Topical Collection "Collection on Clinical Neuroscience"

A topical collection in Brain Sciences (ISSN 2076-3425). This collection belongs to the section "Clinical Neuroscience".

Editor

Prof. Dr. Pierluigi Zoccolotti

Collection Editor
1. Department of Psychology, Sapienza University of Rome, Rome, Italy;
2. Neuropsychology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy;
3. ISTC Institute for Cognitive Sciences and Technologies, CNR, Rome, Italy
Interests: disorders of reading; model dyslexia; eye movements in reading
Special Issues and Collections in MDPI journals

Topical Collection Information

Dear Colleagues,

The “clinical neuroscience” section aims to bring together research on the cognitive, behavioral, and everyday consequences of different nervous system-induced conditions. Topic areas include developmental (e.g., Down syndrome, dyslexia and other learning disabilities, autism spectrum disorders, and epilepsy), and adult (e.g., stroke and traumatic brain injury as well as progressive conditions, including Alzheimer’s disease and Huntington’s disease) domains. Further, contributions in the area of rehabilitation (including neuropsychological interventions as well as neurological interventions and aids) are encouraged. To favor reproducibility of results, we expect researchers to submit their results in as much detail as possible.

Topics include (but are not restricted to) the following:

  • autism
  • Alzheimer’s disease
  • amyotrophic lateral sclerosis
  • anxiety disorders
  • attention deficit hyperactivity disorder
  • brain tumors
  • Down syndrome and other genetic syndromes
  • dyslexia
  • epilepsy
  • Huntington’s disease
  • learning disabilities
  • multiple sclerosis
  • neurological aids
  • neuropsychological rehabilitation
  • pain
  • stroke
  • Tourette syndrome
  • traumatic brain injury

Prof. Dr. Pierluigi Zoccolotti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (40 papers)

2020

Jump to: 2019, 2018

Open AccessArticle
Neurochemical Correlates of Brain Atrophy in Fibromyalgia Syndrome: A Magnetic Resonance Spectroscopy and Cortical Thickness Study
Brain Sci. 2020, 10(6), 395; https://doi.org/10.3390/brainsci10060395 - 20 Jun 2020
Abstract
(1) Background: Recently, a series of clinical neuroimaging studies on fibromyalgia (FM) have shown a reduction in cortical volume and abnormally high glutamate (Glu) and glutamate + glutamine (Glx) levels in regions associated with pain modulation. However, it remains unclear whether the volumetric [...] Read more.
(1) Background: Recently, a series of clinical neuroimaging studies on fibromyalgia (FM) have shown a reduction in cortical volume and abnormally high glutamate (Glu) and glutamate + glutamine (Glx) levels in regions associated with pain modulation. However, it remains unclear whether the volumetric decreases and increased Glu levels in FM are related each other. We hypothesized that higher Glu levels are related to decreases in cortical thickness (CT) and volume in FM patients. (2) Methods: Twelve females with FM and 12 matched healthy controls participated in a session of combined 3.0 Tesla structural magnetic resonance imaging (MRI) and single-voxel MR spectroscopy focused on the thalami and ventrolateral prefrontal cortices (VLPFC). The thickness of the cortical and subcortical gray matter structures and the Glu/Cr and Glx/Cr ratios were estimated. Statistics included an independent t-test and Spearman’s test. (3) Results: The Glu/Cr ratio of the left VLPFC was negatively related to the CT of the left inferior frontal gyrus (pars opercularis (p = 0.01; r = −0.75) and triangularis (p = 0.01; r = −0.70)). Moreover, the Glx/Cr ratio of the left VLPFC was negatively related to the CT of the left middle anterior cingulate gyrus (p = 0.003; r = −0.81). Significantly lower CTs in FM were detected in subparts of the cingulate gyrus on both sides and in the right inferior occipital gyrus (p < 0.001). (4) Conclusions: Our findings are in line with previous observations that high glutamate levels can be related, in a concentration-dependent manner, to the morphological atrophy described in FM patients. Full article
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Open AccessArticle
Inter-Day Reliability and Changes of Surface Electromyography on Two Postural Muscles Throughout 12 Weeks of Hippotherapy on Patients with Cerebral Palsy: A Pilot Study
Brain Sci. 2020, 10(5), 281; https://doi.org/10.3390/brainsci10050281 - 06 May 2020
Abstract
Cerebral palsy (CP) is an umbrella term covering a group of permanent developmental disorders of movement and posture characterized by highly variable clinical features. The aim of this study was to assess the short-term and mid-term effects of neurorehabilitation via hippotherapy on the [...] Read more.
Cerebral palsy (CP) is an umbrella term covering a group of permanent developmental disorders of movement and posture characterized by highly variable clinical features. The aim of this study was to assess the short-term and mid-term effects of neurorehabilitation via hippotherapy on the contractile properties of two key postural muscles during functional sitting in such patients. Thirty-minute hippotherapy sessions were conducted biweekly for 12 weeks in 18 patients (18.1 ± 5.7 years old). Surface electromyography (EMG) was implemented bilaterally in rectus abdominis and adductor magnus. We quantitatively analyzed the amplitude of EMG signals in the time domain and its spectral characteristics in the frequency domain. EMGs were recorded at the beginning and end of each session on day one and at week six and week twelve. Statistical analysis revealed a substantial inter-day reliability of the EMG signals for both muscles, validating the methodological approach. To a lesser extent, while beyond the scope of the current study, quantitative changes suggested a more selective recruitment/contractile properties’ shift of the examined muscles. Exploring postural control during functional activities would contribute to understanding the relationship between structural impairment, activity performance and patient capabilities, allowing the design of neurorehabilitation programs aimed at improving postural and functional skills according to each individual’s needs. The present study provides basic quantitative data supporting the body of scientific evidence making hippotherapy an approach of choice for CP neurorehabilitation. Full article
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Open AccessReview
Brain Tumor Analysis Empowered with Deep Learning: A Review, Taxonomy, and Future Challenges
Brain Sci. 2020, 10(2), 118; https://doi.org/10.3390/brainsci10020118 - 22 Feb 2020
Cited by 1
Abstract
Deep Learning (DL) algorithms enabled computational models consist of multiple processing layers that represent data with multiple levels of abstraction. In recent years, usage of deep learning is rapidly proliferating in almost every domain, especially in medical image processing, medical image analysis, and [...] Read more.
Deep Learning (DL) algorithms enabled computational models consist of multiple processing layers that represent data with multiple levels of abstraction. In recent years, usage of deep learning is rapidly proliferating in almost every domain, especially in medical image processing, medical image analysis, and bioinformatics. Consequently, deep learning has dramatically changed and improved the means of recognition, prediction, and diagnosis effectively in numerous areas of healthcare such as pathology, brain tumor, lung cancer, abdomen, cardiac, and retina. Considering the wide range of applications of deep learning, the objective of this article is to review major deep learning concepts pertinent to brain tumor analysis (e.g., segmentation, classification, prediction, evaluation.). A review conducted by summarizing a large number of scientific contributions to the field (i.e., deep learning in brain tumor analysis) is presented in this study. A coherent taxonomy of research landscape from the literature has also been mapped, and the major aspects of this emerging field have been discussed and analyzed. A critical discussion section to show the limitations of deep learning techniques has been included at the end to elaborate open research challenges and directions for future work in this emergent area. Full article
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Open AccessArticle
Mindfulness and Psychological Flexibility are Inversely Associated with Caregiver Burden in Parkinson’s Disease
Brain Sci. 2020, 10(2), 111; https://doi.org/10.3390/brainsci10020111 - 20 Feb 2020
Cited by 1
Abstract
Parkinson’s disease (PD) is a neurodegenerative movement disorder with progressive impairments in activities of daily living. With disease progression, people with PD (PwP) need more help and care from their spouses or professional caregivers. Identifying factors that help caregivers to cope with their [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative movement disorder with progressive impairments in activities of daily living. With disease progression, people with PD (PwP) need more help and care from their spouses or professional caregivers. Identifying factors that help caregivers to cope with their burden is needed to frame future interventions for PwP caregivers. Mindfulness and psychological flexibility might be factors contributing to resilience against the burden of giving care. In this cross-sectional questionnaire-based study, 118 PwP and their respective primary caregivers were included. Caregivers reported moderate burden and only mild depressive symptoms. Mindfulness measured by the Mindfulness Attention and Awareness scale (p 0.003) and psychological flexibility measured by Acceptance and Actions Questionnaire II (p 0.001) correlated negatively with caregiver burden. Data from this study indicate mindfulness and psychological flexibility are factors contributing to resilience against caregiver burden. Future interventions to reduce burden in PwP caregivers might be improved by the inclusion of mindfulness training programs. Full article
Open AccessArticle
Retrospective and Randomized Analysis of Influence and Correlation of Clinical and Molecular Prognostic Factors in a Mono-Operative Series of 122 Patients with Glioblastoma Treated with STR or GTR
Brain Sci. 2020, 10(2), 91; https://doi.org/10.3390/brainsci10020091 - 09 Feb 2020
Abstract
Glioblastoma is a solid, infiltrating, and the most frequent highly malignant primary brain tumor. Our aim was to find the correlation between sex, age, preoperative Karnofsky performance status (KPS), presenting with seizures, and extent of resection (EOR) with overall survival (OS), progression-free survival [...] Read more.
Glioblastoma is a solid, infiltrating, and the most frequent highly malignant primary brain tumor. Our aim was to find the correlation between sex, age, preoperative Karnofsky performance status (KPS), presenting with seizures, and extent of resection (EOR) with overall survival (OS), progression-free survival (PFS), and postoperative KPS, along with the prognostic value of IDH1, MGMT, ATRX, EGFR, and TP53 genes mutations and of Ki67 through the analysis of a single-operator series in order to avoid the biases of a multi-operator series, such as the lack of homogeneity in surgical and adjuvant nonsurgical treatments. A randomized retrospective analysis of 122 patients treated by a single first operator at Sapienza University of Rome was carried out. After surgery, patients followed standard Stupp protocol treatment. Exclusion criteria were: (1) patients with primary brainstem and spinal cord gliomas and (2) patients who underwent partial resections (resection < 90%) or a biopsy exclusively for diagnostic purposes. Statistical analysis with a simultaneous regression model was carried out through the use of SPSS 25® (IBM). Results showed statistically significant survival increase in four groups: (1) patients treated with gross total resection (GTR) (p < 0.030); (2) patients with mutation of IDH1 (p < 0.0161); (3) patients with methylated MGMT promoter (p < 0.005); (4) patients without EGFR amplification or EGFRvIII mutation (p < 0.035). Higher but not statistically significant survival rates were also observed in: patients <75 years, patients presenting with seizures at diagnosis, patients affected by lesions in noneloquent areas, as well as in patients with ATRX gene mutation and Ki-67 < 10%. Full article
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Open AccessArticle
Synergistic Effects of Scalp Acupuncture and Repetitive Transcranial Magnetic Stimulation on Cerebral Infarction: A Randomized Controlled Pilot Trial
Brain Sci. 2020, 10(2), 87; https://doi.org/10.3390/brainsci10020087 - 07 Feb 2020
Cited by 1
Abstract
This study investigated the synergistic effects of scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS), known to be effective for cerebral infarction. This outcome-assessor-blinded, randomized controlled clinical trial included a per-protocol analysis to compare the efficacy of SA and electromagnetic convergence stimulation [...] Read more.
This study investigated the synergistic effects of scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS), known to be effective for cerebral infarction. This outcome-assessor-blinded, randomized controlled clinical trial included a per-protocol analysis to compare the efficacy of SA and electromagnetic convergence stimulation (SAEM-CS) and single or no stimulation. The trial was conducted with 42 cerebral infarction patients (control group, 12; SA group, 11; rTMS group, 8; SAEM-CS group, 11). All patient groups underwent two sessions of CSRT per day. SA, rTMS, and SAEM-CS were conducted once per day, 5 days per week, for 3 weeks. The primary outcome was evaluated using the Fugl–Mayer assessment (FMA). FMA Upper Extremity, FMA total, MBI, and FIM scores significantly increased in the rTMS group compared with the control group. Additionally, FMA Upper Extremity, FMA total, MBI and FIM scores significantly increased in the rTMS group compared with the SAEM-CS group. However, there were no significant changes in the SA or SAEM-CS groups. In conclusion, low-frequency rTMS in the contralesional hemisphere may have long-term therapeutic effects on upper extremity motor function recovery and improvements in activities of daily living. SAEM-CS did not show positive synergistic effects of SA and rTMS. Full article
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Open AccessArticle
Balance Training with Electromyogram-Triggered Functional Electrical Stimulation in the Rehabilitation of Stroke Patients
Brain Sci. 2020, 10(2), 80; https://doi.org/10.3390/brainsci10020080 - 02 Feb 2020
Abstract
This study was conducted to investigate the effects of balance training with electromyogram-triggered functional electrical stimulation (EMG-triggered FES) to improve static balance, dynamic balance, and ankle muscle activation in stroke patients. Forty-nine participants (>6 months after stroke) were randomly assigned to the experimental [...] Read more.
This study was conducted to investigate the effects of balance training with electromyogram-triggered functional electrical stimulation (EMG-triggered FES) to improve static balance, dynamic balance, and ankle muscle activation in stroke patients. Forty-nine participants (>6 months after stroke) were randomly assigned to the experimental group (n = 25) and the control group (n = 24). The experimental group underwent balance training with EMG-triggered FES for 40 min a day, 5 days a week, for a 6-week period in addition to general rehabilitation. The control group underwent balance training without EMG-triggered FES along with conventional therapy. Outcome measures included static balance ability, dynamic balance ability, and leg muscle activation. The static and dynamic balance abilities were significantly improved after intervention in both groups (p < 0.05), although the experimental group showed considerably greater improvement than the control group (p < 0.05). Leg muscle activation on the affected side resulted in significant improvements in the experimental group (p < 0.05) when compared with baseline but not in the control group. Balance training with EMG-triggered FES is an acceptable and effective intervention to improve the static balance, dynamic balance, and ankle muscle activation in stroke patients. Full article
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2019

Jump to: 2020, 2018

Open AccessArticle
Cannabis Influences the Putative Cytokines-Related Pathway of Epilepsy among Egyptian Epileptic Patients
Brain Sci. 2019, 9(12), 332; https://doi.org/10.3390/brainsci9120332 - 20 Nov 2019
Abstract
The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels [...] Read more.
The study aims to investigate: (1) the prevalence of cannabis among epileptic patients seen at Mansoura University Hospital, (2) serum levels and gene expression of cytokines in epilepsy patients and the controls. and (3) the possibility that cannabis use affects the cytokine levels in epilepsy patients, triggering its future use in treatment. We recruited 440 epilepsy patients and 200 controls matched for age, gender, and ethnicity. Of the epileptic patients, 37.5% demonstrated lifetime cannabis use with a mean duration of 15 ± 73 years. Serum levels of interleukin IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α), were analyzed and gene expression analysis was conducted only for those cytokines that were different between groups in the serum analysis. The “Epilepsy-only” patients had significantly higher serum and mRNA levels of IL-1α, β, IL-2,6,8, and TNF-α compared to the controls and the “Cannabis+Epilepsy” group (p = 0.0001). IL-10 showed significantly lower levels in the “Epilepsy-only” patients compared to the controls and “Cannabis+Epilepsy” (p = 0.0001). Cannabis use is prevalent among epilepsy patients. Epilepsy is characterized by a pro-inflammatory state supported by high serum and gene expression levels. Cannabis users demonstrated significantly lower levels of inflammatory cytokines compared to epilepsy non-cannabis users which might contribute to its use in the treatment of resistant epilepsy. Full article
Open AccessArticle
Cystometric Measurements in Rats with an Experimentally Induced Traumatic Brain Injury and Voiding Dysfunction: A Time-Course Study
Brain Sci. 2019, 9(11), 325; https://doi.org/10.3390/brainsci9110325 - 14 Nov 2019
Abstract
Traumatic brain injuries (TBIs) are a serious public health issue worldwide with increased mortality as well as severe disabilities and injuries caused by falls and road accidents. Unfortunately, there is no approved therapy for TBIs, and bladder dysfunction is a striking symptom. Accordingly, [...] Read more.
Traumatic brain injuries (TBIs) are a serious public health issue worldwide with increased mortality as well as severe disabilities and injuries caused by falls and road accidents. Unfortunately, there is no approved therapy for TBIs, and bladder dysfunction is a striking symptom. Accordingly, we attempted to analyze bladder dysfunction and voiding efficiency in rats with a TBI at different time-course intervals. Time-dependent analyses were scheduled from the next day until four weeks after a TBI. Experimental animals were grouped and analyzed under the above conditions. Cystometric measurements were used for this analysis and were further elaborated as external urethral sphincter electromyographic (EUS-EMG) activity and cystometrogram (CMG) measurements. Moreover, magnetic resonance imaging (MRI) studies were conducted to investigate secondary injury progression in TBI rats, and results were compared to normal control (NC) rats. Results of EUS-EMG revealed that the burst period, active period, and silent period in TBI rats were drastically reduced compared to NC rats, but they increased later and reached a stagnant phase. Likewise, in CMG measurements, bladder function, the voided volume, and voiding efficiency decreased immediately after the TBI, and other parameters like the volume threshold, inter-contraction interval, and residual volume drastically increased. Later, those levels changed, and all observed results were compared to NC rats. MRI results revealed the prevalence of cerebral edema and the progression of secondary injury. All of the above-stated results of the experiments were extensively substantiated. Thus, these innovative findings of our study model will surely pave the way for new therapeutic interventions for TBI treatment and prominently highlight their applications in the field of neuroscience in the future. Full article
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Open AccessPerspective
Intranasal Pregabalin Administration: A Review of the Literature and the Worldwide Spontaneous Reporting System of Adverse Drug Reactions
Brain Sci. 2019, 9(11), 322; https://doi.org/10.3390/brainsci9110322 - 13 Nov 2019
Abstract
Background: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also [...] Read more.
Background: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also exist. A narrative review was performed to provide an overview of current knowledge about nasal PRG use. Methods: A narrative review of the currently available literature of nasal PRG use was performed by searching the MEDLINE, EMBASE, and Web of Science databases. The abstracts and articles identified were reviewed and examined for relevance. Secondly, a request regarding reports of cases of nasal PRG administration was performed in the worldwide spontaneous reporting system of adverse drug reactions of the European Medicines Agency (EMA, EudraVigilance database). Results: The literature search resulted in two reported cases of nasal PRG use. In the analysis of the EMA-database, 13 reported cases of nasal PRG use (11 male (two not specified), mean age of users = 34.2 years (four not specified)) were found. In two cases fatalities occurred related to PRG nasal use. Conclusions: Even if only little evidence can be found in current literature, the potential for misuse/abuse of PRG via nasal route might be of particular importance in the near future in PRG users who misuse it. Physicians should be aware of these alternative routes of administration. Full article
Open AccessPerspective
Myelin Pathology: Involvement of Molecular Chaperones and the Promise of Chaperonotherapy
Brain Sci. 2019, 9(11), 297; https://doi.org/10.3390/brainsci9110297 - 30 Oct 2019
Abstract
The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal [...] Read more.
The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1, or HSP60, or Cpn60) and CCT (chaperonin-containing TCP-1). Our aim is to make scientists and physicians aware of the possibility and advantages of classifying patients depending on the presence or absence of a chaperonopathy. In turn, this subclassification will allow the development of novel therapeutic strategies (chaperonotherapy) by using molecular chaperones as agents or targets for treatment. Full article
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Open AccessArticle
Speed-Interactive Pedaling Training Using Smartphone Virtual Reality Application for Stroke Patients: Single-Blinded, Randomized Clinical Trial
Brain Sci. 2019, 9(11), 295; https://doi.org/10.3390/brainsci9110295 - 27 Oct 2019
Abstract
This study aimed to investigate the effects of speed-interactive pedaling training (SIPT) using a smartphone virtual reality application to improve lower limb motor function, trunk sitting balance, and gait in stroke patients. Forty-two patients who had previously experienced a stroke and could sit [...] Read more.
This study aimed to investigate the effects of speed-interactive pedaling training (SIPT) using a smartphone virtual reality application to improve lower limb motor function, trunk sitting balance, and gait in stroke patients. Forty-two patients who had previously experienced a stroke and could sit independently participated in the study. The subjects were assigned to the SIPT group (n = 21) and the control group (n = 21). The SIPT group had cycle training with SIPT for 40 min a day, five days a week, in a six-week period, in addition to conventional therapy. The control group had cycle training without SIPT and conventional therapy. The Fugl–Meyer Assessment, postural sway, modified functional reach test, trunk impairment scale, and spatiotemporal parameters of gait were used to assess the changes in lower extremity function, the static balance of sitting, the dynamic balance of sitting, and gait ability after the intervention. The Fugl–Meyer Assessment, postural sway, modified functional reach test, trunk impairment scale, and gait ability in the SIPT group were significantly better compared to that of the control group (p < 0.05). Based on this result, we propose that SIPT, which improves function, balance, and gait, could be used as an effective training method to improve patients’ functional activities in the clinical setting. The results of this study suggest that SIPT could be used as an effective training method to restore a patient’s function by improving trunk balance and motor function. Full article
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Open AccessCase Report
Amantadine Improves Delayed Neuropsychiatric Sequelae of Carbon Monoxide Poisoning: A Case Report
Brain Sci. 2019, 9(11), 292; https://doi.org/10.3390/brainsci9110292 - 25 Oct 2019
Abstract
Carbon monoxide (CO) poisoning causes severe brain damage, including delayed neuropsychiatric sequelae (DNS), which occur after a lucid interval following recovery from the insult of acute CO poisoning. We describe a 39-year-old male who developed DNS, including gait disturbance, trunk ataxia, and fecal/urine [...] Read more.
Carbon monoxide (CO) poisoning causes severe brain damage, including delayed neuropsychiatric sequelae (DNS), which occur after a lucid interval following recovery from the insult of acute CO poisoning. We describe a 39-year-old male who developed DNS, including gait disturbance, trunk ataxia, and fecal/urine incontinence, after remission of acute CO poisoning. Furthermore, he showed confusion, with disorientation in terms of time and space. All symptoms, including cognitive impairment, were dramatically improved by amantadine monotherapy. The present case illustrates the possibility of amantadine treatment for cognitive impairment as well as Parkinsonism induced by CO poisoning. Full article
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Open AccessArticle
Effects of Methylphenidate on Cognitive Function in Adults with Traumatic Brain Injury: A Meta-Analysis
Brain Sci. 2019, 9(11), 291; https://doi.org/10.3390/brainsci9110291 - 24 Oct 2019
Abstract
This meta-analysis evaluated the effects of methylphenidate (MPH) on cognitive outcome and adverse events in adults with traumatic brain injuries (TBI). We searched PubMed, EMBASE, and PsycINFO for randomized controlled trials (RCTs) published before July 2019. Studies that compared the effects of MPH [...] Read more.
This meta-analysis evaluated the effects of methylphenidate (MPH) on cognitive outcome and adverse events in adults with traumatic brain injuries (TBI). We searched PubMed, EMBASE, and PsycINFO for randomized controlled trials (RCTs) published before July 2019. Studies that compared the effects of MPH and placebos in adults with TBI were included. The primary outcome was cognitive function, while the secondary outcome was adverse events. Meta-regression and sensitivity analysis were conducted to evaluate heterogeneity. Seventeen RCTs were included for qualitative analysis, and ten RCTs were included for quantitative analysis. MPH significantly improved processing speed, measured by Choice Reaction Time (standardized mean difference (SMD): −0.806; 95% confidence interval (CI): −429 to −0.182, p = 0.011) and Digit Symbol Coding Test (SMD: −0.653; 95% CI: −1.016 to −0.289, p < 0.001). Meta-regression showed that the reaction time was inversely associated with the duration of MPH. MPH administration significantly increased heart rate (SMD: 0.553; 95% CI: 0.337 to 0.769, p < 0.001), while systolic or diastolic blood pressure did not exhibit significant differences. Therefore, MPH elicited better processing speed in adults with TBI. However, MPH use could significantly increase heart rate. A larger study is required to evaluate the effect of dosage, age, or optimal timing on treatment of adults with TBI. Full article
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Open AccessArticle
High Serum Caspase-Cleaved Cytokeratin-18 Levels and Mortality of Traumatic Brain Injury Patients
Brain Sci. 2019, 9(10), 269; https://doi.org/10.3390/brainsci9100269 - 10 Oct 2019
Cited by 1
Abstract
Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study [...] Read more.
Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study was to analyze whether serum CCCK-18 levels determined during the first week after TBI could predict early mortality (at 30 days). Methods: Severe TBI patients were included (considering severe when Glasgow Coma Scale < 9) in this observational and multicentre study. Serum CCCK-18 levels were determined at day 1 of TBI, and at days 4 and 8 after TBI. Results: Serum CCCK-18 levels at day 1 of TBI, and in the days 4 and 8 after TBI were higher (p < 0.001) in non-surviving than in surviving patients (34 and 90 patients, respectively) and could predict early mortality (p < 0.001 in the area under the curve). Conclusions: The new findings from our study were that serum CCCK-18 levels at any moment of the first week of TBI were higher in non-surviving patients and were able to predict early mortality. Full article
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Open AccessArticle
Ascending Axonal Degeneration of the Corticospinal Tract in Pure Hereditary Spastic Paraplegia: A Cross-Sectional DTI Study
Brain Sci. 2019, 9(10), 268; https://doi.org/10.3390/brainsci9100268 - 09 Oct 2019
Cited by 1
Abstract
Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 [...] Read more.
Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 age and gender matched healthy controls. DTI was performed using a 3 T clinical scanner with whole brain tract-based spatial statistical (TBSS) analysis of the obtained fractional anisotropy (FA) data as well as a region-of-interest (ROI)-based analysis of affected tracts including the cervical spinal cord. We further conducted correlation analyses between DTI data and clinical characteristics. Results: TBSS analysis in HSP patients showed significantly decreased fractional anisotropy of the corpus callosum and the corticospinal tract compared to healthy controls. ROI-based analysis confirmed significantly lower FA in HSP compared to controls in the internal capsule (0.77 vs. 0.80, p = 0.048), the corpus callosum (0.84 vs. 0.87, p = 0.048) and the cervical spinal cord (0.72 vs. 0.79, p = 0.003). FA values of the cervical spinal cord significantly correlated with disease duration. Conclusion: DTI metrics of the corticospinal tract from the internal capsule to the cervical spine suggest microstructural damage and axonal degeneration of motor neurons. The CST at the level of the cervical spinal cord is thereby more severely affected than the intracranial part of the CST, suggesting an ascending axonal degeneration of the CST. Since there is a significant correlation with disease duration, FA may serve as a future progression marker for assessment of the disease course in HSP. Full article
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Open AccessArticle
Tissue Plasminogen Activator and MRI Signs of Cerebral Small Vessel Disease
Brain Sci. 2019, 9(10), 266; https://doi.org/10.3390/brainsci9100266 - 05 Oct 2019
Cited by 1
Abstract
Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify [...] Read more.
Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify the relationship between tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and magnetic resonance imaging (MRI) signs of SVD. We examined 71 patients (23 men and 48 women; mean age: 60.5 ± 6.9 years) with clinical and MRI signs of SVD, and 21 healthy volunteers with normal MRIs. All subjects underwent 3T MRI and measurements of t-PA and PAI-1 levels. An increase in t-PA level is correlated with the volume of white matter hyperintensities (WMH) (R = 0.289, p = 0.034), severity on the Fazekas scale (p = 0.000), and with the size of subcortical (p = 0.002) and semiovale (p = 0.008) perivascular spaces. The PAI-1 level is not correlated with the t-PA level or MRI signs of SVD. The correlation between t-PA and the degree of WMH and perivascular spaces’ enlargement, without a correlation with PAI-1 and lacunes, is consistent with the importance of t-PA in BBB disruption and its role in causing brain damage in SVD. Full article
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Open AccessArticle
The Serum Melatonin Levels and Mortality of Patients with Spontaneous Intracerebral Hemorrhage
Brain Sci. 2019, 9(10), 263; https://doi.org/10.3390/brainsci9100263 - 01 Oct 2019
Cited by 2
Abstract
Objective: Providing melatonin in animal models with spontaneous intracerebral hemorrhage (SIH) has been associated with beneficial effects. However, to our knowledge, there are no published data on circulating melatonin levels regarding the prognosis of SIH patients. Therefore, the objectives of this study [...] Read more.
Objective: Providing melatonin in animal models with spontaneous intracerebral hemorrhage (SIH) has been associated with beneficial effects. However, to our knowledge, there are no published data on circulating melatonin levels regarding the prognosis of SIH patients. Therefore, the objectives of this study were to determine whether serum melatonin levels in SIH patients were associated with early mortality and whether they could be used as prognostic biomarkers. Methods: This observational and prospective study included patients with supratentorial and clinically severe SIH (defined as Glasgow Coma Scale GCS <9) admitted to the Intensive Care Units of six Spanish hospitals. Serum melatonin levels were determined at the time of severe SIH diagnosis. Mortality at 30 days was the study end-point. Results: Non-surviving patients (n = 46) showed higher serum melatonin levels (p < 0.001) than surviving (n = 54) patients. An area under the curve was found for the prediction of 30-day mortality by serum melatonin levels of 0.89 (95% CI = 0.81–0.94; p < 0.001). Multiple logistic regression analysis showed an association of serum melatonin levels with 30-day mortality (Odds Ratio = 8.16; 95% CI = 2.30–28.95; p = 0.001) after controlling for midline shift, glycemia, early evacuation of SIH, and Intracerebral hemorrhage (ICH) score. Conclusions: The novel findings by our study were the presence of higher serum melatonin levels in non-surviving patients than in surviving patients and the association of these levels with mortality. Full article
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Open AccessArticle
Serum Levels of Tumor Necrosis Factor-α and Loudness Dependence of Auditory Evoked Potentials at Pretreatment and Posttreatment in Patients with Major Depressive Disorder
Brain Sci. 2019, 9(10), 253; https://doi.org/10.3390/brainsci9100253 - 26 Sep 2019
Abstract
Background: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), are associated with the pathophysiology of major depressive disorder (MDD). Several studies have reported that increased TNF-α might be associated with tryptophan depletion, which eventually could result in MDD. However, other studies revealed that [...] Read more.
Background: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), are associated with the pathophysiology of major depressive disorder (MDD). Several studies have reported that increased TNF-α might be associated with tryptophan depletion, which eventually could result in MDD. However, other studies revealed that TNF-α increased serotonin firing in raphe. Therefore, whether TNF-α increases or decreases serotonin activity remains unclear. Here, we aimed to determine the relationship between serum TNF-α level and central serotonergic activity using the loudness dependence of auditory evoked potentials (LDAEP) and standardized low-resolution brain electromagnetic tomography (sLORETA), as well as to evaluate the effects of antidepressants on TNF-α levels. Methods: LDAEP, serum TNF-α level, and depression severity were measured in 64 MDD outpatients pre and post 3 months of treatment. Results: Pretreatment TNF-α levels were negatively correlated with the pretreatment N1 sLORETA-LDAEP, P2 sLORETA-LDAEP, and N1/P2 sLORETA-LDAEP (p < 0.05). In multiple regression analysis for N1/P2 sLORETA-LDAEP, lower N1/P2 sLORETA-LDAEP was significantly related to higher TNF-α (CE = −0.047, p = 0.017) when all subjects were dichotomized based on the median TNF-α level (7.16 pg/mL) into pretreatment low- and high-TNF-α groups. In addition, the pretreatment Beck Depression Inventory, P2 LDAEP, and N1/P2 sLORETA-LDAEP were greater in the high-TNF-α groups than in the low-TNF-α groups (p < 0.05). Moreover, the posttreatment TNF-α level was significantly decreased compared to the pretreatment TNF-α level (z = −2.581, p = 0.01). However, the posttreatment TNF-α levels were not associated with posttreatment LDAEP. Conclusions: Higher TNF-α level is associated with decreased LDAEP, which could indicate compensatory elevation of central serotonin activity in outpatients with MDD, although this effect disappeared and TNF-α level was reduced after three months of antidepressant treatment. Full article
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Open AccessArticle
Improvement of Cognitive Function after Continuous Positive Airway Pressure Treatment for Subacute Stroke Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial
Brain Sci. 2019, 9(10), 252; https://doi.org/10.3390/brainsci9100252 - 25 Sep 2019
Cited by 2
Abstract
Background: Obstructive sleep apnea (OSA) is common after stroke. Various studies on continuous positive airway pressure (CPAP) therapy for OSA after stroke have been published. However, there have been no studies from Korea and Asia. The present Korean study aimed to determine whether [...] Read more.
Background: Obstructive sleep apnea (OSA) is common after stroke. Various studies on continuous positive airway pressure (CPAP) therapy for OSA after stroke have been published. However, there have been no studies from Korea and Asia. The present Korean study aimed to determine whether CPAP treatment during inpatient rehabilitation of stroke patients with sleep disorders, especially OSA, improves function, cognition, sleep quality, and daytime sleepiness. Methods: This single-blind randomized controlled study included 40 stroke patients with OSA between November 2017 and November 2018. The patients were divided into the CPAP treatment group (CPAP and rehabilitation; n = 20) and control group (only rehabilitation; n = 20). The intervention period was 3 weeks. The primary outcomes were function and cognition improvements, and the secondary outcomes were sleep-related improvements. Results: CPAP treatment started at an average of 4.6 ± 2.8 days after admission. Both groups showed improvements in stroke severity, function, and cognition after the 3-week intervention. However, after the intervention, the degree of change in attention and calculation was significantly higher in the CPAP treatment group than in the control group. Additionally, the improvements in sleep quality and daytime sleepiness were greater in the CPAP treatment group than in the control group. Conclusion: CPAP treatment can improve cognitive function, sleep quality, and daytime sleepiness, and it should be considered as part of the rehabilitation program for patients with stroke. Our findings might help in the treatment of stroke patients with OSA in Korea. Full article
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Open AccessCase Report
Parkinsonism with a Hint of Huntington’s from 29 CAG Repeats in HTT
Brain Sci. 2019, 9(10), 245; https://doi.org/10.3390/brainsci9100245 - 22 Sep 2019
Abstract
Huntington’s disease is caused by at least 36 cytosine-adenine-guanine (CAG) repeats in an HTT gene allele, but repeat tracts in the intermediate range (27–35 repeats) also display a subtle phenotype. This patient had a slightly elongated CAG repeat tract (29 repeats), a prominent [...] Read more.
Huntington’s disease is caused by at least 36 cytosine-adenine-guanine (CAG) repeats in an HTT gene allele, but repeat tracts in the intermediate range (27–35 repeats) also display a subtle phenotype. This patient had a slightly elongated CAG repeat tract (29 repeats), a prominent family history of Parkinson’s disease (PD), and a clinical phenotype mostly consistent with PD, but early dystonia and poor levodopa response. Neurophysiological test results were more consistent with Huntington’s disease (HD) than PD. It is suggested that the intermediate allele modulated the clinical phenotype of PD in this patient. Full article
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Open AccessArticle
Effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) on Delay Discounting in Major Depressive Disorder: An Open-Label Uncontrolled Pilot Study
Brain Sci. 2019, 9(9), 230; https://doi.org/10.3390/brainsci9090230 - 11 Sep 2019
Cited by 2
Abstract
Background: Delay discounting (DD) refers to the decrease of a present subjective value of a future reward as the delay of its delivery increases. Major depressive disorder (MDD), besides core emotional and physical symptoms, involves difficulties in reward processing. Depressed patients often display [...] Read more.
Background: Delay discounting (DD) refers to the decrease of a present subjective value of a future reward as the delay of its delivery increases. Major depressive disorder (MDD), besides core emotional and physical symptoms, involves difficulties in reward processing. Depressed patients often display greater temporal discounting rates than healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique applied in several countries to adult patients with treatment resistant depression. Studies suggest that this technique can be used to modulate DD, but no trial has assessed its effects on depressed patients. Methods: In this open-label uncontrolled trial, 20 patients diagnosed with MDD and at least stage II treatment resistance criteria underwent 20 HF-rTMS sessions over the dorsolateral prefrontal cortex (dlPFC; 10 Hz, 110% MT, 20 min). Pre-post treatment DD rates were compared. Effects on impulsivity, personality factors, and depressive symptoms were also evaluated. Results: No significant effect of HF-rTMS over the left dlPFC on DD of depressed individuals was observed, although rates seemed to increase after sessions. However, treatment resulted in significant improvement on cognitive impulsivity and depressive symptoms, and was well-tolerated. Conclusion: Despite the limitations involved, this pilot study allows preliminary evaluation of HF-rTMS effects on DD in MDD, providing substrate for further research. Full article
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Open AccessArticle
A Comprehensive Examination of Percutaneous Endoscopic Gastrostomy and Its Association with Amyotrophic Lateral Sclerosis Patient Outcomes
Brain Sci. 2019, 9(9), 223; https://doi.org/10.3390/brainsci9090223 - 04 Sep 2019
Cited by 4
Abstract
There is literature discord regarding the impact of percutaneous endoscopic gastrostomy (PEG), or “feeding tube”, on amyotrophic lateral sclerosis (ALS) outcomes. We assess one of the largest retrospective ALS cohorts to date (278 PEG users, 679 non-users). Kruskal–Wallis and Kaplan–Meier analysis compared cohort [...] Read more.
There is literature discord regarding the impact of percutaneous endoscopic gastrostomy (PEG), or “feeding tube”, on amyotrophic lateral sclerosis (ALS) outcomes. We assess one of the largest retrospective ALS cohorts to date (278 PEG users, 679 non-users). Kruskal–Wallis and Kaplan–Meier analysis compared cohort medians and survival duration trends. A meta-analysis determined the aggregate associative effect of PEG on survival duration by combining primary results with 7 published studies. Primary results (p < 0.001) and meta-analysis (p < 0.05) showed PEG usage is associated with an overall significant increase in ALS survival duration, regardless of onset type. Percent predicted forced vital capacity (FVC %predict) ≥50 at PEG insertion significantly increases survival duration (p < 0.001); FVC %predict ≥60 has the largest associative benefit (+6.7 months, p < 0.05). Time elapsed from ALS onset until PEG placement is not predictive (p > 0.05). ALSFRS-R survey assessment illustrates PEG usage does not slow functional ALS pathology (p > 0.05), but does stabilize weight and/or body mass index (BMI) (p < 0.05). Observed clinical impression of mood (CIM), was not impacted by PEG usage (p > 0.05). Overall results support PEG as a palliative intervention for ALS patients with ≥50 FVC %predict at PEG insertion. Full article
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Open AccessArticle
Entropy Analysis of High-Definition Transcranial Electric Stimulation Effects on EEG Dynamics
Brain Sci. 2019, 9(8), 208; https://doi.org/10.3390/brainsci9080208 - 20 Aug 2019
Abstract
A foundation of medical research is time series analysis—the behavior of variables of interest with respect to time. Time series data are often analyzed using the mean, with statistical tests applied to mean differences, and has the assumption that data are stationary. Although [...] Read more.
A foundation of medical research is time series analysis—the behavior of variables of interest with respect to time. Time series data are often analyzed using the mean, with statistical tests applied to mean differences, and has the assumption that data are stationary. Although widely practiced, this method has limitations. Here we present an alternative statistical approach with sample analysis that provides a summary statistic accounting for the non-stationary nature of time series data. This work discusses the use of entropy as a measurement of the complexity of time series, in the context of Neuroscience, due to the non-stationary characteristic of the data. To elucidate our argument, we conducted entropy analysis on a sample of electroencephalographic (EEG) data from an interventional study using non-invasive electrical brain stimulation. We demonstrated that entropy analysis could identify intervention-related change in EEG data, supporting that entropy can be a useful “summary” statistic in non-linear dynamical systems. Full article
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Open AccessArticle
Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART
Brain Sci. 2019, 9(8), 195; https://doi.org/10.3390/brainsci9080195 - 09 Aug 2019
Cited by 3
Abstract
Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people’s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when [...] Read more.
Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people’s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera™). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p < 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms. Full article
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Open AccessArticle
Comparison of Transcranial Direct Current Stimulation Electrode Montages for the Lower Limb Motor Cortex
Brain Sci. 2019, 9(8), 189; https://doi.org/10.3390/brainsci9080189 - 06 Aug 2019
Cited by 2
Abstract
Transcranial direct current stimulation (tDCS) has been widely explored as a neuromodulatory adjunct to modulate corticomotor excitability and improve motor behavior. However, issues with the effectiveness of tDCS have led to the exploration of empirical and experimental alternate electrode placements to enhance neuromodulatory [...] Read more.
Transcranial direct current stimulation (tDCS) has been widely explored as a neuromodulatory adjunct to modulate corticomotor excitability and improve motor behavior. However, issues with the effectiveness of tDCS have led to the exploration of empirical and experimental alternate electrode placements to enhance neuromodulatory effects. Here, we conducted a preliminary study to compare a novel electrode montage (which involved placing 13 cm2 electrodes anterior and posterior to the target location) to the traditionally used electrode montage (13 cm2 stimulating electrode over the target area and the 35 cm2 reference electrode over the contralateral orbit). We examined the effects of tDCS of the lower limb motor area (M1) by measuring the corticomotor excitability (CME) of the tibialis anterior muscle using transcranial magnetic stimulation in twenty healthy participants. We examined behavioral effects using a skilled motor control task performed with the ankle. We did not find one electrode montage to be superior to the other for changes in the CME or motor control. When the group was dichotomized into responders and non-responders (based on upregulation in CME), we found that the responders showed significant upregulation from baseline after tDCS for both montages. However, only the responders in the traditional montage group showed significant changes in motor control after tDCS. These results do not support the superiority of the new anterior–posterior montage over the traditional montage. Further work with a larger cohort and multiple cumulative sessions may be necessary to confirm our results. Full article
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Open AccessReview
Major Depressive Disorder Is Associated with Impaired Interoceptive Accuracy: A Systematic Review
Brain Sci. 2019, 9(6), 131; https://doi.org/10.3390/brainsci9060131 - 06 Jun 2019
Cited by 5
Abstract
Interoception is the sense of the physiological condition of the entire body. Impaired interoception has been associated with aberrant activity of the insula in major depressive disorder (MDD) during heartbeat perception tasks. Despite clinical relevance, studies investigating interoceptive impairments in MDD have never [...] Read more.
Interoception is the sense of the physiological condition of the entire body. Impaired interoception has been associated with aberrant activity of the insula in major depressive disorder (MDD) during heartbeat perception tasks. Despite clinical relevance, studies investigating interoceptive impairments in MDD have never been reviewed systematically according to the guidelines of the PRISMA protocol, and therefore we collated studies that assessed accuracy in detecting heartbeat sensations (interoceptive accuracy, IAc) in MDD (databases: PubMed/Medline, PsycINFO, and PsycARTICLES). Out of 389 records, six studies met the inclusion criteria. The main findings suggest that (i) moderately depressed samples exhibit the largest interoceptive deficits as compared with healthy adults. (ii) difficulties in decision making and low affect intensity are correlated with low IAc, and (iii) IAc seems to normalize in severely depressed subjects. These associations may be confounded by sex, anxiety or panic disorder, and intake of selective serotonin reuptake inhibitors. Our findings have implications for the development of interoceptive treatments that might relieve MDD-related symptoms or prevent relapse in recurrent depression by targeting the interoceptive nervous system. Full article
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Open AccessArticle
Effects of GLP-1 Receptor Activation on a Pentylenetetrazole—Kindling Rat Model
Brain Sci. 2019, 9(5), 108; https://doi.org/10.3390/brainsci9050108 - 14 May 2019
Cited by 2
Abstract
Objectives: To study the possible anti-seizure and neuroprotective effect of glucagon like peptide 1 (GLP1) analogue (liraglutide) in a pentylenetetrazole (PTZ) induced kindled rat model and its underlying mechanisms. Methods: Thirty Sprague Dawley rats were allocated into 3 equal groups; i) [...] Read more.
Objectives: To study the possible anti-seizure and neuroprotective effect of glucagon like peptide 1 (GLP1) analogue (liraglutide) in a pentylenetetrazole (PTZ) induced kindled rat model and its underlying mechanisms. Methods: Thirty Sprague Dawley rats were allocated into 3 equal groups; i) Normal group: normal rats received normal saline, ii) PTZ (kindling) group: received PTZ (50 mg/Kg intraperitoneally (i.p.)) every other day for 2 weeks and iii) PTZ + GLP1 group: same as the PTZ group but rats received liraglutide (75 µg/kg i.p. daily) for 2 weeks before PTZ injection. Seizure severity score, seizure latency and duration were assessed. Also, the expression of caspase-3 (apoptotic marker) and β-catenin (Wnt pathway) by western blotting, markers of oxidative stress (GSH, CAT and MDA) by biochemical assay and the expression of LC3 (marker of autophagy) and heat shock protein 70 (Hsp70) by immunostaining were assessed in hippocampal regions of brain tissues. Results: PTZ caused a significant increase in Racine score and seizure duration with a significant decrease in seizure latency. These effects were associated with a significant increase in MDA, β-catenin, caspase-3, Hsp70 and LC3 in brain tissues (p < 0.05). Meanwhile, liraglutide treatment caused significant attenuation in PTZ-induced seizures, which were associated with significant improvement in markers of oxidative stress, reduction in LC3, caspase-3 and β-catenin and marked increase in Hsp70 in hippocampal regions (p < 0.05). Conclusion: Activation of GLP1R might have anticonvulsant and neuroprotective effects against PTZ-induced epilepsy. These effects could be due to suppression of oxidative stress, apoptosis and autophagy and upregulation of Hsp70. Full article
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Open AccessArticle
Anodal Transcranial Direct Current Stimulation over the Vertex Enhances Leg Motor Cortex Excitability Bilaterally
Brain Sci. 2019, 9(5), 98; https://doi.org/10.3390/brainsci9050098 - 29 Apr 2019
Cited by 1
Abstract
In many studies, anodal transcranial Direct Current Stimulation (tDCS) is applied near the vertex to simultaneously facilitate leg motor cortex (M1) of both hemispheres and enhance recovery of gait and balance in neurological disorders. However, its effect on the excitability of leg M1 [...] Read more.
In many studies, anodal transcranial Direct Current Stimulation (tDCS) is applied near the vertex to simultaneously facilitate leg motor cortex (M1) of both hemispheres and enhance recovery of gait and balance in neurological disorders. However, its effect on the excitability of leg M1 in either hemisphere is not well known. In this double-blind sham-controlled study, corticospinal excitability changes induced in leg M1 of both hemispheres by anodal (2 mA for 20 minutes) or sham tDCS (for 20 min) over the vertex were evaluated. Peak amplitudes of Transcranial Magnetic Stimulation (TMS) induced motor evoked potentials (MEPs) were measured over the contralateral Tibialis Anterior (TA) muscle before and up to 40 min after tDCS in 11 normal participants. Analysis of data from all participants found significant overall increase in the excitability of leg M1 after tDCS. However, in individual subjects there was variability in observed effects. In 4 participants, 20 min of tDCS increased mean MEPs of TAs on both sides; in 4 participants there was increased mean MEP only on one side and in 3 subjects there was no change. It’s not known if the benefits of tDCS in improving gait and balance are dependent on excitability changes induced in one or both leg M1; such information may be useful to predict treatment outcomes. Full article
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Open AccessOpinion
Noninvasive Brain Stimulation and Psychotherapy in Anxiety and Depressive Disorders: A Viewpoint
Brain Sci. 2019, 9(4), 82; https://doi.org/10.3390/brainsci9040082 - 14 Apr 2019
Cited by 8
Abstract
Among the most prevalent psychiatric conditions stand anxiety and depression. Psychotherapy and medications are considered effective treatments in these clinical settings. However, pharmacotherapy and psychotherapy (i.e., cognitive behavioral therapy (CBT)) administered in monotherapy or in a combined regimen do not result in satisfactory [...] Read more.
Among the most prevalent psychiatric conditions stand anxiety and depression. Psychotherapy and medications are considered effective treatments in these clinical settings. However, pharmacotherapy and psychotherapy (i.e., cognitive behavioral therapy (CBT)) administered in monotherapy or in a combined regimen do not result in satisfactory outcomes in all patients. Therefore, finding new treatments would be of great help. In the last three decades, noninvasive brain stimulation (NIBS) has emerged as a safe tool to improve several neuropsychiatric symptoms. The following work revisits the available reports that assessed the add-on value of NIBS techniques when combined to psychotherapy (CBT or related interventions) in mood and anxiety disorders. The available protocols targeted the prefrontal cortex, a region that was previously found to have an enhanced activity or functional connectivity after psychotherapeutic interventions. Promising yet scarce evidence exists on this matter. A discrepancy exists among the available reports regarding the type and duration of interventions, the patients’ clinical profiles, and the presence of a sham intervention. NIBS may have acted by enhancing psychotherapy effects on the top-down cognitive control of emotions. Combining both therapies may result in promising effects, but future large-scale trials are needed to judge the utility of this combination in psychiatric populations. Full article
Open AccessArticle
EEG Window Length Evaluation for the Detection of Alzheimer’s Disease over Different Brain Regions
Brain Sci. 2019, 9(4), 81; https://doi.org/10.3390/brainsci9040081 - 14 Apr 2019
Cited by 4
Abstract
Alzheimer’s Disease (AD) is a neurogenerative disorder and the most common type of dementia with a rapidly increasing world prevalence. In this paper, the ability of several statistical and spectral features to detect AD from electroencephalographic (EEG) recordings is [...] Read more.
Alzheimer’s Disease (AD) is a neurogenerative disorder and the most common type of dementia with a rapidly increasing world prevalence. In this paper, the ability of several statistical and spectral features to detect AD from electroencephalographic (EEG) recordings is evaluated. For this purpose, clinical EEG recordings from 14 patients with AD (8 with mild AD and 6 with moderate AD) and 10 healthy, age-matched individuals are analyzed. The EEG signals are initially segmented in nonoverlapping epochs of different lengths ranging from 5 s to 12 s. Then, a group of statistical and spectral features calculated for each EEG rhythm (δ, θ, α, β, and γ) are extracted, forming the feature vector that trained and tested a Random Forests classifier. Six classification problems are addressed, including the discrimination from whole-brain dynamics and separately from specific brain regions in order to highlight any alterations of the cortical regions. The results indicated a high accuracy ranging from 88.79% to 96.78% for whole-brain classification. Also, the classification accuracy was higher at the posterior and central regions than at the frontal area and the right side of temporal lobe for all classification problems. Full article
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Open AccessReview
Sensorimotor Control in Dystonia
Brain Sci. 2019, 9(4), 79; https://doi.org/10.3390/brainsci9040079 - 11 Apr 2019
Cited by 3
Abstract
This is an overview of the sensorimotor impairments in dystonia, a syndrome characterized by sustained or intermittent aberrant movement patterns leading to abnormal movements and/or postures with or without a tremulous component. Dystonia can affect the entire body or specific body regions and [...] Read more.
This is an overview of the sensorimotor impairments in dystonia, a syndrome characterized by sustained or intermittent aberrant movement patterns leading to abnormal movements and/or postures with or without a tremulous component. Dystonia can affect the entire body or specific body regions and results from a plethora of etiologies, including subtle changes in gray and white matter in several brain regions. Research over the last 25 years addressing topics of sensorimotor control has shown functional sensorimotor impairments related to sensorimotor integration, timing, oculomotor and head control, as well as upper and lower limb control. In the context of efforts to update the classification of dystonia, sensorimotor research is highly relevant for a better understanding of the underlying pathology, and potential mechanisms contributing to global and regional dysfunction within the central nervous system. This overview of relevant research regarding sensorimotor control in humans with idiopathic dystonia attempts to frame the dysfunction with respect to what is known regarding motor control in patients and healthy individuals. We also highlight promising avenues for the future study of neuromotor control that may help to further elucidate dystonia etiology, pathology, and functional characteristics. Full article
Open AccessArticle
Parkinsonism Risk Factors in Salt Lake City, Utah: A Community-Based Study
Brain Sci. 2019, 9(3), 71; https://doi.org/10.3390/brainsci9030071 - 23 Mar 2019
Cited by 1
Abstract
Background: The prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented. Methods: A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency [...] Read more.
Background: The prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented. Methods: A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency for constipation) and three exploratory instruments (for hallucinations, cognitive and olfactory complaints.) It was sent by mail and email to patients aged 50 and over at two University of Utah community clinics in Salt Lake City. A total of 7888 unique patients were sent the survey, and 1607 responses were recorded (response rate 20%). Those whose age was missing (n = 117) or less than 50 years (n = 10) were excluded from the analysis. Results: Of the 1406 without personal diagnosis of neurodegenerative disease 62.7% were female, and median age was 63. Family history (FH) of Parkinson’s disease was endorsed by 9%, constipation (defined as a bowel movement less than once per day) by 19%, mild cognitive complaints (MCI) 15.8%, dream enactment 13.7%, subjective hyposmia or anosmia 18.2%, and at least one potential psychotic symptom in 37.6%. Multivariable logistic regression showed male gender, mild cognitive complaints, hearing voices, and at least one potentially psychotic symptom to be significantly associated with dream enactment. Conclusions: This survey shows that dream enactment, a strong predictor of risk for synucleinopathy, is relatively common in the older population; because such individuals rarely come to medical attention of a sleep clinic, such survey research may be useful to identify and recruit at-risk individuals for trials aimed at preventing neurodegenerative disease. Full article
Open AccessArticle
Electrode Placement in Transcranial Direct Current Stimulation—How Reliable Is the Determination of C3/C4?
Brain Sci. 2019, 9(3), 69; https://doi.org/10.3390/brainsci9030069 - 22 Mar 2019
Abstract
The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. [...] Read more.
The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. M1 is identified by C3 and C4 of the 10/20 EEG system yet the reliability of 10/20 EEG measurements by novice research raters is unknown. We investigated the reliability of the 10/20 EEG measurements for C3 and C4 in 25 adult participants. Two novice raters were assessed for inter-rater reliability. Both raters received two hours of instruction from a registered neurodiagnostic technician. One of the raters completed the measurements across two testing days for intra-rater reliability. Relative reliability was determined using the intraclass coefficient (ICC) and absolute reliability. We observed a low to fair inter and intra-rater ICC for motor cortex measurements. The absolute reliability was <1.0 cm by different novice raters and on different days. Although a low error was observed, consideration of the integrity of the targeted region of the brain is critical when designing tDCS interventions in clinical populations who may have compromised brain structure, due to a lesion or altered anatomy. Full article
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Open AccessArticle
Effect of Paired Associative Stimulation on Corticomotor Excitability in Chronic Smokers
Brain Sci. 2019, 9(3), 62; https://doi.org/10.3390/brainsci9030062 - 15 Mar 2019
Cited by 2
Abstract
Chronic smoking has been shown to have deleterious effects on brain function and is an important risk factor for ischemic stroke. Reduced cortical excitability has been shown among chronic smokers compared with non-smokers to have a long-term effect and so far no study [...] Read more.
Chronic smoking has been shown to have deleterious effects on brain function and is an important risk factor for ischemic stroke. Reduced cortical excitability has been shown among chronic smokers compared with non-smokers to have a long-term effect and so far no study has assessed the effect of smoking on short-term motor learning. Paired associative stimulation (PAS) is a commonly used method for inducing changes in excitability of the motor cortex (M1) in a way that simulates short-term motor learning. This study employed PAS to investigate the effect of chronic cigarette smoking on plasticity of M1. Stimulator output required to elicit a motor-evoked potential (MEP) of approximately 1 mV was similar between the groups prior to PAS. MEP response to single pulse stimuli increased in the control group and remained above baseline level for at least 30 min after the intervention, but not in the smokers who showed no significant increase in MEP size. The silent period was similar between groups at all time points of the experiment. This study suggests that chronic smoking may have a negative effect on the response to PAS and infers that chronic smoking may have a deleterious effect on the adaptability of M1. Full article
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Open AccessArticle
Electrode Location in a Microelectrode Recording-Based Model of the Subthalamic Nucleus Can Predict Motor Improvement After Deep Brain Stimulation for Parkinson’s Disease
Brain Sci. 2019, 9(3), 51; https://doi.org/10.3390/brainsci9030051 - 01 Mar 2019
Cited by 2
Abstract
Motor improvement after deep brain stimulation (DBS) in the subthalamic nucleus (STN) may vary substantially between Parkinson’s disease (PD) patients. Research into the relation between improvement and active contact location requires a correction for anatomical variation. We studied the relation between active contact [...] Read more.
Motor improvement after deep brain stimulation (DBS) in the subthalamic nucleus (STN) may vary substantially between Parkinson’s disease (PD) patients. Research into the relation between improvement and active contact location requires a correction for anatomical variation. We studied the relation between active contact location relative to the neurophysiological STN, estimated by the intraoperative microelectrode recordings (MER-based STN), and contralateral motor improvement after one year. A generic STN shape was transformed to fit onto the stereotactically defined MER sites. The location of 43 electrodes (26 patients), derived from MRI-fused CT images, was expressed relative to this patient-specific MER-based STN. Using regression analyses, the relation between contact location and motor improvement was studied. The regression model that predicts motor improvement based on levodopa effect alone was significantly improved by adding the one-year active contact coordinates (R2 change = 0.176, p = 0.014). In the combined prediction model (adjusted R2 = 0.389, p < 0.001), the largest contribution was made by the mediolateral location of the active contact (standardized beta = 0.490, p = 0.002). With the MER-based STN as a reference, we were able to find a significant relation between active contact location and motor improvement. MER-based STN modeling can be used to complement imaging-based STN models in the application of DBS. Full article
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Open AccessReview
Assessing Anxiety Disorders Using Wearable Devices: Challenges and Future Directions
Brain Sci. 2019, 9(3), 50; https://doi.org/10.3390/brainsci9030050 - 01 Mar 2019
Cited by 2
Abstract
Wearable devices (WD) are starting to increasingly be used for interventions to promote well-being by reducing anxiety disorders (AD). Electrocardiogram (ECG) signal is one of the most commonly used biosignals for assessing the cardiovascular system as it significantly reflects the activity of the [...] Read more.
Wearable devices (WD) are starting to increasingly be used for interventions to promote well-being by reducing anxiety disorders (AD). Electrocardiogram (ECG) signal is one of the most commonly used biosignals for assessing the cardiovascular system as it significantly reflects the activity of the autonomic nervous system during emotional changes. Little is known about the accuracy of using ECG features for detecting ADs. Moreover, during our literature review, a limited number of studies were found that involve ECG collection using WD for promoting mental well-being. Thus, for the sake of validating the reliability of ECG features for detecting anxiety in WD, we screened 1040 articles, and only 22 were considered for our study; specifically 6 on panic, 4 on post-traumatic stress, 4 on generalized anxiety, 3 on social, 3 on mixed, and 2 on obsessive-compulsive anxiety disorder articles. Most experimental studies had controversial results. Upon reviewing each of these papers, it became apparent that the use of ECG features for detecting different types of anxiety is controversial, and the use of ECG-WD is an emerging area of research, with limited evidence suggesting its reliability. Due to the clinical nature of most studies, it is difficult to determine the specific impact of ECG features on detecting ADs, suggesting the need for more robust studies following our proposed recommendations. Full article
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Open AccessCase Report
Missed Diagnosis of Major Depressive Disorder with Catatonia Features
Brain Sci. 2019, 9(2), 31; https://doi.org/10.3390/brainsci9020031 - 02 Feb 2019
Cited by 2
Abstract
Catatonia is often a presentation of extreme anxiety and depression. Missing the diagnosis of catatonia would lead to improper treatment, which could be life-threatening. A thorough physical and psychiatric assessment is required for detecting the catatonic symptoms, especially, mutism and negativism in patients [...] Read more.
Catatonia is often a presentation of extreme anxiety and depression. Missing the diagnosis of catatonia would lead to improper treatment, which could be life-threatening. A thorough physical and psychiatric assessment is required for detecting the catatonic symptoms, especially, mutism and negativism in patients with depression. We discuss the case of a 58-year-old female that was incorrectly diagnosed and treated for major depressive disorder (MDD). The patient was then correctly diagnosed with MDD with catatonic features and improved once benzodiazepine (BZD) was started. The preferred BZD was lorazepam, with a success rate of complete remission of up to 80% in adults. Treatment was started with lorazepam 1–2 mg and improvement was seen within the first ten minutes. We believed the addition of BZD in a psychotropic regimen could improve both catatonia and depression, and should be continued for 3–6 months to prevent relapses and recurrences. Full article

2018

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Open AccessArticle
Alterations in Motor Cortical Representation of Muscles Following Incomplete Spinal Cord Injury in Humans
Brain Sci. 2018, 8(12), 225; https://doi.org/10.3390/brainsci8120225 - 16 Dec 2018
Abstract
(1) Background: The primary motor cortex (M1) experiences reorganization following spinal cord injury (SCI). However, there is a paucity of research comparing bilateral M1 organization in SCI and questions remain to be answered. We explored the presence of somatotopy within the M1 representation [...] Read more.
(1) Background: The primary motor cortex (M1) experiences reorganization following spinal cord injury (SCI). However, there is a paucity of research comparing bilateral M1 organization in SCI and questions remain to be answered. We explored the presence of somatotopy within the M1 representation of arm muscles, and determined whether anatomical shifts in these representations occur, and investigated the symmetry in organization between the two hemispheres.; (2) Methods: Transcranial magnetic stimulation (TMS) was used to map the representation of the biceps, flexor carpi radialis and abductor pollicis brevis (APB) bilaterally in nine individuals with chronic incomplete cervical spinal cord injury and nine aged- and handed-matched uninjured controls. TMS was delivered over a 6 × 5 point grid that encompassed M1 using an intensity specific to the resting motor threshold for each muscle tested.; (3) Results: Results indicate that, compared to controls, muscle representations in SCI are shifted medially but preserve a general somatotopic arrangement, and that territory dedicated to the APB muscle is greater.; (4) Conclusions: These findings demonstrate differences in the organization of M1 between able-bodied controls and those with incomplete cervical SCI. This altered organization may have future implications in understanding the functional deficits observed in SCI and rehabilitation techniques aimed at restoring function. Full article
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Open AccessFeature PaperReview
Nutrition, Energy Expenditure, Dysphagia, and Self-Efficacy in Stroke Rehabilitation: A Review of the Literature
Brain Sci. 2018, 8(12), 218; https://doi.org/10.3390/brainsci8120218 - 07 Dec 2018
Cited by 3
Abstract
While significant research has been performed regarding the use of thrombolytic agents and thrombectomy in the setting of acute stroke, other factors, such as nutritional status of stroke patients, is a less explored topic. The topic of nutrition is critical to the discussion [...] Read more.
While significant research has been performed regarding the use of thrombolytic agents and thrombectomy in the setting of acute stroke, other factors, such as nutritional status of stroke patients, is a less explored topic. The topic of nutrition is critical to the discussion of stroke, as up to half of stroke survivors may be considered malnourished at discharge. Dysphagia, old age, restricted upper limb movement, visuospatial impairment, and depression are all important risk factors for malnutrition in this cohort. The purpose of this review is to analyze current literature discussing neuroprotective diets, nutritional, vitamin, and mineral supplementation, dysphagia, and post-stroke coaching in stroke patients. Full article
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