Brain Sciences

The known theories discussing the essence of consciousness have been recently updated. This prompts an attempt to integrate these explanations concerning several distinct components of the consciousness phenomenon such as the ego, and qualia perceptions. Therefore, it is useful to consider the latest publications on the ‘Orch OR’ and ‘cemi’ theories, which assume that quantum processing occurs in microtubules and that the brain’s endogenous electromagnetic field is important. The authors combine these explanations with their own theory describing the neural circuits realizing imagery. They try to present such an interdisciplinary, integrated theoretical model in a manner intuitively understandable to people with a typical medical education. In order to do this, they even refer to intuitively understandable metaphors. The authors maintain that an effective comprehension of consciousness is important for health care professionals because its disorders are frequent medical symptoms in emergencies, during general anesthesia and in the course of cognitive disorders in elderly people. The authors emphasize the current possibilities to verify these theses regarding the essence of consciousness thanks to the development of functional brain imaging methods—magnetoencephalography, transcranial magnetic stimulation—as well as clinical studies on the modification of perceptions and feelings by such techniques as mindfulness and the use of certain psychoactive substances, especially among people with self-awareness and identity disorders. Full article

The search for and development of new neuroprotective (or cerebroprotective) drugs, as well as suitable methods for their preclinical efficacy evaluation, are priorities for current biomedical research. Alpha-2 adrenergic agonists, such as mafedine and dexmedetomidine, are a highly appealing group of drugs capable of reducing neurological deficits which result from brain trauma and vascular events in both experimental animals and human patients. Thus, our aim was to assess the effects of mafedine and dexmedetomidine on the brain’s electrical activity in a controlled cortical-impact model of traumatic brain injury (TBI) in rats. The functional status of the animals was assessed by electrocorticography (ECoG), using ECoG electrodes which were chronically implanted in different cortical regions. The administration of intraperitoneal mafedine sodium at 2.5 mg∙kg⁻¹ at 1 h after TBI induction, and daily for the following 6 days, restored interhemispheric connectivity in remote brain regions and intrahemispheric connections within the unaffected hemisphere at post-TBI day 7. Animals that had received mafedine sodium also demonstrated an improvement in cortical responses to photic and somatosensory stimulation. Dexmedetomidine at 25 μg∙kg⁻¹ did not affect the brain’s electrical activity in brain-injured rats. Our results confirm the previously described neuroprotective effects of mafedine sodium and suggest that ECoG registration and analysis are a viable method evaluating drug efficacy in experimental animal models of TBI. Full article

According to the Unaccusative Hypothesis, intransitive verbs are divided into unaccusative and unergative ones based on the distinction of their syntactic properties, which has been proved by previous theoretical and empirical evidence. However, debate has been raised regarding whether intransitive verbs in Mandarin Chinese can be split into unaccusative and unergative ones syntactically. To analyze this theoretical controversy, the present study employed functional magnetic resonance imaging to compare the neural processing of deep unaccusative, unergative sentences, and passive sentences (derived structures undergoing a syntactic movement) in Mandarin Chinese. The results revealed no significant difference in the neural processing of deep unaccusative and unergative sentences, and the comparisons between passive sentences and the other sentence types revealed activation in the left superior temporal gyrus (LSTG) and the left middle frontal gyrus (LMFG). These findings indicate that the syntactic processing of unaccusative and unergative verbs in Mandarin Chinese is highly similar but different from that of passive verbs, which suggests that deep unaccusative and unergative sentences in Mandarin Chinese are both base-generated structures and that there is no syntactic distinction between unaccusative and unergative verbs in Mandarin Chinese. Full article

Musical training has been shown to have a positive influence on a variety of skills, including auditory-based tasks and nonmusical cognitive and executive functioning tasks; however, because previous investigations have yielded mixed results regarding the relationship between musical training and these skills, the purpose of this study was to examine and compare the auditory processing skills of children who receive focused, daily musical training with those with more limited, generalized musical training. Sixteen typically developing children (second–fourth grade) from two different schools receiving different music curricula were assessed on measures of pitch discrimination, temporal sequencing, and prosodic awareness. The results indicated significantly better scores in pitch discrimination abilities for the children receiving daily, focused musical training (School 1) compared to students attending music class only once per week, utilizing a more generalized elementary school music curriculum (School 2). The findings suggest that more in-depth and frequent musical training may be associated with better pitch discrimination abilities in children. This finding is important given that the ability to discriminate pitch has been linked to improved phonological processing skills, an important skill for developing spoken language and literacy. Future investigations are needed to determine whether the null findings for temporal sequencing and prosodic awareness can be replicated or may be different for various grades and tasks for measuring these abilities. Full article

Objective: Hereditary transthyretin amyloidosis (ATTRv) represents a diagnostic challenge considering the great variability of clinical presentation and multiorgan involvement. In the present study, we report the prevalence of kidney involvement and kidney function over time in a cohort of ATTRv patients with different transthyretin gene mutations. Patients and Methods: For this study, we systematically collected data from all patients with a diagnosis of ATTRv followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. Kidney involvement was defined as presence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² obtained with CKD-EPI equation, abnormal urinary protein excretion (UPE) (>150 mg/24 h) and/or albuminuria >30 mg/24 h (or mg/g creatinine). The analysis included data from 46 patients with 122 measurements of serum creatinine. Results: Among the 46 patients included in the analysis, kidney involvement was present in 37%, with 15% showing reduced eGFR and 22% abnormal UPE (63% of patients with available UPE data). No single predictor was associated with either eGFR values or its slope over time. Conclusions: Kidney involvement is quite common in patients with ATTRv regardless of the underlying genetic variant. In particular, abnormal UPE appears to be a common feature of the disease. Full article

Response inhibition, whether reactive or proactive, is mostly investigated in a narrow cognitive framework. We argue that it be viewed within a broader frame than the action being inhibited, i.e., in the context of emotion and motivation of the individual at large. This is particularly important in the clinical domain, where the motivational strength of an action can be driven by threat avoidance or reward seeking. The cognitive response inhibition literature has focused on stopping reactively with responses in anticipation of clearly delineated external signals, or proactively in limited contexts, largely independent of clinical phenomena. Moreover, the focus has often been on stopping efficiency and its correlates rather than on inhibition failures. Currently, the cognitive and clinical perspectives are incommensurable. A broader context may explain the apparent paradox where individuals with disorders characterised by maladaptive action control have difficulty inhibiting their actions only in specific circumstances. Using Obsessive Compulsive Disorder as a case study, clinical theorising has focused largely on compulsions as failures of inhibition in relation to specific internal or external triggers. We propose that the concept of action tendencies may constitute a useful common denominator bridging research into motor, emotional, motivational, and contextual aspects of action control failure. The success of action control may depend on the interaction between the strength of action tendencies, the ability to withhold urges, and contextual factors. Full article

Some eating patterns, such as restrained eating and uncontrolled eating, are risk factors for eating disorders. However, it is not yet clear whether they are associated with neurocognitive differences. In the current study, we analyzed whether eating patterns can be used to classify participants into meaningful clusters, and we examined whether there are neurocognitive differences between the clusters. Adolescents (n = 108; 12 to 17 years old) and adults (n = 175, 18 to 40 years old) completed the Three Factor Eating Questionnaire, which was used to classify participants according to their eating profile using k means clustering. Participants also completed personality questionnaires and a neuropsychological examination. A subsample of participants underwent a brain MRI acquisition. In both samples, we obtained a cluster characterized by high uncontrolled eating patterns, a cluster with high scores in restrictive eating, and a cluster with low scores in problematic eating behaviors. The clusters were equivalent with regards to personality and performance in executive functions. In adolescents, the cluster with high restrictive eating showed lower cortical thickness in the inferior frontal gyrus compared to the other two clusters. We hypothesize that this difference in cortical thickness represents an adaptive neural mechanism that facilitates inhibition processes. Full article

Heterogeneity among Alzheimer’s disease (AD) patients confounds clinical trial patient selection and therapeutic efficacy evaluation. This work defines separable AD clinical sub-populations using unsupervised machine learning. Clustering (t-SNE followed by k-means) of patient features and association rule mining (ARM) was performed on the ADNIMERGE dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Patient sociodemographics, brain imaging, biomarkers, cognitive tests, and medication usage were included for analysis. Four AD clinical sub-populations were identified using between-cluster mean fold changes [cognitive performance, brain volume]: cluster-1 represented least severe disease [+17.3, +13.3]; cluster-0 [−4.6, +3.8] and cluster-3 [+10.8, −4.9] represented mid-severity sub-populations; cluster-2 represented most severe disease [−18.4, −8.4]. ARM assessed frequently occurring pharmacologic substances within the 4 sub-populations. No drug class was associated with the least severe AD (cluster-1), likely due to lesser antecedent disease. Anti-hyperlipidemia drugs associated with cluster-0 (mid-severity, higher volume). Interestingly, antioxidants vitamin C and E associated with cluster-3 (mid-severity, higher cognition). Anti-depressants like Zoloft associated with most severe disease (cluster-2). Vitamin D is protective for AD, but ARM identified significant underutilization across all AD sub-populations. Identification and feature characterization of four distinct AD sub-population “clusters” using standard clinical features enhances future clinical trial selection criteria and cross-study comparative analysis. Full article

Introduction: High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic heterogenicity and immune evasion pathways. The present literature review strives to provide an updated overview of the novel gene therapies for HGGs treatment, highlighting evidence from clinical trials, molecular mechanisms, and future perspectives. Methods: An extensive literature review was conducted through PubMed/Medline and ClinicalTrials.gov databases, using the keywords “high-grade glioma,” “glioblastoma,” and “malignant brain tumor”, combined with “gene therapy,” “oncolytic viruses,” “suicide gene therapies,” “tumor suppressor genes,” “immunomodulatory genes,” and “gene target therapies”. Only articles in English and published in the last 15 years were chosen, further screened based on best relevance. Data were analyzed and described according to the PRISMA guidelines. Results: Viruses were the most vehicles employed for their feasibility and transduction efficiency. Apart from liposomes, other viral vehicles remain largely still experimental. Oncolytic viruses and suicide gene therapies proved great results in phase I, II preclinical, and clinical trials. Tumor suppressor, immunomodulatory, and target genes were widely tested, showing encouraging results especially for recurrent HGGs. Conclusions: Oncolytic virotherapy and suicide genes strategies are valuable second-line treatment options for relapsing HGGs. Immunomodulatory approaches, tumor suppressor, and target genes therapies may implement and upgrade standard chemoradiotherapy. Future research aims to improve safety profile and prolonging therapeutic effectiveness. Further clinical trials are needed to assess the efficacy of gene-based therapies. Full article

Even if for many years hemispheric asymmetries have been considered as a uniquely human feature, an increasing number of studies have described hemispheric asymmetries for various behavioral functions in several nonhuman species. An aspect of animal lateralization that has attracted particular attention has concerned the hemispheric asymmetries for emotions, but human and animal studies on this subject have been developed as independent lines of investigation, without attempts for their integration. In this perspective article, after an illustration of factors that have hampered the integration between human and animal studies on emotional lateralization, I will pass to analyze components and stages of the processing of emotions to distinguish those which point to a continuum between humans and many animal species, from those which suggest a similarity only between humans and great apes. The right lateralization of sympathetic functions (involved in brain and bodily activities necessary in emergency situations) seems consistent across many animal species, whereas asymmetries in emotional communication and in structures involved in emotional experience, similar to those observed in humans, have been documented only in primates. Full article

Non-Suicidal Self-Injury (NSSI) is the self-inflicted destruction of body tissues without suicidal intent with a prevalence of 1.5% to 6.7% in the youth population. At present, it is not clear which emotional and behavioral components are specifically associated with it. Therefore, we studied NSSI in a clinical sample of youth using the Ottawa Self-injury Inventory and the Barratt Impulsiveness Scale 11. The Mann–Whitney test was used to compare the numerical responses provided to the tests. We found 54 patients with NSSI, with a mean age of 17 years. Scores were analyzed in the total sample and in four subgroups. In the total sample, Internal Emotion and External Emotion Regulation, Craving, Non-Planning and Total Impulsivity were significantly associated with NSSI. There were statistically significant differences in Craving between patients with multiple NSSI episodes, suicide attempts and multiple injury modes and patients of other corresponding subgroups, in Internal Emotion Regulation, Sensation Seeking and Motor Impulsivity between NSSI patients with suicide attempts and no suicide attempts, and in Cognitive Impulsivity between NSSI patients with multiple injury modes and one injury mode. It is necessary to carefully evaluate the components underlying NSSI in order to activate personalized treatment options. Full article

Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 (Galectin-8) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target. Full article

Mental Fatigue (MF) has been associated with reduced physical performance but the mechanisms underlying this result are unclear. A reduction in excitability of the corticomotor system is a way mental fatigue could negatively impact physical performance. Carbohydrate (CHO) mouth rinse (MR) has been shown to increase corticomotor excitability. PURPOSE: The purpose of this study was to determine if CHO MR impacts corticomotor excitability after MF. METHODS: Fifteen subjects (nine females, six males; age = 23 ± 1 years; height = 171 ± 2 cm; body mass = 69 ± 3 kg; BMI = 23.8 ± 0.7) completed two sessions under different MR conditions (Placebo (PLAC), 6.4% glucose (CHO)) separated by at least 48 h and applied in a double-blinded randomized fashion. Motor-evoked potential (MEP) of the left first dorsal interosseous (FDI) was determined by transcranial magnetic stimulation (TMS) before and after MF. Perceived MF was recorded before and after the MF task using a 100 mm visual analog scale (VAS). RESULTS: MF was greater following PLAC (+30.4 ± 4.0 mm) than CHO (+19.4 ± 3.9 mm) (p = 0.005). MEP was reduced more following PLAC (−16.6 ± 4.4%) than CHO (−3.7 ± 4.7%) (p < 0.001). CONCLUSIONS: CHO MR was successful at attenuating the reduction in corticomotor excitability after MF. Carbohydrate mouth rinse may be a valuable tool at combating the negative consequences of mental fatigue. Full article

Background: Morphological alterations in intracranial pressure (ICP) pulse waveform (ICPW) secondary to intracranial hypertension (ICP >20 mmHg) and a reduction in intracranial compliance (ICC) are well known indicators of neurological severity. The exclusive exploration of modifications in ICPW after either the loss of skull integrity or surgical procedures for intracranial hypertension resolution is not a common approach studied. The present study aimed to assess the morphological alterations in ICPW among neurocritical care patients with skull defects and decompressive craniectomy (DC) by comparing the variations in ICPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of acute brain injury were included. A continuous record of 10 min-length for the beat-by-beat analysis of ICPW was performed, with ICP elevation produced by means of ultrasound-guided manual internal jugular vein compression at the end of the record. ICPW features (peak amplitude ratio (P2/P1), time interval to pulse peak (TTP) and pulse amplitude) were counterweighed between baseline and compression periods. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. A total of 21 (36%) presented no skull defects, 21 (36%) belonged to group 2, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±15.11 for intact, 15.33 for group 2 and ±20.81 mmHg for group 3, with ICP-induced elevation also similar between groups (p = 0.56). Significant elevation was observed for the P2/P1 ratio for groups 1 and 2, whereas a reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, but a reduction of 0.03 for group 3, p = 0.01), and no significant results were obtained for TTP and pulse amplitudes. Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPW indicated DC to be protective for further influences of ICP elevations over the brain. The analysis of ICPW seems to be an alternative to real-time ICC assessment. Full article

We investigated the effects of prior stress on rats’ responses to 50-kHz (appetitive) and 22-kHz (aversive) ultrasonic playback. Rats were treated with 0, 1, 6 or 10 shocks (1 s, 1.0 mA each) and were exposed to playbacks the following day. Previous findings were confirmed: (i) rats moved faster during 50-kHz playback and slowed down after 22-kHz playback; (ii) they all approached the speaker, which was more pronounced during and following 50-kHz playback than 22-kHz playback; (iii) 50-kHz playback caused heart rate (HR) increase; 22-kHz playback caused HR decrease; (iv) the rats vocalized more often during and following 50-kHz playback than 22-kHz playback. The previous shock affected the rats such that singly-shocked rats showed lower HR throughout the experiment and a smaller HR response to 50-kHz playback compared to controls and other shocked groups. Interestingly, all pre-shocked rats showed higher locomotor activity during 50-kHz playback and a more significant decrease in activity following 22-kHz playback; they vocalized more often, their ultrasonic vocalizations (USV) were longer and at a higher frequency than those of the control animals. These last two observations could point to hypervigilance, a symptom of post-traumatic stress disorder (PTSD) in human patients. Increased vocalization may be a valuable measure of hypervigilance used for PTSD modeling. Full article

Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1^G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1^G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity. Full article

Impaired sense of smell occurs in a fraction of patients with COVID-19 infection, but its effect on cerebral activity is unknown. Thus, this case report investigated the effect of COVID-19 infection on frontotemporal cortex activity during olfactory stimuli. In this preliminary study, patients who recovered from COVID-19 infection (n = 6) and healthy controls who never contracted COVID-19 (n = 6) were recruited. Relative changes in frontotemporal cortex oxy-hemoglobin during olfactory stimuli was acquired using functional near-infrared spectroscopy (fNIRS). The area under curve (AUC) of oxy-hemoglobin for the time interval 5 s before and 15 s after olfactory stimuli was derived. In addition, olfactory function was assessed using the Sniffin’ Sticks 12-identification test (SIT-12). Patients had lower SIT-12 scores than healthy controls (p = 0.026), but there were no differences in oxy-hemoglobin AUC between healthy controls and patients (p > 0.05). This suggests that past COVID-19 infection may not affect frontotemporal cortex function, and these preliminary results need to be verified in larger samples. Full article

Psychomotor development in the first year of life is possible due to activity and then integration of primitive (neonatal) reflexes. The presence of active primitive reflexes (APRs) in preschool and school-aged children indicates neuromotor immaturity. Studies show dependencies between the preserved activity of primary reflexes and developmental problems such as learning difficulties (problems with reading, writing, reduced mathematics skills, and dyslexia), difficulties with coordination, and attention deficit. The primary purpose of this study is to present the activity of three tonic reflexes in a sample of 112 Polish children aged 4–6 in relation to their motor skills. The children were examined for the presence of the asymmetric tonic neck reflex (ATNR), symmetric tonic neck reflex (STNR), and tonic labyrinthine reflex (TLR). Motor performance was examined with the MOT 4–6. Statistical analysis shows an inverse correlation between the score in the test of reflexes and motor efficiency (MOT 4–6) at p < 0.05 (−0.33). Children with increased reflex activity presented a lower level of motor efficiency. The multiple regression model showed that with the older age of the child and the decrease in the level of reflex activity, the motor skills of children improve. Thus, there is a need for early screening of primitive reflexes in children. Properly selected exercises and therapeutic activities aimed at integrating APRs in children with developmental difficulties can improve their motor skills, perceptual abilities, and emotional behavior. Full article

KAT6A syndrome is a Mendelian Disorder of the Epigenetic Machinery characterized by intellectual disability and profound expressive language impairment. This study aimed to further characterize behavior and sleep in this syndrome. 26 participants between the ages of 3 and 35 years with KAT6A syndrome were assessed via parental informant using the Adaptive Behavior Assessment System version 3 (ABAS-3), Achenbach Child or Adult Behavior Checklist (CBCL/ABCL), and a Modified Simonds and Parraga Sleep Questionnaire (MSPSQ). The ABAS reports conceptual, social, and practical domains of adaptive function as well as a general composite score for adaptive function. The CBCL/ABCL is an inventory that measures internalizing, externalizing, and DSM-oriented problem domains. The MSPSQ is a mix of qualitative and quantitative sleep information that includes behavioral and medical sleep problems. Mean values for all domains of the ABAS-3 were in the extremely low range. Additionally, sleep was very dysfunctional in this cohort. Sixty percent of respondents reported feeling there was a sleep problem, 64% take medication for sleep, and 68% have sought treatment or advice for sleep. Only 12% of these participants have sleep apnea suggesting that sleep problems in this disorder are unrelated to sleep-disordered breathing. Interestingly, there were extremely low rates of all types of behaviors reported among participants on the CBCL/ABCL. No significant differences were seen based on genotype grouping in adaptive function, sleep, or behavior. This study further delineates the phenotype of the KAT6A syndrome and emphasizes the need for supports for adaptive functioning as well as detailed attention to the behavioral aspects of sleep in this condition. Full article