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International Journal of Molecular... Aug 2022The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine... (Meta-Analysis)
Meta-Analysis Review
The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine (Gln), Glx, and N-acetylaspartate (NAA). Proton Magnetic Resonance Spectroscopy (H-MRS) allows one to quantify these metabolites in the human brain. Thus, we conducted a systematic review and meta-analysis of the literature to compare their levels between BD patients and healthy controls (HC). The main inclusion criteria for inclusion were H-MRS studies comparing levels of Glu, Gln, Glx, and NAA in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampi between patients with BD in clinical remission or a major depressive episode and HC. Thirty-three studies were included. NAA levels were significantly lower in the left white matter PFC (wmPFC) of depressive and remitted BD patients compared to controls and were also significantly higher in the left dorsolateral PFC (dlPFC) of depressive BD patients compared to HC. Gln levels were significantly higher in the ACC of remitted BD patients compared to in HC. The decreased levels of NAA of BD patients may be related to the alterations in neuroplasticity and synaptic plasticity found in BD patients and may explain the deep white matter hyperintensities frequently observed via magnetic resonance imagery.
Topics: Aspartic Acid; Bipolar Disorder; Depressive Disorder, Major; Glutamic Acid; Glutamine; Humans; Proton Magnetic Resonance Spectroscopy
PubMed: 36012234
DOI: 10.3390/ijms23168974 -
Neural Plasticity 2022Neuropathic pain and neuropsychiatric symptoms are common complications reported by the traumatic brain injury (TBI) population. Although a growing body of research has... (Meta-Analysis)
Meta-Analysis Review
Neuropathic pain and neuropsychiatric symptoms are common complications reported by the traumatic brain injury (TBI) population. Although a growing body of research has indicated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the management of neurological and psychiatric disorders, little evidence has been presented to support the effects of rTMS on neuropathic pain and neuropsychiatric symptoms in patients with TBI in all age groups. In addition, a better understanding of the potential factors that might influence the therapeutic effect of rTMS is necessary. The objective of this preregistered systematic review and meta-analysis was to quantify the effects of rTMS on physical and psychological symptoms in individuals with TBI. We systematically searched six databases for randomized controlled trials (RCTs) of rTMS in TBI patients reporting pain and neuropsychiatric outcomes published until March 20, 2022. The mean difference (MD) with 95% confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size. Twelve RCTs with 276 TBI patients were ultimately selected from 1605 records for systematic review, and 11 of the studies were included in the meta-analysis. Overall, five of the included studies showed a low risk of bias. The effects of rTMS on neuropathic pain were statistically significant (MD = -1.00, 95% CI -1.76 to -0.25, = 0.009), with high heterogeneity ( = 76%). A significant advantage of 1 Hz rTMS over the right dorsolateral prefrontal cortex (DLPFC) in improving depression (MD = -6.52, 95% CI -11.58 to -1.46, = 0.01) was shown, and a significant improvement was noted in the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) scores of mild TBI patients after rTMS (MD = -5.87, 95% CI -10.63 to -1.11, = 0.02). However, no significance was found in cognition measurement. No major adverse events related to rTMS were reported. Moderate evidence suggests that rTMS can effectively and safely improve neuropathic pain, while its effectiveness on depression, postconcussion symptoms, and cognition is limited. More trials with a larger number of participants are needed to draw firm conclusions. This trial is registered with PROSPERO (PROSPERO registration number: CRD42021242364.
Topics: Brain Injuries, Traumatic; Cognition; Humans; Mental Disorders; Neuralgia; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 35945967
DOI: 10.1155/2022/2036736 -
Frontiers in Neurology 2022Time perception comprises the subjective experience of passing of time and of the duration of an event. Although already described in some neurological and psychiatric...
INTRODUCTION
Time perception comprises the subjective experience of passing of time and of the duration of an event. Although already described in some neurological and psychiatric conditions, there is a paucity of details regarding this neurocognitive change in stroke patients. We aimed to describe time perception dysfunction in stroke patient.
METHODS
We performed a systematic review of the literature in Pubmed, PsycInfo and EMBASE including manuscripts from their inception until December 2020. We collected data regarding the type of time perception that was detected, type of stroke, most common location of lesions, evaluation tests that were used and time of evaluation after stroke onset.
RESULTS
A total of 27 manuscripts were selected, concerning a total of 418 patients ( = 253 male; 60.5%). Most manuscripts ( = 21) evaluated patients with ischaemic lesions ( = 407; 97.4%). The majority referred to evaluations between 2 months and seven years after stroke. Underestimation in temporal evaluation in sub- and supra-second was the most common dysfunction ( = 165; 41.7%). Overestimation of time ( = 116; 27.8%) and impaired time interval comparison ( = 88; 22.2%) were also found. Most patients had right hemisphere lesions ( = 219 patients; 52.4%). Common reported lesion locations included the thalamus, insula, basal ganglia, dorsolateral prefrontal cortex, parietal cortex including supramarginal, angular gyrus and right inferior parietal cortex and cerebellum.
CONCLUSION
There are multiple stroke locations associated with time perception dysfunction, which highlights the complex system involved in time perception. There is still scarce knowledge about specific time perception deficits after stroke. Most studies rely in psychometric analysis without clear clinical and functional translation, namely regarding impact on daily activities.
PubMed: 35928126
DOI: 10.3389/fneur.2022.938367 -
EClinicalMedicine Oct 2022Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive form of brain stimulation that positively regulates the motor and non-motor symptoms of Parkinson's...
BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive form of brain stimulation that positively regulates the motor and non-motor symptoms of Parkinson's disease (PD). Although, most reviews and meta-analysis have shown that rTMS intervention is effective in treating motor symptoms and depression, very few have used randomised controlled trials (RCTs) to analyse the efficacy of this intervention in PD. We aimed to review RCTs of rTMS in patients with PD to assess the efficacy of rTMS on motor and non-motor function in patients with PD.
METHODS
In this systematic review and meta-analysis, we searched PubMed, MEDLINE and Web of Science databases for RCTs on rTMS in PD published between January 1, 1988 to January 1, 2022. Eligible studies included sham-controlled RCTs that used rTMS stimulation for motor or non-motor symptoms in PD. RCTs not focusing on the efficacy of rTMS in PD were excluded. Summary data were extracting from those RCTs by two investigators independently. We then calculated standardised mean difference with random-effect models. The main outcome included motor and non-motor examination of scales that were used in PD motor or non-motor assessment. This study was registered with PROSPERO, CRD42022329633.
FINDINGS
Fourteen studies with 469 patients met the criteria for our meta-analysis. Twelve eligible studies with 381 patients were pooled to analyse the efficacy of rTMS on motor function improvement. The effect size on motor scale scores was 0.51 ( < 0.0001) and were not distinctly heterogeneous (I = 29%). Five eligible studies with 202 patients were collected to evaluate antidepressant-like effects. The effect size on depression scale scores was 0.42 ( = 0.004), and were not distinctly heterogeneous (I = 25%), indicating a significant anti-depressive effect (P = 0.004). The results suggest that high-frequency of rTMS on primary motor cortex (M1) is effective in improving motor symptoms; while the dorsolateral prefrontal cortex (DLPFC) may be a potentially effective area in alleviating depressive symptom.
INTERPRETATION
The findings suggest that rTMS could be used as a possible adjuvant therapy for PD mainly to improve motor symptoms, but could have potential efficacy on depressive symptoms of PD. However, further investigation is needed.
FUNDING
The National Natural Science Foundation of China (NO: 81873777, 82071414), Initiated Foundation of Zhujiang Hospital (NO: 02020318005), Scientific Research Foundation of Guangzhou (NO: 202206010005), and Science and Technology Program of Guangdong of China (NO: 2020A0505100037).
PubMed: 35923424
DOI: 10.1016/j.eclinm.2022.101589 -
Schizophrenia (Heidelberg, Germany) Apr 2022Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here,... (Review)
Review
Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen's d) with 95% confidence intervals (95%CI) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.
PubMed: 35853882
DOI: 10.1038/s41537-022-00248-6 -
NeuroImage. Clinical 2022Repetitive Transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depressive disorder (MDD). However, neural mechanisms contributing to rTMS... (Review)
Review
INTRODUCTION
Repetitive Transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depressive disorder (MDD). However, neural mechanisms contributing to rTMS effects on depressive symptoms, cognition, and behavior are unclear. Proton magnetic resonance spectroscopy (MRS), a noninvasive neuroimaging technique measuring concentrations of biochemical compounds within the brain in vivo, may provide mechanistic insights.
METHODS
This systematic review summarized published MRS findings from rTMS treatment trials to address potential neurometabolic mechanisms of its antidepressant action. Using PubMed, Google Scholar, Web of Science, and JSTOR, we identified twelve empirical studies that evaluated changes in MRS metabolites in a within-subjects, pre- vs. post-rTMS treatment design in patients with MDD.
RESULTS
rTMS protocols ranged from four days to eight weeks duration, were applied at high frequency to the left dorsolateral prefrontal cortex (DLPFC) in most studies, and were conducted in patients aged 13-to-70. Most studies utilized MRS point resolved spectroscopy acquisitions at 3 Tesla in the bilateral anterior cingulate cortex and DLPFC. Symptom improvements were correlated with rTMS-related increases in the concentration of glutamatergic compounds (glutamate, Glu, and glutamine, Gln), GABA, and N-acetylated compounds (NAA), with some results trend-level.
CONCLUSIONS
This is the first in-depth systematic review of metabolic effects of rTMS in individuals with MDD. The extant literature suggests rTMS stimulation does not produce changes in neurometabolites independent of clinical response; increases in frontal lobe glutamatergic compounds, N-acetylated compounds and GABA following high frequency left DLPFC rTMS therapy were generally associated with clinical improvement. Glu, Gln, GABA, and NAA may mediate rTMS treatment effects on MDD symptomatology through intracellular mechanisms.
Topics: Depression; Depressive Disorder, Major; Glutamic Acid; Glutamine; Humans; Neocortex; Prefrontal Cortex; Transcranial Magnetic Stimulation; Treatment Outcome; gamma-Aminobutyric Acid
PubMed: 35738081
DOI: 10.1016/j.nicl.2022.103049 -
Frontiers in Neurology 2022Neuroimaging studies have shown gray matter structural and functional alterations in patients with idiopathic blepharospasm (iBSP) but with variations. Here we aimed to...
BACKGROUND
Neuroimaging studies have shown gray matter structural and functional alterations in patients with idiopathic blepharospasm (iBSP) but with variations. Here we aimed to investigate the specific and common neurostructural/functional abnormalities in patients with iBSP.
METHODS
A systematic literature search from PubMed, Web of Science and Embase was conducted to identify relevant publications. We conducted separate meta-analysis for whole-brain voxel-based morphometry (VBM) studies and for functional imaging studies, and a multimodal meta-analysis across VBM and functional studies in iBSP, using anisotropic effect size-based signed differential mapping.
RESULTS
The structural database comprised 129 patients with iBSP and 144 healthy controls whilst the functional database included 183 patients with iBSP and 253 healthy controls. The meta-analysis of VBM studies showed increased gray matter in bilateral precentral and postcentral gyri, right supplementary motor area and bilateral paracentral lobules, while decreased gray matter in right superior and inferior parietal gyri, left inferior parietal gyrus, left inferior temporal gyrus, left fusiform gyrus and parahippocampal gyrus. The meta-analysis of functional studies revealed hyperactivity in right dorsolateral superior frontal gyrus, left thalamus and right fusiform gyrus, while hypoactivity in left temporal pole, left insula, left precentral gyrus, bilateral precuneus and paracentral lobules, right supplementary motor area and middle frontal gyrus. The multimodal meta-analysis identified conjoint anatomic and functional changes in left precentral gyrus, bilateral supplementary motor areas and paracentral lobules, right inferior occipital gyrus and fusiform gyrus.
CONCLUSIONS
The patterns of conjoint and dissociated gray matter alterations identified in the meta-analysis may enhance our understanding of the pathophysiological mechanisms underlying iBSP.
PubMed: 35734475
DOI: 10.3389/fneur.2022.889714 -
JAMA Psychiatry Aug 2022Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear.
OBJECTIVE
To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms.
DATA SOURCES
The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021.
STUDY SELECTION
A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model.
MAIN OUTCOMES AND MEASURES
The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms.
RESULTS
Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups.
CONCLUSIONS AND RELEVANCE
In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted.
Topics: Adult; Brain; Female; Humans; Male; Middle Aged; Network Meta-Analysis; Schizophrenia; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Young Adult
PubMed: 35731533
DOI: 10.1001/jamapsychiatry.2022.1513 -
Frontiers in Psychiatry 2022A growing number of studies have suggested that transcranial magnetic stimulation (TMS) may represent a novel technique with both investigative and therapeutic potential...
BACKGROUND
A growing number of studies have suggested that transcranial magnetic stimulation (TMS) may represent a novel technique with both investigative and therapeutic potential for autism spectrum disorder (ASD). However, a full spectrum of the adverse effects (AEs) of TMS used in ASD has not been specifically and systematically evaluated.
OBJECTIVE
This systematic review and meta-analysis was to assess the prevalence of AEs related to TMS in ASD and to further explore the potentially related factors on the AEs.
METHODS
A systematic literature research of articles published before 31 December 2020 was conducted in the databases of PubMed, Embase, Cochrane Library, Ovid, PsycINFO, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP, and WANFANG DATA. AEs reported in the studies were carefully examined and synthesized to understand the safety and tolerability of TMS among ASD. Then, subgroup and sensitivity analyses were performed to examine the potentially related factors on the AEs. PROSPERO registration number: CRD42021239827.
RESULTS
Eleven studies were included in the meta-analysis. The pooled prevalence with 95% confidence interval (CI) of AEs was calculated (overall AEs: 25%, 95% CI 18-33%; headache: 10%, 95% CI 3-19%; facial discomfort: 15%, 95% CI 4-29%; irritability 21%, 95% CI 8-37%; pain at the application site: 6%, 95% CI 0-19%; headedness or dizziness: 8%, 95% CI 0-23%). All reported AEs were mild and transient with relatively few serious AEs and can be resolved after having a rest or medication. In addition, the following variables showed no significant change in overall prevalence of AEs: the purpose of using TMS, mean age of participants, whether the stimulation site was dorsolateral pre-frontal cortex (DLPFC), intensity of TMS, and the number of stimulation sessions.
CONCLUSION
The overall prevalence of reported AEs of TMS among ASD was 25%. No identified ASD-specific risk factors for TMS-induced AEs were found. Further studies are needed to clarify the variation in the prevalence.
SYSTEMATIC REVIEW REGISTRATION
www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=239827, PROSPERO, identifier: CRD42021239827.
PubMed: 35677871
DOI: 10.3389/fpsyt.2022.875591 -
Frontiers in Neurology 2022Tinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems...
Sequential Prefrontal and Temporoparietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Tinnitus With and Without Comorbid Depression: A Case Series and Systematic Review.
BACKGROUND
Tinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone.
MATERIALS AND METHODS
Ten subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature.
RESULTS
Subjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1-12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90-180 days).
CONCLUSIONS
Sequential rTMS approaches for the treatment of tinnitus-particularly those administering low-frequency treatment at left DLPFC-merit further investigation.
PubMed: 35665054
DOI: 10.3389/fneur.2022.831832