Electrophysiological correlates of emotional face processing after mild traumatic brain injury in preschool children.

Evidence suggests that social skills are affected by childhood mild traumatic brain injury (mTBI), but the neural and affective substrates of these difficulties are still underexplored. In particular, nothing is known about consequences on the perception of emotional facial expressions, despite its critical role in social interactions and the importance of the preschool period in the development of this ability. This study thus aimed to investigate the electrophysiological correlates of emotional facial expressions processing after early mTBI. To this end, 18 preschool children (mean age 53 ± 8 months) who sustained mTBI and 15 matched healthy controls (mean age 55 ± 11 months) were presented with pictures of faces expressing anger, happiness, or no emotion (neutral) while event-related potentials (ERP) were recorded. The main results revealed that P1 amplitude was higher for happy faces than for angry faces, and that N170 latency was shorter for emotional faces than for neutral faces in the control group only. These findings suggest that preschool children who sustain mTBI do not present the early emotional effects that are observed in healthy preschool children at visuospatial and visual expertise stages. This study provides new evidence regarding the consequences of childhood mTBI on socioemotional processing, by showing alterations of emotional facial expressions processing, an ability known to underlie social competence and appropriate social interactions.

Spatiotemporal dynamics of affective picture processing revealed by intracranial high-gamma modulations.

Our comprehension of the neural mechanisms underlying emotional information processing has largely benefited from noninvasive electrophysiological and functional neuroimaging techniques in recent years. However, the spatiotemporal dynamics of the neural events occurring during emotional processing remain imprecise due to the limited combination of spatial and temporal resolution provided by these techniques. This study examines the modulations of high-frequency activity of intracranial electroencephalography recordings associated with affective picture valence, in epileptic patients awaiting neurosurgery. Recordings were obtained from subdural grids and depth electrodes in eight patients while they viewed a series of unpleasant, pleasant and neutral pictures from the International Affective Picture System. Broadband high-gamma (70-150 Hz) power was computed for separate 100-ms time windows and compared according to ratings of emotional valence. Compared to emotionally neutral or pleasant pictures, unpleasant stimuli were associated with an early and long-lasting (≈200-1,000 ms) bilateral increase in high-gamma activity in visual areas of the occipital and temporal lobes, together with a late and transient (≈500-800 ms) decrease found bilaterally in the lateral prefrontal cortex (PFC). Pleasant pictures were associated with increased gamma activity in the occipital cortex, compared to the emotionally neutral stimuli. Consistent with previous studies, our results provide direct evidence of emotion-related modulations in the visual ventral pathway during picture processing. Results in the lateral PFC also shed light on the neural mechanisms underlying its role in negative emotions processing. This study demonstrates the utility of intracranial high-gamma modulations to study emotional process with a high spatiotemporal precision.

Comparing cortical auditory processing in children with typical and atypical benign epilepsy with centrotemporal spikes: Electrophysiologic evidence of the role of non-rapid eye movement sleep abnormalities.

OBJECTIVE: The mismatch negativity (MMN) is an objective measure of central auditory discrimination. MMN alterations have been shown in children with language and/or developmental disorders. In benign focal epilepsies, neuropsychological disorders are often reported and linked to interictal epileptic discharges (IEDs) during non-rapid eye movement (NREM) sleep. There are few studies reporting MMN in children with benign epilepsy with centrotemporal spikes (BECTS) and sleep IEDs. Moreover, no MMN recording has yet been reported in atypical BECTS children with continuous spike-and-wave during sleep (CSWS). We retrospectively compared MMN in typical and atypical BECTS children, particularly addressing the impact of NREM sleep IEDs on auditory discrimination. Moreover, we attempted a neuropsychological characterization of patients. METHODS: The MMN was recorded in 9 normal controls and 23 patients (14 typical BECTS and 9 atypical BECTS) in an oddball paradigm with syllable stimuli. MMN, sleep electroencephalography (EEG) and neuropsychological evaluation were realized in the same testing session. RESULTS: Measurable MMN responses to speech stimuli were identified in both the control and patient groups. A significant difference between control and atypical BECTS children was found with respect to amplitude (p = 0.0061). Atypical BECTS also showed a lower MMN amplitude with respect to typical BECTS, but this difference did not reach statistical significance (p = 0.0545). Statistical comparisons between groups revealed no differences in latency. Among the neuropsychological variables, academic difficulties were significantly more prominent in the patients with atypical BECTS (p = 0.04). SIGNIFICANCE: CSWS EEG pattern affects auditory discrimination and may have a long-lasting impact on academic skills acquisition, whereas in typical BECTS children with a lower degree of IED NREM sleep, plastic brain reorganization or the preservation of participating networks may prevent such difficulty. Early electrophysiologic identification of auditory discrimination deficits in epileptic children could be used in early rehabilitation, thereby reducing the risk of developing neuropsychological disorders.

Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions.

Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.

Neuropsychological performance before and after partial or complete insulectomy in patients with epilepsy.

Resection of the insular cortex is becoming more frequent as it is increasingly recognized that a nonnegligible proportion of surgical candidates with drug-resistant epilepsy have an epileptogenic zone that involves the insula. In the last decades, however, the insula has been proposed to be involved in several neuropsychological functions, and there is a lack of documentation on whether partial or complete insulectomy results in permanent cognitive impairments in this clinical population. In this study, we conducted standard preoperative and postoperative neuropsychological assessments in 18 patients undergoing epilepsy surgery that included the removal of the insula in the right (n=13) or the left (n=5) hemisphere. Postoperative testing was conducted at least five months after surgery. Cognitive impairments were common and heterogeneous prior to surgery, with language and verbal memory impairments being especially frequent among patients in whom epileptic seizures originated from the left hemisphere. After surgery, declines and improvements occurred on a variety of outcomes, although new deficits were relatively infrequent among patients who had obtained normal performance at baseline. Statistical comparisons between preoperative and postoperative assessments revealed significant deterioration of only one outcome - the color naming condition of the Stroop test - which relies on oro-motor speed and lexical access. These findings suggest that partial or complete resection of the insular cortex in patients with drug-refractory epilepsy can be conducted without major permanent neuropsychological impairments in a vast majority of patients. However, small decrements in specific cognitive functions can be expected, which should also be taken into account when considering the surgical option in this clinical population.

Neuropsychological functioning in children with temporal lobe epilepsy and hippocampal atrophy without mesial temporal sclerosis: a distinct clinical entity?

Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. However, in other cases, it has been suggested that HA without MTS may constitute a distinct epileptic entity. Hippocampal atrophy without MTS was defined as HA without T2-weighted hyperintensity, loss of internal architecture, or associated lesion seen on the MRI data. To date, no study has focused on the cognitive pattern of children with epilepsy with HA without MTS. The objectives of the present study were to characterize the cognitive profile of these children and to investigate the presence (or the absence) of material-specific memory deficits in these young patients, as found in patients with MTS. Toward this end, 16 young patients with epilepsy with either left or right HA without MTS completed a set of neuropsychological tests, assessing overall intelligence, verbal memory and nonverbal memory, and some aspects of attention and executive functions. Results showed normal intellectual functioning without specific memory deficits in these patients. Furthermore, comparison between patients with left HA and patients with right HA failed to reveal a material-specific lateralized memory pattern. Instead, attention and executive functions were found to be impaired in most patients. These results suggest that HA may constitute a distinct epileptic entity, and this information may help health-care providers initiate appropriate and timely interventions.

Preserved priming effect in individuals with schizophrenia: cues towards rehabilitation.

INTRODUCTION: Individuals with schizophrenia and affective disorders show relatively intact implicit memory as compared to declarative memory. Implicit memory is usually assessed with skill learning and priming tasks. Whereas priming is thought to involve storage changes in the posterior neocortex, skill learning is thought to rely more on the corticostriatal pathway. Since frontostriatal and frontotemporal dysfunctions are, respectively, found in schizophrenia and affective disorders, we hypothesised that individuals with schizophrenia and first-episode psychosis would exhibit disturbances in skill learning, but not priming. METHODS: Thirty-five patients (11 first-episode psychosis; 11 schizophrenia; 13 affective disorders) and 10 controls completed a procedural learning and priming task. Participants had to identify fragmented images throughout five training sessions. The improvement of the threshold at which the images could be identified between the first and last session was used as an index of procedural learning. In a final session, the identification thresholds for old and new images were compared to assess the priming effect. RESULTS: Whereas individuals with schizophrenia and first-episode psychosis showed impaired skill learning, the priming effect was similar in all groups. CONCLUSION: Even though some aspects of learning and memory are affected in schizophrenia, our results suggest that the posterior cortical pathway remains efficient at modulating the priming effect. This intact ability could be used to guide the elaboration of new rehabilitation programmes.

Impact of BDNF Val66Met polymorphism on olfactory functions of female concussed athletes.

BACKGROUND: Concussions exert persistent effects on asymptomatic athletes, especially women. Among chief mechanisms of concussion recovery are alterations of neuronal plasticity. Olfactory function, often impaired following a concussion, greatly involves plasticity and, therefore, appears as a good candidate to study the deleterious effects of concussions. The BDNF Val66Met polymorphism (BDNFMet), which reduces availability of BDNF in the brain, has surprisingly been associated with better recovery following concussion. OBJECTIVE: This study examines the mediating effect of BDNFMet on olfactory functions in asymptomatic concussed female athletes. METHODS: Participants, 105 female university athletes, were divided into four groups based on their history of concussion (Concussion/No concussion) and BDNF polymorphism (BDNF Val66Val/Val66Met). Odour threshold, discrimination and identification were measured using the Sniffin' Sticks Inventory Test. RESULTS: Concussed female BDNFMet athletes performed significantly better than BDNFVal counterparts on threshold (F(1, 34) = 4.73, p < 0.05), discrimination (F(1, 52) = 5.36, p < 0.05), identification tests (F(1, 52) = 5.65, p < 0.05) and total olfactory scores (F(1, 34) = 9.54, p < 0.05). CONCLUSION: These results support a genotypic effect of the BDNF Val66Met polymorphism on long-term olfactory function following a concussion in young female athletes.

Recognizing an object from the sum of its parts: an intracranial study on alpha rhythms.

Little is known about the relation of alpha rhythms and object recognition. Alpha has been generally proposed to be associated with attention and memory and to be particularly important for the mediation of long-distance communication between neuronal populations. However, how these apply to object recognition is still unclear. This study aimed at describing the spatiotemporal dynamics of alpha rhythms while recognizing fragmented images of objects presented for the first time and presented again 24 hr later. Intracranial electroencephalography was performed in six epileptic patients undergoing presurgical evaluation. Time-frequency analysis revealed a strong alpha activity, mainly of the evoked type, propagating from posterior cerebral areas to anterior regions, which was similar whether the objects were recognized or not. Phase coherence analysis, however, showed clear phase synchronization specific for the moment of recognition. Twenty-four hr later, frontal regions displayed stronger alpha activity and more distributed phase synchronization than when images were presented for the first time. In conclusion, alpha amplitude seems to be related to nonspecific mechanism. Phase coherence analysis suggests a communicational role of alpha activity in object recognition, which may be important for the comparison between bottom-up representations and memory templates.

Sports concussions and aging: a neuroimaging investigation.

Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

A frequency-tagging electrophysiological method to identify central and peripheral visual field deficits.

BACKGROUND: The aim of this study was to develop a fast and efficient electrophysiological protocol to examine the visual field's integrity, which would be useful in pediatric testing. METHODS: Steady-state visual-evoked potentials (ssVEPs) to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) recorded at Oz were collected from 22 participants from 5 to 34 years old and from 5 visually impaired adolescents (12-16 years old). Responses from additional leads (POz, O1, O2), and the impact of gaze deviation on the signals, were also investigated in a subgroup of participants. RESULTS: Steady-state visual-evoked potentials responses were similar at all electrode sites, although the signal from the central stimulation was significantly higher at Oz and was highly sensitive in detecting gaze deviation. No effect of age or sex was found, indicating similar ssVEP responses between adults and healthy children. Visual acuity was related to the central signal when comparing healthy participants with four central visual impaired adolescents. Clinical validation of our electrophysiological protocol was also achieved in a 15-year-old adolescent with a severe peripheral visual deficit, as assessed with Goldmann perimetry. CONCLUSIONS: A single electrode over Oz is sufficient to gather both central and peripheral visual signals and also to control for gaze deviation. Our method presents several advantages in evaluating visual fields integrity, as it is fast, reliable, and efficient, and applicable in children as young as 5 years old. However, a larger sample of healthy children should be tested to establish clinical norms.

Functional specialization for auditory-spatial processing in the occipital cortex of congenitally blind humans.

The study of the congenitally blind (CB) represents a unique opportunity to explore experience-dependant plasticity in a sensory region deprived of its natural inputs since birth. Although several studies have shown occipital regions of CB to be involved in nonvisual processing, whether the functional organization of the visual cortex observed in sighted individuals (SI) is maintained in the rewired occipital regions of the blind has only been recently investigated. In the present functional MRI study, we compared the brain activity of CB and SI processing either the spatial or the pitch properties of sounds carrying information in both domains (i.e., the same sounds were used in both tasks), using an adaptive procedure specifically designed to adjust for performance level. In addition to showing a substantial recruitment of the occipital cortex for sound processing in CB, we also demonstrate that auditory-spatial processing mainly recruits the right cuneus and the right middle occipital gyrus, two regions of the dorsal occipital stream known to be involved in visuospatial/motion processing in SI. Moreover, functional connectivity analyses revealed that these reorganized occipital regions are part of an extensive brain network including regions known to underlie audiovisual spatial abilities (i.e., intraparietal sulcus, superior frontal gyrus). We conclude that some regions of the right dorsal occipital stream do not require visual experience to develop a specialization for the processing of spatial information and to be functionally integrated in a preexisting brain network dedicated to this ability.

Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate+glutamine.

Transcranial magnetic stimulation (TMS) can provide an index of intracortical excitability/inhibition balance. However, the neurochemical substrate of these measures remains unclear. Pharmacological studies suggest the involvement of GABAA and GABAB receptors in TMS protocols aimed at measuring intracortical inhibition, but this link remains inferential. Proton magnetic resonance spectroscopy ((1)H-MRS) permits measurement of GABA and glutamate + glutamine (Glx) concentrations in the human brain and might help in the direct empirical assessment of the relationship between TMS inhibitory measures and neurotransmitter concentrations. In the present study, MRS-derived relative concentrations of GABA and Glx measured in the left M1 of healthy participants were correlated with TMS measures of intracortical inhibition. Glx levels were found to correlate positively with TMS-induced silent period duration, whereas no correlation was found between GABA concentration and TMS measures. The present data demonstrate that specific TMS measures of intracortical inhibition are linked to shifts in cortical Glx, rather than GABA neurotransmitter levels. Glutamate might specifically interact with GABAB receptors, where higher MRS-derived Glx concentrations seem to be linked to higher levels of receptor activity.

Abnormal motor cortex excitability is associated with reduced cortical thickness in X monosomy.

Turner syndrome (TS) is a noninherited genetic disorder caused by the absence of one or part of one X chromosome. It is characterized by physical and cognitive phenotypes that include motor deficits that may be related to neuroanatomical abnormalities of sensorimotor pathways. Here, we used transcranial magnetic stimulation (TMS) and cortical thickness analysis to assess motor cortex excitability and cortical morphology in 17 individuals with TS (45, X) and 17 healthy controls. Exploratory analysis was performed to detect the effect of parental origin of the X chromosome (X(mat), X(pat)) on both measures. Results showed that long-interval intracortical inhibition was reduced and motor threshold (MT) was increased in TS relative to controls. Areas of reduced thickness were observed in the precentral gyrus of individuals with TS that correlated with MT. A significant difference between X(mat) (n = 11) and X(pat) (n = 6) individuals was found on the measure of long-interval intracortical inhibition. These findings demonstrate the presence of converging anatomical and neurophysiological abnormalities of the motor system in X monosomy.

Noninvasive continuous functional near-infrared spectroscopy combined with electroencephalography recording of frontal lobe seizures.

PURPOSE: To investigate spatial and metabolic changes associated with frontal lobe seizures. METHODS: Functional near-infrared spectroscopy combined with electroencephalography (EEG-fNIRS) recordings of patients with confirmed nonlesional refractory frontal lobe epilepsy (FLE). KEY FINDINGS: Eighteen seizures from nine patients (seven male, mean age 27 years, range 13-46 years) with drug-refractory FLE were captured during EEG-fNIRS recordings. All seizures were coupled with significant hemodynamic variations that were greater with electroclinical than with electrical seizures. fNIRS helped in the identification of seizures in three patients with more subtle ictal EEG abnormalities. Hemodynamic changes consisted of local increases in oxygenated (HbO) and total hemoglobin (HbT) but heterogeneous deoxygenated hemoglobin (HbR) behavior. Furthermore, rapid hemodynamic alterations were observed in the homologous contralateral region, even in the absence of obvious propagated epileptic activity. The extent of HbO activation adequately lateralized the epileptogenic side in the majority of patients. SIGNIFICANCE: EEG-fNIRS reveals complex spatial and metabolic changes during focal frontal lobe seizures. Further characterization of these changes could improve seizure detection, localization, and understanding of the impact of focal seizures.

Motor system alterations in retired former athletes: the role of aging and concussion history.

BACKGROUND: Retired athletes with a history of sports concussions experience cognitive and motor declines with aging, and the risk of severe neurodegenerative conditions is magnified in this population. The present study investigated the effects of aging on motor system metabolism and function in former university-level athletes who sustained their last concussion several decades prior to testing. METHODS: To test the hypothesis that age and remote concussions induce functional as well as metabolic alterations of the motor system, we used proton magnetic resonance spectroscopy to detect metabolic abnormalities in the primary motor cortex and the serial reaction time task (SRTT) to evaluate motor learning. RESULTS: Our results indicate that motor learning is significantly reduced in former concussed athletes relative to controls. In addition, glutamate/H2O ratio in M1 was disproportionately reduced in concussed athletes with advancing age and was found to strongly correlate with motor learning impairments. CONCLUSION: Findings from this study provide evidence that the acquisition of a repeated motor sequence is compromised in the aging concussed brain and that its physiological underpinnings could implicate disproportionate reductions of M1 glutamate concentrations with advancing age.

Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes.

Persistent motor/cognitive alterations and increased prevalence of Alzheimer's disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. To test the hypothesis that increased GABAergic inhibition after repeated concussions suppresses LTP/LTD and contributes to learning impairments, we used a paired associative stimulation (PAS) protocol to induce LTP/LTD-like effects in primary motor cortex (M1) jointly with an implicit motor learning task (serial reaction time task, SRTT). Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.

Prevalence of nonlesional focal epilepsy in an adult epilepsy clinic.

PURPOSE: To evaluate the prevalence of nonlesional focal epilepsy in an adult epilepsy clinic and its refractoriness to antiepileptic drug therapy. BACKGROUND: Focal epilepsy is frequently, but not always, associated with structural epileptogenic lesions identifiable on magnetic resonance imaging (MRI). METHODS: We analyzed the data from all patients evaluated at an adult epilepsy clinic from January 2002 to December 2011. Clinical and paraclinical findings were used to diagnose focal epilepsy. Magnetic resonance imaging were reviewed and classified as normal, with an epileptogenic lesion, or with a lesion of unclear epileptogenicity. Epileptogenic lesions were further categorized as tumours, vascular malformations, gliosis (including hippocampal atrophy/sclerosis), and malformations of cortical development. Our study group included patients with no lesions on MRI. Pharmacoresistance of patients with nonlesional focal epilepsy was assessed using the ILAE and Perucca's criterias. RESULTS: Out of 1521 patients evaluated (mean age 44 years; range 14-93 years), 843 had focal epilepsy. Magnetic resonance imaging data, available for 806 (96%) subjects, showed epileptogenic lesions in 65%, no obvious epileptogenic lesions in 31% and lesions of unclear epileptogenicity in 4%. Magnetic resonance imaging-identified lesions included gliosis due to an acquired insult (52% including 17% of hippocampal atrophy or sclerosis), tumours (29%), vascular malformations (16%) and malformations of cortical development (10%). Fifty-two percent of nonlesional focal epileptic patients were drug-refractory. CONCLUSION: In a tertiary epilepsy clinic, close to a third of patients with focal epilepsy were found to be nonlesional, half of which were drug-resistant.

Neurometabolic and microstructural alterations following a sports-related concussion in female athletes.

BACKGROUND: Sports-related concussions are a major public health concern affecting millions of individuals annually. Neurometabolic and microstructural alterations have been reported in the chronic phase following a concussion in male athletes, while no study has investigated these alterations in female athletes. METHODS: Neurometabolic and microstructural alterations following a concussion were investigated by comparing 10 female athletes with a concussion and 10 control female athletes, using magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI). Athletes with concussion were scanned at least 7 months post-concussion (mean = 18.9 months). RESULTS: MRS revealed a significant lower level of myo-inositol in the hippocampus and the primary motor cortices (M1) bilaterally. DTI analysis using Tract-Based Spatial Statistics (TBSS) showed no difference in fractional anisotropy (FA) while higher level of mean diffusivity (MD) in athletes with concussion was detected in large white matter tracts including the forceps minors, inferior/superior longitudinal fasciculi, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, anterior thalamic radiations and corticospinal tract. Moreover, a region of interest approach for the corpus callosum revealed a significant lower level of FA in the segment containing fibres projecting to M1. CONCLUSIONS: This study demonstrates persistent neurometabolic and microstructural alterations in female athletes suffering a sports-related concussion.

A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms.

PURPOSE: Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms. METHODS: In a randomized controlled trial, patients received a standardized therapy plus flunarizine or placebo. The standardized treatment consisted of vigabatrin as first-line therapy. Nonresponders were switched to intramuscular synthetic adrenocorticotropic hormone (sACTH depot) after 2 weeks and, if necessary, to topiramate after two additional weeks. The Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as outcome measures 24 months after the intervention. KEY FINDINGS: Sixty-eight of 101 children diagnosed over 3 years in seven centers in Canada received either adjunctive flunarizine or placebo. Sixty-five of the 68 children (96%) became spasm-free within 8 weeks and no late relapse occurred. Bayley and Vineland results were available at baseline and at 24 months in 45 children. There was no significant difference in the BSID developmental quotient between the flunarizine- and placebo-treated children at baseline (44.3 ± 35.5 vs. 30.9 ± 29.8; p = 0.18) or 24 months later (56.9 ± 33.3 vs. 46 ± 34.2; p = 0.29). However, the 10 flunarizine-treated children with no identified etiology had a better outcome than the eight controls at 24 months on both the Vineland Scale (84.1 ± 11.3 vs. 72.3 ± 9.8; p = 0.03) and the Bayley Scale (87.6 ± 14.7 vs. 69.9 ± 25.3; p = 0.07). SIGNIFICANCE: Our study failed to demonstrate a protective effect of flunarizine on cognitive outcome in a cohort of children with IS. An analysis of subgroups suggested that flunarizine may further improve cognitive outcome in children with no identified etiology.