Jidan Zhong

Merged Group Tractography Evaluation with Selective Automated Group Integrated Tractography.

Introduction: Tractography analysis in group-based studies across large populations has been difficult to implement. We propose Selective Automated Group Integrated Tractography (SAGIT), an automated group tractography software platform that incorporates multiple diffusion magnetic resonance imaging (dMRI) practices which will allow great accessibility to group-wise dMRI. We use a merged tractography approach that permits evaluation of tractography datasets at the group level. We also introduce an image normalized overlap score (NOS) that measures the quality of the group tractography results. We deploy SAGIT to evaluate deterministic and probabilistic constrained spherical deconvolution (CSTdet, CSTprob) tractography, eXtended Streamline Tractography (XST), and diffusion tensor tractography (DTT) in their ability to delineate different neuroanatomy, as well as validating NOS across these different brain regions. Materials and methods: Magnetic resonance sequences were acquired from 42 healthy adults. Anatomical and group registrations were performed using Automated Normalization Tools. Cortical segmentation was performed using FreeSurfer. Four tractography algorithms were used to delineate six sets of neuroanatomy: fornix, facial/vestibular-cochlear cranial nerve complex, vagus nerve, rubral–cerebellar decussation, optic radiation, and auditory radiation. The tracts were generated both with and without region of interest filters. The generated visual reports were then evaluated by five neuroscientists. Results: At a group level, merged tractography demonstrated that different methods have different fiber distribution characteristics. CSTprob is prone to false-positives, and thereby suitable in anatomy with strong priors. CSTdet and XST are more conservative, but have greater difficulty resolving hemispherical decussation and distant crossing projections. DTT consistently shows the worst reproducibility across the anatomies. Linear regression of rater scores against NOS shows significant (p < 0.05) correlation of the two sets of scores in filtered tractography. However, correlations are not significant (p > 0.05) for unfiltered tractography. Conclusion: The tractography results demonstrated reliable and consistent performance of SAGIT across multiple subjects and techniques. Through SAGIT, we quantifiably demonstrated that different algorithms showed different strengths and weaknesses at a group level. While no single algorithm seems to be suitable for all anatomical tasks, it is useful to consider the use of a mix of algorithms for different anatomical segments. SAGIT appears to be a promising group-wise tractography analysis approach for this purpose.

Intracortical inhibition abnormality during the remission phase of multiple sclerosis is related to upper limb dexterity and lesions

OBJECTIVE The impact of inhibitory cortical activity on motor impairment of people with relapsing-remitting multiple sclerosis (RRMS) has not been fully elucidated despite its relevance to neurorehabilitation. The present study assessed the extent to which transcranial magnetic stimulation (TMS)-based metrics of intracortical inhibition are related to motor disability and brain damage. METHODS Participants included forty-three persons with RRMS in the remitting phase and twenty-nine healthy controls. We stimulated the dominant hemisphere and recorded from the dominant hand to assess short-interval intracortical inhibition (SICI) and cortical silent period (CSP) duration. Disability was evaluated with the Multiple Sclerosis Functional Composite (MSFC). Regional cortical thickness and lesion volume were measured. RESULTS RRMS participants with dominant upper limb dexterity impairments had prolonged CSP, but equivalent SICI, compared to participants with preserved function. CSP was not related to walking or cognitive performance. Higher normalized lesion volume correlated with longer CSP duration. When adjusting for normalized lesion volume, longer CSP significantly predicted worse dominant upper extremity impairment. CONCLUSIONS High intracortical inhibition possibly contributes to (or prevents remission from) motor impairment. Lesions may be associated with intracortical inhibition shifts. SIGNIFICANCE CSP duration and lesion burden should be considered when developing interventions aiming to mitigate motor impairment.

Predicting pain relief: Use of pre-surgical trigeminal nerve diffusion metrics in trigeminal neuralgia

Trigeminal neuralgia (TN) is a chronic neuropathic facial pain disorder that commonly responds to surgery. A proportion of patients, however, do not benefit and suffer ongoing pain. There are currently no imaging tools that permit the prediction of treatment response. To address this paucity, we used diffusion tensor imaging (DTI) to determine whether pre-surgical trigeminal nerve microstructural diffusivities can prognosticate response to TN treatment. In 31 TN patients and 16 healthy controls, multi-tensor tractography was used to extract DTI-derived metrics—axial (AD), radial (RD), mean diffusivity (MD), and fractional anisotropy (FA)—from the cisternal segment, root entry zone and pontine segment of trigeminal nerves for false discovery rate-corrected Students t-tests. Ipsilateral diffusivities were bootstrap resampled to visualize group-level diffusivity thresholds of long-term response. To obtain an individual-level statistical classifier of surgical response, we conducted discriminant function analysis (DFA) with the type of surgery chosen alongside ipsilateral measurements and ipsilateral/contralateral ratios of AD and RD from all regions of interest as prediction variables. Abnormal diffusivity in the trigeminal pontine fibers, demonstrated by increased AD, highlighted non-responders (n = 14) compared to controls. Bootstrap resampling revealed three ipsilateral diffusivity thresholds of response—pontine AD, MD, cisternal FA—separating 85% of non-responders from responders. DFA produced an 83.9% (71.0% using leave-one-out-cross-validation) accurate prognosticator of response that successfully identified 12/14 non-responders. Our study demonstrates that pre-surgical DTI metrics can serve as a highly predictive, individualized tool to prognosticate surgical response. We further highlight abnormal pontine segment diffusivities as key features of treatment non-response and confirm the axiom that central pain does not commonly benefit from peripheral treatments.

Cortical Damage and Disability in Multiple Sclerosis: Relation to Intracortical Inhibition and Facilitation

BACKGROUND Multimodal research combining biomarkers of intracortical activity and cortical damage could shed light on pathophysiological and adaptive neural processes related to the clinical severity of neurological conditions such as multiple sclerosis (MS). OBJECTIVE Among people with relapsing-remitting and progressive forms of MS, we assessed the extent to which transcranial magnetic stimulation (TMS)-based biomarkers of excitatory and inhibitory cortical activity are related to cortical damage and clinical impairment. METHODS Participants included 18 healthy individuals and 36 people with MS who had a relapsing-remitting or progressive clinical course. Using TMS, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and cortical silent period (CSP) were obtained. Cortical volume and cortical magnetization transfer ratio (MTR) were quantified. Disability was assessed with Multiple Sclerosis Functional Composite (MSFC). RESULTS Lower mean MTR within the cerebral cortex correlated with shorter CSP among MS participants with a progressive, but not a relapsing-remitting, clinical course. Within the cortical hand knob region targeted with TMS, lower MTR was correlated with lower SICI only among individuals with relapsing-remitting MS. Longer CSP, higher ICF, lower cortical MTR, and sex were all independent significant predictors of poor upper extremity motor performance, while only cortical MTR was a significant independent predictor of total MSFC score among people with MS. CONCLUSIONS Cortical damage and cortical activity (both inhibitory and excitatory) may contribute to the severity of motor disability experienced by people with MS. When interpreting TMS-based outcomes, cortical integrity, clinical course, and symptom type should be considered.

Affective Circuitry Alterations in Patients with Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a severe chronic neuropathic facial pain disorder. Affect-related behavioral and structural brain changes have been noted across chronic pain disorders, but have not been well-studied in TN. We examined the potential impact of TN (37 patients: 23 with right-sided TN, 14 with left-sided TN), compared to age- and sex-matched healthy controls, on three major white matter tracts responsible for carrying affect-related signals—i.e., cingulum, fornix, and medial forebrain bundle. Diffusion magnetic resonance imaging (dMRI), deterministic multi-tensor tractography for tract modeling, and a model-driven region-of-interest approach was used. We also used volumetric gray matter analysis on key targets of these pathways (i.e., hippocampus, cingulate cortex subregions, nucleus accumbens, and ventral diencephalon). Hypotheses included: (1) successful modeling of tracts; (2) altered white matter microstructure of the cingulum and medial forebrain bundle (via changes in dMRI metrics such as fractional anisotropy, and mean, axial, and radial diffusivities) compared to controls; (3) no alterations in the control region of the fornix; (4) corresponding decreases in gray matter volumes. Results showed (1) all 325 tracts were successfully modeled, although 11 were partially complete; (2) The cingulum and medial forebrain bundle (MFB) were altered in those with TN, with dMRI metric changes in the middle (p = 0.001) and posterior cingulum (p < 0.0001), and the MFB near the ventral tegmental area (MFB-VTA) (p = 0.001). The posterior cingulum and MFB-VTA also showed unilateral differences between right- and left-sided TN patients; (3) No differences were noted at any fornix subdivision; (4) decreased volumes were noted for the hippocampus, posterior cingulate, nucleus accumbens, and ventral diencephalon. Together, these results support the notion of selectively altered affective circuits in patients with TN, which may be related to the experience of negative affect and the increased comorbidity of mood and anxiety disorders in this population.

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis.

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting‐state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting‐state fMRI, T1‐weighted and T2‐weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease‐related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting‐state fMRI, T1‐weighted, T2‐weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262–4275, 2016.

Multivariate pattern classification of brain white matter connectivity predicts classic trigeminal neuralgia

Abstract Trigeminal neuralgia (TN) is a severe form of chronic facial neuropathic pain. Increasing interest in the neuroimaging of pain has highlighted changes in the root entry zone in TN, but also group-level central nervous system gray and white matter (WM) abnormalities. Group differences in neuroimaging data are frequently evaluated with univariate statistics; however, this approach is limited because it is based on single, or clusters of, voxels. By contrast, multivariate pattern analyses consider all the models neuroanatomical features to capture a specific distributed spatial pattern. This approach has potential use as a prediction tool at the individual level. We hypothesized that a multivariate pattern classification method can distinguish specific patterns of abnormal WM connectivity of classic TN from healthy controls (HCs). Diffusion-weighted scans in 23 right-sided TN and matched controls were processed to extract whole-brain interregional streamlines. We used a linear support vector machine algorithm to differentiate interregional normalized streamline count between TN and HC. This algorithm successfully differentiated between TN and HC with an accuracy of 88%. The structural pattern emphasized WM connectivity of regions that subserve sensory, affective, and cognitive dimensions of pain, including the insula, precuneus, inferior and superior parietal lobules, and inferior and medial orbital frontal gyri. Normalized streamline counts were associated with longer pain duration and WM metric abnormality between the connections. This study demonstrates that machine-learning algorithms can detect characteristic patterns of structural alterations in TN and highlights the role of structural brain imaging for identification of neuroanatomical features associated with neuropathic pain disorders.

Corrigendum to “Intracortical inhibition abnormality during the remission phase of multiple sclerosis is related to upper limb dexterity and lesions” [Clin. Neurophysiol. 127 (2016) 1503–1511]

a Integrated Program in Neuroscience, McGill University, 3801 University Street, Room 141, Montreal, Que. H3A 2B4, Canada Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, Que. H3H 2R9, Canada Department of Neurology and Neurosurgery, McGill University, 845 Rue Sherbrooke Ouest, Montréal, Que., Canada Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Que. H3A 2B4, Canada

An In vivo Multi-Modal Structural Template for Neonatal Piglets Using High Angular Resolution and Population-Based Whole-Brain Tractography

An increasing number of applications use the postnatal piglet model in neuroimaging studies, however, these are based primarily on T1 weighted image templates. There is a growing need for a multimodal structural brain template for a comprehensive depiction of the piglet brain, particularly given the growing applications of diffusion weighted imaging for characterizing tissue microstructures and white matter organization. In this study, we present the first multimodal piglet structural brain template which includes a T1 weighted image with tissue segmentation probability maps, diffusion weighted metric templates with multiple diffusivity maps, and population-based whole-brain fiber tracts for postnatal piglets. These maps provide information about the integrity of white matter that is not available in T1 images alone. The availability of this diffusion weighted metric template will contribute to the structural imaging analysis of the postnatal piglet brain, especially models that are designed for the study of white matter diseases. Furthermore, the population-based whole-brain fiber tracts permit researchers to visualize the white matter connections in the piglet brain across subjects, guiding the delineation of a specific white matter region for structural analysis where current diffusion data is lacking. Researchers are able to augment the tracts by merging tracts from their own data to the population-based fiber tracts and thus improve the confidence of the population-wise fiber distribution.