• Neuroinformatics

Aerobic exercise has been shown to impact brain structure and cognition in children and adults. Exercise-induced activation of a growth protein known as brain derived neurotrophic factor (BDNF) is thought to contribute to such relationships. To date, however, no study has examined how aerobic fitness relates to cortical brain structure during development and if BDNF genotype moderates these relationships. Using structural magnetic resonance imaging (MRI) and FreeSurfer, the current study examined how aerobic fitness relates to volume, thickness, and surface area in 34 male adolescents, 15 to 18 years old. Moreover, we examined if the val66met BDNF genotype moderated these relationships. We hypothesized that aerobic fitness would relate to greater thickness and volumes in frontal, parietal, and motor regions, and that these relationships would be less robust in individuals carrying a Met allele, since this genotype leads to lower BDNF expression. We found that aerobic fitness positively related to right rostral middle frontal cortical volume in all adolescents. However, results also showed BDNF genotype moderated the relationship between aerobic fitness and bilateral medial precuneus surface area, with a positive relationship seen in individuals with the Val/Val allele, but no relationship detected in those adolescents carrying a Met allele. Lastly, using self-reported levels of aerobic activity, we found that higher-fit adolescents showed larger right medial pericalcarine, right cuneus and left precuneus surface areas as compared to their low-fit peers. Our findings suggest that aerobic fitness is linked to cortical brain development in male adolescents, and that more research is warranted to determine how an individual’s genes may influence these relationships.

Abstract Purpose To study clinical profile, neurodevelopmental outcome and its predictors in children with acute symptomatic seizures (ASS). Methods Short-term neurodevelopmental outcome and predictors of poor outcomes were prospectively assessed in 105 consecutive children with ASS aged 3 months-12 years Results Mean age was 51.2+42.2months (3–144 months); 67.2% were males. Central nervous system (CNS) infection in 82%, status epilepticus in 15.2%, abnormal neuroimaging in 62.8% and abnormal electroencephalography in 22.3% were noted. At discharge, 27.6% had poor outcome including death (13%); CNS infections were significantly associated with poor outcome compared to ASS of other aetiologies (32.6% vs 5.2%, p=0.02). Low GCS (OR 4.9, 95%CI 1.2–20.7), abnormal electroencephalograph (OR 4.3, 95%CI 1–16.9) and neuroimaging (OR 12.1, 95%CI 1.4–105.2) were independent predictors of poor outcome. After 6 months, 16% children had delayed neurodevelopment and cognition; 6% had seizure recurrences. Abnormal electroencephalograph (p=0.002; OR 6.8, 95%CI 2.0–23.1), abnormal neuroimaging (p=0.015; OR 9.47, 95%CI 1.18–75.8),>1 anti-epileptic (p=0.00; OR 9.9, 95%CI 2.88–33.9), intubation (p=0.004; OR 6.25, 95%CI 1.79–21.7) and poor outcome at discharge (p=0.02; OR 4.44, 95%CI1.38–14.2) predicted abnormal neurodevelopment. Conclusions CNS infections are the most common cause of ASS in children from developing countries. Abnormal neurodevelopment and seizure recurrences on short-term follow-up are seen in a minority of children.

SummaryIntroductionRespiratory events occurring under non-invasive ventilation (NIV) may produce sleep fragmentation. Alternatives to polysomnography (PSG) should be validated for providing simple monitoring tools for patients treated at home with NIV.ObjectivesTo study the value of pulse wave amplitude (PWA) reduction as a surrogate marker of cortical micro-arousals associated with respiratory events occurring during NIV.Methods27 PSG tracings under NIV recorded in 9 stable patients with Obesity Hypoventilation Syndrome (OHS), under 3 different ventilator modes (no back-up rate, low or high back-up rate) were analyzed. For all respiratory events (obstructive, central, or mixed event), the association with EEG-micro-arousals, PWA reduction of more than 30% and the presence of associated SpO2 desaturation ≥4% was recorded.Results2474 respiratory events during NREM sleep were analyzed. 73.6% were associated with an EEG-MA, 91.4% with a ≥4% decrease in SpO2, and 74.9% with a significant PWA reduction. Sensitivity of PWA for the detection of an EEG-micro-arousal related to a respiratory event was 89.1% [95%CI: 76.7–95.3]. Positive predictive value (PPV) was 87.0% [95%CI: 75.0–94.0]. Sensitivity of PWA was highest in the S mode, compared to both other S/T modes, p = <0.001. Sensitivity of PWA was also higher for central and mixed events, compared to obstructive respiratory events, p = <0.05.ConclusionsPWA reduction is a sensitive marker with a high PPV for the detection of EEG-MA associated with respiratory events during NREM sleep in stable OHS patients treated by NIV. In this situation, PWA could be used to improve scoring of hypopneas and allow an appropriate assessment of sleep fragmentation related to respiratory events.

Methylmercury (MeHg), an environmental contaminant primarily found in fish and seafood, may pose long-term health risks to pregnant women and their developing children. The objective of this study was to determine whether co-consumption of nutritional supplements would alter the effects of MeHg on reproductive and developmental toxicity using a rodent model. Adult female rats were fed a diet containing additional selenium (1 ppm), additional vitamin E (225 IU/kg) or a combination of the two for 4 weeks before oral dosing of MeHg (1.25 mg/kg/day). Treatment with MeHg and dietary supplementation continued throughout pregnancy after which the dams were allowed to deliver their offspring. In addition to routine evaluations including periodic body weight measurements and daily clinical signs observations, dams and pups were evaluated for auditory startle habituation and pups were evaluated for developmental landmarks and reflexology. The dams and offspring were euthanized approximately 4 weeks after birth of the offspring. Results indicated that treatment with MeHg caused adverse effects on both reproduction of the dams and decreased progeny survival. However, the dams showed significant improvement in body weight gain during lactation and average auditory startle response time when the diet was enriched with both selenium and vitamin E. The combination of both vitamin E and Se also resulted in a significant increase in post-natal survival when compared to MeHg-treated group. There was no nutrient effect on the MeHg toxicity shown in offspring physical landmarks, performance in reflex tests and assessment of simple auricular startle response. Also, accelerated development as indicated by earlier opening in the pups of the supplemental diet groups was observed. These results suggest that antioxidant nutrients in the diet may alter MeHg reproductive and developmental toxicity. The underlying and human health implications warrant further investigations.

Diagnosis of the antiphospholipid syndrome (APS) requires that a patient have both a clinical event (thrombosis or pregnancy loss) and persistently positive antiphospholipid antibodies (aPL). Although stroke and transient ischemic attack are the most common neurologic manifestations of APS, both cognitive dysfunction and magnetic resonance imaging (MRI) white matter hyperintensities can occur in aPL-positive patients (with or without APS). Relatively little is known about the cognitive pattern in aPL-positive patients; MRI white matter hyperintensities may be related to underlying attentional and executive cognitive impairment. Studies with sophisticated neuroimaging techniques aimed to better understand MRI white matter hyperintensities may eventually facilitate our understanding of cognitive dysfunction in aPL-positive patients.

Audiovisual speech has a stereotypical rhythm that is between 2 and 7 Hz, and deviations from this frequency range in either modality reduce intelligibility. Understanding how audiovisual speech evolved requires investigating the origins of this rhythmic structure. One hypothesis is that the rhythm of speech evolved through the modification of some pre-existing cyclical jaw movements in a primate ancestor. We tested this hypothesis by investigating the temporal structure of lipsmacks and teeth-grinds of macaque monkeys and the neural responses to these facial gestures in the superior temporal sulcus (STS), a region implicated in the processing of audiovisual communication signals in both humans and monkeys. We found that both lipsmacks and teeth-grinds have consistent but distinct peak frequencies and that both fall well within the 2–7 Hz range of mouth movements associated with audiovisual speech. Single neurons and local field potentials of the STS of monkeys readily responded to such facial rhythms, but also responded just as robustly to yawns, a nonrhythmic but dynamic facial expression. All expressions elicited enhanced power in the delta (0–3Hz), theta (3–8Hz), alpha (8–14Hz) and gamma (> 60 Hz) frequency ranges, and suppressed power in the beta (20–40Hz) range. Thus, STS is sensitive to, but not selective for, rhythmic facial gestures. Taken together, these data provide support for the idea that that audiovisual speech evolved (at least in part) from the rhythmic facial gestures of an ancestral primate and that the STS was sensitive to and thus ‘prepared’ for the advent of rhythmic audiovisual communication.

Stroke is considered to be one of the most important causes of death worldwide. Global ischemia causes widespread brain injury and infarctions in various regions of the brain. Oxidative stress can be considered an important factor in the development of tissue damage, which is caused because of arterial occlusion with subsequent reperfusion. Kapikacchu or Mucuna pruriens, commonly known as velvet bean, is well known for its aphrodisiac activities. It is also used in the treatment of snakebites, depressive neurosis, and Parkinson's disease. Although this plant has different pharmacological actions, its neuroprotective activity has received minimal attention. Thus, this study was carried out with the aim of evaluating the neuroprotective action of M. pruriens in bilateral carotid artery occlusion-induced global cerebral ischemia in Wistar rats. The carotid arteries of both sides were occluded for 30 min and reperfused to induce global cerebral ischemia. The methanolic plant extract was administered to the study animals for 10 days. The brains of the Wistar rats were isolated by decapitation and observed for histopathological and biochemical changes. Cerebral ischemia resulted in significant neurological damage in the brains of the rats that were not treated by M. pruriens. The group subjected to treatment by the M. pruriens extract showed significant protection against brain damage compared with the negative control group, which indicates the therapeutic potential of this plant in ischemia.

Light and electron microscopic observations are reported on a brain biopsy of a man of 59 with a rare familial disease of the CNS and a 5-year clinical course. Electron micrographs of the frontal biopsy reveal plaque-like deposits composed of amyloid cores, often multicentric in the cortex and subcortical white matter. They are localized between enlarged astrocytic processes. In the neuropil they are sometimes associated with abnormal neuritic processes, in the white matter with processes of fibrous astroglia and basement membranes. There are no signs of primary neuritic or synaptic involvement in the plaque formation which is more obviously associated with altered astrocytic processes. Moreover, degenerative alterations in the cortical vessels and slight astroglial spongiform changes as well as oligodendroglial proliferation can be found. Plaques are considered to be mainly of the kuru type; the relationship with transmissible spongiform encephalopathies is discussed.

Alterations in white matter integrity have been well documented in chronic epilepsy and during epileptogenesis. However, the relationship between white matter integrity and a predisposition towards epileptogenesis has been understudied. The FAST rat strain exhibit heightened susceptibility towards kindling epileptogenesis whereas SLOW rats are highly resistant. FAST rats also display behavioral phenotypes reminiscent of those observed in neurodevelopmental disorders that commonly comorbid with epilepsy. In this study, we aim to identify differences in white matter integrity that may contribute to a predisposition towards epileptogenesis and its associated comorbidities in 6 month old FAST (n = 10) and SLOW (n = 10) male rats. Open field and water consumption tests were conducted to confirm the behavioral phenotype difference between FAST and SLOW rats followed by ex-vivo diffusion-weighted magnetic resonance imaging to identify differences in white matter integrity. Diffusion tensor imaging scalar values namely fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were compared in the anterior commissure, corpus callosum, external capsule, internal capsule, fimbria and optic tract. Electron microscopy was used to evaluate microstructural alterations in myelinated axons. Behavioral phenotyping confirmed higher activity levels (distance moved on days 2–4, p < 0.001; number of rearings on days 2 and 4, p < 0.05 at both days) and polydipsia (p < 0.001) in FAST rats. Comparative analysis of diffusion tensor imaging scalars found a significant decrease in fractional anisotropy in the corpus callosum (p < 0.05) of FAST versus SLOW rats. Using electron microscopy, alterations in myelinated axons including increased axon diameter (p < 0.001) and reduced g-ratio (p < 0.001) in the midline of the corpus callosum in 6 month old FAST (n = 3) versus SLOW (n = 4) male rats. These findings suggest that differences in white matter integrity between FAST and SLOW rats could be a contributing factor to the differential seizure susceptibility and behavioral phenotypes observed in these strains.