Judith Verhoeven

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.

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.

Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients

A subgroup of patients with breast cancer suffers from mild cognitive impairment after chemotherapy. To uncover the neural substrate of these mental complaints, we examined cerebral white matter (WM) integrity after chemotherapy using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. Postchemotherapy breast cancer patients (n = 17) and matched healthy controls (n = 18) were recruited for DTI and neuropsychological testing, including the self‐report cognitive failure questionnaire (CFQ). Differences in DTI WM integrity parameters [fractional anisotropy (FA) and mean diffusivity (MD)] between patients and healthy controls were assessed using a voxel‐based two‐sample‐t‐test. In comparison with healthy controls, the patient group demonstrated decreased FA in frontal and temporal WM tracts and increased MD in frontal WM. These differences were also confirmed when comparing this patient group with an additional control group of nonchemotherapy‐treated breast cancer patients (n = 10). To address the heterogeneity observed in cognitive function after chemotherapy, we performed a voxel‐based correlation analysis between FA values and individual neuropsychological test scores. Significant correlations of FA with neuropsychological tests covering the domain of attention and processing/psychomotor speed were found in temporal and parietal WM tracts. Furthermore, CFQ scores correlated negatively in frontal and parietal WM. These studies show that chemotherapy seems to affect WM integrity and that parameters derived from DTI have the required sensitivity to quantify neural changes related to chemotherapy‐induced mild cognitive impairment. Hum Brain Mapp 32:480–493, 2011.

Construction of a stereotaxic DTI atlas with full diffusion tensor information for studying white matter maturation from childhood to adolescence using tractography-based segmentations.

Reconstruction of white matter (WM) fiber tracts based on diffusion tensor imaging (DTI) is increasingly being used in clinical and research settings to study normal and pathological WM tissue as well as the maturation of this WM tissue. Such fiber tracking (FT) methodology, however, is highly dependent on the manual delineation of anatomical landmarks and the algorithm settings, often rendering the reproducibility and reliability questionable. Predefining these regions of interest on a fractional anisotropy (FA) atlas in standard space has already been shown to improve the reliability of FT results. In this paper, we constructed a new DTI atlas, which contains the complete diffusion tensor information in ICBM152 coordinates. From this high‐dimensional DTI atlas, and using robust FT protocols, we reconstructed a large number of WM tracts. Subsequently, we created tract masks from these fiber tract bundles and evaluated the atlas framework by comparing the reproducibility of the results obtained from our standardized tract masks with regions‐of‐interest labels from the conventional FA‐based WM atlas. Finally, we assessed laterality and age‐related WM changes in 42 normal subjects aged 0 to 18 years using these tractography‐derived tract segmentations. In agreement with previous literature, we observed an FA increase with age, which was mainly due to the decrease of perpendicular diffusivity. In addition, major functional pathways in the language, motor, and limbic system, showed a significant asymmetry in terms of the observed diffusion metrics. Hum Brain Mapp, 2010.

Integrity of the inferior longitudinal fasciculus and impaired object recognition in children: a diffusion tensor imaging study

Aim  In this study, we explored the integrity of the inferior longitudinal fasciculus (ILF) by means of diffusion tensor imaging tractography in children with visual perceptual impairment, and more specifically, object recognition deficits, compared with typically developing children.

Is There a Common Neuroanatomical Substrate of Language Deficit between Autism Spectrum Disorder and Specific Language Impairment

Discussion of an overlap between specific language impairment (SLI) and autism spectrum disorder (ASD) is on going. The most intriguing overlap between both phenotypes is the similarity in the observed language deficits described in SLI and a subgroup of ASD with co-occurring linguistic impairment, ASD-LI. Examining whether a similar neuroanatomical substrate underlies this phenotypical linguistic overlap, we studied the white matter microstructural properties of the superior longitudinal fascicle (SLF) of 19 ASD-LI adolescents (mean age 13.8 ± 1.6 years) and 21 age-matched controls and compared them with 13 SLI children (mean age 10.1 ± 0.4 years) and 12 age-matched controls. A linguistic profile assessment and a diffusion tensor imaging analysis of the SLF were performed. Linguistic testing revealed a mixed receptive-expressive disorder profile in both groups, confirming their overlap at phenotypical level. At neuroanatomical level, no significant differences in mean SLF fractional anisotropy (FA) and mean SLF apparent diffusion coefficient values between ASD-LI participants and controls were seen. By contrast, the mean SLF FA was significantly reduced in the SLI children as compared with their controls. The observation of structural SLF disturbances in SLI but not in ASD-LI suggests the existence of a different neuroanatomical substrate for the language deficits in both disorders.

Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernickes and Brocas areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

Structural and functional underconnectivity as a negative predictor for language in autism.

The development of language, social interaction, and communicative skills are remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the interplay between their brain connectivity and language performance remains largely understudied. Using diffusion tensor imaging tractography and resting‐state fMRI, the authors explored the structural and functional connectivity of the language network and its relation to the language profile in a group of healthy control subjects (N = 25) and a group of children with ASD (N = 17). The authors hypothesized that in children with ASD, a neural connectivity deficit of the language network can be related to the observed abnormal language function. They found an absence of the right‐hemispheric arcuate fascicle (AF) in 28% (7/25) of the healthy control children and in 59% (10/17) of the children with ASD. In contrast to healthy control children, the absence of the right‐hemispheric AF in children with autism was related to a lower language performance as indicated by a lower verbal IQ, lower scores on the Peabody Picture Vocabulary Test, and lower language scores on the Dutch version of the Clinical Evaluation of Language Fundamentals (CELF‐4NL). In addition, through iterative fMRI data analyses, the language impairment of children with ASD could be linked to a marked loss of intrahemispheric functional connectivity between inferior frontal and superior temporal regions, known as the cortical language network. Both structural and functional underconnectivity patterns coincide and are related to an abnormal language function in children with ASD. Hum Brain Mapp 35:3602–3615, 2014.

Functional Organization of the Action Observation Network in Autism: A Graph Theory Approach

Background The ability to recognize, understand and interpret other’s actions and emotions has been linked to the mirror system or action-observation-network (AON). Although variations in these abilities are prevalent in the neuro-typical population, persons diagnosed with autism spectrum disorders (ASD) have deficits in the social domain and exhibit alterations in this neural network. Method Here, we examined functional network properties of the AON using graph theory measures and region-to-region functional connectivity analyses of resting-state fMRI-data from adolescents and young adults with ASD and typical controls (TC). Results Overall, our graph theory analyses provided convergent evidence that the network integrity of the AON is altered in ASD, and that reductions in network efficiency relate to reductions in overall network density (i.e., decreased overall connection strength). Compared to TC, individuals with ASD showed significant reductions in network efficiency and increased shortest path lengths and centrality. Importantly, when adjusting for overall differences in network density between ASD and TC groups, participants with ASD continued to display reductions in network integrity, suggesting that also network-level organizational properties of the AON are altered in ASD. Conclusion While differences in empirical connectivity contributed to reductions in network integrity, graph theoretical analyses provided indications that also changes in the high-level network organization reduced integrity of the AON.

Fragile Spectral and Temporal Auditory Processing in Adolescents with Autism Spectrum Disorder and Early Language Delay

We investigated low-level auditory spectral and temporal processing in adolescents with autism spectrum disorder (ASD) and early language delay compared to matched typically developing controls. Auditory measures were designed to target right versus left auditory cortex processing (i.e. frequency discrimination and slow amplitude modulation (AM) detection versus gap-in-noise detection and faster AM detection), and to pinpoint the task and stimulus characteristics underlying putative superior spectral processing in ASD. We observed impaired frequency discrimination in the ASD group and suggestive evidence of poorer temporal resolution as indexed by gap-in-noise detection thresholds. These findings question the evidence of enhanced spectral sensitivity in ASD and do not support the hypothesis of superior right and inferior left hemispheric auditory processing in ASD.