Controlling for lesions, kinematics and physiological noise: impact on fMRI results of spastic post-stroke patients.

Functional magnetic resonance imaging (fMRI) is a widely used technique for assessing brain function in both healthy and pathological populations. Some factors, such as motion, physiological noise and lesion presence, can contribute to signal change and confound the fMRI data, but fMRI data processing techniques have been developed to correct for these confounding effects. Fifteen spastic subacute stroke patients underwent fMRI while performing a highly controlled task (i.e. passive extension of their affected and unaffected wrists). We investigated the impact on activation maps of lesion masking during preprocessing and first- and second-level analyses, and of adding wrist extension amplitudes and physiological data as regressors using the Statistical Parametric Mapping toolbox (SPM12). We observed a significant decrease in sensorimotor region activation after the addition of lesion masks and movement/physiological regressors during the processing of stroke patients' fMRI data. Our results demonstrate that:•The unified segmentation routine results in good normalization accuracy when dealing with stroke lesions regardless of their size;•Adding a group lesion mask during the second-level analysis seems to be a suitable option when none of the patients have lesions in target regions. Otherwise, no masking is acceptable;•Movement amplitude is a significant contributor to the sensorimotor activation observed during passive wrist extension in spastic stroke patients;•Movement features and physiological noise are relevant factors when interpreting for sensorimotor activation in studies of the motor system in patients with brain lesions. They can be added as nuisance covariates during large patient groups' analyses.

Individual and dyadic rope turning as a window into social coordination.

The spontaneous and intentional movement coordination between peoples is well understood. Less is known about such interactions when the coordination is subordinate to the task and when the task involves, next to vision, mechanically induced haptic and kinesthetic coupling between dyadic partners. We therefore investigated dyadic jump rope turning. Fifteen dyadic pairs conjointly turned a jump rope to which five markers were equidistantly attached, and whose movements were recorded in 3D. In addition, each participant turned one side of the rope while the other side was quasi-fixed in an individual baseline condition. The participants' goal was to turn the rope regularly and smoothly. Individual spontaneous turning frequencies differed substantially across participants. Yet, dyadic pairs spontaneously turned the rope at a common frequency, indicative of frequency entrainment. The dyadic rope rotations were less variable despite weaker between near-hand marker coordination than the individual rope rotations, and the degree of performance improvement was most pronounced for participants who were paired with a partner who performed better in the individual condition. The direction and relative strength of the coupling between partners varied substantially across dyads, but the degree of coupling asymmetry had no substantial effect on the rope tuning quality. The absolute degree in which dyadic partners adjusted to each other, however, scaled moderately with their turning performance. Although the individual performances did not predict the dyadic performances, the difference in individual performance between dyadic partners had some predictive value for the dyadic performance. In combination, these results indicate that the partners were functionally adapting to each other in order to satisfy the task goal and suggest that the relative performance differences rather than the individual performances has predictive value for conjoint action.

Focal Malonate Injection Into the Internal Capsule of Rats as a Model of Lacunar Stroke.

Background: Stroke is the first cause of disability in adults in western countries. Infarct of the internal capsule (IC) may be related to motor impairment and poor prognosis in stroke patients. Functional deficits due to medium-sized infarcts are difficult to predict, except if the specific site of the lesion is taken into account. None of the few pre-clinical models recapitulating this type of stroke has shown clear, reproducible, and long-lasting sensorimotor deficits. Here, we developed a rat model of lacunar infarction within the IC, key structure of the sensorimotor pathways, by precise injection of malonate. Methods: The mitochondrial toxin malonate was injected during stereotactic surgery into the IC of rat brains. Rats were divided in three groups: two groups received malonate solution at 1.5M (n = 12) or at 3M (n = 10) and a sham group (n = 5) received PBS. Three key motor functions usually evaluated following cerebral lesion in the clinic strength, target reaching, and fine dexterity were assessed in rats by a forelimb grip strength test, a skilled reaching task (staircase) for reaching and dexterity, and single pellet retrieval task. Sensorimotor functions were evaluated by a neurological scale. Live brain imaging, using magnetic resonance (MRI), and post-mortem immunohistochemistry in brain slices were performed to characterize the lesion site after malonate injection. Results: Intracerebral injection of malonate produced a 100% success rate in inducing a lesion in the IC. All rats receiving the toxin, regardless the dose injected, had similar deficits in strength and dexterity of the contralateral forepaw, and showed significant neurological impairment. Additionally, only partial recovery was observed with respect to strength, while no recovery was observed for dexterity and neurological deficit. MRI and immunostaining show volume size and precise location of the lesion in the IC, destruction of axonal structures and Wallerian degeneration of fibers in the area above the injection site. Conclusions: This pre-clinical model of lacunar stroke induces a lesion in the IC with measurable and reproducible sensorimotor deficits, and limited recovery with stabilization of performance 2 weeks post-injury. Future therapies in stroke may be successfully tested in this model.

Corticospinal Tract Tracing in the Marmoset with a Clinical Whole-Body 3T Scanner Using Manganese-Enhanced MRI.

Manganese-enhanced MRI (MEMRI) has been described as a powerful tool to depict the architecture of neuronal circuits. In this study we investigated the potential use of in vivo MRI detection of manganese for tracing neuronal projections from the primary motor cortex (M1) in healthy marmosets (Callithrix Jacchus). We determined the optimal dose of manganese chloride (MnCl2) among 800, 400, 40 and 8 nmol that led to manganese-induced hyperintensity furthest from the injection site, as specific to the corticospinal tract as possible, and that would not induce motor deficit. A commonly available 3T human clinical MRI scanner and human knee coil were used to follow hyperintensity in the corticospinal tract 24h after injection. A statistical parametric map of seven marmosets injected with the chosen dose, 8 nmol, showed the corticospinal tract and M1 connectivity with the basal ganglia, substantia nigra and thalamus. Safety was determined for the lowest dose that did not induce dexterity and grip strength deficit, and no behavioral effects could be seen in marmosets who received multiple injections of manganese one month apart. In conclusion, our study shows for the first time in marmosets, a reliable and reproducible way to perform longitudinal ME-MRI experiments to observe the integrity of the marmoset corticospinal tract on a clinical 3T MRI scanner.