Brain Sci., Volume 10, Issue 12 (December 2020) – 123 articles

Acute brain injuries pose a great threat to global health, having significant impact on mortality and disability. Patients with acute brain injury may develop distant organ failure, even if no systemic diseases or infection is present. The severity of non-neurologic organs’ dysfunction depends on the extremity of the insult to the brain. In this comprehensive review we sought to describe the organ-related consequences of acute brain injuries. The clinician should always be aware of the interplay between central nervous system and non-neurological organs, that is constantly present. Cerebral injury is not only a brain disease, but also affects the body as whole, and thus requires holistic therapeutical approach. Full article

Autism spectrum disorder (ASD) is conceived as a neurodevelopmental disorder. The scientific literature welcomes studies that reflect the possible singularities that people with ASD may present both in their daily lives and at an educational level. The main objective of this study is to analyze the scientific production on the term autism in Web of Science, focused on the educational field, in order to identify the research trends in this field of study. The intention is to offer researchers who study autism in the educational field some clear research directions. A bibliometric-type methodology was developed using the scientific mapping technique. For this purpose, a performance analysis and a co-word analysis were carried out. Work was conducted with an analysis unit of 5512 documents. The results show that the volume of production has been irregular from the beginning to the present. The collection of documents on the subject began to be relevant, in terms of the volume of production, from 2007, and this has persisted to the present. It is concluded that there are two lines of research. The first is the line focused on mothers of children with ASD and the second is the line of research focused on young people with ASD. In addition, since 2012, new lines of research have been generated, focused on the diagnosis and inclusion of these students in educational centers. Full article

We performed a systematic literature review of neuroimaging, predominantly focusing on magnetic resonance imaging (MRI) findings associated with neurological manifestations of coronavirus disease-2019 (COVID-19). We screened articles from PubMed, Google Scholar and Scopus, looking for reports that would potentially have neuroimaging findings in patients with COVID-19. Data analysis was performed with patient-based data based on the availability of clinical characteristics and outcomes for each individual patient from the studies. Chi square and Wilcoxon rank-sum tests were used to report COVID-19 severity and outcomes based on neurological imaging indicators and pathophysiology. A total of 171 patients with COVID-19 having neurological complications, from 134 studies, were identified in our review. The most common neuroimaging finding was ischemic stroke (62, 36.2%) cases, followed by CNS inflammatory disorder (44, 25.7%), and hemorrhagic stroke (41, 24.0%). Around 51% of all the fatal COVID-19 cases had an ischemic stroke. Among patients with ischemic stroke, the mean age of those who suffered from COVID-19 infection was 57.5 years (SD = 15.4) whereas it was 50.7 years (SD = 15.1) among those without stroke/other diagnosis. Fatality was more common in patients with ischemic stroke compared to those with other diagnosis (40% vs. 22%, p = 0.011). The most frequently published neuroimaging findings in patients with COVID-19 were ischemic stroke, CNS inflammatory disorder, and hemorrhagic disorder. In those studies, ischemic stroke was associated with fatality, and was more frequently seen in older patients. Based on our findings, early usage of MRI in COVID-19 patients may be recommended. Full article

Abnormal saccadic eye movements, such as longer anti-saccade latency and lower pro-saccade accuracy, are common in children with attention-deficit/hyperactivity disorder (ADHD). The present study aimed to investigate the effectiveness of computerized eye-tracking training on improving saccadic eye movements in children with ADHD. Eighteen children with ADHD (mean age = 8.8 years, 10 males) were recruited and assigned to either the experimental (n = 9) or control group (n = 9). The experimental group underwent an accumulated 240 min of eye-tracking training within two weeks, whereas the control group engaged in web game playing for the same amount of time. Saccadic performances were assessed using the anti- and pro-saccade tasks before and after training. Compared to the baseline, only the children who underwent the eye-tracking training showed significant improvements in saccade latency and accuracy in the anti- and pro-saccade tasks, respectively. In contrast, the control group exhibited no significant changes. These preliminary findings support the use of eye-tracking training as a safe non-pharmacological intervention for improving the saccadic eye movements of children with ADHD. Full article

Postoperative choice of the most effective deep brain stimulation (DBS) contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. Previous studies showed that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from calculating stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed for each contact during test stimulation with 2mA. Individual DRTTs were identified from diffusion tensor imaging and contacts were ranked by their stimulation overlap with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT overlap on tremor control. In all investigated DBS leads, the contact with the best clinical effect was the contact with the highest or second-highest DRTT overlap. At the group level, the DRTT-overlap explained 26.7% of the variance in the clinical outcomes (p < 0.001). Our data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future. Full article

Individuals with insomnia present unique patterns of electroencephalographic (EEG) asymmetry between homologous regions of each brain hemisphere, yet few studies have assessed asymmetry within the same hemisphere. Increase in intrahemispheric asymmetry during rapid eye movement (REM) sleep in good sleepers (GS) and disruption of REM sleep in insomnia sufferers (INS) both point out that this activity may be involved in the pathology of insomnia. The objective of the present exploratory study was to evaluate and quantify patterns of fronto-central, fronto-parietal, fronto-occipital, centro-parietal, centro-occipital and parieto-occipital intrahemispheric asymmetry in GS and INS, and to assess their association with sleep-wake misperception, daytime anxiety and depressive symptoms, as well as insomnia severity. This paper provides secondary analysis of standard EEG recorded in 43 INS and 19 GS for three nights in a sleep laboratory. Asymmetry measures were based on EEG power spectral analysis within 0.3–60 Hz computed between pairs of regions at frontal, central, parietal and occipital derivations. Repeated-measures ANOVAs were performed to assess group differences. Exploratory correlations were then performed on asymmetry and sleep-wake misperception, as well as self-reported daytime anxiety and depressive symptoms, and insomnia severity. INS presented increased delta and theta F3/P3 asymmetry during REM sleep compared with GS, positively associated with depressive and insomnia complaints. INS also exhibited decreased centro-occipital (C3/O1, C4/O2) and parieto-occipital (P3–O1, P4/O2) theta asymmetry during REM. These findings suggest that INS present specific patterns of intrahemispheric asymmetry, partially related to their clinical symptoms. Future studies may investigate the extent to which asymmetry is related to sleep-wake misperception or memory impairments. Full article

Aging is associated with structural and functional changes in the hippocampus, and hippocampal dysfunction represents a risk marker of Alzheimer’s disease. Previously, we demonstrated age-related changes in reactive and proactive control in the stop signal task, each quantified by the stop signal reaction time (SSRT) and sequential effect computed as the correlation between the estimated stop signal probability and go trial reaction time. Age was positively correlated with the SSRT, but not with the sequential effect. Here, we explored hippocampal gray matter volume (GMV) and activation to response inhibition and to p(Stop) in healthy adults 18 to 72 years of age. The results showed age-related reduction of right anterior hippocampal activation during stop success vs. go trials, and the hippocampal activities correlated negatively with the SSRT. In contrast, the right posterior hippocampus showed higher age-related responses to p(Stop), but the activities did not correlate with the sequential effect. Further, we observed diminished GMVs of the anterior and posterior hippocampus. However, the GMVs were not related to behavioral performance or regional activities. Together, these findings suggest that hippocampal GMVs and regional activities represent distinct neural markers of cognitive aging, and distinguish the roles of the anterior and posterior hippocampus in age-related changes in cognitive control. Full article

Much of the spotlight for coronavirus disease 2019 (COVID-19) is on the acute symptoms and recovery. However, many recovered patients face persistent physical, cognitive, and psychological symptoms well past the acute phase. Of these symptoms, fatigue is one of the most persistent and debilitating. In this “perspective article,” we define fatigue as the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors due to the COVID-19 disease and propose a model to explain potential factors contributing to post-COVID-19 fatigue. According to our model, fatigue is dependent on conditional and physiological factors. Conditional dependency comprises the task, environment, and physical and mental capacity of individuals, while physiological factors include central, psychological, and peripheral aspects. This model provides a framework for clinicians and researchers. However, future research is needed to validate our proposed model and elucidate all mechanisms of fatigue due to COVID-19. Full article

Since the early 2000s, herbal mixtures containing synthetic cannabinoids (SCs), broadly known as Spice/K2, have been marketed as a legal marijuana surrogate and have become very popular among adolescents. Adolescence is a critical period of development, which is associated with an increased vulnerability to the central effects of drugs. Despite growing concerns about the negative effects of the use of SCs, newly synthetized compounds are increasingly detected in drugs seized by the authorities, posing a serious threat to public health. 5F-MDMB-PICA has been recently detected and classified as a highly potent agonist of CB1 and CB2 cannabinoid receptors. Here, we first investigated the rewarding properties of 5F-MDMB-PICA in C57BL/6 adolescent and adult mice by in vivo brain microdialysis. Data showed that acute administration of a selected dose of 5F-MDMB-PICA (0.01 mg/kg i.p.) stimulates the release of dopamine in the nucleus accumbens shell of adolescent, but not of adult, mice. To further investigate the consequences of repeated exposure to this dose of 5F-MDMB-PICA, a separate group of adolescent mice was treated for 14 consecutive days and evaluated for behavioral abnormalities at adulthood, starting from 7 days after drug discontinuation. Data showed that this group of adult mice displayed an anxiety-like and compulsive-like state as revealed by an altered performance in the marble burying test. Our study suggests an alarming vulnerability of adolescent mice to the effects of 5F-MDMB-PICA. These findings provide a useful basis for understanding and evaluating both early and late detrimental effects that may derive from the use of SCs during adolescence. Full article

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM). A considerable difference was noted in E-field values and distribution at different brain areas. We observed that the volume of activated cortex varied from 3000 to 7000 mm³ between the selected nine clinically relevant coil locations. Coil orientation also changed the induced E-field by a maximum of 10%, and we noted the least optimal values at the standard coil orientation pointing to the nose. The volume of gray matter activated varied by 10% on average between stimulation sites in homologous brain areas in the two hemispheres of the brain. This FEM simulation model clearly demonstrates the importance of TMS parameters for optimal results in clinically relevant brain areas. The results show that TMS parameters cannot be interchangeably used between individuals, hemispheres, and brain areas. The focality of the TMS induced E-field along with its optimal magnitude should be considered as critical TMS parameters that should be individually optimized. Full article

Background and objectives: Stroke is the third most common cause of mortality in developed countries and the primary cause of neurological disability in adults. Recombinant tissue plasminogen activator administered intravenously within 4.5 h from the onset of symptoms constitutes a gold standard in the treatment of acute ischemic stroke. Prompt hospital admission is the prerequisite of effective thrombolysis. Therefore, stroke awareness in the general population is the key factor in timely recognition of the acute stroke victims and determines proper actions. Therefore, the purpose of this study was to determine the awareness of stroke in the general population of the Silesian voivodeship, the most populated region of Poland. We assessed also the “adequate knowledge of stroke”, a combined measure of the optimal level of stroke awareness, as a prerequisite for effective stroke management, and aimed to identify most impacting factor for adequate stoke knowledge, to help shaping education strategies. Materials and Methods: A proprietary anonymous questionnaire consisting of 15 items related to stroke was used in this research. A total of 1134 individuals were surveyed. Additionally to the knowledge of individual aspects of stroke, we assessed “adequate knowledge of stroke”, which was combined measure of risk factors, symptoms, and actions in the case of acute stroke. Results: The accurate definition of stroke was selected by 834 participants (73.5%). The vast majority of them indicated that a stroke is an emergency (92.8%) and medical assistance is required (97.5%). However, 42.4% of respondents did not know any specific symptom of stroke and only 38.6% participants were able to list two or more risk factors, which resulted in only 36.3% of individuals with adequate knowledge of stroke. Education duration, previous occurrence of stroke in relatives or friends, gender and place of residence were identified as independent predictors of adequate knowledge of stroke. Conclusions: 1. Knowledge of stroke in the population of southern Poland is low and may be considered insufficient to address the needs of timely management in the action chain. 2. Previous occurrence of stroke in the relatives or friends is the most impacting factor for adequate knowledge of stroke. Full article

Obsessive-compulsive disorder (OCD) is a debilitating disorder with an approximate lifetime prevalence of 1–3%. Despite advances in leading treatment modalities, including pharmacotherapy and psychotherapy, some cases remain treatment resistant. Non-invasive brain stimulation has been explored in this treatment-resistant population with some promising findings; however, a lack of methodological rigor has reduced the quality of the findings. The current paper presents the protocol for conducting research into the efficacy of transcranial direct current stimulation (tDCS) in the treatment of OCD. A double-blind randomised controlled trial (RCT) will be conducted involving active tDCS vs. sham tDCS on 40 general OCD patients. The intervention consists of 2 mA anodal stimulation over the pre-supplementary motor area (pre-SMA) with the cathode positioned over the orbitofrontal cortex (OFC). Participants will receive 10 sessions of 20 min of either sham- or active-tDCS over 4 weeks. Outcomes will be categorical and dimensional measures of OCD, as well as related secondary clinical measures (depression, anxiety, quality of life), and neurocognitive functions (inhibitory control, cognitive flexibility). Full article

An exponential growing number of individuals are accessing genetic risk information via direct to consumer companies. Alcohol dependence is the third most accessed genetic risk score on a publicly available direct to consumer website. Better understanding of the degree to which individuals are interested in receiving personalized genetic feedback, the factors that relate to interest, and genetic knowledge will be critical to lay the foundation for precision medicine initiatives, especially for substance use and psychiatric outcomes, where less is known. To assess interest in receiving genetic feedback for alcohol use disorder (AUD) and understanding of genetic concepts related to psychiatric conditions, we conducted a survey with participants recruited from a registry that enrolled incoming cohorts of freshmen at an urban public university; 205 participants (76.5% female; 58.9% self-reported as White; M_age = 24.48 years) completed the survey. Results indicated that participants are highly interested in receiving genetic feedback for AUD (79.0%) but there is a lack of understanding of complex genetic concepts in a sizable proportion of the sample (25.4%). Additional research is needed to assess how to address this lack of knowledge before genetic feedback for AUD can be returned in a way that benefits the individual. Full article

Transcranial static magnetic stimulation (tSMS) has been known to reduce human cortical excitability. Here, we investigated whether tSMS would modulate visuo-spatial cognition in healthy humans. Subjects performed a visuo-spatial task requiring judgements about the symmetry of pre-bisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 150 ms on a computer monitor. Task performance was examined before, immediately after, and 10 min after tSMS/sham stimulation of 20 min over the posterior parietal cortex (PPC: P4 from the international 10–20 system) or superior temporal gyrus (STG: C6). Nine out of 16 subjects misjudged pre-bisected lines by consistently underestimating the length of the right-side segment (judging lines to be exactly pre-bisected when the transector was located to the left of the midpoint, or judging the left-side segment to be longer when the transector was located at the midpoint). In these subjects showing a leftward bias, tSMS over the right STG reduced the magnitude of the leftward bias. This did not occur with tSMS over the right PPC or sham stimulation. In the remaining right-biased subjects, no intervention effect was observed with any stimulation. Our findings indicate that application of tSMS over the right STG modulates visuo-spatial cognition in healthy adults. Full article

Navigated transcranial magnetic stimulation (nTMS) is a modality for noninvasive cortical mapping. Specifically, nTMS motor mapping is an objective measure of motor function, offering quantitative diagnostic information regardless of subject cooperation or consciousness. Thus far, it has mostly been restricted to the outpatient setting. This study evaluates the feasibility of nTMS motor mapping in the intensive care unit (ICU) setting and solves the challenges encountered in this special environment. We compared neuronavigation based on computed tomography (CT) and magnetic resonance imaging (MRI). We performed motor mappings in neurocritical patients under varying conditions (e.g., sedation or hemicraniectomy). Furthermore, we identified ways of minimizing electromyography (EMG) noise in the interference-rich ICU environment. Motor mapping was performed in 21 patients (six females, median age: 69 years). In 18 patients, motor evoked potentials (MEPs) were obtained. In three patients, MEPs could not be evoked. No adverse reactions occurred. We found CT to offer a comparable neuronavigation to MRI (CT maximum e-field 52 ± 14 V/m vs. MRI maximum e-field 52 ± 11 V/m; p = 0.6574). We detailed EMG noise reduction methods and found that propofol sedation of up to 80 mcg/kg/h did not inhibit MEPs. Yet, nTMS equipment interfered with exposed pulse oximetry. nTMS motor mapping application and use was illustrated in three clinical cases. In conclusion, we present an approach for the safe and reliable use of nTMS motor mapping in the ICU setting and outline possible benefits. Our findings support further studies regarding the clinical value of nTMS in critical care settings. Full article

Hypoxic-Ischemic (HI) brain injury in the neonate contributes to life-long cognitive impairment. Early diagnosis and therapeutic interventions are critical but limited. We previously reported in a rat model of HI two interventional approaches that improve cognitive and sensory function: administration of Inter-alpha Inhibitor Proteins (IAIPs) and early experience in an eight-arm radial water maze (RWM) task. Here, we expanded these studies to examine the combined effects of IAIPs and multiple weeks of RWM assessment beginning with juvenile or adolescent rats to evaluate optimal age windows for behavioral interventions. Subjects were divided into treatment groups; HI with vehicle, sham surgery with vehicle, and HI with IAIPs, and received either juvenile (P31 initiation) or adolescent (P52 initiation) RWM testing, followed by adult retesting. Error rates on the RWM decreased across weeks for all conditions. Whereas, HI injury impaired global performance as compared to shams. IAIP-treated HI subjects tested as juveniles made fewer errors as compared to their untreated HI counterparts. The juvenile group made significantly fewer errors on moderate demand trials and showed improved retention as compared to the adolescent group during the first week of adult retesting. Together, results support and extend our previous findings that combining behavioral and anti-inflammatory interventions in the presence of HI improves subsequent learning performance. Results further indicate sensitive periods for behavioral interventions to improve cognitive outcomes. Specifically, early life cognitive experience can improve long-term learning performance even in the presence of HI injury. Results from this study provide insight into typical brain development and the impact of developmentally targeted therapeutics and task-specific experience on subsequent cognitive processing. Full article

The present investigation explores the role of bottom-up and top-down factors in the recognition of emotional facial expressions during binocular rivalry. We manipulated spatial frequencies (SF) and emotive features and asked subjects to indicate whether the emotional or the neutral expression was dominant during binocular rivalry. Controlling the bottom-up saliency with a computational model, physically comparable happy and fearful faces were presented dichoptically with neutral faces. The results showed the dominance of emotional faces over neutral ones. In particular, happy faces were reported more frequently as the first dominant percept even in the presence of coarse information (at a low SF level: 2–6 cycle/degree). Following current theories of emotion processing, the results provide further support for the influence of positive compared to negative meaning on binocular rivalry and, for the first time, showed that individuals perceive the affective quality of happiness even in the absence of details in the visual display. Furthermore, our findings represent an advance in knowledge regarding the association between the high- and low-level mechanisms behind binocular rivalry. Full article

Dry needling (DN) is an emerging technique commonly used in neurological and musculoskeletal pain conditions, but there have been no previous studies in patients with multiple sclerosis (pwMS). This trial aims to assess the efficacy of deep DN, compared with sham placebo DN, on gait performance, spasticity level, pain, electromyographic activity, range-of-movement (ROM) and quality of life in pwMS. Forty adults with MS were randomly assigned to one study group. The DN group will undergo 2 sessions (once per week) using DN over the rectus femoris (RF) and gastrocnemius medialis (GM) muscles at the lower extremity with higher spasticity. The placebo group will receive the same protocol using a sham placebo needle (Dong Bang needle). Outcome measures will include gait performance, using the GaitRite^® system, spasticity level with the Modified Ashworth Scale, superficial electromyographic activity of RF and GM, pain (pressure algometer), ROM (goniometer), and quality of life (Musiqol). This study is the first investigating the short-term effect of DN, compared with placebo, in pwMS, and taking into account the possible changes in the electromyographic activity of the lower limb. Therefore, the results may help to understand the suitability of using this technique in the clinical setting for this population. Trial registration: ACTRN12619000880145. Full article

Blood lactate concentrations are often used to assess global tissue perfusion in critically ill patients; however, there are scarce data on lactate concentrations after subarachnoid hemorrhage (SAH). We aimed to assess the prognostic role of serial blood lactate measurements on hospital mortality and neurological outcomes at 3 months after SAH. We reviewed all SAH patients admitted to the intensive care unit from 2007 to 2019 and recorded the highest daily arterial lactate concentration for the first 6 days. Patients with no lactate concentration were excluded. Hyperlactatemia was defined as a blood lactate concentration >2.0 mmol/L. A total of 456 patients were included: 158 (35%) patients died in hospital and 209 (46%) had an unfavorable outcome (UO) at 3 months. The median highest lactate concentration was 2.7 (1.8–3.9) mmol/L. Non-survivors and patients with UO had significantly higher lactate concentrations compared to other patients. Hyperlactatemia increased the chance of dying (OR 4.19 (95% CI 2.38–7.39)) and of having UO in 3 months (OR 4.16 (95% CI 2.52–6.88)) after adjusting for confounding factors. Therefore, initial blood lactate concentrations have prognostic implications in patients with SAH; their role in conjunction with other prognostic indicators should be evaluated in prospective studies. Full article

Balance control systems involve complex systems directing muscle activity to prevent internal and external influences that destabilize posture, especially when body positions change. The computerized dynamic posturography stability score has been established to be the most repeatable posturographic measure using variations of the modified Clinical Test of Sensory Integration in Balance (mCTSIB). However, the mCTSIB is a standard group of tests relying largely on eyes-open and -closed standing positions with the head in a neutral position, associated with probability of missing postural instabilities associated with head positions off the neutral plane. Postural stability scores are compromised with changes in head positions after concussion. The position of the head and neck induced by statically maintained head turns is associated with significantly lower stability scores than the standardized head neutral position of the mCTSIB in Post-Concussion Syndrome (PCS) subjects but not in normal healthy controls. This phenomenon may serve as a diagnostic biomarker to differentiate PCS subjects from normal ones as well as serving as a measurement with which to quantify function or the success or failure of a treatment. Head positions off the neutral plane provide novel biomarkers that identify and differentiate subjects suffering from PCS from healthy normal subjects. Full article

Our objective was to describe the electrophysiological properties of the extracellular action potential (AP) picked up through microelectrode recordings (MERs). Five patients were operated under general anesthesia for centromedian deep brain stimulation (DBS). APs from the same cell were pooled to obtain a mean AP (mAP). The amplitudes and durations for all 2/3 phases were computed from the mAP, together with the maximum (dV_max) and minimum (dV_min) values of the first derivative, as well as the slopes of different phases during repolarization. The mAPs are denominated according to the phase polarity (P/N for positive/negative). We obtained a total of 1109 mAPs, most of the positive (98.47%) and triphasic (93.69%) with a small P/N deflection (V_phase1) before depolarization. The percentage of the different types of mAPs was different for the nuclei addressed. The relationship between dV_max and the depolarizing phase is specific. The descending phase of the first derivative identified different phases during the repolarizing period. We observed a high correlation between V_phase1 and the amplitudes of either depolarization or repolarization phases. Human thalamic nuclei differ in their electrophysiological properties of APs, even under general anesthesia. Capacitive current, which is probably responsible for V_phase1, is very common in thalamic APs. Moreover, subtle differences during repolarization are neuron-specific. Full article

The stereotype content model (SCM; Fiske, Cuddy, Glick and Xu, 2002) identifies four basic categories of stereotyped social groups: high warmth-high competence (HW-HC), high warmth-low competence (HW-LC), low warmth-high competence (LW-HC), and low warmth-low competence (LW-LC). However, many of these groups have not been directly examined in stereotype activation research. The purpose of the present research was to extend stereotype activation research to groups that more fully represent those identified under the SCM. Employing explicit sequential priming task, participants responded to prime-target stimulus pairs that were either congruent or incongruent with stereotypes of social groups from all four SCM quadrants in two studies in the current investigation. Study 1 was to determine the behavioral pattern of explicit stereotype activation among four quadrants (the sample included 60 Chinese undergraduate students, 51%—female). Study 2 further employed event-related brain potentials (ERPs) technique to track the time course and electrophysiological underpinnings of explicit stereotype activation (the sample included 22 right-handed Chinese undergraduate students, 76%—female). In Study 1, participants responded more quickly and accurately on stereotype congruent trials than incongruent trials for all social groups except LW-LC groups. This reverse priming effect on LW-LC social groups in RTs was also replicated in Study 2. ERPs findings further showed that incongruent targets elicited larger N400 amplitudes than congruent targets for all four SCM quadrants. Moreover, congruent targets elicited larger P2 than incongruent targets, but only found for the LW-LC social groups. In addition, congruent targets elicited larger amplitudes of late positive component than incongruent targets for the low warmth (LW-LC and LW-HC) groups. Together, these results highlight the unique processing that LW-LC groups receive throughout the cognitive stream, ultimately manifesting in distinctive behavioral responses. Unconscious activation of egalitarian goals, disgust, and distrust accounts are discussed. Full article

Cognitive inflexibility is a well-documented, yet non-specific corollary of many neurological diseases. Computational modeling of covert cognitive processes supporting cognitive flexibility may provide progress toward nosologically specific aspects of cognitive inflexibility. We review computational models of the Wisconsin Card Sorting Test (WCST), which represents a gold standard for the clinical assessment of cognitive flexibility. A parallel reinforcement-learning (RL) model provides the best conceptualization of individual trial-by-trial WCST responses among all models considered. Clinical applications of the parallel RL model suggest that patients with Parkinson’s disease (PD) and patients with amyotrophic lateral sclerosis (ALS) share a non-specific covert cognitive symptom: bradyphrenia. Impaired stimulus-response learning appears to occur specifically in patients with PD, whereas haphazard responding seems to occur specifically in patients with ALS. Computational modeling hence possesses the potential to reveal nosologically specific profiles of covert cognitive symptoms, which remain undetectable by traditionally applied behavioral methods. The present review exemplifies how computational neuropsychology may advance the assessment of cognitive flexibility. We discuss implications for neuropsychological assessment and directions for future research. Full article

In amyotrophic lateral sclerosis (ALS), magnetic resonance imaging (MRI) allows investigation at the microstructural level, employing techniques able to reveal white matter changes. In the current study, a diffusion tensor imaging (DTI) analysis, with a collection of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) indexes, was performed in ALS patients to correlate geno- and phenotype features with MRI data, to investigate an in-vivo correlation of different neuropathological patterns. All patients who underwent the MR-DTI analysis were retrospectively recruited. MRI scan was collected within three months from diagnosis. FA and ADC values were collected in corpus callosum (CC), corona radiata (CR), cerebral peduncle (CR), cerebellar peduncle (CbP) and corticospinal tract at posterior limb of internal capsule (CST). DTI analysis performed in the whole ALS cohort revealed significant FA reduction and ADC increase in all selected regions, as widespread changes. Moreover, we observed a higher value of FA in rCR in bulbar patients. A positive correlation between ALS Functional Rating Scale-Revised and FA in rCP was evident. In consideration of the non-invasiveness, the reliability and the easy reproducibility of the method, we believe that brain MRI with DTI analyses may represent a valid tool usable as a diagnostic marker in ALS. Full article

In contrast to the large body of research on the effects of stress-induced cortisol on memory consolidation in young people, far less attention has been devoted to understanding the effects of stress-induced testosterone on this memory phase. This study examined the psychobiological (i.e., anxiety, cortisol, and testosterone) response to the Maastricht Acute Stress Test and its impact on free recall and recognition for emotional and neutral material. Thirty-seven healthy young men and women were exposed to a stress (MAST) or control task post-encoding, and 24 h later, they had to recall the material previously learned. Results indicated that the MAST increased anxiety and cortisol levels, but it did not significantly change the testosterone levels. Post-encoding MAST did not affect memory consolidation for emotional and neutral pictures. Interestingly, however, cortisol reactivity was negatively related to free recall for negative low-arousal pictures, whereas testosterone reactivity was positively related to free recall for negative-high arousal and total pictures. This study provides preliminary evidence about a different reactivity of testosterone and cortisol to the MAST as well as on their effects on consolidation. Our results suggest a different pattern of relationships between these steroid hormones and the arousal of the negative images. Full article

Cognitive workload is increasingly recognized as an important determinant of performance in cognitive tests and daily life activities. Cognitive workload is a measure of physical and mental effort allocation to a task, which can be determined through self-report or physiological measures. However, the reliability and validity of these measures have not been established in older adults with a wide range of cognitive ability. The aim of this study was to establish the test–retest reliability of the National Aeronautics and Space Administration Task Load Index (NASA-TLX) and Index of Cognitive Activity (ICA), extracted from pupillary size. The convergent validity of these measures against event-related potentials (ERPs) was also investigated. A total of 38 individuals with scores on the Montreal Cognitive Assessment ranging between 17 and 30 completed a working memory test (n-back) with three levels of difficulty at baseline and at a two-week follow-up. The intraclass correlation coefficients (ICC) values of the NASA-TLX ranged between 0.71 and 0.81, demonstrating good to excellent reliability. The mean ICA scores showed fair to good reliability, with ICCs ranging between 0.56 and 0.73. The mean ICA and NASA-TLX scores showed significant and moderate correlations (Pearson’s r ranging between 0.30 and 0.33) with the third positive peak of the ERP at the midline channels. We conclude that ICA and NASA-TLX are reliable measures of cognitive workload in older adults. Further research is needed in dissecting the subjective and objective constructs of cognitive workload. Full article

Although substantial heritability has been reported and candidate genes have been identified, we are far from understanding the etiopathogenetic pathways underlying developmental dyslexia (DD). Reading-related endophenotypes (EPs) have been established. Until now it was unknown whether they mediated the pathway from gene to reading (dis)ability. Thus, in a sample of 223 siblings from nuclear families with DD and 79 unrelated typical readers, we tested four EPs (i.e., rapid auditory processing, rapid automatized naming, multisensory nonspatial attention and visual motion processing) and 20 markers spanning five DD-candidate genes (i.e., DYX1C1, DCDC2, KIAA0319, ROBO1 and GRIN2B) using a multiple-predictor/multiple-mediator framework. Our results show that rapid auditory and visual motion processing are mediators in the pathway from ROBO1-rs9853895 to reading. Specifically, the T/T genotype group predicts impairments in rapid auditory and visual motion processing which, in turn, predict poorer reading skills. Our results suggest that ROBO1 is related to reading via multisensory temporal processing. These findings support the use of EPs as an effective approach to disentangling the complex pathways between candidate genes and behavior. Full article

Introduction: Recent studies confirm the association of literacy difficulties with higher risk of both childhood behavioral and mental disorders. When co-morbid problems occur, it is likely that each will require separate treatment. The management of major depressive disorder (MDD) for a 9.5 years old girl with specific learning difficulties (SLD), a protracted clinical course, and a family history of affective disorders, was challenging for the interdisciplinary team of our clinic, dealing with learning disabilities. Aim: The research and examination of the first-onset major depressive disorder (MDD) in a child with specific learning disabilities and its impact on school performance. This case report examines the potential contributory factors, but also the recent evidence on the co-morbidity between literacy difficulties and mental illnesses in children. Method: Reporting a two years follow-up of a 9.5 years old child with SLD suffering from childhood depression. Results: A 9.5 years old child with no history of affective disorders, but with a family history of first-degree and second-degree relative suffering from childhood-onset, recurrent, bipolar or psychotic depression. The child was assessed by a child psychiatrist during a period of 2 years, with an average of follow-ups between 1 or 2 weeks. The discussion highlights diagnostic and treatment pitfalls, as well as developmental issues. Practical interventions are suggested. Conclusion: A psychiatrically charged familial environment, including a mother suffering from anxiety disorder and behavioral disorder, contribute significantly to the development of depression in early age. An early medical intervention would be the key for successful treatment. The combination of psychotherapy and antidepressants (mostly selective serotonin reuptake inhibitors (SSRIs)) is the suggested therapy for childhood MDD. Full article

Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication with up to 40–60% long-term morbidity. This study evaluates the distribution and burden of MRI changes as a prognostic indicator of neurodevelopmental (ND) outcomes at 18–24 months in HIE infants who were treated with therapeutic hypothermia (TH). Term or late preterm infants who were treated with TH for HIE were analyzed between June 2012 and March 2016. Brain MRI scans were obtained from 107 TH treated infants. For each infant, diffusion weighted brain image (DWI) sequences from a 3T Siemens scanner were obtained for analysis. Of the 107 infants, 36 of the 107 infants (33.6%) had normal brain MR images, and 71 of the 107 infants (66.4%) had abnormal MRI findings. The number of clinical seizures was significantly higher in the abnormal MRI group (p < 0.001) than in the normal MRI group. At 18–24 months, 76 of the 107 infants (70.0%) showed normal ND stages, and 31 of the 107 infants (29.0%) exhibited abnormal ND stages. A lesion size count >500 was significantly associated with abnormal ND. Similarly, the total lesion count was larger in the abnormal ND group (14.16 vs. 5.29). More lesions in the basal ganglia (BG) and thalamus areas and a trend towards more abnormal MRI scans were significantly associated with abnormal ND at 18–24 months. In addition to clinical seizure, a larger total lesion count and lesion size as well as lesion involvement of the basal ganglia and thalamus were significantly associated with abnormal neurodevelopment at 18–24 months. Full article

Accurate estimation of the functional independence of patients with unresponsive wakefulness syndrome (UWS) is essential to adjust family and clinical expectations and plan long-term necessary resources. Although different studies have described the clinical course of these patients, they have methodological limitations that could restrict generalization of the results. This study investigates the neurobehavioral progress of 100 patients with UWS consecutively admitted to a neurorehabilitation center using systematic weekly assessments based on standardized measures, and the functional independence staging of those patients who emerged from a minimally conscious state (MCS) during the first year post-emergence. Our results showed that one year after emergence, most patients were severely dependent, although some of them showed extreme or moderate severity. Clinically meaningful functional improvement was less likely to occur in cognitively-demanding activities, such as activities of daily living and executive function. Consequently, the use of specific and staging functional independence measures, with domain-specific evaluations, are recommended to detect the functional changes that might be expected in these patients. The information provided by these instruments, together with that obtained from repeated assessments of the preserved consciousness with standardized instruments, could help clinicians to adjust expectations and plan necessary resources for this population. Full article