Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Anatomical bases of fast parietal grasp control in humans: A diffusion-MRI tractography study.

The dorso-posterior parietal cortex (DPPC) is a major node of the grasp/manipulation control network. It is assumed to act as an optimal forward estimator that continuously integrates efferent outflows and afferent inflows to modulate the ongoing motor command. In agreement with this view, a recent per-operative study, in humans, identified functional sites within DPPC that: (i) instantly disrupt hand movements when electrically stimulated; (ii) receive short-latency somatosensory afferences from intrinsic hand muscles. Based on these results, it was speculated that DPPC is part of a rapid grasp control loop that receives direct inputs from the hand-territory of the primary somatosensory cortex (S1) and sends direct projections to the hand-territory of the primary motor cortex (M1). However, evidence supporting this hypothesis is weak and partial. To date, projections from DPPC to M1 grasp zone have been identified in monkeys and have been postulated to exist in humans based on clinical and transcranial magnetic studies. This work uses diffusion-MRI tractography in two samples of right- (n = 50) and left-handed (n = 25) subjects randomly selected from the Human Connectome Project. It aims to determine whether direct connections exist between DPPC and the hand control sectors of the primary sensorimotor regions. The parietal region of interest, related to hand control (hereafter designated DPPChand), was defined permissively as the 95% confidence area of the parietal sites that were found to disrupt hand movements in the previously evoked per-operative study. In both hemispheres, irrespective of handedness, we found dense ipsilateral connections between a restricted part of DPPChand and focal sectors within the pre and postcentral gyrus. These sectors, corresponding to the hand territories of M1 and S1, targeted the same parietal zone (spatial overlap > 92%). As a sensitivity control, we searched for potential connections between the angular gyrus (AG) and the pre and postcentral regions. No robust pathways were found. Streamline densities identified using AG as the starting seed represented less than 5 % of the streamline densities identified from DPPChand. Together, these results support the existence of a direct sensory-parietal-motor loop suited for fast manual control and more generally, for any task requiring rapid integration of distal sensorimotor signals.

Higher in vivo Cortical Intracellular Volume Fraction Associated with Lithium Therapy in Bipolar Disorder: A Multicenter NODDI Study.

BACKGROUND: MRI studies in patients with bipolar disorder have suggested that lithium is associated with grey matter increases that may underlie its therapeutic effects. However, the relationship between grey matter volume and cellular microstructural changes is not straightforward, as modifications of different cellular compartments of grey matter may be involved. OBJECTIVES: Our aim was to test the hypothesis that dendritic density is higher in patients undergoing lithium therapy than in patients without lithium, using advanced modelling of water diffusion investigated with MRI. METHOD: We included 41 patients and 40 controls matched for age and gender from two sites. All subjects underwent 3T MRI with 3 shells of diffusion. We used neurite orientation dispersion and density imaging to compare the grey matter neurite density between patients undergoing lithium therapy or not and control subjects. RESULTS: We found a significant group effect in the left prefrontal region (p = 0.001, Bonferroni corrected): patients without lithium had a lower frontal neurite density than controls (p = 0.009), while those on lithium had a higher mean neurite density than those without (p < 0.001). Patients on lithium were not different from controls (p = 0.08). CONCLUSIONS: This is the first study to report in vivo evidence of preserved neurite density of the prefrontal cortex in humans associated with lithium intake. Changes of intracellular volume fraction are thought to reflect changes of grey matter microstructural organization. This reinforces the hypothesis of lithium having a positive effect on the neuronal compartment in humans.