Name of all authors as they appear in the published original article (INSERT ONLY IF correcting author names or adding authors. Insert the correct version of the author list)Affiliations of all authors as they appear in the published original version of the article (1Department of Neurology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China2Department of Neurology, The Second People's Hospital of Hefei, Affiliated Hefei Hospital of Anhui Medical University, Hefei 230011, China)* Correspondence: Yanghua Tian, Email: ayfytyh@126.comKeywords: glial fibrillary acidic protein astrocytopathy; respiratory failure; plasma exchange; efficacyCorrigendum on: Plasma exchange for two patients with autoimmune GFAP astrocytopathy with rapid progression to respiratory failure: A case report. Incorrect AffiliationIn the published article, there was an error in affiliation(s) of the author Qi Li. Instead of "[Qi Li, MD, PhD2]", it should be "[Qi Li, MD, PhD1]". The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, with approximately 6 million people affected worldwide. Vesicular monoamine transporter 2 (VMAT2) dysfunction has recently become a hot topic in the pathophysiology of PD, and the advent of transgenic mice has also accelerated the development of behavioral studies in animal models. However, there are only a few systematic behavioral tests that embrace abundant motor and nonmotor performance in a unique mutant mouse model that corresponds to the varied symptoms observed in human PD. The aim of this study is to evaluate the responsibility of the unique reduction of dopamine in the varied motor and nonmotor symptoms of PD via transgenic mice model. We analyzed neurotransmitter concentrations in the brain tissue of 18-month-old mutant mice with selective inactivation of one allele of Vmat2 in dopaminergic neurons (VMAT2DATcre-HET) to confirm the selective reduction of dopamine, and then examined behavioral functions. Neurochemical tests showed lower dopamine concentrations in specific brain regions of VMAT2DATcre-HET mice, especially the ventral tegmental area/substantia nigra and striatum, together with relatively unchanging concentrations of norepinephrine and serotonin, demonstrating the dopaminergic specificity of this mouse model. Behavioral tasks showed impairments in several motor functions and major defects in olfactory abilities in the VMAT2DATcre-HET mice; however, no significant changes were found in the majority of nonmotor tests, such as emotional performance and sleep patterns. We concluded from this study that the selective inactivation of one allele of the Vmat2 gene in dopaminergic neurons was related to dopamine reduction, resulting in phenotypes resembling some of the major deficits in PD, especially motor symptoms and olfactory function.
Abstract Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin‐targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top‐down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression.
Abstract Background Schizotypal traits are considered as heritable traits and the endophenotype for schizophrenia. A common variant in NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Methods In present study, we compared the difference of brain function between different genotype of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using resting-state functional magnetic resonance image (rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). Results Our results suggested that the carriers with AA genotype showed reduced FCS in left occipital cortex than the carriers with AG and GG genotype and the carriers with AG genotype showed reduced FCS in left occipital cortex than the carriers with GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with GG genotype, but not within the carriers with AA or AG genotype. Conclusions Our results suggested that the common variant in NOTCH4 gene, rs204993, modulate the function of occipital cortex, which may contribute to the schizotypal traits. These findings provided insight for genetic effect on schizotypal traits and its potential neural substrate.
Electroconvulsive therapy (ECT) is an effective and rapid treatment for major depressive disorder (MDD). However, the neurobiological underpinnings of ECT are still largely unknown. Recent studies have identified dysregulated brain networks in MDD. Therefore, we hypothesized that ECT may improve MDD symptoms through reorganizing these networks. To test this hypothesis, we used resting-state functional connectivity to investigate changes to the intra- and internetwork architecture of five reproducible resting-state networks: the default mode network (DMN), dorsal attention network (DAN), executive control network (CON), salience network (SAL), and sensory-motor network. Twenty-three MDD patients were assessed before and after ECT, along with 25 sex-, age-, and education-matched healthy controls. At the network level, enhanced intranetwork connectivities were found in the CON in MDD patients after ECT. Furthermore, enhanced internetwork connectivities between the DMN and SAL, and between the CON and DMN, DAN, and SAL were also identified. At the nodal level, the posterior cingulate cortex had increased connections with the left posterior cerebellum, right posterior intraparietal sulcus (rpIPS), and right anterior prefrontal cortex. The rpIPS had increased connections with the medial PFC (mPFC) and left anterior cingulate cortex. The left lateral parietal had increased connections with the dorsal mPFC (dmPFC), left anterior prefrontal cortex, and right anterior cingulate cortex. The dmPFC had increased connection with the left anterolateral prefrontal cortex. Our findings indicate that enhanced interactions in intra- and internetworks may contribute to the ECT response in MDD patients. These findings provide novel and important insights into the neurobiological mechanisms underlying ECT.
Abstract Background: The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. Methods: Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. We then compared more highly (higher CR) and less highly educated (lower CR) subjects at the same level of cognitive impairment. Results: In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. In mild and moderate AD groups, subjects with higher CR had smaller regional GMV of the dACC and lower ReHo in the left ITC than the subjects with lower CR. No significant differences were found in severe AD and aMCI groups. Conclusions: Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.
Freezing of gait (FOG), defined as an episodic inability to generate effective stepping despite the intention to walk [[1]Giladi N. Nieuwboer A. Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stage.Mov Disord Off J Mov Disord Soc. 2008; 23: S423-S425Crossref PubMed Scopus (262) Google Scholar], is associated with a high risk of falling, limitation of activities and poor quality of life. FOG is one of the most disabling symptoms of Parkinson's disease (PD) and there is currently no effective therapy. Alternative therapies, such as repetitive transcranial magnetic stimulation (rTMS), have been used in an attempt to alleviate FOG, but the clinical benefit is limited [[2]Kim Y.W. Shin I.S. Moon H.I. Lee S.C. Yoon S.Y. Effects of non-invasive brain stimulation on freezing of gait in parkinsonism: a systematic review with meta-analysis.Park Relat Disord. 2019; 64: 82-89Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar]. A recent study indicated that accelerated theta-burst stimulation (TBS) for patients with depression, with 18000 pulses per day, significantly increased the remission ratio [[3]Cole E.J. Stimpson K.H. Bentzley B.S. Gulser M. Cherian K. Tischler C. et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.Am J Psychiatr. 2020; 177 (appiajp201919070720): 716-726Crossref PubMed Scopus (88) Google Scholar]. Here, we examined the efficacy of this accelerated high-dose TBS (ahTBS) protocol in the treatment of FOG. PD patients were prospectively recruited in the First Affiliated Hospital of Anhui Medical University from April 2020 to August 2021 [[4]Ji G.J. Liu T. Li Y. Liu P. Sun J. Chen X. et al.Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease.Human Brain Mapp. 2020; Google Scholar]. The inclusion criteria were as follows: (a) diagnosis of idiopathic PD according to the UK Brain Bank Criteria, confirmed by a neurologist (author K.W. or P.H.) with expertise in movement disorders; (b) ongoing treatment with a stable dose of any medication for 2 months; (c) 40 years of age or older; and (d) Mini-Mental State Examination (MMSE) score >24. Exclusion criteria were as follows: (a) a history of addiction, psychiatric disorders, or neurological diseases other than PD; (b) focal brain lesions on T1-/T2-weighted fluid-attenuated inversion recovery images; (c) anti-PD medication adjustments during rTMS treatment; (d) history of substance abuse within the past 6 months; (e) nonremovable metal objects in or around the head; (f) previously received rTMS treatment; and (g) prior history of seizure or history in first-degree relatives. FOG was diagnosed by two experienced experts (P.H. and K.W.) using objective tests (e.g., step-over obstacles), and unresponsive to drug treatment. The protocol was approved by the Ethics Committee of Anhui Medical University and all participants provided written consent. TMS was performed using a Magstim Rapid2 transcranial magnetic stimulator (Magstim Company, Whitland, UK) with a 70-mm air cooled figure-of-eight coil. All stimulations were guided by the participant's anatomical image (1 × 1 × 1 mm3) and a frameless neuronavigation system (Brainsight; Rogue Research, Montreal, QC, Canada). Treatment comprised ahTBS, targeted to the primary motor cortex of the right lower leg. The target in Montreal Neurological Institute space (coordinates: −10, −24, 75) was transformed into individual high-resolution structural images by applying an inverse matrix produced during brain structure segmentation using SPM12 (www.fil.ion.ucl.ac.uk/spm). Fifty intermittent TBS sessions (1800 pulses per session, 50 minute inter-session interval [[3]Cole E.J. Stimpson K.H. Bentzley B.S. Gulser M. Cherian K. Tischler C. et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.Am J Psychiatr. 2020; 177 (appiajp201919070720): 716-726Crossref PubMed Scopus (88) Google Scholar]) were delivered as ten daily sessions over five consecutive days at 80% resting motor threshold (RMT). RMT was determined on the first day of the experiment by a five-step procedure. Briefly, the electromyography (EMG) signal of the abductor pollicis brevis muscle was recorded using Ag/AgCl surface electrodes, and displayed with the Rogue EMG device when the left "hand knob" area was activated by a single pulse stimulation. The RMT was defined as the lowest intensity evoking a small response (>50 μV) in more than 5 of 10 consecutive trials. The turning time in Standing Start 180° Turning Test (SS-180) [[5]Kim M.S. Chang W.H. Cho J.W. Youn J. Kim Y.K. Kim S.W. et al.Efficacy of cumulative high-frequency rTMS on freezing of gait in Parkinson's disease.Restor Neurol Neurosci. 2015; 33: 521-530PubMed Google Scholar] was selected as the primary outcome because of its objectivity and importance in daily life. The test, which was repeated four times on each test occasion, was videotaped and was carried out before and one day after the intervention. The Freezing of Gait Questionnaire (FOGQ) was used as a secondary outcome. All assessments took place in the medication "on" state at the same time of the day for each patient. Dopaminergic therapy was stable from two months before the study until the end of the study. Twenty PD patients were initially estimated, and 12 of them (mean age = 72, Table 1) with severe FOG (see attached videos) were included in this study. All the patients found the treatment tolerable and eleven out of twelve (91.7%) showed a dramatic improvement in the SS-180 turning test after treatment, as can be easily seen in the attached videos.Table 1Patient demographics and treatment response to accelerated high-dose magnetic stimulations.Sex/age (y)/education (y)Duration (y)/H–Y/LEDD (mg)Measures before and after treatment (pre/post)Measures at follow upTurning timeaThe SS-180 test was repeated four times on each test occasion, twice from left to right and twice from right to left. Average scores were used to calculate percentage improvement relative to baseline.Turning stepsFOGQTurning timeaThe SS-180 test was repeated four times on each test occasion, twice from left to right and twice from right to left. Average scores were used to calculate percentage improvement relative to baseline.Turning stepsFOGQF/69/05/2/60016.3/5.132.3/13.021/184.09.719M/79/165/1/43828.0/6.129.0/11.322/136.812.321F/70/03/3/50022.3/10.956.8/33.322/1910.727.319M/62/128/2/75045.2/5.083.3/9.520/164.910.321F/64/124/3/40012.6/12.632.8/33.320/176.113.519F/68/54/4/57593.9/66.685.0/76.522/1423.439.018M/82/59/4/375131.6/75.9133.5/92.021/21103.8112.823M/76/12/3/200202/76255/12122/2255.3111.520F/76/52/3/010.1/6.426/11.518/117.31218M/77/95/2.5/66323.6/13.388.25/40.321/2114.55423M/76/93/2.5/65073.77/6.1113/15.521/2114.63017F/69/91/3/57521/4.551.8/10.322/316.332.522Mean4/2.8/44056.7/24.082.2/39.021/1622.338.720F = female, H–Y = Hoehn and Yahr stage, LEED = levodopa equivalent daily dose, M = male.a The SS-180 test was repeated four times on each test occasion, twice from left to right and twice from right to left. Average scores were used to calculate percentage improvement relative to baseline. Open table in a new tab F = female, H–Y = Hoehn and Yahr stage, LEED = levodopa equivalent daily dose, M = male. There was a significant improvement in turning time (paired t = 3.1, P = 0.009), number of steps (paired t = 3.7, P = 0.003), and FOGQ (paired t = 2.9, P = 0.014) after treatment (Table 1). After one-month, these remarkable improvements remained well both in time (paired t = 2.86, P = 0.0155), steps (paired t = 3.9, P = 0.0025), and FOGQ (paired t = 1.7, P = 0.126). The improvement ratio (relative to baseline) in time, number of steps, and FOGQ were 55.9%, 51.6%, and 22.1% after treatment respectively, and remained in one-month follow up (56.8%, 54.6%, and 4.6%, respectively). This study reveals that ahTBS provides remarkable relief from FOG in 91.7% of PD patients after five days treatment without adverse events. To the best of our knowledge, this high efficacy is unprecedented in the literature describing treatment of FOG [[2]Kim Y.W. Shin I.S. Moon H.I. Lee S.C. Yoon S.Y. Effects of non-invasive brain stimulation on freezing of gait in parkinsonism: a systematic review with meta-analysis.Park Relat Disord. 2019; 64: 82-89Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar]. It suggests that ahTBS is an effective therapy for FOG in PD patients. Optimally-spaced high dose may contribute to this high efficacy. Conventional rTMS studies usually applied thousands of pulses per day, which was extremely less than other effective clinical therapy, such as deep brain stimulation (∼500,000 pluses per day) [[6]Williams N.R. Okun M.S. Deep brain stimulation (DBS) at the interface of neurology and psychiatry.J Clin Invest. 2013; 123: 4546-4556Crossref PubMed Scopus (77) Google Scholar]. However, continuously adding the rTMS dose may increase the side effect but not necessarily enhance the treatment effects. According to previous neuroplasticity and clinical studies [[3]Cole E.J. Stimpson K.H. Bentzley B.S. Gulser M. Cherian K. Tischler C. et al.Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression.Am J Psychiatr. 2020; 177 (appiajp201919070720): 716-726Crossref PubMed Scopus (88) Google Scholar,[7]Kramar E.A. Babayan A.H. Gavin C.F. Cox C.D. Jafari M. Gall C.M. et al.Synaptic evidence for the efficacy of spaced learning.Proc Natl Acad Sci U S A. 2012; 109: 5121-5126Crossref PubMed Scopus (96) Google Scholar], we used a long inter-session interval (i.e., 1 hour) to produce cumulative effects. With this setting, the FOG symptoms were rapidly alleviated and the treatment effect sustained for at least one month without relapse trend. Our sample size is relatively small because this study has focused on PD patients with severe FOG and excluded patients with mild FOG. Nevertheless, our findings strongly suggest the clinical efficacy of hdTBS, thus a randomized clinical trial is warranted in the future. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study was funded by the National Key R&D Program of China (No. 2018YFC1314200 to P.H.); the National Natural Science Foundation of China (Nos. 81971689 to G.-J. J., 31970979 , 91432301 , 31571149 , 82090034 and 2016YFC1300604 to K. W.; No. 82171917 to P.P. H., No. 81971072 to X.C.; No. 81790652 to H. L.; No. 81803130 to X.C.; No. 32071054 to Y.T.); Doctoral Foundation of Anhui Medical University (No. XJ201532 to G.-J. J.); and Collaborative Innovation Center of Neuropsychiatric Disorder and Mental Health of Anhui Province . The following are the Supplementary data to this article:https://www.brainstimjrnl.com/cms/asset/1578b511-0f7e-4b57-93d6-b3a35393dfb4/mmc1.mp4Loading ... 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Cerebral small vessel disease (CSVD) is a primary vascular disease of cognitive impairment. Previous studies have predominantly focused on brain linear features. However, the nonlinear measure, brain entropy (BEN), has not been elaborated. Thus, this study aims to investigate if BEN abnormalities could manifest in CSVD patients with cognitive impairment.
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