Cinzia Calautti

Functional Neuroimaging Studies of Motor Recovery After Stroke in Adults: A Review

Background— The precise mechanisms of and biological basis for motor recovery after stroke in adults are still largely unknown. Reorganization of the motor system after stroke as assessed by functional neuroimaging is an intriguing but challenging new field of research. Provocative but equivocal findings have been reported to date. Summary of Review— We present an overview of functional neuroimaging studies (positron emission tomography or functional MRI) of motor tasks in patients recovered or still recovering from motor deficit after stroke. After a brief account of the connectivity of motor systems and the imaging findings in normal subjects, the literature concerning stroke patients is reviewed and discussed, and a general model is proposed. Conclusions— Both cross-sectional and longitudinal studies have demonstrated that the damaged adult brain is able to reorganize to compensate for motor deficits. Rather than a complete substitution of function, the main mechanism underlying recovery of motor abilities involves enhanced activity in preexisting networks, including the disconnected motor cortex in subcortical stroke and the infarct rim after cortical stroke. Involvement of nonmotor and contralesional motor areas has been consistently reported, with the emerging notion that the greater the involvement of the ipsilesional motor network, the better is the recovery. This hypothesis is supported by the enhanced activity of the ipsilesional primary motor cortex induced by motor training and acute pharmacological interventions, in parallel with improved motor function. Further longitudinal studies assessing the relationships between such changes and actual recovery, as well as manipulating such changes by rehabilitation or pharmacological maneuvers, should provide further information on these fundamental questions. This review closes with some perspectives for future research.

Post-stroke plastic reorganisation in the adult brain.

Recovery of function after a stroke is attributable to several factors, including events in the first few days (eg, reabsorption of perilesional oedema, tissue reperfusion). However, consistent reorganisation and recovery after a stroke takes weeks or months. In the early stages, recovery from stroke can vary greatly among patients with identical clinical symptoms. Neuroimaging techniques that enable us to assess baseline and task-related functions, and neurophysiological techniques that measure brain function in real time, can be used to study the recovery of brain lesions after a stroke. In this review, we discuss important neuroimaging and neurophysiological studies of post-stroke brain reorganisation.

The relationship between motor deficit and hemisphere activation balance after stroke: A 3T fMRI study.

Functional imaging during movement of the hand affected by a stroke has shown excess activation of the contralesional motor network, implying less physiological hemisphere activation balance. Although this may be adaptive, the relationship between the severity of motor deficit and the hemisphere activation balance for the four major cortical motor areas has not been systematically studied. We prospectively studied 19 right-handed patients with first-ever stroke (age range 61+/-10 years) in the stable phase of recovery (>3 months after onset), using auditory-paced index-thumb (IT) tapping of the affected hand at 1.25 Hz as the fMRI paradigm. The hemisphere activation balance for the primary motor (M1), primary somatosensory (S1), supplementary motor (SMA) and dorsal premotor (PMd) areas was measured by a modified weighted laterality index (wLI), and correlations with motor performance (assessed by the affected/unaffected ratio of maximum IT taps in 15 s, termed IT-R) were computed. There were statistically significant negative correlations between IT-R and the wLI for M1 and S1, such that the more the hemispheric balance shifted contralesionally, the worse the performance. Furthermore, worse performance was related to a greater amount of contralesional, but not ipsilesional, activation. No significant correlation between IT-R and the wLI was obtained for the SMA and PMd, which functionally have stronger bilateral organization. These findings suggest that the degree of recovery of fine finger motion after stroke is determined by the extent to which activation balance in the primary sensory motor areas--where most corticospinal fibers originate--departs from normality. This observation may have implications for therapy.

Sequential activation brain mapping after subcortical stroke: changes in hemispheric balance and recovery.

We prospectively studied 5 patients while they were recovering from left-sided subcortical stroke affecting the cortico-spinal tract, and examined them twice with H215O-PET over several months while performing an identical task with the affected hand. Concomitant motor recovery was assessed by measuring the number of thumb-to-index tappings performed in 15 s at each PET session. Across patients, the hemispheric activation balance tended to shift over time toward the unaffected hemisphere, but the magnitude of this shift was highly variable from patient to patient and significantly correlated with recovery. Thus, in subcortical stroke, a shift of activation balance towards the unaffected hemisphere appears associated with lesser initial recovery and, conversely, the more this physiological balance is maintained over time the better the recovery.

Does healthy aging affect the hemispheric activation balance during paced index-to-thumb opposition task? An fMRI study

Normal aging is generally associated with declining performance in cognitive and fine motor tasks. Previous functional imaging studies have been inconsistent regarding the effect of aging on primary motor cortex (M1) activation during finger movement, showing increased, unchanged or decreased activation contralaterally, and more consistently increased activation ipsilaterally. Furthermore, no study has addressed the effect of age on M1 hemispheric activation balance. We studied 18 optimally healthy right-handed subjects, age range 18-79 years (mean +/- SD: 47 +/- 17) using 3 T fMRI and right index finger-thumb tapping auditory-paced at 1.25 Hz. The weighted Laterality Index (wLI) for M1 was obtained according to Fernandez et al. (2001) [Fernandez, G., de Greiff, A., von Oertzen, J., Reuber, M., Lun, S., Klaver, P., et al. 2001. Language mapping in less than 15 min: real-time functional MRI during routine clinical investigation. Neuroimage 14 585-594], with some modifications. The wLI, as well as the total activation on each side, were assessed against age using non-parametric correlation. There was a highly significant negative correlation between age and wLI such that the older the subjects, the lower the wLI. Furthermore, there was a highly significant positive correlation between total activation for ipsilateral M1 and age, and a nearly significant trend for contralateral M1. This study documents that during execution of a simple paced motor task, the older the subject the less lateralized the M1 activation balance as a result of increasing amount of activation on both sides, more significantly so ipsilaterally. Thus, in aging, enhanced M1 recruitment bilaterally is required to produce the same motor performance, suggesting a compensatory process. These findings are in line with cognitive studies indicating a tendency for the aging brain to reduce its functional lateralization, perhaps from less efficient transcallosal connections.

Displacement of primary sensorimotor cortex activation after subcortical stroke: a longitudinal PET study with clinical correlation.

Five patients with left striatocapsular infarction were studied twice with PET during auditory-cued right thumb-index tapping, around 2 months after stroke and again around 8 months after stroke. At PET1 and PET2, the ipsilesional primary sensorimotor (SM1) activation peak Talairach coordinates were compared to those from seven aged-matched healthy controls. At PET1, there was a significant posterior displacement of SM1 activation peak, which confirms a previous report and may represent unmasking/disinhibition of motor representations. Over time, there was no significant change in the coordinates, and no significant correlation between coordinate changes from PET1 to PET2 and concomitant motor recovery. The implications of posterior displacement of SM1 activation peak for recovery therefore remain elusive.

The relationship between motor deficit and primary motor cortex hemispheric activation balance after stroke: longitudinal fMRI study

Background In the chronic stage of stroke, previous work has shown that the worse the hand motor deficit, the greater the shift of primary motor cortex (M1) activation towards the contralesional hemisphere (ie, unphysiological) balance. Whether the same relationship applies at earlier stages of recovery in serially studied patients is not known. Methods fMRI of fixed-rate auditory-cued affected index-thumb tapping was obtained at two time points (mean 36 and 147u2005days poststroke) in a cohort of nine patients with ischaemic stroke (age: 56±9u2005years; three women/six men; seven subcortical, one medullary and one cortical). On each fMRI day, the unaffected/affected ratio of maximal index tapping rate (IT-R) was obtained. To assess the M1 hemispheric activation balance, the authors computed the classic Laterality Index (LI). The correlation between LI and IT-R was computed for each time point separately. Results The expected correlation between LI-M1 and IT-R, that is, motor performance worse with more unphysiological LI, prevailed at both time points (Kendall p=0.008 and 0.058, respectively), with no statistically significant difference between the two regressions. The same analysis for the dorsal premotor cortex and the supplementary motor area showed no significant correlation at either time-point. Conclusion These results from a small cohort of longitudinally assessed patients suggest that the relationship between M1 laterality index and hand motor performance appears independent of time since onset of stroke. This in turn may suggest that attempting to restore the hemispheric balance by enhancing ipsilesional M1 and/or constraining contralesional M1 activity may have consistent efficacy throughout recovery.

The neural substrates of impaired finger tapping regularity after stroke

Not only finger tapping speed, but also tapping regularity can be impaired after stroke, contributing to reduced dexterity. The neural substrates of impaired tapping regularity after stroke are unknown. Previous work suggests damage to the dorsal premotor cortex (PMd) and prefrontal cortex (PFCx) affects externally-cued hand movement. We tested the hypothesis that these two areas are involved in impaired post-stroke tapping regularity. In 19 right-handed patients (15 men/4 women; age 45-80 years; purely subcortical in 16) partially to fully recovered from hemiparetic stroke, tri-axial accelerometric quantitative assessment of tapping regularity and BOLD fMRI were obtained during fixed-rate auditory-cued index-thumb tapping, in a single session 10-230 days after stroke. A strong random-effect correlation between tapping regularity index and fMRI signal was found in contralesional PMd such that the worse the regularity the stronger the activation. A significant correlation in the opposite direction was also present within contralesional PFCx. Both correlations were maintained if maximal index tapping speed, degree of paresis and time since stroke were added as potential confounds. Thus, the contralesional PMd and PFCx appear to be involved in the impaired ability of stroke patients to fingertap in pace with external cues. The findings for PMd are consistent with repetitive TMS investigations in stroke suggesting a role for this area in affected-hand movement timing. The inverse relationship with tapping regularity observed for the PFCx and the PMd suggests these two anatomically-connected areas negatively co-operate. These findings have implications for understanding the disruption and reorganization of the motor systems after stroke.

Quantification of index tapping regularity after stroke with tri-axial accelerometry

OBJECTIVEnQuantifying intrinsic components of movement may help to better understand the nature of motor deficits after stroke. Here we quantify the ability of stroke patients to finger tap in rhythm with auditory cues given at physiological rate.nnnMETHODSnUsing tri-axial accelerometry, we measured tapping regularity (Regularity Index) during auditory-cued index-to-thumb tapping at 1.25 Hz in 20 prospectively selected right-handed chronic stroke patients (mean age 61 yrs) and 20 right-handed healthy subjects (7 young and 13 age matched; mean age 24 and 58 yrs, respectively). With the aim to validate our method, two measures of clinical deficit, the European Stroke Scale (ESS) and the maximum number of index-thumb taps in 15s (IT-Max) were recorded on the same day.nnnRESULTSnThere was no effect of age or hand used on the Regularity Index in the control subjects. In patients, the Regularity Index of their affected hand was significantly worse compared to their unaffected hand and to age-matched controls (p<0.05 and p<0.01, respectively). The Regularity Index significantly correlated with the ESS and IT-Max in the clinically expected direction (p=0.025 and 0.001, respectively).nnnCONCLUSIONnThese data indicate that our method has validity to quantify finger-tapping regularity. After stroke, there is a deficit in the ability to keep pace with auditory cues that correlates, but does not equate, with other indices of motor function. Quantifying tapping regularity may provide novel insights into the mechanisms underlying recovery of finger dexterity after stroke.

Corrigendum to “The relationship between motor deficit and hemisphere activation balance after stroke: A 3 T fMRI study” [NeuroImage 34 (2007) 322–331]

The authors recently spotted two errors in this article. In the Methods section, “Image processing” subheading, the sentence “Data sets were rejected if head displacement was greater than 5 mm in any direction” should read “Data sets were rejected if head displacement was greater than 2 mm in any direction”. In Fig. 4, an error occurred when transcribing the data point in the extreme right in the top right scatterplot (“Contralesional M1”). The statistical significance of the correlation is unchanged (Spearmans rho=+0.618, p=0.0088). The overall interpretation of the study is therefore unchanged. The new figure is printed here for the readers convenience.