Structural Connectivity in Ventral Language Pathways Characterizes Nonverbal Autism

Autism spectrum disorder (ASD) involves a large variety of language capacities, from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difficulties of scanning at this severe end of the autism spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining the language connectivity network in nonverbal ASD (nvASD): the arcuate (AF), inferior fronto-occipital (IFOF), inferior longitudinal (ILF) and uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to normative benchmarks from matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract –Hemisphere (2:Left/Right) x Group (3:TD/vASD/nvASD). Results revealed (i) a main effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a significant interaction of hemisphere and group in the UF, which showed reduced volume in the left hemisphere when compared to the right, in the vASD group only; and (iii) main effects of hemisphere in both the AF (left-lateralized in volume) and the ILF (left-lateralized in FA). These results do not replicate deficits of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, which is in line with semantic deficits observed behaviourally in this group.

Effects of Piano Training in Unilateral Cerebral Palsy Using Probabilistic and Deterministic Tractography: A Case Report

Cerebral palsy (CP) is an umbrella term encompassing motor and often additional disabilities, resulting from insult to the developing brain and remaining throughout life. Imaging-detected alterations in white matter microstructure affect not only motor but also sensorimotor pathways. In this context, piano training is believed to promote sensorimotor rehabilitation for the multiplicity of skills and neuronal processes it involves and integrates. However, it remains unknown how this contribution may occur. Here, effects of 1.5 years of piano training in an adolescent with unilateral CP were investigated through tests of manual function and by comparing fractional anisotropy, mean diffusivity, radial and axial diffusivity in neuronal pathways pre- vs. post-training. In the absence of a control condition and of data from a larger cohort, both probabilistic neighborhood and deterministic tractography were employed to reduce bias associated with a single-case analysis and/or with user-input. No changes in manual function were detected with the tests performed. In turn, the two tractography methods yielded similar values for all studied metrics. Furthermore, post-hoc analyses yielded increased fractional anisotropy accompanied by decreases in mean diffusivity in the bilateral dorsal cingulate that were at least as large as and more consistent than in the bilateral corticospinal tract. This suggests contributions of training to the development of non-motor processes. Reduced anisotropy and correspondingly high mean diffusivity were observed for the bilateral corticospinal tract as well as for the right arcuate and the inferior longitudinal fasciculus, two sensory processing-related pathways, confirming the importance of sensorimotor rehabilitation in CP.

Use of probabilistic tractography to provide reliable distinction of the motor and sensory thalamus for prospective targeting during asleep deep brain stimulation

OBJECTIVE Accurate electrode placement is key to effective deep brain stimulation (DBS). The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for the treatment of essential tremor (ET). Retrospective tractography-based analysis of electrode placement has associated successful outcomes with modulation of motor input to VIM, but no study has yet evaluated the feasibility and efficacy of prospective presurgical tractography-based targeting alone. Therefore, the authors sought to demonstrate the safety and efficacy of probabilistic tractography–based VIM targeting in ET patients and to perform a systematic comparison of probabilistic and deterministic tractography. METHODS Fourteen patients with ET underwent preoperative diffusion imaging. Probabilistic tractography was applied for preoperative targeting, and deterministic tractography was performed as a comparison between methods. Tractography was performed using the motor and sensory areas as initiation seeds, the ipsilateral thalamus as an inclusion mask, and the contralateral dentate nucleus as a termination mask. Tract-density maps consisted of voxels with 10% or less of the maximum intensity and were superimposed onto anatomical images for presurgical planning. Target planning was based on probabilistic tract-density images and indirect target coordinates. Patients underwent robotic image-guided, image-verified implantation of directional DBS systems. Postoperative tremor scores with and without DBS were recorded. The center of gravity and Dice similarity coefficients were calculated and compared between tracking methods. RESULTS Prospective probabilistic targeting of VIM was successful in all 14 patients. All patients experienced significant tremor reduction. Formal postoperative tremor scores were available for 9 patients, who demonstrated a mean 68.0% tremor reduction. Large differences between tracking methods were observed across patients. Probabilistic tractography–identified VIM fibers were more anterior, lateral, and superior than deterministic tractography–identified fibers, whereas probabilistic tractography–identified ventralis caudalis fibers were more posterior, lateral, and superior than deterministic tractography–identified fibers. Deterministic methods were unable to clearly distinguish between motor and sensory fibers in the majority of patients, but probabilistic methods produced distinct separation. CONCLUSIONS Probabilistic tractography–based VIM targeting is safe and effective for the treatment of ET. Probabilistic tractography is more precise than deterministic tractography for the delineation of VIM and the ventralis caudalis nucleus of the thalamus. Deterministic algorithms tended to underestimate separation between motor and sensory fibers, which may have been due to its limitations with crossing fibers. Larger studies across multiple centers are necessary to further validate this method.

Right-hemisphere compensation during word production: A single case of left-hemisphere young stroke

Our understanding of post-stroke language recovery and underlying neuroplasticity is largely based on older age groups, who have increasing brain pathology and potentially more bilateral language functioning. We present the case of A., a 23 y.o. woman with chronic aphasia from a left-hemisphere stroke. Deterministic tractography indicated that A.’s language-relevant white matter structures were severely damaged. Using magnetoencephalography (MEG), we explored A.’s conceptual preparation and subsequent word planning abilities. Context-driven and Bare picture-naming tasks revealed substantial naming deficits, manifesting as word-finding difficulties and semantic paraphasias about half of the time. Naming was however facilitated by semantically constraining lead-in sentences. Altogether, this pattern indicates intact conceptual preparation but disrupted lexical and phonological retrieval abilities. MEG revealed that A.’s naming-related neural responses differed from that of a matched control. Source localisation showed active but differential recruitment of right-hemisphere structures (300-400 ms post-picture onset) during both correct naming (right temporo-parietal regions) and anomic (right inferior frontal gyrus) attempts. We consider that, despite A.’s young age, the presumed strong degree of language lateralisation and extensive structural damage limited her recovery. Although A.’s right hemisphere responded in a timely manner during word planning, its lexical and phonological retrieval abilities remained modest.

Associations of behavioral problems and white matter properties of the cerebellar peduncles in boys and girls born full term and preterm

Accumulating evidence suggests that the role of cerebellum includes regulation of behaviors; Cerebellar impairment may lead to behavioral problems. Behavioral problems differ by sex: internalizing problems are more common in girls, externalizing problems in boys. Behavioral problems are also elevated in children born preterm (PT) compared to children born full-term (FT). The current study examined internalizing and externalizing problems in 8-year-old children in relation to sex, birth-group, FA of the cerebellar peduncles, and interactions among these predictor variables. Participants (N=78) were 44 boys (28 PT) and 34 girls (15 PT). We assessed behavioral problems via standardized parent-reports and FA of the cerebellar peduncles using deterministic tractography. Internalizing problems were higher in children born PT compared to children born FT (p=.032); the interaction of sex and birth-group was significant (p=.044). When considering the contribution of the mean-tract FA of cerebellar peduncles to behavioral problems, there was a significant interaction of sex and mean-tract FA of the ICP with internalizing problems; the slope was negative in girls (p=.020) but not boys. In boys, internalizing problems were only associated with mean-tract FA ICP in those born preterm (p=.010). We found no other significant associations contributing to internalizing or externalizing problems. Thus, we found sexual dimorphism and birth-group differences in the association of white matter metrics of the ICP and internalizing problems in school-aged children. The findings inform theories of the origins of internalizing behavioral problems in middle childhood and may suggest approaches to treatment at school age.

Constrained-Spherical Deconvolution Tractography in the Evaluation of the Corticospinal Tract in Glioma Surgery

Introduction: Tractography has demonstrated utility for surgical resection in the setting of primary brain tumors involving eloquent white matter (WM) pathways.Methods: Twelve patients with glioma in or near eloquent motor areas were analyzed. The motor status was recorded before and after surgery. Two different tractography approaches were used to generate the motor corticospinal tract (CST): Constrained spherical deconvolution probabilistic tractography (CSD-Prob) and single tensor deterministic tractography (Tens-DET). To define the degree of disruption of the CST after surgical resection of the tumor, we calculated the percentage of the CST affected by surgical resection, which was then correlated with the postoperative motor status. Moreover, the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the CST generated by the CSD-Prob and the Tens-DET was measured and compared between the ipsilesional and contralesional side.Results: The CST was identified in all patients and its trajectory was displaced by the tumor. Only the CSD-Prob approach showed the CST with the characteristic fan-like projections from the precentral gyrus to the brainstem. Disruption of the CST was identified in 6/6 with postoperative motor deficit by CSD-Prob approach and in 5/6 in the Tens-DET. The degree of disruption was significantly associated with the motor deficit with the CSD-Prob approach (rho = −0.88, p = 0.021). However, with the Tens-DET approach the CST disruption did not show significant association with the motor function (rho = −0.27, p = 0.6). There was a significant decrease in FA (p = 0.006) and a significant increase in MD (p = 0.0004) and RD (p = 0.005) on the ipsilesional CST compared with the contralesional CST only with the CSD-Prob approach.Conclusion: CSD-Prob accurately represented the known anatomy of the CST and provided a meaningful estimate of microstructural changes of the CST affected by the tumor and its macrostructural damage after surgery. Newer surgical planning stations should include advanced models and algorithms of tractography in order to obtain more meaningful reconstructions of the WM pathways during glioma surgery.

Fractional anisotropy thresholding for deterministic tractography of the roots of the brachial plexus

Diffusion tensor imaging (DTI) metrics, such as the fractional anisotropy (FA) and estimates of diffusivity are sensitive to the microstructure of peripheral nerves and may be displayed as tractograms. However, the ideal conditions for tractography of the roots of the brachial plexus are unclear, which represents the rationale for this study. Ten healthy adults were scanned using a Siemens Prisma (3T) and single-shot echo-planar imaging (b-value 0/1000 s/mm2, 64 directions, 2.5 mm3 with 4 averages; repeated in opposing phase encoding directions). Susceptibility correction and tractography were performed in DSI Studio by two independent raters. The effect of FA thresholding at increments of 0.01 (from 0.04 to 0.10) were tested. The mean FA varied between subjects by 2% (95% CI 1%, 3%). FA thresholds of 0.04, 0.05 and 0.06 all propagated 96% of tracts representing the roots; thresholding at 0.07 yielded 4% fewer tracts (p = 0.2), 0.08 yielded 11% fewer tracts (p = 0.008), 0.09 yielded 15% fewer tracts (p = 0.001) and 0.1 yielded 20% fewer tracts (p < 0.001). There was < 0.1% inter-rater variability in the measured FA and 99% agreement for tractography (κ = 0.92, p < 0.001). The fractional anisotropy thresholds required to generate tractograms of the roots of the brachial plexus appears to be lower than those used in the brain. We provide estimates of the probability of generating true tracts for each spinal nerve root of the brachial plexus, at different fractional anisotropy thresholds.