Identifying interindividual variability of social perception and associated brain anatomical correlations in children with autism spectrum disorder using eye-tracking and diffusion tensor imaging MRI (DTI-MRI).

Even though deficits in social cognition constitute a core characteristic of autism spectrum disorders, a large heterogeneity exists regarding individual social performances and its neural basis remains poorly investigated. Here, we used eye-tracking to objectively measure interindividual variability in social perception and its correlation with white matter microstructure, measured with diffusion tensor imaging MRI, in 25 children with autism spectrum disorder (8.5 ± 3.8 years). Beyond confirming deficits in social perception in participants with autism spectrum disorder compared 24 typically developing controls (10.5 ± 2.9 years), results revealed a large interindividual variability of such behavior among individuals with autism spectrum disorder. Whole-brain analysis showed in both autism spectrum disorder and typically developing groups a positive correlation between number of fixations to the eyes and fractional anisotropy values mainly in right and left superior longitudinal tracts. In children with autism spectrum disorder a correlation was also observed in right and left inferior longitudinal tracts. Importantly, a significant interaction between group and number of fixations to the eyes was observed within the anterior portion of the right inferior longitudinal fasciculus, mainly in the right anterior temporal region. This additional correlation in a supplementary region suggests the existence of a compensatory brain mechanism, which may support enhanced performance in social perception among children with autism spectrum disorder.

Case Report: Zolpidem's paradoxical restorative action: A case report of functional brain imaging.

Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca's area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery.

Periodic electroencephalographic discharges and epileptic spasms involve cortico-striatal-thalamic loops on Arterial Spin Labeling Magnetic Resonance Imaging.

Periodic discharges are a rare peculiar electroencephalogram pattern, occasionally associated with motor or other clinical manifestations, usually observed in critically ill patients. Their underlying pathophysiology remains poorly understood. Epileptic spasms in clusters and periodic discharges with motor manifestations share similar electroencephalogram pattern and some aetiologies of unfavourable prognosis such as subacute sclerosing panencephalitis or herpes encephalitis. Arterial spin labelling magnetic resonance imaging identifies localizing ictal and inter-ictal changes in neurovascular coupling, therefore assumed able to reveal concerned cerebral structures. Here, we retrospectively analysed ictal and inter-ictal arterial spin labelling magnetic resonance imaging in patients aged 6 months to 15 years (median 3 years 4 months) with periodic discharges including epileptic spasms, and compared these findings with those of patients with drug-resistant focal epilepsy who never presented periodic discharges nor epileptic spasms as well as to those of age-matched healthy controls. Ictal electroencephalogram was recorded either simultaneously with arterial spin labelling magnetic resonance imaging or during the close time lapse of patients' periodic discharges, whereas inter-ictal examinations were performed during the patients' active epilepsy but without seizures during the arterial spin labelling magnetic resonance imaging. Ictal arterial spin labelling magnetic resonance imaging was acquired in five patients with periodic discharges [subacute sclerosing panencephalitis (1), stroke-like events (3), West syndrome with cortical malformation (1), two of them also had inter-ictal arterial spin labelling magnetic resonance imaging]. Inter-ictal group included patients with drug-resistant epileptic spasms of various aetiologies (14) and structural drug-resistant focal epilepsy (8). Cortex, striatum and thalamus were segmented and divided in six functional subregions: prefrontal, motor (rostral, caudal), parietal, occipital and temporal. Rest cerebral blood flow values, absolute and relative to whole brain, were compared with those of age-matched controls for each subregion. Main findings were diffuse striatal as well as cortical motor cerebral blood flow increase during ictal examinations in generalized periodic discharges with motor manifestations (subacute sclerosing panencephalitis) and focal cerebral blood flow increase in corresponding cortical-striatal-thalamic subdivisions in lateralized periodic discharges with or without motor manifestations (stroke-like events and asymmetrical epileptic spasms) with straight topographical correlation with the electroencephalogram focus. For inter-ictal examinations, patients with epileptic spasms disclosed cerebral blood flow changes in corresponding cortical-striatal-thalamic subdivisions (absolute-cerebral blood flow decrease and relative-cerebral blood flow increase), more frequently when compared with the group of drug-resistant focal epilepsies, and not related to Vigabatrin treatment. Our results suggest that corresponding cortical-striatal-thalamic circuits are involved in periodic discharges with and without motor manifestations, including epileptic spasms, opening new insights in their pathophysiology and new therapeutical perspectives. Based on these findings, we propose a model for the generation of periodic discharges and of epileptic spasms combining existing pathophysiological models of cortical-striatal-thalamic network dynamics.

A CBF decrease in the left supplementary motor areas: New insight into postoperative pediatric cerebellar mutism syndrome using arterial spin labeling perfusion MRI.

Postoperative pediatric cerebellar mutism syndrome (pCMS), characterized mainly by delayed onset transient mutism is a poorly understood complication that may occur after pediatric medulloblastoma (MB) resection. Our aim was to investigate postoperative changes in whole-brain cerebral blood flow (CBF) at rest in pCMS patients using arterial spin labeling (ASL) perfusion imaging. This study compared preoperative and postoperative T2-weighted signal abnormalities and CBF using a voxel-wise, whole-brain analysis in 27 children undergoing MB resection, including 11 patients who developed mutism and 16 who did not. Comparison of postoperative T2 signal abnormalities between patients who developed pCMS (mean age 7.0 years) and those who did not showed that pCMS (mean age 8.9 years) patients were significantly more likely to present with T2-weighted hyperintensities in the right dentate nucleus (DN) (p = 0.02). Comparison of preoperative and postoperative CBF in patients with pCMS showed a significant postoperative CBF decrease in the left pre-supplementary motor area (pre-SMA) (p = 0.007) and SMA (p = 0.009). In patients who did not develop pCMS, no significant differences were observed. Findings provide evidence of an association between pCMS, injury to the right DN, and left pre-SMA/SMA hypoperfusion, areas responsible for speech. This supports the relevance of CBF investigations in pCMS.

Arterial spin labeling brain MRI study to evaluate the impact of deafness on cerebral perfusion in 79 children before cochlear implantation.

Age at implantation is considered to be a major factor, influencing outcomes after pediatric cochlear implantation. In the absence of acoustic input, it has been proposed that cross-modal reorganization can be detrimental for adaptation to the new electrical input provided by a cochlear implant. Here, through a retrospective study, we aimed to investigate differences in cerebral blood flow (CBF) at rest prior to implantation in children with congenital deafness compared to normally hearing children. In addition, we looked at the putative link between pre-operative rest-CBF and the oral intelligibility scores at 12 months post-implantation. Finally, we observed the evolution of perfusion with age, within brain areas showing abnormal rest-CBF associated to deafness, in deaf children and in normally hearing children. In children older than 5 years old, results showed a significant bilateral hypoperfusion in temporal regions in deaf children, particularly in Heschl's gyrus, and a significant hyperperfusion of occipital regions. Furthermore, in children older than 5 years old, whole brain voxel-by-voxel correlation analysis between pre-operative rest-CBF and oral intelligibility scores at 12 months post-implantation, showed significant negative correlation localized in the occipital regions: children who performed worse in the speech perception test one year after implantation were those presenting higher preoperative CBF values in these occipital regions. Finally, when comparing mean relative perfusion (extracted from the temporal regions found abnormal on whole-brain voxel-based analysis) across ages in patients and controls, we observed that the temporal perfusion evolution was significantly different in deaf children than in normally hearing children. Indeed, while temporal perfusion increased with age in normally hearing children, it remained stable in deaf children. We showed a critical period around 4 years old, where in the context of auditory deprivation, there is a lack of synaptic activity in auditory regions. These results support the benefits of early cochlear implantation to maximize the effectiveness of auditory rehabilitation and to avoid cross-modal reorganization.

Rest Functional Brain Maturation during the First Year of Life.

The first year of life is a key period of brain development, characterized by dramatic structural and functional modifications. Here, we measured rest cerebral blood flow (CBF) modifications throughout babies' first year of life using arterial spin labeling magnetic resonance imaging sequence in 52 infants, from 3 to 12 months of age. Overall, global rest CBF significantly increased during this age span. In addition, we found marked regional differences in local functional brain maturation. While primary sensorimotor cortices and insula showed early maturation, temporal and prefrontal region presented great rest CBF increase across the first year of life. Moreover, we highlighted a late and remarkably synchronous maturation of the prefrontal and posterior superior temporal cortices. These different patterns of regional cortical rest CBF modifications reflect a timetable of local functional brain maturation and are consistent with baby's cognitive development within the first year of life.

Neural and behavioral signature of human social perception.

Social behavior is extremely variable among individuals, and the neural basis of this variability is still poorly understood. In this study, we aimed to investigate the neural basis of interindividual variability in the first step of social behavior, that is, social perception. For that purpose, we first used eye-tracking to measure social perception during the passive visualization of socially relevant movie clips. Second, we correlated eye-tracking data with measures of rest cerebral blood flow (CBF) obtained using arterial spin-labeling (ASL) MRI, an index of local rest brain function. The results showed a large interindividual variability in the number of fixations to the eyes of characters during passive visualization of movie clips displaying social interactions. Moreover, individual patterns remained stable across time, suggesting an individual signature of social behavior. Whole-brain analyses showed significant positive correlation between the number of fixations to the eyes and rest CBF: individuals who looked more to the eyes were those with higher rest CBF levels within the right superior temporal regions. Our results indicate the existence of a neural and behavioral signature associated with the interindividual variability in social perception.