Brain Sci., Volume 7, Issue 6 (June 2017) – 15 articles

Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. In recent years, it has become more evident that neurodegeneration, including neuronal damage and axonal injury, underlies permanent disability in MS. This manuscript reviews some of the mechanisms that could be responsible for neurodegeneration and axonal damage in MS and highlights the potential role that dysfunctional heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and antibodies to hnRNP A1 may play in MS pathogenesis. Full article

Magnetic resonance imaging (MRI) has the potential to serve as a biomarker for Parkinson’s disease (PD). However, the type or types of biomarker it could provide remain to be determined. At this time there is not sufficient sensitivity or specificity for MRI to serve as an early diagnostic biomarker, i.e., it is unproven in its ability to determine if a single individual is normal, has mild PD, or has some other forms of degenerative parkinsonism. However there is accumulating evidence that MRI may be useful in staging and monitoring disease progression (staging biomarker), and also possibly as a means to monitor pathophysiological aspects of disease and associated response to treatments, i.e., theranostic marker. As there are increasing numbers of manuscripts that are dedicated to diffusion- and neuromelanin-based imaging methods, this review will focus on these topics cursorily and will delve into pharmacodynamic imaging as a means to get at theranostic aspects of PD. Full article

Huntington’s disease is a disorder that results in motor, cognitive, and psychiatric problems. The symptoms often take different forms and the presence of disturbances of the psychic sphere reduces patients’ autonomy and quality of life, also impacting patients’ social life. It is estimated that a prevalence between 33% and 76% of the main psychiatric syndromes may arise in different phases of the disease, often in atypical form, even 20 years before the onset of chorea and dementia. We present a narrative review of the literature describing the main psychopathological patterns that may be found in Huntington’s disease, searching for a related article in the main database sources (Medline, ISI Web of Knowledge, Scopus, and Medscape). Psychiatric conditions were classified into two main categories: affective and nonaffective disorders/symptoms; and anxiety and neuropsychiatric features such as apathy and irritability. Though the literature is extensive, it is not always convergent, probably due to the high heterogeneity of methods used. We summarize main papers for pathology and sample size, in order to present a synoptic vision of the argument. Since the association between Huntington’s disease and psychiatric symptoms was demonstrated, we argue that the prevalent and more invalidating psychiatric components should be recognized as early as possible during the disease course in order to best address psychopharmacological therapy, improve quality of life, and also reduce burden on caregivers. Full article

This paper argues that the repetitive behaviour and restrictive interests (RBRI) displayed by individuals with Down syndrome have mostly positive functions. However, as research has developed from interests in Obsessional Compulsive Disorder or Autistic Spectrum Disorder, unfortunately a view has arisen that RBRI in individuals with Down syndrome are also likely to be pathological. This is particularly the case in adults. The paper reviews: (a) measures employed and the perspectives that have been used; (b) the development in typically developing individuals, those with Down syndrome, and those with other conditions associated with intellectual disability; (c) positive and possible negative effects of RBRI; and (d) the need for more research. The conclusion is that, for their level of development, RBRI are helpful for most individuals with Down syndrome. Full article

Learned associations between stimuli and responses (S–R associations) make important contributions to behavioral and neural priming. The current study investigated the automaticity and flexibility of these S–R associations and whether the global task context in which they occur modulates the impact of S–R retrieval on priming. Participants engaged in a semantic repetition priming task in which S–R retrieval is known to influence priming. Across participants, repetition priming occurred in global task contexts (i.e., combination of activated task sets) that either remained consistent or shifted across time. In the stable context group, the global task context at study matched that at test, whereas in the shifting context group, the global task context at study differed from that at test. Results revealed that the stability of the global task context did not affect the magnitude of S–R contributions to priming and that S–R contributions to priming were significant in both the stable and shifting context groups. These results highlight the robustness of S–R contributions to priming and indicate that S–R associations can flexibly transfer across changes in higher-level task states. Full article

A multiple sclerosis (MS) diagnosis often relies upon clinical presentation and qualitative analysis of standard, magnetic resonance brain images. However, the accuracy of MS diagnoses can be improved by utilizing advanced brain imaging methods. We assessed the accuracy of a new neuroimaging marker, visual-evoked cerebral metabolic rate of oxygen (veCMRO₂), in classifying MS patients and closely age- and sex-matched healthy control (HC) participants. MS patients and HCs underwent calibrated functional magnetic resonance imaging (cfMRI) during a visual stimulation task, diffusion tensor imaging, T₁- and T₂-weighted imaging, neuropsychological testing, and completed self-report questionnaires. Using resampling techniques to avoid bias and increase the generalizability of the results, we assessed the accuracy of veCMRO₂ in classifying MS patients and HCs. veCMRO₂ classification accuracy was also examined in the context of other evoked visuofunctional measures, white matter microstructural integrity, lesion-based measures from T₂-weighted imaging, atrophy measures from T₁-weighted imaging, neuropsychological tests, and self-report assays of clinical symptomology. veCMRO₂ was significant and within the top 16% of measures (43 total) in classifying MS status using both within-sample (82% accuracy) and out-of-sample (77% accuracy) observations. High accuracy of veCMRO₂ in classifying MS demonstrated an encouraging first step toward establishing veCMRO₂ as a neurodiagnostic marker of MS. Full article

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection. Full article

Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders. Full article

Despite recent giant leaps in understanding Gilles de la Tourette’s syndrome (now Tourette Disorder in the DSM 5), accurate multi-modal description, rigorous assessment procedures, and the improvement of evidence-based treatment currently pose a considerable challenge. In this context, the current special edition aims to elaborate three important dimensions in Tourette Disorder. Firstly, the effective characterization and etiological basis of the disorder are reviewed, since such characterization impacts accurate assessment. Secondly, subsequent articles cover the comprehensive evaluation and assessment of tic disorders, essential for treatment planning. Thirdly, the final group of articles propose novel and innovative treatment strategies for pharmacologically and behaviorally reducing tic frequency. In the current editorial address, two main issues seem crucial to the development of interventions for Tourette disorder. Primarily, integrating new technology in treatments, while supporting cognitive and behavioral recovery through learning self-controlled strategies. Additionally, the dissemination of study results to frontline resources, needs streamlining and empirically validated treatments for tic disorders should be the subject of knowledge translation to community organizations and be more widely available to the public. Full article

When a speaker talks, the consequences of this can both be heard (audio) and seen (visual). A novel visual phonemic restoration task was used to assess behavioral discrimination and neural signatures (event-related potentials, or ERP) of audiovisual processing in typically developing children with a range of social and communicative skills assessed using the social responsiveness scale, a measure of traits associated with autism. An auditory oddball design presented two types of stimuli to the listener, a clear exemplar of an auditory consonant–vowel syllable /ba/ (the more frequently occurring standard stimulus), and a syllable in which the auditory cues for the consonant were substantially weakened, creating a stimulus which is more like /a/ (the infrequently presented deviant stimulus). All speech tokens were paired with a face producing /ba/ or a face with a pixelated mouth containing motion but no visual speech. In this paradigm, the visual /ba/ should cause the auditory /a/ to be perceived as /ba/, creating an attenuated oddball response; in contrast, a pixelated video (without articulatory information) should not have this effect. Behaviorally, participants showed visual phonemic restoration (reduced accuracy in detecting deviant /a/) in the presence of a speaking face. In addition, ERPs were observed in both an early time window (N100) and a later time window (P300) that were sensitive to speech context (/ba/ or /a/) and modulated by face context (speaking face with visible articulation or with pixelated mouth). Specifically, the oddball responses for the N100 and P300 were attenuated in the presence of a face producing /ba/ relative to a pixelated face, representing a possible neural correlate of the phonemic restoration effect. Notably, those individuals with more traits associated with autism (yet still in the non-clinical range) had smaller P300 responses overall, regardless of face context, suggesting generally reduced phonemic discrimination. Full article

Background: This study looked to validate the acoustic wave technology of the Storz-D-Actor that inflicted a consistent closed-head, traumatic brain injury (TBI) in rats. We studied a range of single pulse pressures administered to the rats and observed the resulting decline in motor skills and memory. Histology was observed to measure and confirm the injury insult. Methods: Four different acoustic wave pressures were studied using a single pulse: 0, 3.4, 4.2 and 5.0 bar (n = 10 rats per treatment group). The pulse was administered to the left frontal cortex. Rotarod tests were used to monitor the rats’ motor skills while the water maze test was used to monitor memory deficits. The rats were then sacrificed ten days post-treatment for histological analysis of TBI infarct size. Results: The behavioral tests showed that acoustic wave technology administered an effective insult causing significant decreases in motor abilities and memory. Histology showed dose-dependent damage to the cortex infarct areas only. Conclusions: This study illustrates that the Storz D-Actor effectively induces a repeatable TBI infarct, avoiding the invasive procedure of a craniotomy often used in TBI research. Full article

Electroencephalography (EEG) and magnetoencephalography (MEG) are non-invasive electrophysiological methods, which record electric potentials and magnetic fields due to electric currents in synchronously-active neurons. With MEG being more sensitive to neural activity from tangential currents and EEG being able to detect both radial and tangential sources, the two methods are complementary. Over the years, neurophysiological studies have changed considerably: high-density recordings are becoming de rigueur; there is interest in both spontaneous and evoked activity; and sophisticated artifact detection and removal methods are available. Improved head models for source estimation have also increased the precision of the current estimates, particularly for EEG and combined EEG/MEG. Because of their complementarity, more investigators are beginning to perform simultaneous EEG/MEG studies to gain more complete information about neural activity. Given the increase in methodological complexity in EEG/MEG, it is important to gather data that are of high quality and that are as artifact free as possible. Here, we discuss some issues in data acquisition and analysis of EEG and MEG data. Practical considerations for different types of EEG and MEG studies are also discussed. Full article

Abstract: Adolescents and young adults with Down syndrome (DS) can present a rapid regression with loss of independence and daily skills. Causes of regression are unknown and treatment is most of the time symptomatic. We did a retrospective cohort study of regression cases: patients were born between 1959 and 2000, and were followed from 1984 to now. We found 30 DS patients aged 11 to 30 years old with history of regression. Regression occurred regardless of the cognitive level (severe, moderate, or mild intellectual disability (ID)). Patients presented psychiatric symptoms (catatonia, depression, delusions, stereotypies, etc.), partial or total loss of independence in activities of daily living (dressing, toilet, meals, and continence), language impairment (silence, whispered voice, etc.), and loss of academic skills. All patients experienced severe emotional stress prior to regression, which may be considered the trigger. Partial or total recovery was observed for about 50% of them. In our cohort, girls were more frequently affected than boys (64%). Neurobiological hypotheses are discussed as well as preventative and therapeutic approaches. Full article

With the aging of the U.S. population, the number of cognitively disabled persons is expected to substantially increase in coming decades, underscoring the urgent need for effective interventions. Here, we review the current evidence linking psychosocial factors to late-life cognitive loss and consider the study design needed to illuminate the biologic bases of the associations. We then examine an ongoing study that includes several of the key design elements, the Rush Memory and Aging Project. In this longitudinal clinical-pathological cohort study, indicators of personality, social connectedness, and psychological well-being were shown to predict late-life cognitive outcomes. Participants who died underwent a uniform neuropathologic examination to quantify common dementia-related pathologies. Some psychosocial indicators were associated with cerebral infarction; some indicators modified the association of neurodegenerative pathologies with cognitive loss; and the association of some indicators with cognitive outcomes appears to be independent of the pathologies traditionally associated with late-life dementia. These findings suggest that psychosocial behavior influences late-life cognitive health through multiple neurobiologic mechanisms. A better understanding of these mechanisms may lead to novel strategies for preserving cognitive health in old age. Full article

Several studies have reported that persons with Down syndrome (DS) have difficulties recognizing emotions; however, there is insufficient research to prove that a deficit of emotional knowledge exists in DS. The aim of this study was to evaluate the recognition of emotional facial expressions without making use of emotional vocabulary, given the language problems known to be associated with this syndrome. The ability to recognize six emotions was assessed in 24 adolescents with DS. Their performance was compared to that of 24 typically developing children with the same nonverbal-developmental age, as assessed by Raven’s Progressive Matrices. Analysis of the results revealed no global difference; only marginal differences in the recognition of different emotions appeared. Study of the developmental trajectories revealed a developmental difference: the nonverbal reasoning level assessed by Raven’s matrices did not predict success on the experimental tasks in the DS group, contrary to the typically developing group. These results do not corroborate the hypothesis that there is an emotional knowledge deficit in DS and emphasize the importance of using dynamic, strictly nonverbal tasks in populations with language disorders. Full article