Brain Sciences

Background: Electrical muscle stimulation (EMS) is effective for increasing physical function. However, there is no evidence regarding the effects of EMS on muscle mass and physical function in older adults with dementia. The aim of the present study was to quantify the effects of EMS on muscle mass and balance in older adults with dementia. Methods: A total of 32 participants were randomly assigned to an intervention group (n = 16, age = 89.4 ± 4.8 years) and a control group (n = 16, age = 88.1 ± 5.2 years). Participants in the intervention group underwent a general rehabilitation program (20 min for three days/week) and an EMS intervention (23 min for three days/week) for 23 weeks. Participants in the control group underwent general rehabilitation only. The efficacy of EMS was evaluated by lower limb muscle mass, the Berg Balance Scale (BBS), and the functional independence measure (FIM). Results: Muscle mass was significantly increased in the intervention group after 12 weeks (p = 0.008), but average muscle mass in the control group did not change (p = 0.18). Participants in the control group showed a significant decrease in BBS after 12 weeks (p = 0.007), unlike those in the intervention group. Furthermore, there was a strong correlation between the mini-mental state examination (MMSE) results and the change in muscle mass, the BBS, and the FIM in the control group (p < 0.05). Conclusions: These findings suggest that EMS is a useful intervention for increasing muscle mass and maintaining balance function in older adults with dementia. Full article

The study’s aim was a clinical observation concerning the influence of oral health on functional status in stroke patients undergoing neurorehabilitation. This pilot cross-sectional clinical study was performed in 60 subacute phase stroke patients during 12 weeks of treatment. The program was patient-specific and consisted of neurodevelopmental treatment by a comprehensive rehabilitation team. The functional assessment was performed using the Barthel index (BI), Berg balance scale (BBS), functional independence measure (FIM), and Addenbrooke’s cognitive examination III (ACE III) scales. Oral health was assessed according to World Health Organization (WHO) criteria, and it was presented using DMFT, DMFS, gingival index (GI), and plaque index (PlI). Significant improvement in many functional scales was noticed. However, important differences in most dental parameters without relevant changes in GI and PlI after the study were not observed. Reverse interdependence (p < 0.05) was shown between physical functioning (BI, FIM, or BBS) with GI and PlI results, and most dental parameters correlated with ACE III. Using multivariate regression analysis, we showed that ACE III and BI are predictive variables for DMFT, just as FIM is for DS (p < 0.05). The present research revealed that poor oral health status in patients after stroke might be associated with inpatient rehabilitation results. Full article

Background: There is growing interest in the use of new biomarkers such as glycated albumin (GA), but data are limited in acute ischemic stroke. We explored the impact of GA on short-term functional outcomes as measured using the modified Rankin Scale (mRS) at 3 months compared to glycated hemoglobin (HbA1c). Methods: A total of 1163 AIS patients from two hospitals between 2016 and 2019 were included. Patients were divided into two groups according to GA levels (GA < 16% versus GA ≥ 16%). Results: A total of 518 patients (44.5%) were included in the GA ≥ 16% group. After adjusting for multiple covariates, the higher GA group (GA ≥ 16%) had a 1.4-fold risk of having unfavorable mRS (95% CI 1.02–1.847). However, HbA1c was not significantly associated with 3-month mRS. In addition, GA ≥ 16% was independently associated with unfavorable short-term outcomes only in patients without diabetes. Conclusions: In light of these results, GA level might be a novel prognostic biomarker compared to HbA1c for short-term stroke outcome. Although the impact of GA is undervalued in the current stroke guidelines, GA monitoring should be considered in addition to HbA1c monitoring. Full article

Being able to distinguish between safe and risky options is paramount in making functional choices. However, deliberate manipulation of decision-makers emotions can lead to risky behaviors. This study aims at understanding how affective reactions driven by normatively irrelevant affective cues can interfere with risk-taking. Good and Bad decks of the Iowa Gambling Task have been manipulated to make them unpleasant through a negative auditory manipulation. Anticipatory skin conductance response (SCR) and heart rate variability (HRV) have been investigated in line with the somatic marker hypothesis. Results showed fewer selections from Good decks when they were negatively manipulated (i.e., Incongruent condition). No effect of the manipulation was detected when Bad decks were negatively manipulated (i.e., Congruent condition). Higher anticipatory SCR was associated with Bad decks in Congruent condition. Slower heart rate was found before selections from Good decks in Control and Congruent condition and from Bad decks in Incongruent condition. Differences in heart rate between Bad and Good decks were also detected in Congruent condition. Results shed light on how normatively irrelevant affective cues can interfere with risk-taking. Full article

Transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) was found to improve oral and written naming in post-stroke and primary progressive aphasia (PPA), speech fluency in stuttering, a developmental speech-motor disorder, and apraxia of speech (AOS) symptoms in post-stroke aphasia. This paper addressed the question of whether tDCS over the left IFG coupled with speech therapy may improve sound duration in patients with apraxia of speech (AOS) symptoms in non-fluent PPA (nfvPPA/AOS) more than sham. Eight patients with non-fluent PPA/AOS received either active or sham tDCS, along with speech therapy for 15 sessions. Speech therapy involved repeating words of increasing syllable-length. Evaluations took place before, immediately after, and two months post-intervention. Words were segmented into vowels and consonants and the duration of each vowel and consonant was measured. Segmental duration was significantly shorter after tDCS compared to sham and tDCS gains generalized to untrained words. The effects of tDCS sustained over two months post-treatment in trained and untrained sounds. Taken together, these results demonstrate that tDCS over the left IFG may facilitate speech production by reducing segmental duration. The results provide preliminary evidence that tDCS may maximize efficacy of speech therapy in patients with nfvPPA/AOS. Full article

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on these considerations, many studies have investigated the role of circulating Vitamin D levels in patients affected by a cognitive decline to assess Vitamin D’s eventual role as a biomarker or a risk factor in AD. An association between low Vitamin D levels and the onset and progression of AD has been reported, and some interventional studies to evaluate the role of Vitamin D in preventing AD onset have been performed. However, many pitfalls affected the studies available, including substantial discrepancies in the methods used and the lack of standardized data. Despite many studies, it remains unclear whether Vitamin D can have a role in cognitive decline and AD. This narrative review aims to answer two key questions: whether Vitamin D can be used as a reliable tool for diagnosing, predicting prognosis and response to treatment in AD patients, and whether it is a modifiable risk factor for preventing AD onset. Full article

The main aim of the present study was the evaluation of dynamic relationships between dimensions of temperament and motor coordination in 3–7-year-old children in Greece. More specifically, the main objectives of the current study were the test outcomes regarding the psychometric properties (structural validity and internal consistency) of the Greek versions of (a) the Child Behavior Questionnaire—very short format (CBQ—VSF), and (b) the Developmental Coordination Disorder Questionnaire (DCDQ). For the purposes of the present study, 231 parents (202 women and 29 men), aged 23–53 years (mean (M) = 36.7 and standard deviation (SD) = 5.4) completed the aforementioned questionnaires. The sample consisted of 231 children (110 girls and 121 boys) aged 3–7 years (M = 4.75 years and SD = 1.30). For the DCDQ, the confirmatory factor analysis revealed three factors consistent with the factors that emerged from the constructs, with strong internal consistency reliability. Furthermore, regarding the CBQ—VSF, which measures the dimensions of temperament, the implementation of the confirmatory factor analysis indicated three factors and satisfactory internal consistency reliability, as well. Finally, path analysis revealed that temperamental effortful control, which mirrors both inhibitory and self-regulatory capacity, has a positive effect on motor coordination. Full article

Sporadic Alzheimer’s disease (AD) is a complex genetic disease, and the leading cause of dementia worldwide. Over the past 3 decades, extensive pioneering research has discovered more than 70 common and rare genetic risk variants. These discoveries have contributed massively to our understanding of the pathogenesis of AD but approximately half of the heritability for AD remains unaccounted for. There are regions of the genome that are not assayed by mainstream genotype and sequencing technology. These regions, known as the Dark Genome, often harbour large structural DNA variants that are likely relevant to disease risk. Here, we describe the dark genome and review current technological and bioinformatics advances that will enable researchers to shed light on these hidden regions of the genome. We highlight the potential importance of the hidden genome in complex disease and how these strategies will assist in identifying the missing heritability of AD. Identification of novel protein-coding structural variation that increases risk of AD will open new avenues for translational research and new drug targets that have the potential for clinical benefit to delay or even prevent clinical symptoms of disease. Full article

AutoTutor is an automated computer tutor that simulates human tutors and holds conversations with students in natural language. Using data collected from AutoTutor, the following determinations were sought: Can we automatically classify affect states from intelligent teaching systems to aid in the detection of a learner’s emotional state? Using frequency patterns of AutoTutor feedback and assigned user emotion in a series of pairs, can the next pair of feedback/emotion series be predicted? Through a priori data mining approaches, we found dominant frequent item sets that predict the next set of responses. Thirty-four participants provided 200 turns between the student and the AutoTutor. Two series of attributes and emotions were concatenated into one row to create a record of previous and next set of emotions. Feature extraction techniques, such as multilayer-perceptron and naive Bayes, were performed on the dataset to perform classification for affective state labeling. The emotions ‘Flow’ and ‘Frustration’ had the highest classification of all the other emotions when measured against other emotions and their respective attributes. The most common frequent item sets were ‘Flow’ and ‘Confusion’. Full article

Traditionally, quantitative electroencephalography (QEEG) studies collect data within controlled laboratory environments that limit the external validity of scientific conclusions. To probe these validity limits, we used a mobile EEG system to record electrophysiological signals from human participants while they were located within a controlled laboratory environment and an uncontrolled outdoor environment exhibiting several moderate background influences. Participants performed two tasks during these recordings, one engaging brain activity related to several complex cognitive functions (number sense, attention, memory, executive function) and the other engaging two default brain states. We computed EEG spectral power over three frequency bands (theta: 4–7 Hz, alpha: 8–13 Hz, low beta: 14–20 Hz) where EEG oscillatory activity is known to correlate with the neurocognitive states engaged by these tasks. Null hypothesis significance testing yielded significant EEG power effects typical of the neurocognitive states engaged by each task, but only a beta-band power difference between the two background recording environments during the default brain state. Bayesian analysis showed that the remaining environment null effects were unlikely to reflect measurement insensitivities. This overall pattern of results supports the external validity of laboratory EEG power findings for complex and default neurocognitive states engaged within moderately uncontrolled environments. Full article

Functional Electrical Stimulation (FES) has demonstrated to improve walking ability and to induce the carryover effect, long-lasting persisting improvement. Functional magnetic resonance imaging has been used to investigate effective connectivity differences and longitudinal changes in a group of chronic stroke patients that attended a FES-based rehabilitation program for foot-drop correction, distinguishing between carryover effect responders and non-responders, and in comparison with a healthy control group. Bayesian hierarchical procedures were employed, involving nonlinear models at within-subject level—dynamic causal models—and linear models at between-subjects level. Selected regions of interest were primary sensorimotor cortices (M1, S1), supplementary motor area (SMA), and angular gyrus. Our results suggest the following: (i) The ability to correctly plan the movement and integrate proprioception information might be the features to update the motor control loop, towards the carryover effect, as indicated by the reduced sensitivity to proprioception input to S1 of FES non-responders; (ii) FES-related neural plasticity supports the active inference account for motor control, as indicated by the modulation of SMA and M1 connections to S1 area; (iii) SMA has a dual role of higher order motor processing unit responsible for complex movements, and a superintendence role in suppressing standard motor plans as external conditions changes. Full article

The aim of this study was to develop a specific scale to measure anxiety and fear levels in the general Spanish population. For this, a transcultural adaptation to Spanish of the fear of coronavirus disease 2019 (COVID-19) scale, in its original version of 10 items, was carried out. Then, the Anxiety and Fear of COVID-19 Assessment Scale (AMICO, for its acronym in Spanish) was designed by translating the tool and Delphi technique into three rounds. Ten experts participated voluntarily, and inter-observer match rates and the reliability study of the designed scale were calculated. A pilot study was carried out with the final version of the scale for the validity and reliability study. The instrument did not raise problems in semantic and cultural terms during the first and second rounds of the translation process, with an overall weighted Kappa value of 0.9. In the third round, eight new items were designed and consensual, obtaining a weighted overall value of 0.89. The pilot study sample was made up of 445 subjects, of which 60.3% were women with a mean age of 46.2 years. The final version consisted of 16 items, 2 factors, and a Cronbach’s alpha value of 0.92. The AMICO scale was developed to assess the level of anxiety and fear of COVID-19 and proved to be valid and reliable for its use in the adult Spanish population. Full article

Background: Cerebral venous thrombosis (CVT) is a rare variant of stroke in the general population, but an important subtype among pregnancy- and puerperium-related cases. Studies describing its risk factors and clinical characteristics are limited. The aim of our study is to disclose these aspects and compare with cases unrelated to pregnancy and puerperium. Materials and Methods: We performed a retrospective analysis including 88 consecutive cases from a tertiary neurology clinic with a diagnosis of CVT. Ten of the 88 cases (11.3%) appeared during the postpartum period. Results: The mean age of the puerperal CVT cases was 26.5 years. The main pregnancy-related risk factors besides puerperium were cesarean delivery (5/10), preeclampsia (2/10), and stillbirth (1/10). General risk factors for thrombosis, i.e., infection, smoking, and primary hypercoagulability, were identified in 50% of cases. Onset was in the first 3 weeks after delivery, with a mean value of 9.6 ± 5.6 days. Headache was present in 90% of postpartum CVT cases and in 76.1% of non-postpartum female cases. Seizures were more frequent in the postpartum group (60% vs. 34.8%). Onset was acute (<48 h) in 50% of postpartum cases and in 30.4% of the non-postpartum female group. The Rankin score at discharge was significantly lower in the postpartum group (0.22 vs. 0.7, p=0.02), suggesting a more favorable short-term outcome. Conclusions: The early postpartum period represents an important risk for the development of CVT. Cesarean delivery and preeclampsia, besides general risk factors such as infection, smoking, and primary thrombophilia, contribute to enhanced risk. Puerperium-related CVT presents a more favorable outcome compared with CVT with other etiologies. Full article

Motor cortex (M1) paired-pulse TMS (ppTMS) probes excitatory and inhibitory intracortical dynamics by measurement of motor-evoked potentials (MEPs). However, MEPs reflect cortical and spinal excitabilities and therefore cannot isolate cortical function. Concurrent TMS-EEG has the ability to measure cortical function, while limiting peripheral confounds; TMS stimulates M1, whilst EEG acts as the readout: the TMS-evoked potential (TEP). Whilst varying preconditioning stimulus intensity influences intracortical inhibition measured by MEPs, the effects on TEPs is undefined. TMS was delivered to the left M1 using single-pulse and three, ppTMS paradigms, each using a different preconditioning stimulus: 70%, 80% or 90% of resting motor threshold. Corticospinal inhibition was present in all three ppTMS conditions. ppTMS TEP peaks were reduced predominantly under the ppTMS 70 protocol but less so for ppTMS 80 and not at all for ppTMS 90. There was a significant negative correlation between MEPs and N45 TEP peak for ppTMS 70 reaching statistical trends for ppTMS 80 and 90. Whilst ppTMS MEPs show inhibition across a range of preconditioning stimulus intensities, ppTMS TEPs do not. TEPs after M1 ppTMS vary as a function of preconditioning stimulus intensity: smaller preconditioning stimulus intensities result in better discriminability between conditioned and unconditioned TEPs. We recommend that preconditioning stimulus intensity should be minimized when using ppTMS to probe intracortical inhibition. Full article

The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH_(4–7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC-1α and PGC-1α-dependent protein markers of mitochondriogenesis, angiogenesis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC-1α was measured immunohistochemically. The suppression of PGC-1α expression was observed in the penumbra from 24 h to 21 days following PT and reflected decreases in both the number of neurons and PGC-1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC-1α, stimulation of the nuclear translocation of PGC-1α, and increased contents of protein markers for PGC-1α activation. This study opens new prospects for the pharmacological modulation of PGC-1α in the ischemic brain. Full article

Objective: To evaluate the results of bilateral endoscopic optic nerve decompression (EOND) with the opening nerve sheath (ONS) technique in patients with idiopathic intracranial hypertension (IIH). Methods: Between the years of 2017 and 2019, we retrospectively evaluated nine IIH patients with progressive visual impairment despite medical treatment and who were treated with the EOND and ONS techniques. We also demonstrated our surgical technique recipe on postmortem human heads in a stepwise manner. Results: There were 9 patients (7 females and 2 males) between the ages of 21 and 72 included in this study, and the mean age was 40.8. All patients had an impairment in visual acuity and/or their visual field, with signs of papilledema and/or optic atrophy. The patients were followed up with for 9–48 months. Improvements in visual acuity were observed in 7 out of 9 patients (78%). Visual field defects improved in 5 out of 8 patients (62.5%). Papilledema was resolved in all patients (100%). Headaches improved in all symptomatic patients (100%). No intraoperative or postoperative complications were observed. Conclusions: EOND is a safe and effective surgical procedure in selected patients with IIH. Bilateral wide bony decompression and nerve fenestration can also be an additional benefit for headache relief. Further clinical series and long-term follow-up are needed for more precise results. Full article

Alcohol exposure (AE) during the third trimester of pregnancy—a period known as the brain growth spurt (BGS)—could result in a diagnosis of a fetal alcohol spectrum disorder (FASD), a hallmark of which is impaired executive functioning (EF). Coordinated activity between prefrontal cortex and hippocampus is necessary for EF and thalamic nucleus reuniens (Re), which is required for prefrontal-hippocampal coordination, is damaged following high-dose AE during the BGS. The current experiment utilized high-dose AE (5.25 g/kg/day) during the BGS (i.e., postnatal days 4–9) of Long-Evans rat pups. AE reduces the number of neurons in Re into adulthood and selectively alters the proportion of Re neurons that simultaneously innervate both medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). The AE-induced change unique to Re→(mPFC + vHPC) projection neurons (neuron populations that innervate either mPFC or vHPC individually were unchanged) is not mediated by reduction in neuron number. These data are the first to examine mPFC-Re-HPC circuit connectivity in a rodent model of FASD, and suggest that both short-term AE-induced neuron loss and long-term changes in thalamic connectivity may be two distinct (but synergistic) mechanisms by which developmental AE can alter mPFC-Re-vHPC circuitry and impair EF throughout the lifespan. Full article

Background. Despite considerable interest in the search for a spinal cord injury (SCI) therapy, there is a critical need to develop a panel of diagnostic biomarkers to determine injury severity. In this regard, there is a requirement for continuing research into the fundamental processes of neuroinflammatory and autoimmune reactions in SCI, identifying changes in the expression of cytokines. Methods. In this pilot study, an extended multiplex analysis of the cytokine profiles in the serum of patients at 2 weeks post-SCI (n = 28) was carried out, together with an additional assessment of neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunosorbent assay. A total of 16 uninjured subjects were enrolled as controls. Results. The data obtained showed a large elevation of IFNγ (>52 fold), CCL27 (>13 fold), and CCL26 (>8 fold) 2 weeks after SCI. The levels of cytokines CXCL5, CCL11, CXCL11, IL10, TNFα, and MIF were different between patients with baseline American Spinal Injury Association Impairment Scale (AIS) grades of A or B, whilst IL2 (>2 fold) and MIP-3a (>6 fold) were significantly expressed in the cervical and thoracic regions. There was a trend towards increasing levels of NSE. However, the difference in NSE was lost when the patient set was segregated based on AIS group. Conclusions. Our pilot research demonstrates that serum concentrations of cytokines can be used as an affordable and rapid detection tool to accurately stratify SCI severity in patients. Full article

Freezing of gait (FOG) in Parkinson’s disease (PD) occurs frequently in situations with high environmental complexity. The supplementary motor cortex (SMC) is regarded as a major network node that exerts cortical input for motor control in these situations. We aimed at assessing the impact of single-session (excitatory) intermittent theta burst stimulation (iTBS) of the SMC on established walking during FOG provoking situations such as passing through narrow spaces and turning for directional changes. Twelve PD patients with FOG underwent two visits in the off-medication state with either iTBS or sham stimulation. At each visit, spatiotemporal gait parameters were measured during walking without obstacles and in FOG-provoking situations before and after stimulation. When patients passed through narrow spaces, decreased stride time along with increased stride length and walking speed (i.e., improved gait) was observed after both sham stimulation and iTBS. These effects, particularly on stride time, were attenuated by real iTBS. During turning, iTBS resulted in decreased stride time along with unchanged stride length, a constellation compatible with increased stepping frequency. The observed iTBS effects are regarded as relative gait deterioration. We conclude that iTBS over the SMC increases stepping frequency in PD patients with FOG, particularly in FOG provoking situations. Full article