Brain Sciences

Autism spectrum disorder (ASD) and cerebral palsy (CP) are some of the most common neurodevelopmental diseases. They have multifactorial origin, which means that each case may manifest differently from the others. In patients with ASD, symptoms associated with deficits in social communication and characteristic, repetitive types of behaviors or interests are predominant, while in patients with CP, motor disability is diagnosed with accompanying cognitive impairment of various degrees. In order to minimize their adverse effects, it is necessary to promptly diagnose and incorporate appropriate management, which can significantly improve patient quality of life. One of the therapeutic possibilities is stem cell therapy, already known from other branches of medicine, with high hopes for safe and effective treatment of these diseases. Undoubtedly, in the future we will have to face the challenges that will arise due to the still existing gaps in knowledge and the heterogeneity of this group of patients. The purpose of this systematic review is to summarize briefly the latest achievements and advances in stem cell therapy for ASD and CP. Full article

Introduction: Postural abnormalities are common in patients with Parkinson’s disease (PD) and lead to gait abnormalities. Relationships between changes in the trunk posture of PD patients and gait profile score (GPS) and gait spatiotemporal parameters are poorly investigated. The aim of the current study was to investigate the relationships between trunk posture, GPS, and gait spatiotemporal parameters, in patients with PD. Materials and Methods: Twenty-three people with PD and nineteen age-matched healthy people participated in this study. A 3D gait kinematical analysis was applied to all participants using the Plug-In Gait Full Body^TM tool. Trunk and limb kinematics patterns and gait spatio-temporal parameters of patients with PD and the control group were compared. Additionally, correlations between trunk kinematics patterns, gait spatio-temporal parameters, and GPS of the PD group were tested. Results: Cadence, opposite foot off, step time, single support, double support, foot off, gait speed, trunk kinematics, and GPS showed significant differences between the two groups (p ≤ 0.05). Posture of the trunk during gait was not related to the spatio-temporal parameters and gait profile score in the PD group. The trunk flexor pattern influenced GPS domains, mainly of the ankle and the knee. Discussion and Conclusions: Flexed posture of the trunk in patients with PD seems to influence both ankle and knee movement patterns during the gait. The GPS analysis provided direct and simplified kinematic information for the PD group. These results may have implications for understanding the importance of considering the positioning of the trunk during gait. Full article

A 23-year-old woman was presented to the Emergency Unit with intracranial hypertension syndrome and blindness in her left eye which had started recently. A cranial native computed tomography scan and a magnetic resonance imaging (MRI) with contrast examinations revealed a giant intracranial cystic lesion, extending into the left frontal lobe, which was compressing the optic chiasm and eroding the internal plate of the left frontal bone. Surgical craniotomy was performed for evacuation and decompression, but during the craniotomy the cyst ruptured. After assessing the degree of erosion of the internal bone plate, we concluded that the primary origin of the cyst was intraosseous. With the dura mater being intact, abundant lavage with H₂O₂ was applied and the bone flap was replaced after rigorous bone scraping. Imaging control at six and twelve months identified no recurrence of the cyst. In the literature, hydatid cysts located in the skull bone are very rare and most of them rupture intraoperatively. Given their extremely low incidence in developed countries, any neurosurgeons’ experience with such pathology is limited and in some cases surgery cannot be delayed. In the case of intracerebral hydatid cysts, a neurosurgeon usually has only one shot at surgery, so simple and quick-to-access therapeutic guidelines must be developed in order to inform the choice of surgical technique. We conclude that the most successful surgical approach could be double concentric craniotomy. This surgical technique is used in intracerebral tumors, which also have an important bone invasion. Full article

Plasmalogens are alkenyl-acyl glycerophospholipids and decreased in post-mortem Alzheimer’s disease (AD) brains. The aim of this study is to investigate the time-dependent changes of plasmalogens in the hippocampus of an AD model mouse (J20). Plasmalogen levels at 3, 6, 9, 12 and 15 months were analyzed by liquid-chromatography-targeted-multiplexed-selected-reaction-monitoring-tandem-mass-spectrometry (LC-SRM/MS). Reactive oxygen species (ROS) levels were evaluated using dichlorofluorescein diacetate (DCF-DA). Plasmalogen synthesizing enzyme glycerone-phosphate O-acyltransferase (GNPAT) and late endosome marker Rab7 levels were quantified by Western blotting. GNPAT localization, changes of neuronal and glial cell numbers were evaluated by immunostaining. Compared to wild-type mice (WT), total plasmalogen-ethanolamine, but not plasmalogen-choline levels, were increased at 9 months and subsequently decreased at 15 months in J20 mice. A principal component analysis of plasmalogen-ethanolamine species could separate WT and J20 mice both at 9 and 15 months. Both GNPAT and Rab7 protein were increased in J20 mice at 9 months, whereas GNPAT was decreased at 15 months. ROS levels were increased in J20 mice except for 9 months. Our results suggest that increased plasmalogen-ethanolamine could counteract ROS levels and contribute to the phagocytosis process in J20 mice at 9 months. Such results might indicate a transient protective response of plasmalogen-ethanolamine in AD conditions. Full article

Previous studies have shown that Ginkgo biloba extract (GbE) reduces food intake and body mass gain and regulates proteins related to lipid metabolism in obese rats. In ovariectomized rats, GbE restored the hippocampal and hypothalamic serotonergic system activity, favoring the spontaneous feeding decrement. Considering the promising hypophagic effect of GbE, this study aimed to investigate the effect of a single acute dose on hypothalamic pathways that regulate feeding behavior in male rats. Four-month-old Wistar male rats received either a single acute oral GbE dose (500 mg/kg) or vehicle. Food intake and body mass were measured after 1, 4, 12, and 24 h. Rats were euthanized, and hypothalami were removed for mRNA quantification of anorexigenic (POMC/CART) and orexigenic (AgRP/NPY) neuropeptides, leptin/serotonin receptors (5HT1A, 5HT1B, 5HT2C), and serotonin transporters. We also investigated POMC, 5-HT1B, and 5-HT2C protein levels. A single acute GbE dose induced the hypothalamic POMC, CART, and 5-HT2C gene expression but failed to modify orexigenic effectors. No alterations in food intake, body mass, and hypothalamic protein levels were observed. In summary, the present findings demonstrate the rapid stimulation of pivotal hypothalamic anorexigenic pathways in response to a single GbE administration, reinforcing the GbE hypophagic activity. However, more studies are necessary to evaluate its potential as an appetite modulator. Full article

In 1940, van Wagenen and Herren first proposed the corpus callosotomy (CC) as a surgical procedure for epilepsy. CC has been mainly used to treat drop attacks, which are classified as generalized tonic or atonic seizures. Epileptic spasms (ESs) are a type of epileptic seizure characterized as brief muscle contractions with ictal polyphasic slow waves on an electroencephalogram and a main feature of West syndrome. Resection surgeries, including frontal/posterior disconnections and hemispherotomy, have been established for the treatment of medically intractable ES in patients with unilaterally localized epileptogenic regions. However, CC has also been adopted for ES treatment, with studies involving CC to treat ES having increased since 2010. In those studies, patients without lesions observed on magnetic resonance imaging or equally bilateral lesions predominated, in contrast to studies on resection surgeries. Here, we present a review of relevant literature concerning CC and relevant adaptations. We discuss history and adaptations of CC, and patient selection for epilepsy surgeries due to medically intractable ES, and compared resection surgeries with CC. We propose a surgical selection flow involving resection surgery or CC as first-line treatment for patients with ES who have been assessed as suitable candidates for surgery. Full article

Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logopenic progressive aphasia (LPA) and 9 progressive non-fluent aphasia (PNFA) cases and contrasted their performance with 19 Alzheimer’s disease (AD) cases, 26 behavioural variant frontotemporal dementia (bvFTD) cases and 31 healthy older controls. Relative to the controls, the majority of patient groups displayed significant overall social communication difficulties, with common and unique profiles of impairment evident on the LCQ subscales. Correlation analyses revealed a differential impact of social communication disturbances on functional outcomes in patient and carer well-being, most pronounced for SD and bvFTD. Finally, voxel-based morphometry analyses based on a structural brain MRI pointed to the degradation of a distributed brain network in mediating social communication dysfunction in dementia. Our findings suggest that social communication difficulties are an important feature of PPA, with significant implications for patient function and carer well-being. The origins of these changes are likely to be multifactorial, reflecting the breakdown of fronto-thalamic brain circuits specialised in the integration of complex information. Full article

While outcomes of embodied awareness practices in terms of improved posture and flexibility, movement efficiency, and well-being are often reported, systematic investigations of such training effects and of the actual nature, extent, and neurofunctional correlates of learning mechanisms thought to lie at the core of such practices are very limited. The present study focused on the Feldenkrais method (FM), one of the most established embodied awareness practices, and aimed at investigating the neurofunctional outcomes of the somatic learning process at the core of the method by testing the modulations induced by a standardized FM protocol on the complexity of practicers’ body structural map and on the activity of their sensorimotor network during different movement-related tasks (i.e., gestures observation, execution, and imagery). Twenty-five participants were randomly divided into an experimental group—which completed a 28-session FM protocol based on guided group practice—and a control group, and underwent pre-/post-training psychometric and electrophysiological assessment. Data analysis highlighted, at the end of the FM protocol, a significant increase of EEG markers of cortical activation (task-related mu desynchronization) in precentral regions during action observation and in central regions during action execution and imagery. Also, posterior regions of the sensorimotor network showed systematic activation during all the action-related tasks. Full article

The Emotional Enhancement of Memory (EEM) has been well-demonstrated in adults, but less is known about EEM in children. The present study tested the impact of emotional valence of pictures on episodic memory using behavioral and neurophysiological measures. Twenty-six 8- to 11-year-old children were tested and compared to 30 young adults. Both groups participated in pictures’ intentional encoding tasks while event-related potentials (ERPs) were recorded, followed by immediate free recall tasks. Behavioral results revealed a general EEM in free recall performances in both groups, along with a negativity effect in children. ERP responses revealed a particular sensitivity to negative pictures in children with a late emotion effect at anterior clusters, as well as a greater successful encoding effect for emotional pictures compared to neutral ones. For adults, the emotion effect was more pronounced for positive pictures across all time windows from the centro-parietal to the frontal part, and localized in the left hemisphere. Positive pictures also elicited a greater successful encoding effect at anterior clusters in adults. By combining behavioral and neurophysiological measures to assess the EEM in children compared with adults, our study provides new knowledge concerning the interaction between emotional and memory processes during development. Full article

The ENCALS survival prediction model offers patients with amyotrophic lateral sclerosis (ALS) the opportunity to receive a personalized prognosis of survival at the time of diagnosis. We explored experiences of patients with ALS, caregivers, and physicians with discussing personalized prognosis through interviews with patients and their caregivers, and in a focus group of physicians. Thematic analysis revealed four themes with seven subthemes; these were recognized by the focus group. First, tailored communication: physician’s communication style and information provision mediated emotional impact and increased satisfaction with communication. Second, personal factors: coping style, illness experiences, and information needs affected patient and caregiver coping with the prognosis. Third, emotional impact ranged from happy and reassuring to regret. Fourth, regaining control over the future: participants found it helpful in looking towards the future, and emphasized the importance of quality over quantity of life. Personalized prognosis can be discussed with minimal adverse emotional impact. How it is communicated—i.e., tailored to individual needs—is as important as what is communicated—i.e., a good or poor prognosis. Discussing personalized prognosis may help patients with ALS and their caregivers regain control over the future and facilitate planning of the future (care). For many patients, quality of life matters more than quantity of time remaining. Full article

Research in hearing science is accelerating, and a wealth of data concerning auditory brainstem responses (ABR) in various animal models is published in peer-reviewed journals every year. Recently, we reviewed studies using ABR measurements in tinnitus rat models. We found significant discrepancies in the outcomes of these studies, some due to different research approaches and others due to different methodologies. Thus, the present work aimed to collect comprehensive information on all factors influencing ABR recordings in rats and compile recommendations on ABR data reporting. A questionnaire with queries about animal husbandry, transfer, handling, and the exact test conditions before, during, and after ABR recordings was sent to 125 researchers who published the relevant studies between 2015 and 2021. Eighteen researchers provided detailed answers on factors related to ABR measurements. Based on the analysis of the returned questionnaires, we identified three domains reflecting animal-, equipment-, and experiment-dependent factors that might influence the ABR outcome, thus requiring reporting in published research. The analysis of survey results led to the compilation of recommendations for reporting ABR outcomes supported by a literature review. Following these recommendations should facilitate comparative and meta-analyses of ABR results provided by various research groups. Full article

Speech fluency is a major challenge for young persons who stutter. Reading aloud, in particular, puts high demands on fluency, not only regarding online text decoding and articulation, but also in terms of prosodic performance. A written text has to be segmented into a number of prosodic phrases with appropriate breaks. The present study examines to what extent reading fluency (decoding ability, articulation rate, and prosodic phrasing) may be altered in children (9–12 years) and adolescents (13–17 years) who stutter compared to matched control participants. Read speech of 52 children and adolescents who do and do not stutter was analyzed. Children and adolescents who stutter did not differ from their matched control groups regarding reading accuracy and articulation rate. However, children who stutter produced shorter pauses than their matched peers. Results on prosodic phrasing showed that children who stutter produced more major phrases than the control group and more intermediate phrases than adolescents who stutter. Participants who stutter also displayed a higher number of breath pauses. Generally, the number of disfluencies during reading was related to slower articulation rates and more prosodic boundaries. Furthermore, we found age-related changes in general measures of reading fluency (decoding ability and articulation rate), as well as the overall strength of prosodic boundaries and number of breath pauses. This study provides evidence for developmental stages in prosodic phrasing as well as for alterations in reading fluency in children who stutter. Full article

In clinical practice, patients with language impairments often exhibit suicidal ideation (SI) and suicidal behavior (SB, covering the entire range from suicide attempts, SA, to completed suicides). However, only few studies exist regarding this subject. We conducted a mini-review on the possible associations between neurologic language impairment (on the motor, comprehension, and semantic sides) and SI/SB. Based on the literature review, we hypothesized that language impairments exacerbate psychiatric comorbidities, which, in turn, aggravate language impairments. Patients trapped in this vicious cycle can develop SI/SB. The so-called “affective prosody” provides some relevant insights concerning the interaction between the different language levels and the world of emotions. This hypothesis is illustrated in a clinical case that we reported, consisting of the case of a 74-year old woman who was admitted to a psychiatric emergency department (ED) after a failed SA. Having suffered an ischemic stroke two years earlier, she suffered from incomplete Broca’s aphasia and dysprosody. She also presented with generalized anxiety and depressive symptoms. We observed that her language impairments were both aggravated by the exacerbations of her anxiety and depressive symptoms. In this patient, who had deficits on the motor side, these exacerbations were triggered by her inability to express herself, her emotional status, and suffering. SI was fluctuant, and—one year after the SA—she completed suicide. Further studies are needed to ascertain possible reciprocal and interacting associations between language impairments, psychiatric comorbidities, and SI/SB. They could enable clinicians to better understand their patient’s specific suffering, as brought on by language impairment, and contribute to the refining of suicide risk detection in this sub-group of affected patients. Full article

A better understanding of the transcriptomic modifications that occur in spina bifida may lead to identify mechanisms involved in the progression of spina bifida in utero and the development of new therapeutic strategies that aid in spinal cord regeneration after surgical interventions. In this study, RNA-sequencing was used to identify differentially expressed genes in fetal spinal cords from rats with retinoic acid-induced spina bifida at E15, E17, and E20. Gene ontology, KEGG, and protein–protein interaction analysis were conducted to predict pathways involved in the evolution of the disease. Approximately 3000, 1000 and 300 genes were differentially expressed compared to the control groups at E15, E17 and E20, respectively. Overall, the results suggest common alterations in certain pathways between gestational time points, such as upregulation in p53 and sonic hedgehog signaling at E15 and E17 and downregulation in the myelin sheath at E17 and E20. However, there were other modifications specific to gestational time points, including skeletal muscle development at E15, downregulated glucose metabolism at E17, and upregulated inflammation at E20. In conclusion, this work provides evidence that gestational age during spina bifida repair may be a significant variable to consider during the development of new regenerative therapeutics approaches. Full article

The perception of harmonic complexes provides important information for musical and vocal communication. Numerous studies have shown that musical training and expertise are associated with better processing of harmonic complexes, however, it is unclear whether the perceptual improvement associated with musical training is universal to different pitch models. The current study addresses this issue by measuring discrimination thresholds of musicians (n = 20) and non-musicians (n = 18) to diotic (same sound to both ears) and dichotic (different sounds to each ear) sounds of four stimulus types: (1) pure sinusoidal tones, PT; (2) four-harmonic complex tones, CT; (3) iterated rippled noise, IRN; and (4) interaurally correlated broadband noise, called the “Huggins” or “dichotic” pitch, DP. Frequency difference limens (DLF) for each stimulus type were obtained via a three-alternative-forced-choice adaptive task requiring selection of the interval with the highest pitch, yielding the smallest perceptible fundamental frequency (F0) distance (in Hz) between two sounds. Music skill was measured by an online test of musical pitch, melody and timing maintained by the International Laboratory for Brain Music and Sound Research. Musicianship, length of music experience and self-evaluation of musical skill were assessed by questionnaire. Results showed musicians had smaller DLFs in all four conditions with the largest group difference in the dichotic condition. DLF thresholds were related to both subjective and objective musical ability. In addition, subjective self-report of musical ability was shown to be a significant variable in group classification. Taken together, the results suggest that music-related plasticity benefits multiple mechanisms of pitch encoding and that self-evaluation of musicality can be reliably associated with objective measures of perception. Full article

Cognitive impairments and social-function deficits are severe complaints in neurofibromatosis type 1 (NF1) patients. Empathetic pain perception may be disrupted in NF1 patients because of high-level cognitive deficits. This study investigated the empathy profiles of adult patients with NF1, especially concerning whether explicit and implicit empathetic pain perception are abnormal in this population. We examined empathetic pain perception through a paradigm based on perceiving another person’s pain; in this task, patients were required to make judgments about the presence of pain or the laterality of the body part, as shown in a picture. Twenty NF1 patients without obvious social or communication difficulties completed the task, and the results were compared with results from the normal controls (NCs). Regarding explicit empathetic pain processing, i.e., judging the presence of “pain” or “no pain”, there were no significant differences between patients and controls in accuracy or reaction time. However, in implicit empathetic processing, i.e., judging the laterality of “pain” or “no-pain” pictures, NF1 patients had significantly lower accuracy (p = 0.038) and significantly higher reaction times (p = 0.004) than the NCs. These results were consistent with those of a previous study showing that high-level cognitive deficits were prominent in NF1 patients when performing challenging tasks. The mechanisms and related brain network activity underlying these deficits should receive attention in the future. Full article

Drug-resistant epilepsy can be most limiting for patients, and surgery represents a viable therapy option. With the growing research on the human connectome and the evidence of epilepsy being a network disorder, connectivity analysis may be able to contribute to our understanding of epilepsy and may be potentially developed into clinical applications. In this magnetoencephalographic study, we determined the whole-brain node degree of connectivity levels in patients and controls. Resting-state activity was measured at five frequency bands in 15 healthy controls and 15 patients with focal epilepsy of different etiologies. The whole-brain all-to-all imaginary part of coherence in source space was then calculated. Node degree was determined and parcellated and was used for further statistical evaluation. In comparison to controls, we found a significantly higher overall node degree in patients with lesional and non-lesional epilepsy. Furthermore, we examined the conditions of high/reduced vigilance and open/closed eyes in controls, to analyze whether patient node degree levels can be achieved. We evaluated intraclass-correlation statistics (ICC) to evaluate the reproducibility. Connectivity and specifically node degree analysis could present new tools for one of the most common neurological diseases, with potential applications in epilepsy diagnostics. Full article

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm³ vs. normothermia = 108.1 ± 17.8 mm³; p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment. Full article

REM sleep without atonia (RSWA) is the polysomnographic (PSG) hallmark of rapid eye movement (REM) sleep behavior disorder (RBD), a feature essential for the diagnosis of this condition. Several additional neurophysiological aspects of this complex disorder have also recently been investigated in depth, which constitute the focus of this narrative review, together with RSWA. First, we describe the complex neural network underlying REM sleep and its muscle atonia, focusing on the disordered mechanisms leading to RSWA. RSWA is then described in terms of its polysomnographic features, and the methods (visual and automatic) currently available for its scoring and quantification are exposed and discussed. Subsequently, more recent and advanced neurophysiological features of RBD are described, such as electroencephalography during wakefulness and sleep, transcranial magnetic stimulation, and vestibular evoked myogenic potentials. The role of the assessment of neurophysiological features in the study of RBD is then carefully discussed, highlighting their usefulness and sensitivity in detecting neurodegeneration in the early or prodromal stages of RBD, as well as their relationship with other proposed biomarkers for the diagnosis, prognosis, and monitoring of this condition. Finally, a future research agenda is proposed to help clarify the many still unclear aspects of RBD. Full article