Research article.

Testing the effectiveness of transcranial direct stimulation for the treatment of fatigue in multiple sclerosis. 

Mult. Scler. J. 2017 Sep 22.  doi: https://doi.org/10.1177/1352458517732842.  Download PDF: Remotely…sham-controlled trial.

Leigh E Charvet, Bryan Dobbs, Michael T Shaw, Marom Bikson, Abhishek Datta and Lauren B Krupp.

Abstract:

Background: Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)).

Objective: To evaluate whether tDCS can reduce fatigue in individuals with MS.

Methods: Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 openlabel tDCS treatments (1.5mA; n=15) compared to a cognitive training only condition (n=20). Study 2 was a randomized trial of active (2.0mA, n=15) or sham (n=12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)—Fatigue Short Form.

Results and conclusion: In Study 1, there was modest fatigue reduction in the active group (−2.5±7.4 vs −0.2±5.3, p=0.30, Cohen’s d=−0.35). However, in Study 2 there was statistically significant reduction for the active group (−5.6±8.9 vs 0.9±1.9, p=0.02, Cohen’s d=−0.71). tDCS is a potential treatment for MS-related fatigue.

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Event Time and Location: Wednesday, September 27, 2017, 3PM, Steinman Hall 402

George McConnell, PhD (Stevens Institute of Technology), Why Random Patterns of Deep Brain Stimulation Less Effectively Treat Parkinson’s Disease: Insights from In Vivo Studies

Abstract: Deep Brain Stimulation (DBS) of the subthalamic nucleus effectively treats several motor symptoms of Parkinson’s disease (PD), however, the mechanisms of action of DBS are unknown. Random temporal patterns of DBS are less effective than regular DBS, but the neural basis for this dependence on temporal pattern of stimulation is unclear. We quantified behavior and single-unit neuronal activity in parkinsonian rats to test the hypothesis that the ineffectiveness of irregular DBS is caused by a failure to mask low-frequency oscillatory activity. Irregular DBS relieved symptoms less effectively than regular DBS, even when delivered at a high average rate. The reduced effectiveness of random DBS paralleled a failure to suppress low-frequency oscillatory activity and suggest that long pauses during random DBS are responsible for the reduced effectiveness, because these pauses enable the propagation of low-frequency oscillatory activity. These results demonstrate a correlation between efficacy of DBS, temporal regularity of stimulus trains, and changes in neuronal oscillatory activity in the basal ganglia, highlighting the importance of considering temporal patterns – as opposed to simply the rate – of both stimulation and neuronal firing in studying the mechanisms of DBS for neurological disorders.

Clinical Trial.

Comparison of the Long-Term Effect of Positioning the Cathode in tDCS in Tinnitus Patients. 

Front. Aging Neurosci.  2017, July; 9(217)  doi: 10.3389/fnagi.2017.00217     Download PDF: Comparing long-term effect

Sarah Rabau, Giriraj S. Shekhawat, Mohamed Aboseria, Daniel Griepp, Vincent Van Rompaey,  Marom Bikson6 and Paul Van de Heyning.

Abstract:

Objective: Transcranial direct current stimulation (tDCS) is one of the methods described in the literature to decrease the perceived loudness and distress caused by tinnitus. However, the main effect is not clear and the number of responders to the treatment is variable. The objective of the present study was to investigate the effect of the placement of the cathode on the outcome measurements.

Methods: Patients considered for the trial were chronic non-pulsatile tinnitus patients with complaints for more than 3 months and a Tinnitus Functional Index (TFI) score that exceeded 25. The anode was placed on the right dorsolateral prefrontal cortex (DLPFC). In the first group—“bifrontal”—the cathode was placed on the left DLPFC, while in the second group—“shoulder”—the cathode was placed on the shoulder. Each patient received two sessions of tDCS weekly and eight sessions in total. Evaluations took place on the first visit for an ENT consultation, at the start of therapy, after eight sessions of tDCS and at the follow-up visit, which took place 84 days after the start of the therapy. Subjective outcome measures such as TFI, Visual Analog Scales (VAS) for loudness and percentage of consciousness of tinnitus were administered in every patient.

Results: There was no difference in the results for tinnitus loudness and the distress experienced between the placement of the cathode on the left DLPFC or on the shoulder. In addition, no statistically significant overall effect was found between the four test points. However, up to 39.1% of the patients experienced a decrease in loudness, measured by the VAS for loudness. Moreover, 72% of those in the bifrontal group, but only 46.2% of those in the shoulder group reported some improvement in distress.

Conclusion: While some improvement was noted, this was not statistically significant. Both electrode placements stimulated the right side of the hippocampus, which could be responsible for the effect found in both groups. Further research should rule out the placebo effect and investigate alternative electrode positions.

     

 

Neuromodulation: Technology at the Neural Interface, Clinical Research

Download PDF: Ezquerro_et_al-2017-Neuromodulation-_Technology_at_the_Neural_Interface

The Influence of Skin Redness on Blinding in Transcranial Direct Current Stimulation Studies: A Crossover Trial

Fernando Ezquerro, Adriano H. Moffa, Marom Bikson, Niranjan Khadka, Luana V. M. Aparicio, Bernardo de Sampaio-Junior, Felipe Fregni, Isabela M. Bensenor, Paulo A. Lotufo, Alexandre Costa Pereira, Andre R. Brunoni

Abstract:

Objective
To evaluate whether and to which extent skin redness (erythema) affects investigator blinding in transcranial direct current stimulation (tDCS) trials.
Material and Methods
Twenty-six volunteers received sham and active tDCS, which was applied with saline-soaked sponges of different thicknesses. High-resolution skin images, taken before and 5, 15, and 30 min after stimulation, were randomized and presented to experienced raters who evaluated erythema intensity and judged on the likelihood of stimulation condition (sham vs. active). In addition, semi-automated image processing generated probability heatmaps and surface area coverage of erythema. Adverse events were also collected.
Results
Erythema was present, but less intense in sham compared to active groups. Erythema intensity was inversely and directly associated to correct sham and active stimulation group allocation, respectively. Our image analyses found that erythema also occurs after sham and its distribution is homogenous below electrodes. Tingling frequency was higher using thin compared to thick sponges, whereas erythema was more intense under thick sponges.
Conclusions
Optimal investigator blinding is achieved when erythema after tDCS is mild. Erythema distribution under the electrode is patchy, occurs after sham tDCS and varies according to sponge thickness. We discuss methods to address skin erythema-related tDCS unblinding.

Full PDF: Erythema and tDCS

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Neuromodulation of Axon Terminals

Cerebral Cortex, 2017; 1–9 doi: 10.1093/cercor/bhx158   Download PDF:NeuromodulationofAxons

Darpan Chakraborty, Dennis Q. Truong, Marom Bikson and Hanoch Kaphzan

 

Abstract: Understanding which cellular compartments are influenced during neuromodulation underpins any rational effort to explain and optimize outcomes. Axon terminals have long been speculated to be sensitive to polarization, but experimentally informed models for CNS stimulation are lacking. We conducted simultaneous intracellular recording from the neuron soma and axon terminal (blebs) during extracellular stimulation with weak sustained (DC) uniform electric fields in mouse cortical slices. Use of weak direct current stimulation (DCS) allowed isolation and quantification of changes in axon terminal biophysics, relevant to both suprathreshold (e.g., deep brain stimulation, spinal cord stimulation, and transcranial magnetic stimulation) and subthreshold (e.g., transcranial DCS and transcranial alternating current stimulation) neuromodulation approaches. Axon terminals polarized with sensitivity (mV of membrane polarization per V/ m electric field) 4 times than somas. Even weak polarization (<2 mV) of axon terminals significantly changes action potential dynamics (including amplitude, duration, conduction velocity) in response to an intracellular pulse. Regarding a cellular theory of neuromodulation, we explain how suprathreshold CNS stimulation activates the action potential at terminals while subthreshold approaches modulate synaptic efficacy through axon terminal polarization. We demonstrate that by virtue of axon polarization and resulting changes in action potential dynamics, neuromodulation can influence analog– digital information processing.