[ARTICLE] Cathodal transcranial direct-current stimulation for treatment of drug-resistant temporal lobe epilepsy: A pilot randomized controlled trial – Full Text HTML



To investigate the effect of cathodal transcranial direct-current stimulation (c-tDCS) on seizure frequency in patients with drug-resistant temporal lobe epilepsy (TLE).


Twenty-nine patients with drug-resistant TLE participated in this study. They were randomized to experimental or sham group. Twenty participants (experimental group) received within-session repeated c-tDCS intervention over the affected temporal lobe, and nine (sham group) received sham tDCS. Paired-pulse transcranial magnetic stimulation was used to assess short interval intracortical inhibition (SICI) in primary motor cortex ipsilateral to the affected temporal lobe. SICI was measured from motor evoked potentials recorded from the contralateral first dorsal interosseous muscle. Adverse effects were monitored during and after each intervention in both groups. A seizure diary was given to each participant to complete for 4 weeks following the tDCS intervention. The mean response ratio was calculated from their seizure rates before and after the tDCS intervention.


The experimental group showed a significant increase in SICI compared to the sham group (F = 10.3, p = 0.005). None of the participants reported side effects of moderate or severe degree. The mean response ratio in seizure frequency was −42.14% (standard deviation [SD] 35.93) for the experimental group and −16.98% (SD 52.41) for the sham group.


Results from this pilot study suggest that tDCS may be a safe and efficacious nonpharmacologic intervention for patients with drug-resistant TLE. Further evaluation in larger double-blind randomized controlled trials is warranted.

Key Points

  • Within-session repeated (9-20-9 protocol) c-tDCS has shown no or minimal side effects in patients with drug-resistant temporal lobe epilepsy
  • Cortical excitability was reduced, as measured by SICI, after one application of c-tDCS using the 9-20-9 protocol in patients with drug-resistant temporal lobe epilepsy
  • Seizure rates reduced by 42% after one application of c-tDCS using the 9-20-9 protocol in patients with drug-resistant temporal lobe epilepsy
Epilepsy impacts 50 million people (1% of the population) worldwide.[1] Management for patients with epilepsy includes antiepileptic drugs (AEDs), and for some patients with drug-resistant seizures, surgery. Temporal lobe epilepsy (TLE) is often resistant to AEDs,[2] and >40% of patients with epilepsy have adverse reactions to AEDs. Removing the epileptogenic regions surgically is not always feasible for patients, and the outcome is not ideal in 30–50% of cases.[3] Consequently, alternative methods of seizure control warrant more investigation.

The excitability of the γ-aminobutyric acid (GABA)ergic intracortical inhibitory circuits in primary motor cortex (M1) can be assessed noninvasively in humans by paired-pulse transcranial magnetic stimulation (TMS). In this technique, two stimuli are delivered 1–5 msec apart through the same coil. The first stimulus is subthreshold for a motor response; however, it activates intracortical inhibition (ICI) circuits and reduces the size of the motor evoked potentials (MEPs) elicited by the second stimulus, which is supra-threshold for a motor response.[4] It has been shown that ICI measured using this method reflects the cortical activity of GABAergic interneurons in the M1 area.[5] This inhibition is termed short-interval intracortical inhibition or SICI.

ICI circuits have been assessed extensively with a paired-pulse paradigm in patients with epilepsy.[6-8] Several studies on drug-naive patients with focal epilepsy showed a decrease in SICI in the ipsilateral hemisphere.[9-15] Badawy et al. showed increased M1 excitability and decreased SICI in 35 patients with focal epilepsy 24 h before and after a seizure.

Transcranial direct current stimulation (tDCS) is a well-established cortical stimulation method that can be used noninvasively to modulate neuronal excitability in humans.[16] In this technique, a low intensity current (1–2 mA) is used that can affect the membrane potentials in two ways. Cathodal tDCS (c-tDCS) hyperpolarizes the resting membrane potentials, whereas anodal tDCS acts toward depolarization.[16] Modification of seizure network excitability by tDCS is a potentially valuable noninvasive alternative for reducing the excitability of this abnormal network in patients with epilepsy and thereby reducing the seizure rates in this population.

The aim of this study was to examine the effects of this noninvasive therapeutic approach on seizure frequency in this group of patients. We hypothesized that compared to sham tDCS, application of c-tDCS over the temporal lobe in patients with drug-resistant TLE, decreases seizure frequency and increases intracortical inhibition in the ipsilateral M1 area.

Continue —> Cathodal transcranial direct-current stimulation for treatment of drug-resistant temporal lobe epilepsy: A pilot randomized controlled trial – Zoghi – 2016 – Epilepsia Open – Wiley Online Library

Figure 1.

Experimental set-up. All participants received one session of c-tDCS or sham tDCS paradigm (9-20-9 protocol). The active surface electrode (cathode) was placed over the temporal lobe in the affected hemisphere. The return (anode) electrode was placed over the supraorbital area contralateral to the stimulated hemisphere. SICI was assessed before and after tDCS intervention. Seizure rates were recorded for 4 weeks after tDCS intervention.


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