD symptom severity. Secondary analyses were carried out on relevant clinical factors and safety. Results 21 studies involving 662 patients were included. The pairwise meta-analysis showed that rTMS for OCD is efficacious across all protocols (Hedges' g=-0.502 [95%CI= -0.708, -0.296]). The first NMA, with stimulation protocols clustered only by anatomical location, showed that both dorsolateral prefrontal cortex (dlPFC) stimulation and medial frontal cortex stimulation were efficacious. In the second NMA, considering each unique combination of frequency and location separately, low frequency (LF) pre-supplementary motor area (preSMA) stimulation, high frequency (HF) bilateral dlPFC stimulation, and LF right dlPFC stimulation were all efficacious . LF right dlPFC was ranked highest in terms of efficacy, although the corresponding confidence intervals overlapped with the other two protocols. Limitations Evidence base included mostly small studies, with only a few studies using similar protocols, giving a sparse network. Studies were heterogeneous, and a risk of publication bias was found. Conclusions rTMS for OCD was efficacious compared with sham stimulation. LF right dlPFC, HF bilateral dlPFC and LF preSMA stimulation were all efficacious protocols with significant and comparable clinical improvements. Future studies should further investigate the relative merits of these three protocols.
Topics: Humans; Motor Cortex; Network Meta-Analysis; Obsessive-Compulsive Disorder; Prefrontal Cortex; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 35041869
DOI: 10.1016/j.jad.2022.01.048 -
Frontiers in Human Neuroscience 2021The world's population is aging. With this comes an increase in the prevalence of age-associated diseases, which amplifies the need for novel treatments to counteract...
The world's population is aging. With this comes an increase in the prevalence of age-associated diseases, which amplifies the need for novel treatments to counteract cognitive decline in the elderly. One of the recently discussed non-pharmacological approaches is transcranial direct current stimulation (tDCS). TDCS delivers weak electric currents to the brain, thereby modulating cortical excitability and activity. Recent evidence suggests that tDCS, mainly with anodal currents, can be a powerful means to non-invasively enhance cognitive functions in elderly people with age-related cognitive decline. Here, we screened a recently developed tDCS database (http://tdcsdatabase.com) that is an open access source of published tDCS papers and reviewed 16 studies that applied tDCS to healthy older subjects or patients suffering from Alzheimer's Disease or pre-stages. Evaluating potential changes in cognitive abilities we focus on declarative and working memory. Aiming for more standardized protocols, repeated tDCS applications (2 mA, 30 min) over the left dorso-lateral prefrontal cortex (LDLPFC) of elderly people seem to be one of the most efficient non-invasive brain stimulation (NIBS) approaches to slow progressive cognitive deterioration. However, inter-subject variability and brain state differences in health and disease restrict the possibility to generalize stimulation methodology and increase the necessity of personalized protocol adjustment by means of improved neuroimaging techniques and electrical field modeling.
PubMed: 34776903
DOI: 10.3389/fnhum.2021.730134 -
Frontiers in Human Neuroscience 2021Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD)....
Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with MCI and AD. Although previous meta-analyses included studies carried on patients with MCI and AD, few studies have analyzed patients with MCI independently. This meta-analysis aimed to evaluate the effects and safety of rTMS on cognition function in patients with MCI and factors that may influence such effects. Data used in this study were searched and screened from different databases, including PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Database, and China BioMedical Literature Database (SinoMed). The retrieved studies were carefully reviewed, data were extracted, and the quality of data was assessed. A total of 12 studies involving 329 patients with MCI were included in the present meta-analysis. The analyses results revealed that rTMS improved cognitive function [standardized mean difference (SMD) = 0.83, 95% confidence interval (CI) = 0.44-1.22, = 0.0009] and memory function (SMD = 0.73, 95% CI = 0.48-0.97, < 0.00001) in the MCI + rTMS active group when compared to the sham stimulation group. The showed that: (1) cognitive improvement was more pronounced under high-frequency rTMS stimulation of multiple sites, such as the bilateral dorsolateral prefrontal cortex and (2) more than 10 rTMS stimulation sessions produced higher improvement on cognition function in patients with MCI. This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged period. However, further studies are required to validate these findings and explore more effective stimulation protocols and targets. [http://www.crd.york.ac.uk/PROSPERO/], identifier: CRD 42021238708.
PubMed: 34764859
DOI: 10.3389/fnhum.2021.723715 -
Journal of Affective Disorders Jan 2022Bipolar disorders (BD) are serious mental health disorders that impacts on cognitive and social functioning. We aimed to systematically review and conduct a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bipolar disorders (BD) are serious mental health disorders that impacts on cognitive and social functioning. We aimed to systematically review and conduct a meta-analysis of fMRI correlates of working memory in euthymic people with BD compared to healthy participants.
METHOD
Web of Science, Embase and PubMed databases were systematically searched to identify studies which examined the fMRI correlates of working memory function in euthymic people with BD and healthy participants. Relevant demographic, behavioral and functional MRI (fMRI) data was qualitatively and quantitatively assessed, and the quality of the included studies evaluated. Comparable studies which used the same working memory task were included in a meta-analysis using Seed-Based D Mapping software (SDM).
RESULTS
Twenty-four studies were included in this systematic review. Consistent brain fMRI activity differences were found in key brain areas of the working memory network in euthymic people with BD compared to healthy participants including the ventromedial and dorsolateral prefrontal cortices. Cognitive performance was not significantly different between the two groups. Six studies were suitable to be included in the meta-analysis. There was no significant overlap in areas of brain activation after family-wise correction for multiple comparisons.
LIMITATIONS
Heterogeneity of task paradigms, small sample sizes and inherent difficulty in the interpretation of functional brain activity due to variations between studies were all limitations.
CONCLUSION
The differences in working memory related fMRI activity identified by this study between people with BD and healthy participants are consistent with existing literature reporting impaired working memory performance in BD. This was not accompanied by significant differences in cognitive performance in the reviewed studies, likely due to small sample sizes. Further studies are needed to investigate the relationship between differential brain activity and working memory performance in people with BD.
Topics: Bipolar Disorder; Brain; Cyclothymic Disorder; Dorsolateral Prefrontal Cortex; Humans; Magnetic Resonance Imaging; Memory, Short-Term
PubMed: 34715175
DOI: 10.1016/j.jad.2021.10.084 -
Journal of Clinical Medicine Oct 2021This article aimed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. The PubMed, Medline, Cochrane Library, and Web of...
This article aimed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. The PubMed, Medline, Cochrane Library, and Web of Science databases were searched for articles published through 14 August 2021. We enrolled only randomized controlled trials. The Cochrane Collaboration risk of bias tool was used for quality assessment. Outcomes were analyzed as standardized mean differences (SMDs) with 95% CIs. The beta coefficient and value were adopted for meta-regression. We included 18 studies comprising 643 participants. A significant reduction in disease influence, as measured by the Fibromyalgia Impact Questionnaire, was observed (SMD, -0.700, 95% CI, -1.173 to -0.228), and the reduction was larger in older patients ( = -0.1327, = 0.008). The effect persisted at least two weeks after the final treatment session (SMD, -0.784, 95% CI, -1.136 to -0.432). Reductions in pain, depression, and anxiety were discovered, which persisted for at least two weeks after the last intervention. The effects on pain and depression remained significant up to one and a half months after the final session. No serious adverse events were reported by the included articles. In conclusion, our systematic review and meta-analysis revealed that rTMS is safe and effective for managing multiple domains of fibromyalgia-related symptoms and older patients may have a stronger treatment effect. Larger randomized controlled trials with sufficient male populations are warranted to confirm our findings, detect rare adverse events, and determine the optimal stimulation parameters.
PubMed: 34682790
DOI: 10.3390/jcm10204669 -
Molecular Psychiatry Feb 2022Problematic Usage of the Internet (PUI) has been linked to diverse structural gray matter changes in individual data studies. However, no quantitative synthesis across... (Meta-Analysis)
Meta-Analysis
Problematic Usage of the Internet (PUI) has been linked to diverse structural gray matter changes in individual data studies. However, no quantitative synthesis across studies has been conducted. We aimed to identify gray matter regions showing significant spatial convergence across neuroimaging studies in PUI. We searched PubMed and PsycINFO up to 10/03/2021 and included original, cross-sectional comparative studies that examined structural gray matter imaging in PUI versus control groups; reported a whole-brain analysis; and provided peak coordinates for gray matter differences. From a total of 624 potentially relevant studies, 15 (including 355 individuals with PUI and 363 controls) were included in a meta-analysis of voxel-based morphometry studies. Anatomical likelihood estimation (ALE) meta-analysis was performed using extracted coordinates and identified significant spatial convergence in the medial/superior frontal gyri, the left anterior cingulate cortex/cingulate gyrus, and the left middle frontal/precentral gyri. Datasets contributing to these findings all indicated reduced gray matter in cases compared to controls. In conclusion, voxel-based morphometric studies indicate replicable gray matter reductions in the dorsolateral prefrontal cortex and anterior cingulate cortex in PUI, regions implicated in reward processing and top-down inhibitory control. Further studies are required to understand the nature of gray matter differences across PUI behaviors, as well as the contribution of particular mental health disorders, and the influence of variation in study and sample characteristics.
Topics: Brain; Cerebral Cortex; Cross-Sectional Studies; Gray Matter; Humans; Internet; Magnetic Resonance Imaging
PubMed: 34642454
DOI: 10.1038/s41380-021-01315-7