Stefan Sunaert

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)—a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

LONG‐TERM ELECTRICAL CAPSULAR STIMULATION IN PATIENTS WITH OBSESSIVE‐COMPULSIVE DISORDER

OBJECTIVEBecause of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing, treatment-resistant obsessive-compulsive disorder. METHODSWe stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTSThe psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 ± 8.0) than in the postoperative stimulator-off condition (mean, 32.3 ± 3.9), and this stimulation-induced effect was maintained for at least 21 months after surgery. The Clinical Global Severity score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition to 3.3 (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies, especially in the pons. Digital subtraction analysis of preoperative [18F]2-fluoro-2-deoxy-d-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSIONThese observations indicate that capsular stimulation reduces core symptoms 21 months after surgery in patients with severe, long-standing, treatment-refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography.

Motion-responsive regions of the human brain

Abstract Functional magnetic resonance imaging was used to map motion responsive regions of the human brain by contrasting passive viewing of moving and stationary randomly textured patterns. Regions were retained as motion responsive if they reached significance either in the group analysis or in the majority of hemispheres in single-subject analysis. They include well-known regions, such as V1, hMT/V5+, and hV3A, but also several occipito-temporal, occipito-parietal, parietal, and frontal regions. The time course of the activation was similar in most of these regions. Motion responses were nearly identical for binocular and monocular presentations. Flicker-induced-activation introduced a dichotomy amongst these motion responsive regions. Early occipital and occipito-temporal regions responded well to flicker, while flicker responses gradually vanished as one moved to occipito-parietal and then parietal regions. Finally, over a more than four-fold range, stimulus diameter had little effect on the motion activations, except in V1.

Internal vs external generation of movements: differential neural pathways involved in bimanual coordination performed in the presence or absence of augmented visual feedback.

It is commonly agreed that a functional dissociation with respect to the internal vs external control of movements exists for several brain regions. This has, however, only been tested in relation to the timing and preparation of motor responses, but not to ongoing movement control. Using functional magnetic resonance imaging (fMRI), the present study addressed the neuroanatomical substrate of the internal-external control hypothesis by comparing regional brain activation for cyclical bimanual movements performed in the presence or absence of augmented visual feedback. Subjects performed a bimanual movement pattern, either with the help of on-line visual feedback of the movements (externally guided coordination) or with the eyes closed on the basis of an internal representation of the movement pattern (internally generated coordination). Visual control and baseline rest conditions were also added. Results showed a clear functional dissociation within the network involved in movement coordination. The hMT/V5+, the superior parietal cortex, the premotor cortex, the thalamus, and cerebellar lobule VI showed higher activation levels when movements were guided by visual feedback. Conversely, the basal ganglia, the supplementary motor area, cingulate motor cortex, the inferior parietal, frontal operculum, and cerebellar lobule IV-V/dentate nucleus showed higher involvement when movements were internally generated. Consequently, the present findings suggest the existence of distinct cortico-cortical and subcortico-cortical neural pathways for externally (augmented feedback) and internally guided cyclical bimanual movements. This provides a neurophysiological account for the beneficial effect of providing augmented visual feedback to optimize movements in normal and motor disordered patients.

Brain Areas Involved in Interlimb Coordination: A Distributed Network

Whereas behavioral studies have made significant contributions toward the identification of the principles governing the coordination of limb movements, little is known about the role of higher brain areas that are involved in interlimb coordination. Functional magnetic resonance imaging (fMRI) was used to reveal the brain areas activated during the cyclical coordination of ipsilateral wrist and foot movements. Six normal subjects performed five different tasks that were presented in a random order, i.e., isolated flexion-extension movements of the right wrist (WRIST) and right foot (FOOT), cyclical coordination of wrist and foot according to the isodirectional (ISODIR) and nonisodirectional (NON-ISODIR) mode, and rest (REST). All movements were auditory paced at 66 beats/min. During the coordination of both limb segments, a distributed network was identified showing activation levels in the supplementary motor area (SMA), cingulate motor cortex (CMC), premotor cortex (PMC), primary sensorimotor cortex (M1/S1), and cerebellum that exceeded the sum of the activations observed during the isolated limb movements. In addition, coordination of the limb movements in different directions was associated with extra activation of the SMA as compared to movements in the same direction. It is therefore concluded that the SMA is substantially involved in the coordination of the nonhomologous limbs as part of a distributed motor network. Accordingly, the long-standing exclusive association that has been made between this medial frontal area and bimanual (homologous) coordination needs to be abandoned and extended towards other forms of interlimb coordination (nonhomologous).

Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White Matter and Its Correlation With Impaired Cognitive Functioning

PURPOSE To uncover the neural substrate of cognitive impairment related to adjuvant chemotherapy, we studied cerebral white matter (WM) integrity before and after chemotherapy by using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. PATIENTS AND METHODS Thirty-four young premenopausal women with early-stage breast cancer who were exposed to chemotherapy underwent neuropsychologic testing and DTI before the start of chemotherapy (t1) and 3 to 4 months after treatment (t2). Sixteen patients not exposed to chemotherapy and 19 age-matched healthy controls underwent the same assessment at matched intervals. In all groups, we used paired t tests to study changes in neuropsychologic test scores and whole-brain voxel-based paired t tests to study changes in WM fractional anisotropy (FA; a DTI measure that reflects WM tissue organization), with depression scores and intelligence quotient as included covariates. We correlated changes of neuropsychologic test scores with the mean change of FA for regions that survived the paired t tests in patients treated with chemotherapy. RESULTS In contrast to controls, the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory at t2 compared with t1 (P < .05). In the chemotherapy-treated group, we found significant decreases of FA in frontal, parietal, and occipital WM tracts after treatment (familywise error P < .05), whereas for both control groups, FA values were the same between t1 and t2. Furthermore, performance changes in attention and verbal memory correlated with mean regional FA changes in chemotherapy-treated patients (P < .05). CONCLUSION We report evidence of longitudinal changes in cognitive functioning and cerebral WM integrity after chemotherapy as well as an association between both.

Changes in brain activation during the acquisition of a new bimanual coordination task

Motor skill acquisition is associated with the development of automaticity and induces neuroplastic changes in the brain. Using functional magnetic resonance imaging (fMRI), the present study traced learning-related activation changes during the acquisition of a new complex bimanual skill, requiring a difficult spatio-temporal relationship between the limbs, i.e., cyclical flexion-extension movements of both hands with a phase offset of 90 degrees. Subjects were scanned during initial learning and after the coordination pattern was established. Kinematics of the movements were accurately registered and showed that the new skill was acquired well. Learning-related decreases in activation were found in right dorsolateral prefrontal cortex (DLPFC), right premotor, bilateral superior parietal cortex, and left cerebellar lobule VI. Conversely, learning-related increases in activation were observed in bilateral primary motor cortex, bilateral superior temporal gyrus, bilateral cingulate motor cortex (CMC), left premotor cortex, cerebellar dentate nuclei/lobule III/IV/Crus I, putamen/globus pallidus and thalamus. Accordingly, bimanual skill learning was associated with a shift in activation among cortico-subcortical regions, providing further evidence for the existence of differential cortico-subcortical circuits preferentially involved during the early and advanced stages of learning. The observed activation changes account for the transition from highly attention-demanding task performance, involving processing of sensory information and corrective action planning, to automatic performance based on memory representations and forward control.

The role of anterior cingulate cortex and precuneus in the coordination of motor behaviour

Behavioral studies in humans have shown that bimanual coordination imposes specific demands on the central nervous system that exceed unimanual task control. In the present study we used functional magnetic resonance imaging to investigate the neural correlate of this additional coordination effort, i.e. regions responding more strongly to bimanual movements than inferred from summing up the responses to the unimanual subtasks. Subjects were scanned while performing movements along different directions, either uni‐ or bimanually. During the bimanual condition, trajectories of movement of the left and right hand were spatially incompatible, such that additional effort was required to break away from intrinsically favored mirror‐movements and to integrate movements of both limbs into a new spatial pattern. Our main finding was that the execution of spatially complex bimanual coordination as compared with the unimanual subtasks activated the anterior cingulate cortex (posterior part) as well as the dorso‐anterior precuneus. We hypothesize that the anterior cingulate exerts its modulatory effect on other motor areas, such as the primary motor cortex and the supplementary motor area, in order to suppress intrinsically favored coordination tendencies. Conversely, the precuneus is likely to be involved in shifting attention between different locations in space, which was necessary for monitoring the trajectories of the left and right wrist when both limbs moved in parallel. Our findings suggest that the coordination effort during bimanual and perhaps other modes of coordinated behavior is mediated by regions contributing to higher order functions, which form an interface between cognition and action.

Intact but less accessible phonetic representations in adults with dyslexia

Good Foundations, Poor Access Dyslexia makes reading and spelling difficult. Boets et al. (p. 1251) analyzed whether for adult readers with dyslexia the internal references for word sounds are poorly constructed or whether accessing those references is abnormally difficult. Brain imaging during phonetic discrimination tasks suggested that the internal dictionary for word sounds was correct, but accessing the dictionary was more difficult than normal. The persistent reading problems observed in dyslexia may derive from inefficient communication within the brain. Dyslexia is a severe and persistent reading and spelling disorder caused by impairment in the ability to manipulate speech sounds. We combined functional magnetic resonance brain imaging with multivoxel pattern analysis and functional and structural connectivity analysis in an effort to disentangle whether dyslexics’ phonological deficits are caused by poor quality of the phonetic representations or by difficulties in accessing intact phonetic representations. We found that phonetic representations are hosted bilaterally in primary and secondary auditory cortices and that their neural quality (in terms of robustness and distinctness) is intact in adults with dyslexia. However, the functional and structural connectivity between the bilateral auditory cortices and the left inferior frontal gyrus (a region involved in higher-level phonological processing) is significantly hampered in dyslexics, suggesting deficient access to otherwise intact phonetic representations.

Gliomas: Diffusion Kurtosis MR Imaging in Grading

PURPOSE To assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters in grading gliomas. MATERIALS AND METHODS The institutional review board approved this prospective study, and informed consent was obtained from all patients. Diffusion parameters-mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosis-were compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas (P<.05 significance level, Mann-Whitney-Wilcoxon test, Bonferroni correction). MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were also normalized to the corresponding values in contralateral normal-appearing white matter (NAWM) and the contralateral posterior limb of the internal capsule (PLIC) after age correction and were compared among tumor grades. RESULTS Mean, radial, and axial kurtosis were significantly higher in high-grade gliomas than in low-grade gliomas (P = .02, P = .015, and P = .01, respectively). FA and MD did not significantly differ between glioma grades. All values, except for axial kurtosis, that were normalized to the values in the contralateral NAWM were significantly different between high-grade and low-grade gliomas (mean kurtosis, P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). When values were normalized to those in the contralateral PLIC, none of the considered parameters showed significant differences between high-grade and low-grade gliomas. The highest sensitivity and specificity for discriminating between high-grade and low-grade gliomas were found for mean kurtosis (71% and 82%, respectively) and mean kurtosis normalized to the value in the contralateral NAWM (100% and 73%, respectively). Optimal thresholds for mean kurtosis and mean kurtosis normalized to the value in the contralateral NAWM for differentiating high-grade from low-grade gliomas were 0.52 and 0.51, respectively. CONCLUSION There were significant differences in kurtosis parameters between high-grade and low-grade gliomas; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters.