Brain Sci., Volume 12, Issue 5 (May 2022) – 171 articles

Social distancing norms have been promoted after the COVID-19 pandemic. In this work, we tested interpersonal space (IPS) in 107 subjects through a reaching-comfort distance estimation task. In the main experiment, subjects had to estimate the comfort and reach space between an avatar wearing or not wearing a face mask. We found that IPS was greater between avatars not wearing a mask with respect to stimuli with the mask on, while reaching space was not modulated. IPS increment in the NoMask condition with respect to the Mask condition correlated with anxiety traits, as shown with the State-Trait Anxiety Inventory, rather than with transient aspects related to the pandemic situation. In the control experiment, the avatars with a mask were removed to further explore the conditioning effect provided by the presence of the facial protection in the main experiment. We found a significant difference comparing this condition with the same condition of the main experiment, namely, the distances kept between avatars not wearing a mask in the main experiment were greater than those between the same stimuli in the control experiment. This showed a contextual adaptation of IPS when elements related to the actual pandemic situation were relevant. Additionally, no significant differences were found between the control experiment and the Mask condition of the main experiment, suggesting that participants had internalized social distancing norms and wearing a mask has become the new normal. Our results highlight the tendency of people in underestimating the risk of contagion when in the presence of someone wearing a mask. Full article

This article presents DIANA, a new, process-oriented model of human auditory word recognition, which takes as its input the acoustic signal and can produce as its output word identifications and lexicality decisions, as well as reaction times. This makes it possible to compare its output with human listeners’ behavior in psycholinguistic experiments. DIANA differs from existing models in that it takes more available neuro-physiological evidence on speech processing into account. For instance, DIANA accounts for the effect of ambiguity in the acoustic signal on reaction times following the Hick–Hyman law and it interprets the acoustic signal in the form of spectro-temporal receptive fields, which are attested in the human superior temporal gyrus, instead of in the form of abstract phonological units. The model consists of three components: activation, decision and execution. The activation and decision components are described in detail, both at the conceptual level (in the running text) and at the computational level (in the Appendices). While the activation component is independent of the listener’s task, the functioning of the decision component depends on this task. The article also describes how DIANA could be improved in the future in order to even better resemble the behavior of human listeners. Full article

Adiponectin exhibits pleiotropic effects, including anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective ones. Although some studies have documented brain expression in different rodent models of its receptors, AdipoR1 and AdipoR2, their global distribution remains incomplete. Here, we demonstrated that both AdipoR are widely distributed in the brains of adult mice. Furthermore, by double immunostaining studies, we showed that AdipoR1 and AdipoR2 are mainly expressed in neurons and blood vessels. Then, considering the wide distribution of both receptors and the neuroprotective effects of adiponectin, we tested the therapeutic effect of a single injection of the adiponectin receptor agonist, AdipoRON (5 mg.kg⁻¹), 24 h after stroke in a model of middle cerebral artery occlusion technique (MCAO). Under our experimental conditions, we demonstrated that AdipoRON did not modulate the infarct volume, cell death, neuroinflammatory parameters including microglia activation and oxidative stress. This study suggests that a protocol based on multiple injections of AdipoRON at a higher dose after MCAO could be considered to promote the therapeutic properties of AdipoRON on the brain repair mechanism and recovery. Full article

Chronic low-level blast exposure has been linked with neurological alterations and traumatic brain injury (TBI) biomarkers. Impaired smooth-pursuit eye movements (SPEM) are often associated with TBI. The purpose of this study was to determine whether long-term operators of low-level blast exposure or high-caliber weapons use displayed oculomotor behaviors that differed from controls. Twenty-six members of an elite military unit performed a computerized oculomotor testing task using an eye tracker and completed a concussion assessment questionnaire. The participants were split into a blast exposure group and control group. The blast exposure group had a history of exposure to low-level blasts or high-caliber weapon use. The results revealed significant differences in SPEM, saccades, and fixations between the blast exposure group and control group. The blast exposure group’s eye movements were slower, stopped at more frequent points when following a target, traveled further from the target in terms of both speed and direction, and showed higher rates of variation and inefficiency. Poor oculomotor behavior correlated with a higher symptom severity on the concussion assessment questionnaire. Military special operators exposed to long-term low-level blasts or high-caliber weapons usage displayed an impaired oculomotor behavior in comparison to controls. These findings further our understanding of the impact of long-term low-level blast exposure on the oculomotor behavior of military special operators and may inform practical implications for military training. Full article

Linguistic deficits are frequent symptoms among stroke survivors. The neural mechanism of post-stroke aphasia (PSA) was incompletely understood. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) was widely used among several neuropsychological disorders. However, previous rs-fMRI studies of PSA were limited to very small sample size and the absence of reproducibility with different neuroimaging indexes. The present study performed comparisons with static and dynamic amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) based on modest sample size (40 PSA and 37 healthy controls). Compared with controls, PSA showed significantly increased static ALFF predominantly in the bilateral supplementary motor area (SMA) and right hippocampus-parahippocampus (R HIP-ParaHip) and decreased static ALFF in right cerebellum. The increased dynamic ALFF in SMA and decreased dynamic ALFF in right cerebellum were also found in PSA. The static and dynamic ALFF in right cerebellum was positively correlated with spontaneous speech. The FC between the SMA and R HIP-ParaHip was significantly stronger in patients than controls and positively correlated with ALFF in bilateral SMA. In addition, the FC between the R HIP-ParaHip and the right temporal was also enhanced in patients and negatively correlated with repetition, naming, and comprehension score. These findings revealed consistently abnormal intrinsic neural activity in SMA and cerebellum, which may underlie linguistic deficits in PSA. Full article

Background: Inflammation, particularly cytokine release, contributes to epileptogenesis by influencing the cerebral tissue remodeling and neuronal excitability that occurs after a precipitating epileptogenic insult. While several cytokines have been explored in this process, release kinetics are less well investigated. Determining the time course of cytokine release in the epileptogenic zone is necessary for precisely timed preventive or therapeutic anti-inflammatory interventions. Methods: Hippocampal extracellular levels of six cytokines and chemokines (IL-1β, IL-6, IL-10, CCL2, CCL3, and CCL5) were quantified at various time points during epileptogenesis in a rat model of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) using microdialysis (MD). Results: The analysis of microdialysates demonstrated consistent elevation at all time points during epileptogenesis for IL-1β and IL-10. IL-10 release was maximal on day 1, IL-1β release peaked at day 8. No correlation between local hippocampal IL-1β concentrations and IL-1β blood levels was found. Conclusion: The release kinetics of IL-1β are consistent with its established pro-epileptogenic properties, while the kinetics of IL-10 suggest a counter-regulatory effect. This proof-of-concept study demonstrates the feasibility of intraindividual longitudinal monitoring of hippocampal molecular inflammatory processes via repetitive MD over several weeks and sheds light on the kinetics of hippocampal cytokine release during epileptogenesis. Full article

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sectional study was conducted in a cohort of HD gene carriers compared to not gene carriers (n.134 HD subjects, n.74 not gene mutation carriers). A specific pain interview, alongside a neurological, cognitive and behavioural examination, was performed in order to classify the type of pain, subjective intensity. A significant prevalence of “no Pain” in HD was found, which tended to increase with HD progression and a reduced frequency of pain in the last 3 months. A clear difference was found between manifest and premanifest HD in terms of intensity of pain, which did not change significantly with HD progression; however, a tendency emerges to a progressive reduction. No significant group difference was present in analgesic use, type and the site of pain. These findings could support a lower prevalence of chronic pain in manifest HD. Prevalence and intensity of chronic pain seem directly influenced by the process of neurodegeneration rather than by an incorrect cognitive and emotional functioning. Full article

Objective: Although some meta-analyses have shown a correlation between a high neutrophil-to-lymphocyte ratio (NLR) and low survival in patients with gliomas, their conclusions are controversial, and no study has specifically explored the relationship between a high pre-treatment and pre-operative NLR and low survival in patients with glioblastoma (GBM). Therefore, we further investigated this correlation through meta-analysis. Methods: We searched the PubMed, Metstr, and Cochrane databases in March 2022 for published literature related to high pre-treatment and pre-operative NLR and low survival in patients with GBM. The literature was rigorously searched according to inclusion and exclusion criteria to calculate the overall hazard ratio (HR) and 95% confidence interval (CI) corresponding to a high NLR using a random effects model. Results: The total HR for the pre-treatment and pre-operative NLR was 1.46 (95% CI: 1.17–1.75, p = 0.000, I² = 76.5%), indicating a significant association between a high pre-treatment and pre-operative NLR, and low overall survival in patients with GBM. Sub-group analysis was performed because of the high heterogeneity. The results for the sub-group with a cut-off value of 4 showed an HR of 1.39 (95% CI: 1.12–1.65, p = 0.000, I² = 22.2%), with significantly low heterogeneity, whereas those for the sub-group without a cut-off value of 4 showed an HR of 1.45 (95% CI: 1.01–1.89, p = 0.000, I² = 83.3%). Conclusions: The results of this study demonstrate that a high pre-treatment and pre-operative NLR suggests low survival in patients with GBM based on data from a large sample. Furthermore, the meta-regression analysis results indicate that underlying data, such as age and extent of surgical resection, lead to a high degree of heterogeneity, providing a theoretical basis for further research. Full article

Motor coordination abilities are related to cognitive abilities and academic achievement in children with neurodevelopmental disorders. However, the similarities and differences of these relationships in children with autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (AD/HD) have not been explored. The purpose of this study was to investigate the relationship between motor coordination abilities, cognitive abilities, and academic achievement in Japanese children with ASD and AD/HD. Participants included 20 children with ASD, 20 children with AD/HD, and 20 typically developing children, matched for age and gender. Their motor coordination abilities were assessed with the Movement Assessment Battery for Children-2 (MABC-2). Furthermore, cognitive ability and academic achievement were assessed with the Kauffman Assessment Battery for Children-II (K-ABCII). Results demonstrated that the MABC-2 Total score significantly correlated with the K-ABCII Simultaneous processing, Planning, Total cognitive ability, Writing and Arithmetic scores in children with ASD. However, in children with AD/HD, there was no significant correlation between MABC-2 and K-ABCII subscale scores. The results of this study indicated that the relationship between motor coordination ability, cognitive ability, and academic achievement differs between ASD and AD/HD. This difference might indicate the non-similarity of neurological characteristics and encourage consideration for an approach that accommodates the features of neurodevelopmental disorders in children. Full article

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that is increasingly becoming a global threat to the health and life of the elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate the symptoms of PD patients but cannot completely cure the disease. Therefore, exploring other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable. Over the last two decades, histone deacetylases, as an important group of epigenetic targets, have attracted much attention in drug discovery. This review focused on the current knowledge about histone deacetylases involved in PD pathophysiology and their inhibitors used in PD studies. Further perspectives related to small molecules that can inhibit or degrade histone deacetylases to treat PD were also discussed. Full article

The pathological basis of migraine is not fully understood. Familial hemiplegic migraines (FHM) are monogenic forms of severe migraine, caused by mutations in genes encoding various neuronal and/or astrocytic ion transporting proteins. The leading hypothesis regarding the mechanism underlying migraine in FHM is that enhanced electrical excitability leads to increased extracellular potassium levels with subsequent cortical spreading depression. In this short commentary we would like to propose an additional mechanism distinct from enhanced electrical excitability per se. Rather, we propose that FHM mutations cause substantially increased energy expenditure of neurons for re-establishing ion gradients and/or for increased synaptic activity, a mechanism we call neuronal fatigue. Such a metabolic mechanism had been proposed earlier for common migraine and has received recent experimental evidence in particular for the case of FHM3. The hypothesis could be tested in future studies of FHM related models that would need to take metabolic parameters into account. Full article

Depressive disorders are common among people with epilepsy (PwE). We here aimed to report an unbiased automatic classification of epilepsy comorbid depressive disorder cases via training a linear support vector machine (SVM) model using the interictal heart rate variability (HRV) data. One hundred and eighty-six subjects participated in this study. Among all participants, we recorded demographic information, epilepsy states and neuropsychiatric features. For each subject, we performed simultaneous electrocardiography and electroencephalography recordings both in wakefulness and non-rapid eye movement (NREM) sleep stage. Using these data, we systematically explored the full parameter space in order to determine the most effective combinations of data to classify the depression status in PwE. PwE with depressive disorders exhibited significant alterations in HRV parameters, including decreased time domain and nonlinear domain values both in wakefulness and NREM sleep stage compared with without depressive disorders and non-epilepsy controls. Interestingly, PwE without depressive disorder showed the same level of HRV values as the non-epilepsy control subjects. The SVM classification model of PwE depression status achieved a higher classification accuracy with the combination of HRV parameters in wakefulness and NREM sleep stage. Furthermore, the receiver operating characteristic (ROC) curve of the SVM classification model showed a satisfying area under the ROC curve (AUC: 0.758). Intriguingly, we found that the HRV measurements during NREM sleep are particularly important for correct classification, suggesting a mechanistic link between the dysregulation of heart rate during sleep and the development of depressive disorders in PwE. Our classification model may provide an objective measurement to assess the depressive status in PwE. Full article

Sitting ability in the early post-stroke phase affects functional balance ability and other prognoses. We investigated whether dynamic sitting exercise with delayed visual feedback in the mediolateral and anteroposterior directions affected postural control in the early post-stroke phase. In this pilot randomized controlled trial, 27 hemiparetic stroke patients were randomized to experimental (n = 13) and control (n = 14) groups. Dynamic sitting exercise (30 times/day, 5 days/week) in the mediolateral and anteroposterior directions, with 500-ms-delayed (experimental group) or real-time (control group) visual feedback on a computer, was added to usual physical therapy. We evaluated the postural assessment scale for stroke (PASS), static and dynamic sitting balance tasks, the five-times sit-to-stand test, trunk impairment scale, functional ambulation category, and functional independence measure–motor items. In intention-to-treat analysis, the experimental group demonstrated a significant intervention effect on the PASS score (p < 0.05). The mean percentage of body weight on the moving side in the lateral sitting task and the number of successes in the five-times sit-to-stand test were significantly higher in the experimental group than those in the control group (p < 0.05). Thus, the proposed exercise improves postural control, dynamic sitting balance, and sit-to-stand ability in early post-stroke patients. Full article

Models on L3/Ln acquisition differ with respect to how they envisage degree (holistic vs. selective transfer of the L1, L2 or both) and/or timing (initial stages vs. development) of how the influence of source languages unfolds. This study uses EEG/ERPs to examine these models, bringing together two types of bilinguals: heritage speakers (HSs) (Italian-German, n = 15) compared to adult L2 learners (L1 German, L2 English, n = 28) learning L3/Ln Latin. Participants were trained on a selected Latin lexicon over two sessions and, afterward, on two grammatical properties: case (similar between German and Latin) and adjective–noun order (similar between Italian and Latin). Neurophysiological findings show an N200/N400 deflection for the HSs in case morphology and a P600 effect for the German L2 group in adjectival position. None of the current L3/Ln models predict the observed results, which questions the appropriateness of this methodology. Nevertheless, the results are illustrative of differences in how HSs and L2 learners approach the very initial stages of additional language learning, the implications of which are discussed. Full article

This paper a novel core-strengthening intervention (CSI) delivered using the AllCore360°, a device that targets trunk muscles through a systematic, high-intensity rotating-plank exercise. Three individuals (age: 61.7 ± 3.2 years; range: 58–64 years) with post-stroke hemiplegia participated in 12-sessions of the CSI. The participants completed up to 142 rotating planks at inclination angles (IAs) that ranged from 40° to 65°, over 12 sessions. The interventional effects on the functional outcomes of trunk performance, balance and mobility were assessed using the Trunk Impairment Scale (TIS), the Berg Balance Scale (BBS), the Timed-Up and Go (TUG) test, the 10-m walk test (10MWT), and the 6-min walk test (6MWT). Postural outcomes were assessed using the center of pressure (CoP) data recorded during quiet standing on a balance platform, and neuromuscular outcomes were assessed using electromyography (EMG) during AllCore360° rotations. All participants completed the CSI (minimum of 120 rotations), demonstrating the feasibility of the CSI in chronic stroke. The CoP data suggested improved lateral control of posture during standing across participants (averaging an over 30% reduction in lateral sway), while the EMG data revealed the ability of the CSI to systematically modulate trunk muscle responses. In summary, the current investigation presents the feasibility of a novel delivery method for core strengthening to maximize rehabilitation outcomes in the chronic phase of stroke. Full article

Plants and animals are among the most behaviorally significant superordinate categories for humans. Visually assigning objects to such high-level classes is challenging because highly distinct items must be grouped together (e.g., chimpanzees and geckos) while more similar items must sometimes be separated (e.g., stick insects and twigs). As both animals and plants typically possess complex multi-limbed shapes, the perceptual organization of shape into parts likely plays a crucial rule in identifying them. Here, we identify a number of distinctive growth characteristics that affect the spatial arrangement and properties of limbs, yielding useful cues for differentiating plants from animals. We developed a novel algorithm based on shape skeletons to create many novel object pairs that differ in their part structure but are otherwise very similar. We found that particular part organizations cause stimuli to look systematically more like plants or animals. We then generated other 110 sequences of shapes morphing from animal- to plant-like appearance by modifying three aspects of part structure: sprouting parts, curvedness of parts, and symmetry of part pairs. We found that all three parameters correlated strongly with human animal/plant judgments. Together our findings suggest that subtle changes in the properties and organization of parts can provide powerful cues in superordinate categorization. Full article

Male predominance is a known feature of autism spectrum disorder (ASD). Although ASD mouse models can be useful for elucidating mechanisms underlying abnormal behaviors relevant to human ASD, suitable models to analyze sex differences in ASD pathogenesis remain insufficient. Herein, we used collapsin response mediator protein 4 (Crmp4)-knockout (KO) mice exhibiting ASD-like phenotypes in a male-predominant manner and analyzed ultrasonic vocalizations (USVs) to detect potential differences between genotypes and sexes during the early postnatal period. We recorded isolation-induced USVs emitted from wild-type (WT) and Crmp4-KO littermates and compared the total number of USVs between genotypes and sexes. We classified USVs into 10 types based on internal pitch changes, lengths, and shapes and compared the number of USVs in each type by genotypes and sex. Male Crmp4-KO mice exhibited a reduction in the total number of USVs. Crmp4-KO decreased the number of USVs in 7 out of 10 USV types, and male KO mice exhibited a greater reduction than females in 3 of the 7 types. This study offers a suitable ASD animal model and tool for assessing sex-based communication deficits during the early postnatal period, both of which would be valuable for elucidating the underlying mechanism. Full article

The role of social odors on human social interactions, including face evaluation, has been widely indicated. However, for nonsocial odors, there has not been a consistent conclusion. Therefore, this study aimed to verify the effect of suprathreshold nonsocial odors on facial attractiveness judgment when the visual input is ambiguous. We designed a 3 (odor valence: neutral, pleasant, and unpleasant) × 7 (continuous levels of morphed fuzziness of attractiveness: 37.5% to 62.5%) within-subject experiment. A total of 30 participants (18 females) completed the whole experiment simultaneously for three consecutive days. The results showed that faces presented with pleasant and neutral odors were judged as significantly more attractive than those with unpleasant odors. The intervention effect of odor valence on facial attractiveness differed by fuzzy attractiveness levels. Results also suggested that male faces were perceived as more attractive than female faces no matter the odor conditions. The results of this study provide evidence to support the cross-modal emotion integration effect of olfaction and vision. Follow-up studies need to be conducted to reveal the underlying mechanism of odor valence on visual fact attractive judgment. Full article

Background: Chronic ankle instability (CAI) is a common peripheral joint injury and there is still no consensus on the mechanisms. It is necessary to investigate electrocortical parameters to provide clinical insight into the functional alterations of brain activity after an ankle sprain, which would greatly affect the implementation of rehabilitation plans. The purpose of this study was to assess cortical activation characteristics during drop-jump landing among soccer athletes with CAI. Methods: A total of 24 participants performed the drop-jump landing task on a force platform while wearing a 64-channel EEG system. The differences of power spectral density (PSD) in theta and alpha (alpha-1 and alpha-2) bands were analyzed between two groups (CAI vs. CON) and between two limbs (injured vs. healthy). Results: CAI participants demonstrated significantly higher theta power at the frontal electrode than that in healthy control individuals (F_(1,22) = 7.726, p = 0.011, η²p = 0.260). No difference in parietal alpha-1 and alpha-2 power was found between groups (alpha-1: F_(1,22) = 0.297, p = 0.591, η²p = 0.013; alpha-2: F_(1,22) = 0.118, p = 0.734, η²p = 0.005). No limb differences were presented for any frequency band in selected cortical areas (alpha-1: F_(1,22) = 0.149, p = 0.703, η²p = 0.007; alpha-2: F_(1,22) = 0.166, p = 0.688, η²p = 0.007; theta: F_(1,22) = 2.256, p = 0.147, η²p = 0.093). Conclusions: Theta power at the frontal cortex was higher in soccer athletes with CAI during drop-jump landing. Differences in cortical activation provided evidence for an altered neural mechanism of postural control among soccer athletes with CAI. Full article

Depression is often associated with co-occurring neurocognitive deficits in executive function (EF), processing speed (PS) and emotion regulation (ER), which impact treatment response. Cognitive training targeting these capacities results in improved cognitive function and mood, demonstrating the relationship between cognition and affect, and shedding light on novel targets for cognitive-focused interventions. Computerized cognitive training (CCT) is one such new intervention, with evidence suggesting it may be effective as an adjunct treatment for depression. Parallel research suggests that mindfulness training improves depression via enhanced ER and augmentation of self-referential processes. CCT and mindfulness training both act on anti-correlated neural networks involved in EF and ER that are often dysregulated in depression—the cognitive control network (CCN) and default-mode network (DMN). After practicing CCT or mindfulness, downregulation of DMN activity and upregulation of CCN activity have been observed, associated with improvements in depression and cognition. As CCT is posited to improve depression via enhanced cognitive function and mindfulness via enhanced ER ability, the combination of both forms of training into mindfulness-enhanced CCT (MCCT) may act to improve depression more rapidly. MCCT is a biologically plausible adjunct intervention and theoretical model with the potential to further elucidate and target the causal mechanisms implicated in depressive symptomatology. As the combination of CCT and mindfulness has not yet been fully explored, this is an intriguing new frontier. The aims of this integrative review article are four-fold: (1) to briefly review the current evidence supporting the efficacy of CCT and mindfulness in improving depression; (2) to discuss the interrelated neural networks involved in depression, CCT and mindfulness; (3) to present a theoretical model demonstrating how MCCT may act to target these neural mechanisms; (4) to propose and discuss future directions for MCCT research for depression. Full article

(1) Background: glioma is the most prevalent primary tumor of the human central nervous system and accompanies extremely poor prognosis in patients. The transient receptor potential (TRP) channels family consists of six different families, which are closely associated with cancer cell proliferation, differentiation, migration, and invasion. TRP family genes play an essential role in the development of tumors. Nevertheless, the function of these genes in gliomas is not fully understood. (2) Methods: we analyze the gene expression data of 28 TRP family genes in glioma patients through bioinformatic analysis. (3) Results: the study showed the aberrations of TRP family genes were correlated to prognosis in glioma. Then, we set enrichment analysis and selected 10 hub genes that may play an important role in glioma. Meanwhile, the expression of 10 hub genes was further established according to different grades, survival time, IDH mutation status, and 1p/19q codeletion status. We found that TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, MCOLN1, MCOLN2, and MCOLN3 were significantly correlated to the prognosis in glioma patients. Furthermore, we illustrated that the expression of hub genes was associated with immune activation and immunoregulators (immunoinhibitors, immunostimulators, and MHC molecules) in glioma. (4) Conclusions: we proved that TRP family genes are promising immunotherapeutic targets and potential clinical biomarkers in patients with glioma. Full article

The topic of the therapeutic use of cannabinoids in Parkinson’s disease (PD) is broadly discussed and frequently comes up in the outpatient clinic. So far, there are only a few randomized clinical trials assessing the effects of cannabinoids in PD. We are able to demonstrate a reduction in non-motor symptom (NMS) burden after the administration of nabilone. As impairment of attention and working memory have been described earlier as possible side effects, we assess cognitive performance using saccadic paradigms measured by an eye tracker. We do not observe a significant difference in any of the saccadic paradigms between PD patients on placebo versus those treated with nabilone. We, therefore, conclude that top-down inhibitory control is not affected by the tetrahydrocannabinol analogue. Nabilone did not significantly worsen cognitive performance and appears to be safe to use in selected PD patients who suffer from disabling NMS. Full article

Prepulse inhibition (PPI) is the reduction in the acoustic startle reflex (ASR) when the startling stimulus (pulse) is preceded by a weaker, non-starting stimulus. This can be enhanced by facilitating selective attention to the prepulse against a noise-masking background. On the other hand, the facilitation of selective attention to a target speech can release the target speech from masking, particularly from speech informational masking. It is not clear whether attentional regulation also affects PPI in this kind of auditory masking. This study used a speech syllable as the prepulse to examine whether the masker type and perceptual spatial attention can affect the PPI or the scalp EEG responses to the prepulse in healthy younger-adult humans, and whether the ERPs evoked by the prepulse can predict the PPI intensity of the ASR. The results showed that the speech masker produced a larger masking effect than the noise masker, and the perceptual spatial separation facilitated selective attention to the prepulse, enhancing both the N1 component of the prepulse syllable and the PPI of the ASR, particularly when the masker was speech. In addition, there was no significant correlation between the PPI and ERPs under any of the conditions, but the perceptual separation-induced PPI enhancement and ERP N1P2 peak-to-peak amplitude enhancement were correlated under the speech-masking condition. Thus, the attention-mediated PPI is useful for differentiating noise energetic masking and speech informational masking, and the perceptual separation-induced release of the prepulse from informational masking is more associated with attention-mediated early cortical unmasking processing than with energetic masking. However, the processes for the PPI of the ASR and the cortical responses to the prepulse are mediated by different neural mechanisms. Full article

Background: Recording the calibration data of a brain–computer interface is a laborious process and is an unpleasant experience for the subjects. Domain adaptation is an effective technology to remedy the shortage of target data by leveraging rich labeled data from the sources. However, most prior methods have needed to extract the features of the EEG signal first, which triggers another challenge in BCI classification, due to small sample sets or a lack of labels for the target. Methods: In this paper, we propose a novel domain adaptation framework, referred to as kernel-based Riemannian manifold domain adaptation (KMDA). KMDA circumvents the tedious feature extraction process by analyzing the covariance matrices of electroencephalogram (EEG) signals. Covariance matrices define a symmetric positive definite space (SPD) that can be described by Riemannian metrics. In KMDA, the covariance matrices are aligned in the Riemannian manifold, and then are mapped to a high dimensional space by a log-Euclidean metric Gaussian kernel, where subspace learning is performed by minimizing the conditional distribution distance between the sources and the target while preserving the target discriminative information. We also present an approach to convert the EEG trials into 2D frames (E-frames) to further lower the dimension of covariance descriptors. Results: Experiments on three EEG datasets demonstrated that KMDA outperforms several state-of-the-art domain adaptation methods in classification accuracy, with an average Kappa of 0.56 for BCI competition IV dataset IIa, 0.75 for BCI competition IV dataset IIIa, and an average accuracy of 81.56% for BCI competition III dataset IVa. Additionally, the overall accuracy was further improved by 5.28% with the E-frames. KMDA showed potential in addressing subject dependence and shortening the calibration time of motor imagery-based brain–computer interfaces. Full article

Neuropathic pain is a challenging complaint for patients and clinicians since there are no effective agents available to get satisfactory outcomes even though the pharmacological agents target reasonable pathophysiological mechanisms. This may indicate that other aspects in these mechanisms should be unveiled to comprehend the pathogenesis of neuropathic pain and thus find more effective treatments. Therefore, in the present study, several mechanisms are chosen to be reconsidered in the pathophysiology of neuropathic pain from a quantum mechanical perspective. The mathematical model of the ions quantum tunneling model is used to provide quantum aspects in the pathophysiology of neuropathic pain. Three major pathophysiological mechanisms are revisited in the context of the quantum tunneling model. These include: (1) the depolarized membrane potential of neurons; (2) the cross-talk or the ephaptic coupling between the neurons; and (3) the spontaneous neuronal activity and the emergence of ectopic action potentials. We will show mathematically that the quantum tunneling model can predict the occurrence of neuronal membrane depolarization attributed to the quantum tunneling current of sodium ions. Moreover, the probability of inducing an ectopic action potential in the axons of neurons will be calculated and will be shown to be significant and influential. These ectopic action potentials are generated due to the formation of quantum synapses which are assumed to be the mechanism behind the ephaptic transmission. Furthermore, the spontaneous neuronal activity and the emergence of ectopic action potentials independently from any adjacent stimulated neurons are predicted to occur according to the quantum tunneling model. All these quantum mechanical aspects contribute to the overall hyperexcitability of the neurons and to the pathogenesis of neuropathic pain. Additionally, providing a new perspective in the pathophysiology of neuropathic pain may improve our understanding of how the neuropathic pain is generated and maintained and may offer new effective agents that can improve the overall clinical outcomes of the patients. Full article

Bow Hunter’s syndrome (BHS), also known as rotational vertebral artery occlusion (VAO), is a rare entity in which vertebral artery is reversibly compressed due to rotation or extension of the head, causing vertebrobasilar insufficiency. Because of VAO, BHS should be considered as a possible life-threatening condition. Diverse aetiologies of BHS may trigger a broad spectrum of non-specific symptoms and may result in frequent misdiagnosis of this disorder in daily clinical practice. Herein, we present a case of BHS caused by previously non-described vascular aetiology. Full article

Background: Acceptance and commitment therapy (ACT), a third-generation cognitive behavioral therapy (CBT), has proved its efficacy amidst various mental disorders. A growing body of studies has shown that ACT can improve obsessive-compulsive disorder (OCD) severity in recent years. To assess the effect of ACT on OCD, we carried out a systematic review and meta-analysis to provide a basis for therapists to use different psychological dimensions of ACT for OCD. Methods: PubMed, the Cochrane Library, EMBASE, EBSCO Host, and literature references were searched until May 2021. Randomized controlled trials (RCTs) and other study designs assessing the effect of ACT among adults suffering from OCD were examined. Results: Fourteen studies, including 413 participants, published between 2010 and 2021 were identified. ACT made statistically significant progress in the Yale–Brown Obsessive–Compulsive Scale (YBOCS) compared with control conditions. Conclusion: After reviewing all the ACT studies, we acknowledge the plausibility of ACT in treating OCD and improving its symptoms for the clinical population. ACT can also be an adjunct therapy for other well-established treatments. It also favors targeting psychological inflexibility. Further well-controlled and high-quality RCTs are required for a better conclusion in further studies. Full article

Depression is considered a neuropsychic disease that has global prevalence and is associated with disability. The pathophysiology of depression is not well understood; however, emerging evidence has indicated that neuroinflammation could contribute to developing depression symptoms. One of the factors that have a role in the development of neuroinflammation is the renin–angiotensin system. Therefore, the goal of the current study is to determine the antidepressant-like effects of Aliskiren, a renin inhibitor, against lipopolysaccharide (LPS)-induced depressive-like behavior in mice, glial cell activation, and the upregulation of proinflammatory cytokines in the prefrontal cortex. For behavioral studies, the open field test (OFT), tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT) were used. Inflammatory markers were assessed using real-time polymerase chain reaction (RT-PCR). LPS administration (0.5 mg/kg, intraperitoneal injection (i.p.)) sufficiently reduced the number of crossings in OFT, whereas Aliskiren pretreatment (10 mg/kg, i.p.) attenuated the LPS effect for two hours after LPS injection. The treatments did not show effects on locomotor activity in OFT 24 h after LPS administration. LPS increased the immobility time in TST and FST or reduced sucrose consumption in SPT after 24 h. Aliskiren reversed the effects induced by LPS in TST, FST, and SPT. CD11 b mRNA, a microglial marker, GFAP mRNA, an astroglial marker, and proinflammatory cytokines genes (TNF-α, IL-1β, and IL-6) were upregulated in the prefrontal cortex in LPS exposed animals. However, Aliskiren reduced LPS-induced inflammatory genes in the prefrontal cortex. Hence, the outcomes conclude that Aliskiren prevents depressive illness associated with neuroinflammation in humans. Full article

Patients with Parkinson’s disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how the cerebral 5-HT system associates to disturbances in cognition and mood in PD patients with DBS-STN turned on and off. We used psychological tests and questionnaires to evaluate cognitive function and the effects on mood from turning DBS-STN off. We applied a novel PET neuroimaging methodology to evaluate the integrity of the cerebral serotonin system. We measured 5-HT1BR binding in 13 DBS-STN-treated PD patients, at baseline and after turning DBS off. Thirteen age-matched volunteers served as controls. The measures for cognition and mood were correlated to the 5-HT1BR availability in temporal limbic cortex. 5-HT1BR binding was proportional to working memory performance and inverse proportional to affective bias for face recognition. When DBS is turned off, patients feel less vigorous; the higher the limbic and temporal 5-HT1BR binding, the more they are affected by DBS being turned off. Our study suggests that cerebral 5-HTR binding is associated with non-motor symptoms, and that preservation of serotonergic functions may be predictive of DBS-STN effects. Full article

Developmental Dyscalculia (DD) signifies a failure in representing quantities, which impairs the performance of basic math operations and schooling achievement during childhood. The lack of specificity in assessment measures and respective cut-offs are the most challenging factors to identify children with DD, particularly in disadvantaged educational contexts. This research is focused on a numerical cognition battery for children, designed to diagnose DD through 12 subtests. The aims of the present study were twofold: to examine the prevalence of DD in a country with generally low educational attainment, by comparing z-scores and percentiles, and to test three neurodevelopmental models of numerical cognition based on performance in this battery. Participants were 304 Brazilian school children aged 7–12 years of both sexes (143 girls), assessed by the Zareki-R. Performances on subtests and the total score increase with age without gender differences. The prevalence of DD was 4.6% using the fifth percentile and increased to 7.4% via z-score (in total 22 out of 304 children were diagnosed with DD). We suggest that a minus 1.5 standard deviation in the total score of the Zareki-R is a useful criterion in the clinical or educational context. Nevertheless, a percentile ≤ 5 seems more suitable for research purposes, especially in developing countries because the socioeconomic environment or/and educational background are strong confounder factors to diagnosis. The four-factor structure, based on von Aster and Shalev’s model of numerical cognition (Number Sense, Number Comprehension, Number Production and Calculation), was the best model, with significant correlations ranging from 0.89 to 0.97 at the 0.001 level. Full article