Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: A randomized, double-blind, sham-controlled, and three-arm parallel multicenter study

Abstract Background: Therapeutic options for patients with prolonged disorders of consciousness (PDOC) are very limited, and patients often show little to no progress over time. It is widely recognized that some PDOC patients retain a higher level of cognition that may be apparent on the basis of their external responses, and simply are unable to produce purposeful motor behaviours. This dissociation has been linked to specific impairments in the motor network that lead to a reduction in thalamo-cortical coupling. Here, we will assess whether transcranial direct current stimulation (tDCS) can modulate thalamo-cortical coupling and improve patients’ responsiveness. We will focus on characterising the mechanisms of action of tDCS and the bases for potential individual differences in responsiveness to the stimulation across participants.Methods: This is a multi-centre double-blind randomised crossover feasibility study. It is divided into two streams: (a) MRI stream: 5 PDOC patients will complete 5 anodal, cathodal, and sham stimulation sessions (paired with passive mobilisation of the thumb) in separate weeks. We will measure brain activity and connectivity with functional magnetic resonance imaging and electroencephalography (EEG). We will look at brain structures to assess differences associated with responsiveness. (b) Bedside stream: 10 patients will complete one session of anodal or cathodal stimulation and one session of sham. We will measure brain activity and connectivity with EEG and we will conduct follow up assessments at 3 and 6 months. In both streams we will also look at changes in the clinical profile of patients with the Coma Recovery Scale Revised and in command following behaviour with electromyography and motion tracking. We will assess feasibility on measures of eligibility, recruitment, retention, and completion of tests.Discussion: This feasibility study is the first step towards developing personalised tDCS interventions to restore external responsiveness in PDOC patients. Our results will inform the design of a future trial fully powered for characterising neural, behavioural, and clinical effects of tDCS in PDOC as well as the mechanisms underlying individual differences in responsiveness.

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Functional Network Alterations as Markers for Predicting the Treatment Outcome of Cathodal Transcranial Direct Current Stimulation in Focal Epilepsy

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.637071 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jiaxin Hao ◽

Wenyi Luo ◽

Yuhai Xie ◽

Yu Feng ◽

Wei Sun ◽

...

Keyword(s):

Treatment Outcome ◽

Prediction Model ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Path Length ◽

Focal Epilepsy ◽

Functional Network ◽

Functional Networks ◽

Direct Current Stimulation ◽

The Mean

Background and PurposeTranscranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique for focal epilepsy. Because epilepsy is a disease affecting the brain network, our study was aimed to evaluate and predict the treatment outcome of cathodal tDCS (ctDCS) by analyzing the ctDCS-induced functional network alterations.MethodsEither the active 5-day, −1.0 mA, 20-min ctDCS or sham ctDCS targeting at the most active interictal epileptiform discharge regions was applied to 27 subjects suffering from focal epilepsy. The functional networks before and after ctDCS were compared employing graph theoretical analysis based on the functional magnetic resonance imaging (fMRI) data. A support vector machine (SVM) prediction model was built to predict the treatment outcome of ctDCS using the graph theoretical measures as markers.ResultsOur results revealed that the mean clustering coefficient and the global efficiency decreased significantly, as well as the characteristic path length and the mean shortest path length at the stimulation sites in the fMRI functional networks increased significantly after ctDCS only for the patients with response to the active ctDCS (at least 20% reduction rate of seizure frequency). Our prediction model achieved the mean prediction accuracy of 68.3% (mean sensitivity: 70.0%; mean specificity: 67.5%) after the nested cross validation. The mean area under the receiver operating curve was 0.75, which showed good prediction performance.ConclusionThe study demonstrated that the response to ctDCS was related to the topological alterations in the functional networks of epilepsy patients detected by fMRI. The graph theoretical measures were promising for clinical prediction of ctDCS treatment outcome.

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