Abnormalities in cortical auditory responses in children with central auditory processing disorder.

The main objective of the present study was to identify markers of neural deficits in children with central auditory processing disorder (CAPD) by measuring latency and amplitude of the auditory cortical responses and mismatch negativity (MMN) responses. Passive oddball paradigms were used with nonverbal and verbal stimuli to record cortical auditory-evoked potentials and MMN. Twenty-three children aged 9-12 participated in the study: 10 with normal hearing acuity as well as CAPD and 13 with normal hearing without CAPD. No significant group differences were observed for P1 latency and amplitude. Children with CAPD were observed to have significant N2 latency prolongation and amplitude reduction with nonverbal and verbal stimuli compared to children without CAPD. No significant group differences were observed for the MMN conditions. Moreover, electrode position affected the results in the same manner for both groups of children. The findings of the present study suggest that the N2 response could be a marker of neural deficits in children with CAPD. N2 results suggest that maturational factors or a different mechanism could be involved in processing auditory information at the central level for these children.

Decision-making impairments following insular and medial temporal lobe resection for drug-resistant epilepsy.

Besides the prefrontal cortex, the insula and medial structures of the temporal lobe are thought to be involved in risky decision-making. However, their respective contributions to decision processes remain unclear due to the lack of studies involving patients with isolated insular damage. We assessed adult patients who underwent resection of the insula (n = 13) or of the anterior temporal lobe (including medial structures) (n = 13) as part of their epilepsy surgery, and a group of healthy volunteers (n = 20), on the Iowa Gambling Task (IGT) and on the Cups Task. Groups were matched on sociodemographic, estimated-IQ and surgery-related factors. On the IGT, patients with temporal lobe resection performed significantly worse than both the insular and healthy control groups, as they failed to learn which decks were advantageous on the long-term. On the Cups Task, the insular and temporal groups both showed impaired sensitivity to expected value in the loss domain, when compared with healthy controls. These findings provide clinical evidence that the insula and mesiotemporal structures are specifically involved in risky decision-making when facing a potential loss, and that temporal structures are also involved in learning the association between behavior and consequences in the long-term.

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.

Mismatch Negativity Recording in Children With Duchenne Muscular Dystrophy: A Preliminary Study Integrating Neurophysiological and Neuropsychological Results.

Many studies on Duchenne muscular dystrophy children support the hypothesis of a specific neuropsychological phenotype affecting mostly phonological skills. This prospective study aimed to shed light on the role of phonological abilities. Fourteen Duchenne muscular dystrophy children and 7 healthy children underwent mismatch negativity. Moreover, verbal intelligence, visuospatial attention, immediate verbal memory, working memory, grammar, vocabulary, visuomotor skills, reading, text comprehension, writing, and arithmetic were tested in Duchenne muscular dystrophy children. No significant difference between control and Duchenne muscular dystrophy children was found neither for mismatch negativity amplitude (P = .191 and .116, respectively) nor for latency (P = .135). Eight (57.14%) patients showed an impairment of immediate verbal memory and of visuomotor skills, 7 (63.64%) patients had a deficit in writing and arithmetic skills, even with a mean normal intelligence quotient. Taken together, the results put in evidence a heterogeneous neuropsychological profile not explainable on the basis of a phonological deficit.

Electrophysiological Evidences of Visual Field Alterations in Children Exposed to Vigabatrin Early in Life.

BACKGROUND: We assessed central and peripheral visual field processing in children with epilepsy who were exposed to vigabatrin during infancy. METHODS: Steady-state visual evoked potentials and pattern electroretinograms to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) were recorded from Oz and at the eye in seven school-age children (10.1 ± 3.5 years) exposed to vigabatrin early in life, compared with children early exposed to other antiepileptic drugs (n = 9) and healthy children (n = 8). The stimulation was made of two concentric circles (0 to 5 and 30 to 60 degrees of angle) and presented at four contrast levels (96%, 64%, 32%, and 16%). RESULTS: Ocular responses were similar in all groups for central but not for the peripheral stimulations, which were significantly lower in the vigabatrin-exposed group at high contrast level. This peripheral retinal response was negatively correlated to vigabatrin exposure duration. Cortical responses to central stimulations, including contrast response functions in the children with epilepsy in both groups, were lower than those in normally developing children. CONCLUSIONS: Alteration of ocular processing was found only in the vigabatrin-exposed children. Central cortical processing, however, was impaired in both epileptic groups, with more pronounced effects in vigabatrin-exposed children. Our study suggests that asymptomatic long-term visual toxicity may still be present at school age, even several years after discontinuation of drug therapy.

Potential brain language reorganization in a boy with refractory epilepsy; an fNIRS-EEG and fMRI comparison.

As part of a presurgical investigation for a resection of a tumor located in the left temporal brain region, we evaluated pre- and postsurgical language lateralization in a right-handed boy with refractory epilepsy. In this study, we compared functional near infrared spectroscopy (fNIRS) results obtained while the participant performed expressive and receptive language tasks with those obtained using functional magnetic resonance imaging (fMRI). This case study illustrates the potential for NIRS to contribute favorably to the localization of language functions in children with epilepsy and cognitive or behavioral problems and its potential advantages over fMRI in presurgical assessment. Moreover, it suggests that fNIRS is sensitive in localizing an atypical language network or potential brain reorganization related to epilepsy in young patients.

Recruitment of the left precentral gyrus in reading epilepsy: A multimodal neuroimaging study.

PURPOSE: In a previous study, we investigated a 42-year-old male patient with primary reading epilepsy using continuous video-electroencephalography (EEG). Reading tasks induced left parasagittal spikes with a higher spike frequency when the phonological reading pathway was recruited compared to the lexical one. Here, we seek to localize the epileptogenic focus in the same patient as a function of reading pathway using multimodal neuroimaging. METHODS AND RESULTS: The participant read irregular words and nonwords presented in a block-design paradigm during magnetoencephalography (MEG), functional near-infrared spectroscopy (fNIRS), and functional magnetic resonance imaging (fMRI) recordings, all combined with EEG. Spike analyses from MEG, fNIRS, and fMRI-EEGs data revealed an epileptic focus in the left precentral gyrus, and spike localization did not differ in lexical and phonological reading. CONCLUSION: This study is the first to investigate ictogenesis in reading epilepsy during both lexical and phonological reading while using three different multimodal neuroimaging techniques. The somatosensory and motor control functions of the left precentral gyrus that are congruently involved in lexical as well as phonological reading can explain the identical spike localization in both reading pathways. The concurrence between our findings in this study and those from our previous one supports the role of the left precentral gyrus in phonological output computation as well as seizure activity in a case of reading epilepsy.

Distinct hemispheric specializations for native and non-native languages in one-day-old newborns identified by fNIRS.

This study assessed whether the neonatal brain recruits different neural networks for native and non-native languages at birth. Twenty-seven one-day-old full-term infants underwent functional near-infrared spectroscopy (fNIRS) recording during linguistic and non-linguistic stimulation. Fourteen newborns listened to linguistic stimuli (native and non-native language stories) and 13 newborns were exposed to non-linguistic conditions (native and non-native stimuli played in reverse). Comparisons between left and right hemisphere oxyhemoglobin (HbO2) concentration changes over the temporal areas revealed clear left hemisphere dominance for native language, whereas non-native stimuli were associated with right hemisphere lateralization. In addition, bilateral cerebral activation was found for non-linguistic stimulus processing. Overall, our findings indicate that from the first day after birth, native language and prosodic features are processed in parallel by distinct neural networks.

Long-Term Abnormalities in the Corpus Callosum of Female Concussed Athletes.

Concussion is an injury affecting millions of individuals annually that can be associated with long-term sequelae. Recent studies have reported long-term abnormalities in the white matter (WM) tracts of male athletes. The corpus callosum (CC) and corticospinal tract (CST) have been shown to be particularly vulnerable to concussion, which may be related to abnormal interhemispheric functional connectivity and motor impairments. These anatomical pathways, however, have not been investigated in female athletes despite the functional significance of the CC and CST to adequate sports performance. In the present study, 8 healthy, unconcussed female athletes (soccer, hockey) were compared with 10 female athletes (soccer, hockey, water polo) 6 months post-concussion. Diffusion tensor imaging (DTI) of the CC and CST was conducted in a 3T magnetic resonance imaging (MRI) scanner. DTI analysis showed no significant differences between groups within the CST but revealed differences between groups in the CC. The concussed group had lower mean diffusivity (t = 2.14; p = 0.048) and lower radial diffusivity (t = 2.91; p = 0.010) in the region of the CC projecting to the prefrontal cortex. A lower volume of WM fibers was found in the region projecting to the premotor and supplementary motor areas (t = 2.14; p = 0.048). Finally, lower axial diffusivity (AD) was observed in the CC area projecting mainly to the parietal and temporal area (t = 2.23; p = 0.041). Long-term alterations in the CC of female athletes appear to affect mostly the anterior part of the CC projecting to the prefrontal and premotor areas. Further studies are needed to determine whether these alterations are associated with a higher risk of sustaining a subsequent concussive injury.

Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum.

Agenesis of the corpus callosum (ACC) is a common brain malformation which can be observed either as an isolated condition or as part of numerous congenital syndromes. Therefore, cognitive and neurological involvements in patients with ACC are variable, from mild linguistic and behavioral impairments to more severe neurological deficits. To date, the underlying genetic causes of isolated ACC remains elusive and causative genes have yet to be identified. We performed exome sequencing on three acallosal siblings from the same non-consanguineous family and identified compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in the protein encoded by the CDK5RAP2 gene, also known as MCPH3, a gene previously reported to cause autosomal recessive primary microcephaly. Our findings suggest a novel role for this gene in the pathogenesis of isolated ACC.

Verbal memory and verbal fluency tasks used for language localization and lateralization during magnetoencephalography.

OBJECTIVE: The aim of this study was to develop a presurgical magnetoencephalography (MEG) protocol to localize and lateralize expressive and receptive language function as well as verbal memory in patients with epilepsy. Two simple language tasks and a different analytical procedure were developed. METHODS: Ten healthy participants and 13 epileptic patients completed two language tasks during MEG recording: a verbal memory task and a verbal fluency task. As a first step, principal component analyses (PCA) were performed on source data from the group of healthy participants to identify spatiotemporal factors that were relevant to these paradigms. Averaged source data were used to localize areas activated during each task and a laterality index (LI) was computed on an individual basis for both groups, healthy participants and patients, using sensor data. RESULTS: PCA revealed activation in the left temporal lobe (300 ms) during the verbal memory task, and from the frontal lobe (210 ms) to the temporal lobe (500 ms) during the verbal fluency task in healthy participants. Averaged source data showed activity in the left hemisphere (250-750 ms), in Wernicke's area, for all participants. Left hemisphere dominance was demonstrated better using the verbal memory task than the verbal fluency task (F1,19=4.41, p=0.049). Cohen's kappa statistic revealed 93% agreement (k=0.67, p=0.002) between LIs obtained from MEG sensor data and fMRI, the IAT, electrical cortical stimulation or handedness with the verbal memory task for all participants. At 74%, agreement results for the verbal fluency task did not reach statistical significance. SIGNIFICANCE: Analysis procedures yielded interesting findings with both tasks and localized language-related activation. However, based on source localization and laterality indices, the verbal memory task yielded better results in the context of the presurgical evaluation of epileptic patients. The verbal fluency task did not add any further information to the verbal memory task as regards language localization and lateralization for most patients and healthy participants that would facilitate decision making prior to surgery.

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.

Early electrophysiological markers of atypical language processing in prematurely born infants.

Because nervous system development may be affected by prematurity, many prematurely born children present language or cognitive disorders at school age. The goal of this study is to investigate whether these impairments can be identified early in life using electrophysiological auditory event-related potentials (AERPs) and mismatch negativity (MMN). Brain responses to speech and non-speech stimuli were assessed in prematurely born children to identify early electrophysiological markers of language and cognitive impairments. Participants were 74 children (41 full-term, 33 preterm) aged 3, 12, and 36 months. Pre-attentional auditory responses (MMN and AERPs) were assessed using an oddball paradigm, with speech and non-speech stimuli presented in counterbalanced order between participants. Language and cognitive development were assessed using the Bayley Scale of Infant Development, Third Edition (BSID-III). Results show that preterms as young as 3 months old had delayed MMN response to speech stimuli compared to full-terms. A significant negative correlation was also found between MMN latency to speech sounds and the BSID-III expressive language subscale. However, no significant differences between full-terms and preterms were found for the MMN to non-speech stimuli, suggesting preserved pre-attentional auditory discrimination abilities in these children. Identification of early electrophysiological markers for delayed language development could facilitate timely interventions.

Cortical thickness in adults with agenesis of the corpus callosum.

Agenesis of the corpus callosum (AgCC) is a congenital malformation that can occur in isolation or in association with other neurological conditions. Although the behavioral manifestations associated with AgCC have been widely studied, the effects of complete absence of the corpus callosum (CC) on cerebral cortex anatomy are still not completely understood. In this study, cortical thickness in adults with complete AgCC was compared to a group of healthy controls. Results showed highly variable patterns of cortical thickness in AgCC individuals, with few areas showing significant and consistent alterations including primary visual cortex, primary somatosensory cortex and primary motor cortex. These results suggest relatively limited effects of AgCC on cortical morphology, which are mostly restricted to primary sensory and motor areas.

Early childhood development of visual texture segregation in full-term and preterm children.

To date, very little is known about the normal development trajectory of visual texture segregation, or how it is affected by preterm birth. The goal of this study was to characterize the development of visual texture segregation using texture segregation visual evoked potentials (tsVEPs) in children born full-term and children born preterm without major neurological impairment. Forty-five full-term and 43 preterm children were tested at either 12, 24 or 36 months of age (corrected age for prematurity at 12 and 24 months old). VEPs were obtained using two lower-level stimuli defined by orientation (oriVEP) and two higher-level stimuli defined by texture (texVEP). TsVEP was obtained by dividing by two the subtraction of oriVEP from texVEP. Results show a clear maturation of the processes underlying visual texture segregation in the full-term group, with a significant N2 latency reduction between 12 and 36 months of age for all conditions. Significant N2 amplitude reduction was observed for oriVEP between 12 and 24 months, as well as for texVEP between 12 and 24 months, and 12 and 36 months. Comparison between full-term and preterm children indicated significantly lower N2 amplitude for the preterm group at 12 months for oriVEP and texVEP. These differences were no longer apparent at 24 months of age, suggesting that children born preterm catch up with their full-term counterparts somewhere between 12 and 24 months of age. Our results appear to reflect a maturational delay in preterm children in both lower-level and higher-level visual processing during, at least, early childhood.

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.

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.

Social information processing following resection of the insular cortex.

The insula has been implicated in social cognition and empathy in several neuroimaging paradigms. Impairments in social information processing, including specific deficits in disgust recognition, have been described following isolated insular damage, although the evidence remains limited to a few case studies. The present study examines social cognition and empathy in a group of fifteen patients for whom the insula was removed as part of their epilepsy surgery. These patients were compared to a lesion-control group of 15 epileptic patients who had a surgery in the anterior temporal lobe that spared the insula, and to 20 healthy volunteers matched on age, sex, and education. Participants were assessed on an Emotion Recognition Task (ERT), the Reading the Mind in the Eyes test, and a self-administered empathy questionnaire. Patients who underwent insular resection showed poorer ability to recognize facial expressions of emotions and had lower scores of perspective taking on the empathy questionnaire than healthy controls. Using results from healthy controls as normative data, emotion recognition deficits were more frequent in insular patients than in both other groups. Specific emotion analyses revealed impairments in fear recognition in both groups of patients, whereas happiness and surprise recognition was only impaired in patients with insular resection. There was no evidence for a deficit in disgust recognition. The findings suggest that unilateral damage to the operculo-insular region may be associated with subtle impairments in emotion recognition, and provide further clinical evidence of a role of the insula in empathic processes. However, the description of 15 consecutive cases of insula-damaged patients with no specific deficit in disgust recognition seriously challenges the assumptions, based on previous case reports, that the insula is specifically involved in disgust processing.

Multisensory integration and child neurodevelopment.

A considerable number of cognitive processes depend on the integration of multisensory information. The brain integrates this information, providing a complete representation of our surrounding world and giving us the ability to react optimally to the environment. Infancy is a period of great changes in brain structure and function that are reflected by the increase of processing capacities of the developing child. However, it is unclear if the optimal use of multisensory information is present early in childhood or develops only later, with experience. The first part of this review has focused on the typical development of multisensory integration (MSI). We have described the two hypotheses on the developmental process of MSI in neurotypical infants and children, and have introduced MSI and its neuroanatomic correlates. The second section has discussed the neurodevelopmental trajectory of MSI in cognitively-challenged infants and children. A few studies have brought to light various difficulties to integrate sensory information in children with a neurodevelopmental disorder. Consequently, we have exposed certain possible neurophysiological relationships between MSI deficits and neurodevelopmental disorders, especially dyslexia and attention deficit disorder with/without hyperactivity.

Hyperacusis following unilateral damage to the insular cortex: a three-case report.

The insula is a multisensory area involved in various brain functions, including central auditory processing. However, its specific role in auditory function remains unclear. Here we report three cases of persistent hypersensitivity to auditory stimuli following damage to the insular cortex, using behavioral and neurophysiological measures. Two patients who complained of auditory disturbance since they suffered an isolated unilateral insular stroke, and one epileptic patient who underwent right insular resection for control of drug-resistant seizures, were involved in this study. These patients, all young adult women, were tested for auditory function more than one year after brain injury, and were compared to 10 healthy control participants matched for age, sex, and education. The assessment included pure-tone detection and speech detection in quiet, loudness discomfort levels, random gap detection, recognition of frequency and duration patterns, binaural separation, dichotic listening, as well as late-latency auditory event-related potentials (ERPs). Each patient showed mild or moderate hyperacusis, as revealed by decreased loudness discomfort levels, which was more important on the side of lesion in two cases. Tests of temporal processing also revealed impairments, in concordance with previous findings. ERPs of two patients were characterised by increased amplitude of the P3b component elicited during a two-tone auditory oddball detection task. This study is the first to report cases of persistent hyperacusis following damage to the insular cortex, and suggests that the insula is involved in modulating the perceived intensity of the incoming auditory stimuli during late-stage processing.