Brain Sci., Volume 14, Issue 2 (February 2024) – 79 articles

Background: The link between epilepsy and alcohol consumption is complex, with conflicting reports. To enhance our understanding of this link, we conducted a study to determine how inherited seizure susceptibility affects voluntary alcohol consumption and influences alcohol withdrawal seizures in male and female genetically epilepsy-prone rats (GEPR-3s) compared to Sprague Dawley (SD) rats. Methods: In the first experiment, animals were given access to two bottles simultaneously, one containing water and the other 7.5%, 15%, or 30% (v/v) alcohol three times a week for each dose after acclimation to drinking water. In a second experiment, animals were tested for acoustically evoked alcohol seizures 24 h after the last session of voluntary alcohol consumption. Results: Analysis revealed that GEPR-3s (males and females) had lower alcohol intake and preference than SD rats, particularly at lower alcohol concentrations. However, female GEPR-3s consumed more alcohol and had a higher alcohol preference than males. Furthermore, withdrawal from voluntary alcohol consumption facilitated the onset and duration of seizures in GEPR-3s. Conclusions: Our study suggests that genetic seizure susceptibility in GEPR-3s is negatively associated with alcohol consumption. However, withdrawal from low to moderate amounts of alcohol intake can promote epileptogenesis in the epileptic GEPR-3s. Full article

Background: Vestibular migraine (VM) is common migraine that occurs in patients with dizziness. Vestibular rehabilitation for managing VM generally remains unclear. Recently, it has been reported that transcranial direct current stimulation (tDCS) has positive effects in alleviating dizziness. This study investigated the effects of tDCS on dizziness and cortical activation in a patient with VM. Methods: We recruited a male patient aged 31 years with no dizziness. The patient watched a video to induce dizziness using a virtual reality device. The study applied the intervention using tDCS for 4 weeks and measured 4 assessments: functional near-infrared spectroscopy (fNIRS), quantitative electroencephalography (qEEG), dizziness handicap inventory, and visual vertigo analog scale. Results: We showed the activation in the middle temporal gyrus and inferior temporal gyrus (ITG) of the left hemisphere and in the superior temporal gyrus and ITG of the right hemisphere in the pre-intervention. After the intervention, the activation of these areas decreased. In the results of qEEG, excessive activation of C3, P3, and T5 in the left hemisphere and C4 in the right hemisphere before intervention disappeared after the intervention. Conclusions: This study indicated that tDCS-based intervention could be considered a viable approach to treating patients with vestibular dysfunction and dizziness caused by VM. Full article

Part I reviews persistent challenges obstructing progress in understanding complex fatigue’s biology. Difficulties quantifying subjective symptoms, mapping multi-factorial mechanisms, accounting for individual variation, enabling invasive sensing, overcoming research/funding insularity, and more are discussed. Part II explores how emerging artificial intelligence and machine and deep learning techniques can help address limitations through pattern recognition of complex physiological signatures as more objective biomarkers, predictive modeling to capture individual differences, consolidation of disjointed findings via data mining, and simulation to explore interventions. Conversational agents like Claude and ChatGPT also have potential to accelerate human fatigue research, but they currently lack capacities for robust autonomous contributions. Envisioned is an innovation timeline where synergistic application of enhanced neuroimaging, biosensors, closed-loop systems, and other advances combined with AI analytics could catalyze transformative progress in elucidating fatigue neural circuitry and treating associated conditions over the coming decades. Full article

Pediatric brain tumors are the major cause of pediatric cancer mortality. They comprise a diverse group of tumors with different developmental origins, genetic profiles, therapeutic options, and outcomes. Despite many technological advancements, the treatment of pediatric brain cancers has remained a challenge. Treatment options for pediatric brain cancers have been ineffective due to non-specificity, inability to cross the blood–brain barrier, and causing off-target side effects. In recent years, nanotechnological advancements in the medical field have proven to be effective in curing challenging cancers like brain tumors. Moreover, nanoparticles have emerged successfully, particularly in carrying larger payloads, as well as their stability, safety, and efficacy monitoring. In the present review, we will emphasize pediatric brain cancers, barriers to treating these cancers, and novel treatment options. Full article

The results examining the direction (bottom-to-top vs. top-to-bottom) of the mental vertical timeline are not conclusive. The visuospatial processing of temporal stimuli along vertical space could influence this time representation. This study aimed to investigate whether and how the visuospatial processing stage modulated the vertical timeline in an online temporal categorization task. In three studies, Italian university students (N = 150) responded more quickly to words expressing the past with a down arrow key, and more quickly to words expressing the future with an up arrow key, irrespective of whether the words were located in the top, middle, or bottom space (Experiment 1), or were presented downward (from top to bottom; Experiment 2A) or upward (from bottom to top Experiment 2B). These results suggest that the representation of time was not influenced by the visuospatial processing. The daily experience with verticality (e.g., to reach the attic, the lift goes up) could explain the bottom-to-top direction of the mental timeline. Full article

We report changes following auditory rehabilitation for interaural asymmetry (ARIA) training in behavioral test performance and cortical activation in children identified with dichotic listening deficits. In a one group pretest–posttest design, measures of dichotic listening, speech perception in noise, and frequency pattern identification were assessed before and 3 to 4.5 months after completing an auditory training protocol designed to improve binaural processing of verbal material. Functional MRI scans were also acquired before and after treatment while participants passively listened in silence or to diotic or dichotic digits. Significant improvements occurred after ARIA training for dichotic listening and speech-in-noise tests. Post-ARIA, fMRI activation increased during diotic tasks in anterior cingulate and medial prefrontal regions and during dichotic tasks, decreased in the left precentral gyrus, right-hemisphere pars triangularis, and right dorsolateral and ventral prefrontal cortices, regions known to be engaged in phonologic processing and working memory. The results suggest that children with dichotic deficits may benefit from the ARIA program because of reorganization of cortical capacity required for listening and a reduced need for higher-order, top-down processing skills when listening to dichotic presentations. Full article

(1) Background: Jugular foramen tumors are complex lesions due to their relationship with critical neurovascular structures within the skull base. It is necessary to have a deep knowledge of the anatomy of the jugular foramen and its surroundings to understand each type of tumor growth pattern and how it is related to the surrounding neurovascular structures. This scope aims to provide a guide with the primary surgical approaches to the jugular foramen and familiarize the neurosurgeons with the anatomy of the region. (2) Methods and (3) Results: A comprehensive description of the surgical approaches to jugular foramen tumors is summarized and representative cases for each tumor type is showcased. (4) Conclusions: Each case should be carefully assessed to find the most suitable approach for the patient, allowing the surgeon to remove the tumor with minimal neurovascular damage. The combined transmastoid retro- and infralabyrinthine transjugular transcondylar transtubercular high cervical approach can be performed in a stepwise fashion for the resection of complex jugular foramen tumors. Full article

Background and Objectives: Impulse control disorders (ICDs) are characterized by potentially harmful actions resulting from disturbances in the self-control of emotions and behavior. ICDs include disorders such as gambling, hypersexuality, binge eating, and compulsive buying. ICDs are known non-motor symptoms in Parkinson’s disease (PD) and are associated primarily with the use of dopaminergic treatment (DRT) and especially dopamine agonists (DA). However, in atypical parkinsonism (APS), such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA), there are only single case reports of ICDs without attempts to determine the risk factors for their occurrence. Moreover, numerous reports in the literature indicate increased impulsivity in PSP. Our study aimed to determine the frequency of individual ICDs in APS compared to PD and identify potential factors for developing ICDs in APS. Materials and Methods: Our prospective study included 185 patients with PD and 35 with APS (27 patients with PSP and 9 with MSA) hospitalized between 2020 and 2023 at the Neurological Department of University Central Hospital in Katowice. Each patient was examined using the Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s Disease (QUIP) to assess ICDs. Additionally, other scales were used to assess the advancement of the disease, the severity of depression, and cognitive impairment. Information on age, gender, age of onset, disease duration, and treatment used were collected from medical records and patient interviews. Results: ICDs were detected in 23.39% of patients with PD (including binge eating in 11.54%, compulsive buying in 10.44%, hypersexuality in 8.79%, and pathological gambling in 4.40%), in one patient with MSA (hypersexuality and pathological gambling), and in 18.52% of patients with PSP (binge eating in 3.70%, compulsive buying in 7.41%, and hypersexuality in 11.11%). We found no differences in the frequency of ICDs between individual diseases (p = 0.4696). We confirmed that the use of higher doses of DA and L-dopa in patients with PD, as well as a longer disease duration and the presence of motor complications, were associated with a higher incidence of ICDs. However, we did not find any treatment effect on the incidence of ICDs in APS. Conclusions: ICDs are common and occur with a similar frequency in PD and APS. Well-described risk factors for ICDs in PD, such as the use of DRT or longer disease duration, are not fully reflected in the risk factors for ICDs in APS. This applies especially to PSP, which, unlike PD and MSA, is a tauopathy in which, in addition to the use of DRT, other mechanisms related to the disease, such as disorders in neuronal loops and neurotransmitter deficits, may influence the development of ICDs. Further prospective multicenter studies recruiting larger groups of patients are needed to fully determine the risk factors and mechanisms of ICD development in APS. Full article

Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents “long-lasting COVID” as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway. Full article

Recently, a recurrent de novo dominant mutation in UBTF (c.628G>A, p.Glu210Lys; UBTF E210K) was identified as the cause of a neurological disorder which has been named UBTF Neuroregression Syndrome (UNS), or Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). To date, only 17 cases have been reported worldwide. The molecular etiology is a pathogenic variant, E210K, within the HMG-box 2 of Upstream Binding Transcription Factor (UBTF). UBTF, a nucleolar protein, plays an important role in ribosomal RNA (rRNA) synthesis, nucleolar integrity, and cell survival. This variant causes unstable preinitiation complexes to form, resulting in altered rDNA chromatin structures, rRNA dysregulation, DNA damage, and ultimately, neurodegeneration. Defining clinical characteristics of the disorder include but are not limited to developmental regression beginning at approximately three years of age, progressive motor dysfunction, declining cognition, ambulatory loss, and behavioral problems. Histological and neuroimaging abnormalities include cortical atrophy, white matter deficits, and enlarged ventricles. Herein, we present a detailed overview of all published cases as well as the functional roles of UBTF to better understand the pathophysiology. Bringing undiagnosed cases to the attention of clinicians and researchers by making them aware of the clinical features will improve research and support the development of therapeutic interventions. Full article

Individuals with Parkinson’s disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R² = 0.32, p = 0.0006) and APA amplitude (R² = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology. Full article

The hippocampus is known to play an important role in memory by processing spatiotemporal information of episodic experiences. By recording synchronized multiple-unit firing events (ripple firings with 300 Hz–10 kHz) of hippocampal CA1 neurons in freely moving rats, we previously found an episode-dependent diversity in the waveform of ripple firings. In the present study, we hypothesized that changes in the diversity would depend on the type of episode experienced. If this hypothesis holds, we can identify the ripple waveforms associated with each episode. Thus, we first attempted to classify the ripple firings measured from rats into five categories: those experiencing any of the four episodes and those before experiencing any of the four episodes. In this paper, we construct a convolutional neural network (CNN) to classify the current stocks of ripple firings into these five categories and demonstrate that the CNN can successfully classify the ripple firings. We subsequently indicate partial ripple waveforms that the CNN focuses on for classification by applying gradient-weighted class activation mapping (Grad-CAM) to the CNN. The method of t-distributed stochastic neighbor embedding (t-SNE) maps ripple waveforms into a two-dimensional feature space. Analyzing the distribution of partial waveforms extracted by Grad-CAM in a t-SNE feature space suggests that the partial waveforms may be representative of each category. Full article

Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast. Full article

Complex motor skills can be acquired while observing a model without physical practice. Transcranial direct-current stimulation (tDCS) applied to the primary motor cortex (M1) also facilitates motor learning. However, the effectiveness of observational practice for bimanual coordination skills is debated. We compared the behavioural and brain causal connectivity patterns following three interventions: primary motor cortex stimulation (M1-tDCS), action-observation (AO) and a combined group (AO+M1-tDCS) when acquiring a bimanual, two-ball juggling skill. Thirty healthy young adults with no juggling experience were randomly assigned to either video observation of a skilled juggler, anodal M1-tDCS or video observation combined with M1-tDCS. Thirty trials of juggling were performed and scored after the intervention. Resting-state EEG data were collected before and after the intervention. Information flow rate was applied to EEG source data to measure causal connectivity. The two observation groups were more accurate than the tDCS alone group. In the AO condition, there was strong information exchange from (L) parietal to (R) parietal regions, strong bidirectional information exchange between (R) parietal and (R) occipital regions and an extensive network of activity that was (L) lateralized. The M1-tDCS condition was characterized by bilateral long-range connections with the strongest information exchange from the (R) occipital region to the (R) temporal and (L) occipital regions. AO+M1-tDCS induced strong bidirectional information exchange in occipital and temporal regions in both hemispheres. Uniquely, it was the only condition that was characterized by information exchange between the (R) frontal and central regions. This study provides new results about the distinct network dynamics of stimulating the brain for skill acquisition, providing insights for motor rehabilitation. Full article

This study looked at the possible effect of the COVID-19 pandemic on individuals who came to our clinic seeking relief from tinnitus. The performance of the subjects during the COVID-19 pandemic was compared with similar individuals who came to our clinic before the pandemic began. The study involved 50 adults with chronic tinnitus, made up of a study group (24 subjects tested during the COVID-19 pandemic of 2020–2021) and a control group before the pandemic began (26 subjects tested from 2013 to 2017). None of the 24 reported having contracted COVID-19. Data collection involved the Tinnitus Handicap Inventory (THI) questionnaire, audiological tests, and quantitative electroencephalography (qEEG). In terms of THI scores, there were no statistically significant differences between the two groups. However, with regard to qEEG, some changes were observed, with significant decreases in alpha and beta band activity in the study group compared to the control group, particularly over the auditory cortex. We conclude that COVID-19 did not have a discernible impact on the general well-being of individuals with tinnitus. However, it did appear to alter brain activity, specifically in the alpha and beta bands over the auditory cortex, and these reults warrant further investigation. Full article

Drug-resistant epilepsy (DRE) is often treated with surgery or neuromodulation. Specifically, responsive neurostimulation (RNS) is a widely used therapy that is programmed to detect abnormal brain activity and intervene with tailored stimulation. Despite the success of RNS, some patients require further interventions. However, having an RNS device in situ is a hindrance to the performance of neuroimaging techniques. Magnetoencephalography (MEG), a non-invasive neurophysiologic and functional imaging technique, aids epilepsy assessment and surgery planning. MEG performed post-RNS is complicated by signal distortions. This study proposes an independent component analysis (ICA)-based approach to enhance MEG signal quality, facilitating improved assessment for epilepsy patients with implanted RNS devices. Three epilepsy patients, two with RNS implants and one without, underwent MEG scans. Preprocessing included temporal signal space separation (tSSS) and an automated ICA-based approach with MNE-Python. Power spectral density (PSD) and signal-to-noise ratio (SNR) were analyzed, and MEG dipole analysis was conducted using single equivalent current dipole (SECD) modeling. The ICA-based noise removal preprocessing method substantially improved the signal-to-noise ratio (SNR) for MEG data from epilepsy patients with implanted RNS devices. Qualitative assessment confirmed enhanced signal readability and improved MEG dipole analysis. ICA-based processing markedly enhanced MEG data quality in RNS patients, emphasizing its clinical relevance. Full article

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is an expensive and intensive treatment and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. This is an exploratory study to assess a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompting required over time to acquire eye contact and joint attention, as well as a positive correlation between the time of exposure to the intervention and the acquisition of abilities. This kind of parent training using video modeling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low-resource settings. Full article

Normal aging is commonly accompanied by a decline in cognitive abilities, including memory, yet some individuals maintain these abilities as they get older. We hypothesize that semantic clustering, as an effective strategy for improving performance on episodic recall tasks, may contribute to the maintenance of youthful memory in older adults. We investigated the dynamics of spontaneous production and utilization of the semantic clustering strategy in two independent samples of older adults who completed a list learning paradigm (N₁ = 40 and N₂ = 29, respectively). Specifically, we predicted and observed that older adults who spontaneously used a semantic clustering strategy throughout the encoding process learned more words by the culmination of the encoding trials (Sample 1, R²= 0.53, p < 0.001; Sample 2, R²= 0.51, p < 0.001), and that those who utilized this strategy during retrieval recalled more words, when compared to older adults who did not produce or utilize a semantic clustering strategy during both a short (Sample 1, R² = 0.81, p < 0.001; Sample 2, R² = 0.70, p < 0.001) and long delay retrieval (Sample 1, R² = 0.83, p < 0.001; Sample 2, R² = 0.77, p < 0.001). We further predicted and observed that older adults who maintained a youthful level of delayed free recall (i.e., “Superagers”) produced (Sample 1, F(1, 38) = 17.81, p < 0.0001; Sample 2, F(1, 27) = 14.45, p < 0.0001) and utilized (Sample 1, F(1, 39) = 25.84, p < 0.0001; Sample 2, F(1, 27) = 12.97, p < 0.01) more semantic clustering than did older individuals with normal memory for their age. These results suggest one cognitive mechanism through which Superagers maintain youthful memory function and raise the possibility that older adults may be able to train themselves to use strategies to promote better memory. Full article

Recent research suggests a possible association between midlife obesity and an increased risk of dementia in later life. However, the underlying mechanisms remain unclear. Little is known about the relationship between body mass index (BMI) and hippocampal subfield atrophy. In this study, we aimed to explore the associations between BMI and hippocampal subfield volumes and cognitive function in non-demented Chinese older adults. Hippocampal volumes were assessed using structural magnetic resonance imaging. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 66 participants were included in the final analysis, with 35 females and 31 males. We observed a significant correlation between BMI and the hippocampal fissure volume in older females. In addition, there was a negative association between BMI and the RBANS total scale score, the coding score, and the story recall score, whereas no significant correlations were observed in older males. In conclusion, our findings revealed sex-specific associations between BMI and hippocampal subfield volumes and cognitive performance, providing valuable insights into the development of effective interventions for the early prevention of cognitive decline. Full article

Crowding occurs when an easily identified isolated stimulus is surrounded by stimuli with similar properties, making it very difficult to identify. Crowding is suggested as a mechanism that creates a bottleneck in object recognition and awareness. Recently, we showed that brief presentation times at the fovea resulted in a significant crowding effect on target identification, impaired the target’s color awareness, and resulted in a slower reaction time. However, when tagging the target with a red letter, the crowding effect is abolished. Crowding is widely considered a grouping; hence, it is pre-attentive. An event-related potential (ERP) study that investigated the spatial–temporal properties of crowding suggested the involvement of higher-level visual processing. Here, we investigated whether ERP’s components may be affected by crowding and tagging, and whether the temporal advantage of ERP can be utilized to gain further information about the crowding mechanism. The participants reported target identification using our standard foveal crowing paradigm. It is assumed that crowding occurs due to a suppressive effect; thus, it can be probed by changes in perceptual (N1, ~160 ms) and attentive (P3 ~300–400 ms) components. We found a suppression effect (less negative ERP magnitude) in N1 under foveal crowding, which was recovered under tagging conditions. ERP’s amplitude components (N1 and P3) and the behavioral proportion correct are highly correlated. These findings suggest that crowding is an early grouping mechanism that may be combined with later processing involving the segmentation mechanism. Full article

The inability to wait for a target before initiating an action (i.e., waiting impulsivity) is one of the main features of addictive behaviors. Current interventions for addiction, such as transcranial Direct Current Stimulation (tDCS), have been suggested to improve this inability. Nonetheless, the effects of tDCS on waiting impulsivity and underlying electrophysiological (EEG) markers are still not clear. Therefore, this study aimed to evaluate the effects of neuromodulation over the right inferior frontal gyrus (rIFG) on the behavior and EEG markers of reward anticipation (i.e., cue and target-P3 and underlying delta/theta power) during a premature responding task. For that, forty healthy subjects participated in two experimental sessions, where they received active and sham tDCS over the rIFG combined with EEG recording during the task. To evaluate transfer effects, participants also performed two control tasks to assess delay discounting and motor inhibition. The active tDCS decreased the cue-P3 and target-P3 amplitudes, as well as delta power during target-P3. While no tDCS effects were found for motor inhibition, active tDCS increased the discounting of future rewards when compared to sham. These findings suggest a tDCS-induced modulation of the P3 component and underlying oscillatory activity during waiting impulsivity and the discounting of future rewards. Full article

The function of cerebral small vessels can be assessed using cerebral vasomotor reactivity (VMR). Our aim in this retrospective cross-sectional study was to investigate a correlation between carotid artery stenosis measured through ultrasonographic morphological and hemodynamic parameters and cerebral VMR. A total of 285 patients (125 males; mean age 54) were included. The breath-holding index (BHI) was used to evaluate cerebral VMR. Ultrasonographic carotid artery parameters were collected: the presence and characteristics of carotid plaques, the degree of carotid diameter stenosis, intima–media thickness (IMT), peak systolic velocity (PSV), and end diastolic velocity (EDV). Additionally, hemodynamic parameters of the middle cerebral artery (MCA) were evaluated, including the mean flow velocity (MFV) and pulsatility index (PI). The following was collected from patients’ medical histories: age, gender, and vascular risk factors. A negative correlation between the BHI and age (r = −0.242, p < 0.01), BHI and the presence of carotid plaques, BHI and IMT (r = −0.203, p < 0.01), and BHI and the PI of MCA on both sides (r = −0.268, p < 0.01) was found. We found a positive correlation between the BHI in the left MCA and EDV in the left internal carotid artery (r = 0.121, p < 0.05). This study shows the correlation between cerebral VMR and carotid stenosis but indicates a higher influence of morphological parameters on VMR values. Full article

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and intelligence), the social complexity hypothesis (thesis of the evolution of communication), and empirical research from comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language, it is argued that social cognition and language are two significantly interconnected capacities of the human species. Here, evidence in support of this view reviews (1) recent developmental studies on language learning in infants and young children, pointing to the important crucial benefits associated with social stimulation for youngsters, including the quality and quantity of incoming linguistic information, dyadic infant/child-to-parent non-verbal and verbal interactions, and other important social cues integral for facilitating language learning and social bonding; (2) studies of the adult human brain, suggesting a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting that the function of these neural areas may connect social cognition with language and social bonding; (3) developmental deficits in language and social cognition, including autism spectrum disorder (ASD), illustrating a unique developmental profile, further linking language, social cognition, and social bonding; and (4) neural biomarkers that may help to identify early developmental disorders of language and social cognition. In effect, the social brain and social complexity hypotheses may jointly help to describe how neurotypical children and adults acquire language, why autistic children and adults exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other organisms with significant computational capacities cannot learn language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain. Full article

Repetitive transcranial magnetic stimulation (rTMS) is used to enhance motor training (MT) performance. The use of rTMS is limited under certain conditions, such as after a stroke with severe damage to the corticospinal tract. This raises the question as to whether repetitive trans-spinal magnetic stimulation (rSMS) can also be used to improve MT. A direct comparison of the effect size between rTMS and rSMS on the same MT is still lacking. Before conducting the study in patients, we determined the effect sizes of different stimulation approaches combined with the same motor training in healthy subjects. Two experiments (E1 and E2) with 96 subjects investigated the effect size of combining magnetic stimulation with the same MT. In E1, high-frequency rTMS, rSMS, and spinal sham stimulation (sham-spinal) were applied once in combination with MT, while one group only received the same MT (without stimulation). In E2, rTMS, rSMS, and sham-spinal were applied in combination with MT over several days. In all subjects, motor tests and motor-evoked potentials were evaluated before and after the intervention period. rTMS had the greatest effect on MT, followed by rSMS and then sham-spinal. Daily stimulation resulted in additional training gains. This study suggests that rSMS increases excitability and also enhances MT performance. This current study provides a basis for further research to discover whether patients who cannot be treated effectively with rTMS would benefit from rSMS. Full article

Previous studies have shown that contextual information may aid in guessing the intention underlying others’ actions in conditions of perceptual ambiguity. Here, we aimed to evaluate the temporal deployment of contextual influence on action prediction with increasing availability of kinematic information during the observation of ongoing actions. We used action videos depicting an actor grasping an object placed on a container to perform individual or interpersonal actions featuring different kinematic profiles. Crucially, the container could be of different colors. First, in a familiarization phase, the probability of co-occurrence between each action kinematics and color cues was implicitly manipulated to 80% and 20%, thus generating contextual priors. Then, in a testing phase, participants were asked to predict action outcome when the same action videos were occluded at five different timeframes of the entire movement, ranging from when the actor was still to when the grasp of the object was fully accomplished. In this phase, all possible action–contextual cues’ associations were equally presented. The results showed that for all occlusion intervals, action prediction was more facilitated when action kinematics deployed in high- than low-probability contextual scenarios. Importantly, contextual priors shaped action prediction even in the latest occlusion intervals, where the kinematic cues clearly unveiled an action outcome that was previously associated with low-probability scenarios. These residual contextual effects were stronger in individuals with higher subclinical autistic traits. Our findings highlight the relative contribution of kinematic and contextual information to action understanding and provide evidence in favor of their continuous integration during action observation. Full article

Negative symptoms and cognitive deficits play a major role in psychosis and significantly influence the functional outcomes of patients, particularly those with a first episode of psychosis (FEP). However, limited research has explored the predictive capacity of cognitive deficits during FEP for subsequent negative symptomatology. Drawing from the Athens FEP research study, we conducted a retrospective longitudinal study in 80 individuals with FEP. All patients were drug naive at admission. Cognitive tests were administered at 1-month and 1-year post-admission, while negative symptomatology was assessed at the same time points using PANSS by trained raters. We considered confounding factors such as age, gender, duration of untreated psychosis (DUP), treatment received, premorbid social adjustment, and premorbid IQ. Univariate regression analysis identified cognitive domains that correlated with negative symptomatology. These, along with the confounders, were incorporated into a multiple regression, with the 1-year PANSS negative scale serving as the dependent variable. Employing the backward elimination technique, we found a statistically significant inverse relationship between the categories completed in the Wisconsin card sorting test (WCST) and the 1-year PANNS negative scale (p = 0.01), beyond the associations with DUP and the 1-month PANSS negative scale. Our results suggest that cognitive flexibility, a key component of executive functions, predicts negative symptom severity one year after FEP. Full article

The amygdala is a core region in the limbic system that is highly sensitive to stress. Astrocytes are key players in stress disorders such as anxiety and depression. However, the effects of stress on the morphology and function of amygdala astrocytes and its potential mechanisms remain largely unknown. Hence, we performed in vivo and in vitro experiments using a restraint stress (RS) rat model and stress-induced astrocyte culture, respectively. Our data show that norepinephrine (NE) content increased, cytotoxic edema occurred, and aquaporin-4 (AQP4) expression was up-regulated in the basolateral amygdala (BLA) obtained from RS rats. Additionally, the p38 mitogen-activated protein kinase (MAPK) pathway was also observed to be significantly activated in the BLA of rats subjected to RS. The administration of NE to in vitro astrocytes increased the AQP4 level and induced cell edema. Furthermore, p38 MAPK signaling was activated. The NE inhibitor alpha-methyl-p-tyrosine (AMPT) alleviated cytotoxic edema in astrocytes, inhibited AQP4 expression, and inactivated the p38 MAPK pathway in RS rats. Meanwhile, in the in vitro experiment, the p38 MAPK signaling inhibitor SB203580 reversed NE-induced cytotoxic edema and down-regulated the expression of AQP4 in astrocytes. Briefly, NE-induced activation of the p38 MAPK pathway mediated cytotoxic edema in BLA astrocytes from RS rats. Thus, our data provide novel evidence that NE-induced p38 MAPK pathway activation may be one of the mechanisms leading to cytotoxic edema in BLA under stress conditions, which also could enable the development of an effective therapeutic strategy against cytotoxic edema in BLA under stress and provide new ideas for the treatment of neuropsychiatric diseases. Full article

Motion speed and direction are two fundamental cues for the mammalian visual system. Neurons in various places of the neocortex show tuning properties in term of firing frequency to both speed and direction. The present study applied a 32-channel electroencephalograph (EEG) system to 13 human subjects while they were observing a single object moving with different speeds in various directions from the center of view to the periphery on a computer monitor. Depending on the experimental condition, the subjects were either required to fix their gaze at the center of the monitor while the object was moving or to track the movement with their gaze; eye-tracking glasses were used to ensure that they followed instructions. In each trial, motion speed and direction varied randomly and independently, forming two competing visual features. EEG signal classification was performed for each cue separately (e.g., 11 speed values or 11 directions), regardless of variations in the other cue. Under the eye-fixed condition, multiple subjects showed distinct preferences to motion direction over speed; however, two outliers showed superb sensitivity to speed. Under the eye-tracking condition, in which the EEG signals presumably contained ocular movement signals, all subjects showed predominantly better classification for motion direction. There was a trend that speed and direction were encoded by different electrode sites. Since EEG is a noninvasive and portable approach suitable for brain–computer interfaces (BCIs), this study provides insights on fundamental knowledge of the visual system as well as BCI applications based on visual stimulation. Full article

Vagus nerve stimulation (VNS) is a long-term adjunctive treatment option in patients with difficult-to-treat depression (DTD). A total of n = 20 patients (mean age 52.6 years) were included in the multicenter, prospective, observational, naturalistic RESTORE-LIFE study and were treated with adjunctive VNS as an add-on to treatment as usual. Exploratory and secondary outcome parameters from a single center were investigated for this present analysis. The overall mean drug load slightly decreased from 4.5 at baseline to 4.4 at 12 months (Z = −0.534, p = 0.594). The drug load was lower in previous electroconvulsive therapy (ECT) responders than in non-responders. There was a reduction in the mean number of hospitalizations per month after VNS implantation (Z = 1.975, p = 0.048) and a significant decrease in the mean Montgomery Åsberg Depression Rating Scale (MADRS) score from 27.3 at baseline to 15.3 at 12 months (T = 4.230, degree of freedom (df) = 19, p = 0.001). A history of ECT response at baseline was associated with greater improvement in the MADRS score after 12 months of VNS (F = 8.171, p = 0.013). The number of neuromodulatory maintenance treatments decreased during the follow-up period. In summary, there was an alleviation in the burden of illness among DTD patients treated with VNS. Full article