Chang-hyun Park

Neural Correlates of the Antinociceptive Effects of Repetitive Transcranial Magnetic Stimulation on Central Pain After Stroke

Background. Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. Objective. The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. Methods. Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. Results. Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. Conclusion. Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

Transcranial direct current stimulation increases resting state interhemispheric connectivity

Transcranial direct current stimulation (tDCS) has been increasingly used to investigate human brain functions. Especially, tDCS on the dorsolateral prefrontal cortex (DLPFC) enhances cognitive functions in both healthy subjects and patients with neuropsychiatric disorders. In spite of its effects on behavioral improvement, neural correlates of tDCS on the DLPFC have not been fully described. In this study, we acquired resting state functional magnetic resonance imaging data before and after real or sham stimulation on the left DLPFC. Resting state functional connectivity of the stimulated brain region was compared between the two groups. Compared to the sham stimulation group, the tDCS group showed increased DLPFC connectivity to the right hemisphere and decreased DLPFC connectivity to the brain regions around the stimulation site in the left hemisphere. Application of tDCS on the DLPFC may induce increased interhemispheric connectivity even at rest, possibly associated with the behavioral effects of tDCS.

Significance of longitudinal changes in the default‐mode network for cognitive recovery after stroke

Although a considerable number of patients suffer from cognitive impairments after stroke, the neural mechanism of cognitive recovery has not yet been clarified. Repeated resting‐state functional magnetic resonance imaging (fMRI) was used in this study to examine longitudinal changes in the default‐mode network (DMN) during the 6 months after stroke, and to investigate the relationship between DMN changes and cognitive recovery. Out of 24 initially recruited right‐hemispheric stroke patients, 11 (eight males, mean age 55.7 years) successfully completed the repeated fMRI protocol. Patients underwent three fMRI sessions at 1, 3 and 6 months after stroke. Their DMNs were analysed and compared with those of 11 age‐matched healthy subjects (nine males, mean age 56.2 years). Correlations between DMN connectivity and improvement of the cognitive performance scores were also assessed. The stroke patients were found to demonstrate markedly decreased DMN connectivity of the posterior cingulate cortex, precuneus, medial frontal gyrus and inferior parietal lobes at 1 month after stroke. At 3 months after stroke, the DMN connectivity of these brain areas was almost restored, suggesting that the period is critical for neural reorganization. The DMN connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere showed a significant correlation with cognitive function recovery in stroke patients, and should be considered a compensatory process for overcoming cognitive impairment due to brain lesion. This is the first longitudinal study to demonstrate the changes in DMN during recovery after stroke and the key regions influencing cognitive recovery.

Which motor cortical region best predicts imagined movement

In brain-computer interfacing (BCI), motor imagery is used to provide a gateway to an effector action or behavior. However, in contrast to the main functional role of the primary motor cortex (M1) in motor execution, the M1s involvement in motor imagery has been debated, while the roles of secondary motor areas such as the premotor cortex (PMC) and supplementary motor area (SMA) in motor imagery have been proposed. We examined which motor cortical region had the greatest predictive ability for imagined movement among the primary and secondary motor areas. For two modes of motor performance, executed movement and imagined movement, in 12 healthy subjects who performed two types of motor task, hand grasping and hand rotation, we used the multivariate Bayes method to compare predictive ability between the primary and secondary motor areas (M1, PMC, and SMA) contralateral to the moved hand. With the distributed representation of activation, executed movement was best predicted from the M1 while imagined movement from the SMA, among the three motor cortical regions, in both types of motor task. In addition, the most predictive information about the distinction between executed movement and imagined movement was contained in the M1. The greater predictive ability of the SMA for imagined movement suggests its functional role that could be applied to motor imagery-based BCI.

Neural correlates of donepezil-induced cognitive improvement in patients with right hemisphere stroke: A pilot study

Donepezil has been proven effective in the treatment of Alzheimers disease and vascular dementia. However, its effects on the cognitive neural network have not been fully investigated. The purpose of this study was to evaluate the effect of donepezil on reorganisation of the cognitive neural network in patients with post-stroke cognitive impairment using functional MRI (fMRI). Fourteen patients with stroke in the right hemisphere were enrolled. Participants were randomly assigned to the experimental or the control group. Donepezil (5 mg) or placebo was administered daily for four weeks. Cognitive function assessment was performed before and immediately after treatment, and repeated one month after cessation of treatment. fMRI was performed before and after treatment. Ten out of 14 patients (six in the experimental group, four in the control group) successfully completed all experimental processes. The experimental group showed significant improvements in the Mini-Mental Status Examination during the post-treatment evaluation and one-month follow-up compared to the pre-treatment evaluation (p < .05). No improvement was observed in the control group. In the experimental group fMRI showed increased activation in both prefrontal areas, both inferior frontal lobes, and in the left inferior parietal lobe. Increased recruitment of the parieto-frontal networks in the selected patients was considered to be a neural correlate of cognitive improvement induced by donepezil.

The brain-derived neurotrophic factor Val66Met polymorphism and degeneration of the corticospinal tract after stroke: a diffusion tensor imaging study

A common single nucleotide polymorphism, Val66Met, in the human brain‐derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long‐term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity.

What is the optimal anodal electrode position for inducing corticomotor excitability changes in transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) non-invasively modulates brain function by inducing neuronal excitability. The conventional hot spot for inducing the highest current density in the hand motor area may not be the optimal site for effective stimulation. In this study, we investigated the influence of the center position of the anodal electrode on changes in motor cortical excitability. We considered three tDCS conditions in 16 healthy subjects: (i) real stimulation with the anodal electrode located at the conventional hand motor hot spot determined by motor evoked potentials (MEPs); (ii) real stimulation with the anodal electrode located at the point with the highest current density in the hand motor area as determined by electric current simulation; and (iii) sham stimulation. Motor cortical excitability as measured by MEP amplitude increased after both real stimulation conditions, but not after sham stimulation. Stimulation using the simulation-derived anodal electrode position, which was found to be posterior to the MEP hot spot for all subjects, induced higher motor cortical excitability. Individual positioning of the anodal electrode, based on the consideration of anatomical differences between subjects, appears to be important for maximizing the effects of tDCS.

Prediction of Motor Recovery Using Diffusion Tensor Tractography in Supratentorial Stroke Patients With Severe Motor Involvement

Objective To investigate whether early stage diffusion tensor tractography (DTT) values predict motor function at 3 months after onset in supratentorial stroke patients with severe motor involvement. Methods A retrospective study design was used to analyze medical records and neuroimaging data of 49 supratentorial stroke patients with severe motor involvement. Diffusion tensor imaging was assessed within 3 weeks after stroke in all patients. Three-dimensional tractography of the ipsilateral corticospinal tract (CST) was performed using the fiber assignment of the continuous tracking algorithm. The two-step DTT analysis was used. The first step was classification according to ipsilateral CST visualization. The second step was a quantitative analysis of the visible-CST group parameters. Motor function was assessed at 2 weeks and at 3 months after stroke. Comparative and correlation analyses were performed between DTT-derived measures and motor assessment scores. Results Motor function of the upper extremity at 3 months after stroke was significantly higher in the visible-CST group than that in the nonvisible-CST group (p<0.05). Early stage fractional anisotropy was of DTT correlated significantly with upper extremity motor function at 3 months after stroke in the visible-CST group (p<0.05). Conclusion These results demonstrate that early DTT-derived measures predict motor recovery in the upper extremity at 3 months after onset in supratentorial stroke patients with severe motor involvement.

Association between the amount of right‐to‐left shunt and infarct patterns in patients with cryptogenic embolic stroke: a transcranial Doppler study

Background Paradoxical embolism has been documented as a mechanism of cryptogenic embolic stroke. We investigated the frequency of right-to-left shunt in patients with cryptogenic embolic stroke and evaluated the factors associated with diffusion-weighted imaging (DWI) lesion pattern. Methods We analyzed data on 157 consecutive patients with acute ischemic stroke because of presumed cryptogenic embolism. Agitated saline transcranial Doppler study was conducted in all patients to detect right-to-left shunt. We evaluated the association of the amount (microemboli ≥20 vs. ≥20) and activity (spontaneous vs. after Valsalva maneuver only) of right-to-left shunt with diffusion-weighted imaging lesion patterns. Results Right-to-left shunt was observed in 96 (61·1%) patients. The multiplicity and distribution of diffusion-weighted imaging lesions did not differ depending on the amount and activity of right-to-left shunt. However, the size of diffusion-weighted imaging lesions differed depending on the amount of right-to-left shunt (P = 0·019). Right-to-left shunt was more frequently observed in patients with small (<1 cm) infarcts than in those with a large infarct (66·7% vs. 45·9%), and most patients with a larger amount of right-to-left shunt were found to have small infarcts on diffusion-weighted imaging (80%). The clinical characteristics, including Framingham stroke risk strategy, did not differ between the groups. Conclusions Our results indicate that the amount of right-to-left shunt determines the Diffusion-weighted imaging lesion patterns and suggest that mechanisms of stroke other than paradoxical mechanism may play an important role in patients with large cryptogenic embolic stroke.

Predicting the Performance of Motor Imagery in Stroke Patients Multivariate Pattern Analysis of Functional MRI Data

Background. In a brain–computer interface for stroke rehabilitation, motor imagery is a preferred means for providing a gateway to an effector action or behavior. However, stroke patients often exhibit failure to comply with motor imagery, and therefore their motor imagery performance is highly variable. Objective. We sought to identify motor cortical areas responsible for motor imagery performance in stroke patients, specifically by using a multivariate pattern analysis of functional magnetic resonance imaging data. Methods. We adopted an imaginary finger tapping task in which motor imagery performance could be monitored for 12 chronic stroke patients with subcortical infarcts and 12 age- and sex-matched healthy controls. We identified the typical activation pattern elicited for motor imagery in healthy controls, as computed over the voxels within each searchlight in the motor cortex. Then we measured the similarity of each individual’s activation pattern to the typical activation pattern. Results. In terms of activation levels, the stroke patients showed no activation in the ipsilesional primary motor cortex (M1); in terms of activation patterns, they showed lower similarity to the typical activation pattern in the area than the healthy controls. Furthermore, the stroke patients were better able to perform motor imagery if their activation patterns in the bilateral supplementary motor areas and ipsilesional M1 were close to the typical activation pattern. Conclusions. These findings suggest functional roles of the motor cortical areas for compliance with motor imagery in stroke, which can be applied to the implementation of motor imagery–based brain–computer interface for stroke rehabilitation.