Non‐invasive magnetic stimulation of the human cerebellum facilitates cortico‐bulbar projections in the swallowing motor system

Background Animal and human brain imaging studies suggest that the cerebellum plays an important role in the control of swallowing. In this study, we probed the interaction between cerebellar and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can modulate cortical swallowing motor circuitry. Methods Healthy volunteers (n = 16, eight men, mean age = 32, range 19–57 years) underwent TMS measurements of pharyngeal electromyography (EMG) recorded from a swallowed intraluminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm, where active or sham TMS conditioning pulses over the cerebellum and control sites were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at varying inter‐stimulus intervals (ISIs) with the cortical response amplitudes being assessed. Key Results Stimulation of the cerebellum over its midline or hemispheres evoked distinct pharyngeal EMG responses. There was no difference in EMG amplitudes following cerebellar hemispheric or midline stimulation (mean 55.5 ± 6.9 vs 42.8 ± 5.9 μV, P = 0.08). In contrast, after cerebellar preconditioning, the cortically evoked responses underwent maximal facilitation at ISIs of 50–200 ms (P < 0.05), an effect not seen with sham or trigeminal nerve preconditioning. Conclusions & Inferences Posterior fossa stimulation excites the cerebellum and evokes direct motor responses within the pharynx. When conditioned with TMS, the cerebellum strongly facilitates the cortical swallowing motor pathways. This finding suggests that the cerebellum exerts a modulatory effect on human swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after neural damage.     

Therapeutic time window of low‐frequency stimulation at entorhinal cortex for amygdaloid‐kindling seizures in rats

The present study was designed to determine whether low‐frequency stimulation (LFS) of the entorhinal cortex (EC) has an anticonvulsive effect, and whether LFS delivered at different times plays different roles. We found that LFS of the EC immediately or 4 s after kindling stimulation had an anticonvulsive effect, and that the latter had a better effect on both kindling and kindled seizures. However, LFS delivered after the cessation of afterdischarge or 10 s after the kindling stimulation, augmented the epileptic activity. So the EC is a potential target for LFS to interfere with epilepsy. Our findings suggest that even in the duration of afterdischarge, there exists a “time window” for LFS treatment, indicating that the time delay of closed‐loop stimulation is crucial for LFS treatment.     

Long‐term deep brain stimulation for essential tremor: 12‐year clinicopathologic follow‐up

We describe the clinical course and postmortem pathological findings in a patient with essential tremor (ET) treated with deep brain stimulation (DBS) for 12 years. This 75 year old woman had a 13‐year history of progressive ET prior to implantation of bilateral quadripolar DBS electrodes in the region of her ventral intermediate thalamic nuclei in 1996, producing immediate relief of arm tremor. Histopathological examination of the brain, performed 12 years after the initial implantation, demonstrated electrode catheter tracts rimmed by 20‐25 micron fibrous sheaths, with multinucleated giant cells and reactive gliosis. Lymphocytic infiltration was seen by L26 immunoreactivity with CD3 (T cells) staining predominating over CD20 (B cells). Cerebellar axonal spheroids and Purkinje cell loss were found. The minimal foreign body reaction and gliosis around the electrodes 12 years after implantation supports the long‐term safety of DBS. The case represents the longest reported follow‐up with autopsy examination after DBS and confirmed histological changes associated with ET. © 2009 Movement Disorder Society     

Non‐invasive brain stimulation for fine motor improvement after stroke: a meta‐analysis

The aim of this study was to determine whether non‐invasive brain stimulation (NIBS) techniques improve fine motor performance in stroke. We searched PubMed, EMBASE, Web of Science, SciELO and OpenGrey for randomized clinical trials on NIBS for fine motor performance in stroke patients and healthy participants. We computed Hedges’ g for active and sham groups, pooled data as random‐effects models and performed sensitivity analysis on chronicity, montage, frequency of stimulation and risk of bias. Twenty‐nine studies (351 patients and 152 healthy subjects) were reviewed. Effect sizes in stroke populations for transcranial direct current stimulation and repeated transcranial magnetic stimulation were 0.31 [95% confidence interval (CI), 0.08–0.55; P = 0.010; Tau², 0.09; I², 34%; Q, 18.23; P = 0.110] and 0.46 (95% CI, 0.00–0.92; P = 0.05; Tau², 0.38; I², 67%; Q, 30.45; P = 0.007). The effect size of non‐dominant healthy hemisphere transcranial direct current stimulation on non‐dominant hand function was 1.25 (95% CI, 0.09–2.41; P = 0.04; Tau², 1.26; I², 93%; Q, 40.27; P < 0.001). Our results show that NIBS is associated with gains in fine motor performance in chronic stroke patients and healthy subjects. This supports the effects of NIBS on motor learning and encourages investigation to optimize their effects in clinical and research settings.     

Does magnetic stimulation of sacral nerve roots modify colonic motility? Results of a randomized double‐blind sham‐controlled study

Abstract  Although sacral nerve root stimulation (SNS) can result in a symptomatic improvement of faecal incontinence, the mechanism of action remains unknown. The aim of this study was to assess whether short-term magnetic SNS can inhibit pharmacologically induced propulsive colonic contractions. Twelve healthy volunteers (median age: 43.5 years old) were studied on two separate occasions and randomized into either active (15 Hz, 100% output intensity for 5 s min⁻¹ for 30 min) or sham rapid rate lumbosacral magnetic stimulation (rLSMS). Colorectal motility was recorded with a manometric catheter located at the most proximal transducer in the left colon and the most distal, in the rectum. Colonic contractions were provoked by instilling Bisacodyl. The effects of rLSMS on colonic, sigmoid and rectal contractions were monitored and recorded after Bisacodyl instillation. The appearance of high-amplitude contractions propagated or not (HAC/HAPC) provoked by Bisacodyl instillation was significantly delayed during active compared to sham stimulation ( P  = 0.03). There was no difference in the characteristics of HAC/HAPC (i.e. frequency, amplitude, duration, velocity of propagation) or the motility index with active or sham stimulation. The perception of urgency tended to be decreased with rLSMS following Bisacodyl instillation. The catheter was expulsed within a median of 16.5 min (range 8–39) after Bisacodyl administration during active stimulation compared to 14 min (range 5–40) during sham stimulation ( P  = 0.03). This study suggests that rLSMS could delay the appearance of the first Bisacodyl-induced colonic contractions.     

Neuromodulation‐dependent effect of gated high‐frequency,LFMS‐like electric field stimulation in mouse cortical slices

Low‐field magnetic stimulation (LFMS) is a gated high‐frequency non‐invasive brain stimulation method (500 Hz gated at 2 Hz) with a proposed antidepressant effect. However, it has remained unknown how such stimulation paradigms modulate neuronal network activity and how the induced changes depend on network state. Here we examined the immediate and outlasting effects of the gated high‐frequency electric field associated with LFMS on the cortical activity as a function of neuromodulatory tone that defines network state. We used a sham‐controlled study design to investigate effects of stimulation (20 min of 0.5 s trains of 500 Hz charge‐balanced pulse stimulation patterned at 0.5 Hz) on neural activity in mouse medial prefrontal cortex in vitro. Bath application of cholinergic and noradrenergic agents enabled us to examine the stimulation effects as a function of neuromodulatory tone. The stimulation attenuated the increase in firing rate of layer V cortical neurons during the post‐stimulation period in the presence of cholinergic activation. The same stimulation had no significant immediate or outlasting effect in the absence of exogenous neuromodulators or in the presence of noradrenergic activation. These results provide electrophysiological insights into the neuromodulatory‐dependent effects of gated high‐frequency stimulation. More broadly, our results are the first to provide a mechanistic demonstration of how behavioral states and arousal levels may modify the effects of non‐invasive brain stimulation.     

Four Year Follow‐up of Dual Electrode Spinal Cord Stimulation for Chronic Pain

This paper reports on 80 patients using dual electrode, spinal cord stimulation (SCS) over a four‐year period Implant status, stimulation mode, anode‐cathode configuration (array), cathode position, paresthesia overlap, explantation rates, complications, Visual Analog Scores (VAS), and overall satisfaction were examined in patients implanted with dual 8 contact, staggered, percutaneous electrodes. All patients had undergone implantation for chronic axial and extremity pain [e.g., Failed Back Surgery Syndrome (FBSS), Complex Regional Pain Syndrome (CRPS)]. Outcomes were evaluated in view of our previous reports in this same group at 24 and 30 months 1 , 2 . Data was collected by a disinterested third party. At 48 months, 18 of the original 80 patients were lost to follow‐up. Of the 62 patients contacted, 33 remained implanted and 29 (47%) had been explanted. After an average evaluation of 85 arrays (PainDoc, Advanced Neuromodulation Systems, Plano, Texas), 88% of patients reported using one or two “best” arrays (bipolar or guarded tripolar) to maintain favorable paresthesia overlap (89%), VAS reduction (8.1 to 4.9), and overall patient satisfaction (63%). These arrays were most commonly positioned about the physiologic midline of the COL3–4 vertebral segments for upper extremity pain, and the T9–10 vertebral segments for low back and lower extremity pain. In contrast to our initial reports where essentially all patients preferred more than two arrays to maintain “best” paresthesia overlap and outcome, only 12% of these same patients maintained this trend in this long‐term follow‐up study. The arrays most commonly selected long‐term as the “best” ones (88% of all electrodes) were narrow (adjacent contact) bipoles and guarded cathode tripoles (< 8 contacts). Thirty‐five percent of patients with thoracic implants achieved paresthesia in the low back at 48 months. Explantation rates and overall patient satisfaction were significantly affected by painful radio frequency (RF) antenna coupling. This data supports the efficacy of dual electrodes in optimizing long‐term SCS paresthesia overlap and complex pain outcomes.     

Two‐year follow‐up on the effect of unilateral subthalamic deep brain stimulation in highly asymmetric Parkinson's disease

Although bilateral subthalamic deep brain stimulation (STN DBS) provides greater relief from the symptoms of Parkinson's disease (PD) than unilateral STN DBS, it has been suggested that unilateral STN DBS may be a reasonable treatment option in selected patients, especially those with highly asymmetric PD. In previous studies on the effect of unilateral STN DBS, the asymmetry of PD symptoms was not prominent and the mean follow‐up durations were only 3 to 12 months. In this study, we report our findings in a series of 8 patients with highly asymmetric PD who were treated with unilateral STN DBS and were followed for 24 months. Serial changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and subscores in the ipsilateral, contralateral, and axial body parts were analyzed. Unilateral STN DBS improved the UPDRS motor score and the contralateral subscore in the on‐medication state for 5 nonfluctuating patients and in the off‐medication state for 3 fluctuating patients. However, the ipsilateral subscore progressively worsened and reversed asymmetry became difficult to manage, which led to compromised medication and stimulator adjustment. At 24 months, all the patients were considering the second‐side surgery. Our results suggest that bilateral STN DBS should be considered even in highly asymmetric PD. © 2008 Movement Disorder Society     

Long‐Term Measurement of Therapeutic Electrode Impedance in Deep Brain Stimulation

Objective: Deep brain stimulation technology now allows a choice between constant current and constant voltage stimulation, yet clinical trials comparing the two are lacking. Impedance instability would theoretically favor constant current stimulation; however, few publications address this with long‐term follow‐up. In this report, we review our series for impedance change and discuss our findings and their implications for future study design. Materials and Methods: A retrospective chart review was performed of all consecutive patients seen in the outpatient clinic for deep brain stimulation adjustments at the University of Wisconsin–Madison from February 2006 to May 2007. The following data were extracted: Quadrapolar contact selection, frequency, voltage, pulse width, and measured impedance at the therapeutic parameters. Patients were selected if consecutive measurements of therapeutic impedances for the same patient were performed with the same frequency, pulse width, voltage, and configuration of active contacts. Results: A total of 63 patients with 110 electrodes had 301 documented programming visits. From these, 16 patients had 20 consecutive measurements with unchanged parameters in 19 electrodes at a median interval of 68 days and median follow‐up of 549 days after implantation. No significant intra‐patient intra‐electrode therapeutic impedance variability was observed in this study (SD = 105.3 Ω, paired t‐test, p= 0.312). In contrast, marked inter‐patient variability in impedance was noted. This variability could not be explained by stimulation target, measurement interval, time since implantation, monopolar vs. bipolar stimulation, stimulation voltage, or stimulation frequency. Conclusions: No significant change in the same electrode therapeutic impedance was identified. Given the assumption that stimulation current is the critical parameter influencing clinical outcomes, these findings would not disadvantage constant voltage stimulation. However, inter‐patient variability suggests a possible advantage for constant current stimulation when generalizing experience and comparisons over multiple patients. Further study of the relationship of stimulation efficacy to stimulation mode and impedance change is warranted.