Left or right ear? A neuroimaging study using combined taVNS/fMRI to understand the interaction between ear stimulation target and lesion location in chronic stroke.

BACKGROUND: Implanted vagus nerve stimulation (VNS) and transcutaneous auricular VNS (taVNS) have been primarily administered clinically to the unilateral-left vagus nerve. This left-only convention has proved clinically beneficial in brain disorders. However, in stroke survivors, the presence of a lesion in the brain may complicate VNS-mediated signaling, and it is important to understand the laterality effects of VNS in stroke survivors to optimize the intervention. OBJECTIVE: To understand whether taVNS delivered to different ear targets relative to the lesion (ipsilesional vs contralesional vs bilateral vs sham) impacts blood oxygenation level dependent (BOLD) signal propagation in stroke survivors. METHODS: We enrolled 20 adults with a prior history of stroke. Each participant underwent a single visit, during which taVNS was delivered concurrently during functional magnetic resonance imaging (fMRI) acquisition. Each participant received three discrete active stimulation conditions (ipsilesional, contralesional, bilateral) and one sham condition in a randomized order. Stimulation-related BOLD signal changes in the active conditions were compared to sham conditions to understand the interaction taVNS and laterality effects. RESULTS: All active taVNS conditions deactivated the contralesional default mode network related regions compared to sham, however only ipsilesional taVNS enhanced the activations in the ipsilesional visuomotor and secondary visual cortex. Furthermore, we reveal an interaction in task activations between taVNS and cortical visuomotor areas, where ipsilesional taVNS significantly increased ipsilesional visuomotor activity and decreased contralesional visuomotor activity compared to sham. CONCLUSION: Laterality of taVNS relative to the lesion is a critical factor in optimizing taVNS in a stroke population, with ipsilesional stimulation providing largest direct brain activation and should be explored further when designing taVNS studies in neurorehabilitation.

The effect of time since stroke, gender, age, and lesion size on thalamus volume in chronic stroke: a pilot study.

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p < 0.0001). In the ipsilesional thalamus, significant effect for intracortical volume (t(68) = 2.76, p = 0.008), age (t(68) = 2.47, p = 0.02), lesion volume (t(68) = - 3.54, p = 0.0008), and age*time since stroke (t(68) = 2.46, p = 0.02) were identified. In the contralesional thalamus, significant effect for intracortical volume (t(68) = 3.2, p = 0.002) and age (t = - 3.17, p = 0.002) were identified. Clinical factors age and intracortical volume influence both ipsi- and contralesional thalamus volume and lesion volume influences the ipsilesional thalamus. Due to the cross-sectional nature of this study, additional research is warranted to understand differences in the neural circuitry and subsequent influence on volumetrics after stroke.

TheraBracelet Stimulation During Task-Practice Therapy to Improve Upper Extremity Function After Stroke: A Pilot Randomized Controlled Study.

BACKGROUND: Peripheral sensory stimulation has been used in conjunction with upper extremity movement therapy to increase therapy-induced motor gains in patients with stroke. The limitation is that existing sensory stimulation methods typically interfere with natural hand tasks and thus are administered prior to therapy, requiring patients' time commitment. To address this limitation, we developed TheraBracelet. This novel stimulation method provides subthreshold (ie, imperceptible) vibratory stimulation to the wrist and can be used during hand tasks/therapy without interfering with natural hand tasks. OBJECTIVE: The objective was to determine the feasibility of using TheraBracelet during therapy to augment motor recovery after stroke. DESIGN: The design was a triple-blinded pilot randomized controlled trial. METHODS: Twelve chronic stroke survivors were assigned to the treatment or control group. All participants completed 2-hour task practice therapy sessions thrice weekly for 2 weeks. Both groups wore a small vibrator on the paretic wrist, which was turned on to provide TheraBracelet stimulation for the treatment group and turned off for the control group to provide sham stimulation. Outcome measures (Box and Block Test [BBT] and Wolf Motor Function Test [WMFT]) were obtained at baseline, 6 days after therapy, and at follow-up 19 days after therapy. RESULTS: The intervention was feasible with no adverse events. The treatment group significantly improved their BBT scores after therapy and at follow-up compared with baseline, whereas the control group did not. For WMFT, the group × time interaction was short of achieving significance. Large effect sizes were obtained (BBT d = 1.43, WMFT d = 0.87). No indication of desensitization to TheraBracelet stimulation was observed. LIMITATIONS: The limitation was a small sample size. CONCLUSIONS: TheraBracelet could be a promising therapy adjuvant for upper extremity recovery after stroke.

Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. OBJECTIVE: We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. METHODS: Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. RESULTS: Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. CONCLUSIONS: Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.

Long-Term Follow-up to a Randomized Controlled Trial Comparing Peroneal Nerve Functional Electrical Stimulation to an Ankle Foot Orthosis for Patients With Chronic Stroke.

BACKGROUND: Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle foot orthoses (AFO) for treatment of foot drop poststroke, but few long-term, randomized controlled comparisons exist. OBJECTIVE: Compare changes in gait quality and function between FES and AFOs in individuals with foot drop poststroke over a 12-month period. METHODS: Follow-up analysis of an unblinded randomized controlled trial (ClinicalTrials.gov #NCT01087957) conducted at 30 rehabilitation centers comparing FES to AFOs over 6 months. Subjects continued to wear their randomized device for another 6 months to final 12-month assessments. Subjects used study devices for all home and community ambulation. Multiply imputed intention-to-treat analyses were utilized; primary endpoints were tested for noninferiority and secondary endpoints for superiority. Primary endpoints: 10 Meter Walk Test (10MWT) and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test (6MWT), GaitRite Functional Ambulation Profile, and Modified Emory Functional Ambulation Profile (mEFAP). RESULTS: A total of 495 subjects were randomized, and 384 completed the 12-month follow-up. FES proved noninferior to AFOs for all primary endpoints. Both FES and AFO groups showed statistically and clinically significant improvement for 10MWT compared with initial measurement. No statistically significant between-group differences were found for primary or secondary endpoints. The FES group demonstrated statistically significant improvements for 6MWT and mEFAP Stair-time subscore. CONCLUSIONS: At 12 months, both FES and AFOs continue to demonstrate equivalent gains in gait speed. Results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings.

The effects of peroneal nerve functional electrical stimulation versus ankle-foot orthosis in patients with chronic stroke: a randomized controlled trial.

BACKGROUND: Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. OBJECTIVE: To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. METHODS: In a multicenter randomized controlled trial (ClinicalTrials.gov #NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. RESULTS: A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. CONCLUSIONS: Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance.

An fMRI study of the differences in brain activity during active ankle dorsiflexion and plantarflexion.

Little is known regarding the differences in active cortical and subcortical systems during opposing movements of an agonist-antagonist muscle group. The objective of this study was to characterize the differences in cortical activation during active ankle dorsiflexion and plantarflexion using functional MRI (fMRI). Eight right-handed healthy adults performed auditorily cued right ankle dorsiflexions and plantarflexions during fMRI. Differences in activity patterns between dorsiflexion and plantarflexion during fMRI were assessed using between- and within-subject voxel-wise t-tests. Results indicated that ankle dorsiflexion recruited significantly more regions in left M1, the supplementary motor area (SMA) bilaterally, and right cerebellum. Both movements activated similar left hemisphere regions in the putamen and thalamus. Dorsiflexion activated additional areas in the right putamen. Results suggest that ankle dorsiflexion and plantarflexion may be controlled by both shared and independent neural circuitry. This has important implications for functional investigations of gait pathology and how rehabilitation may differentially affect each movement.