Table 1 Effects of activity enhancement on neurological disorders featuring hyperexcitability

Acquired epilepsy

Multi-electrode arrays recording of neuronal culture in vitro.

Electrical stimulation (0.05–50 Hz)

Higher stimulation frequency transforms burst activity to dispersed spiking reminiscent of the awake cortex in vivo

(Madhavan et al. 2006; Wagenaar et al. 2005)

Temporal lobe epilepsy in rats in vivo

Electrical stimulation of subiculum after kindling or pilocarpine injection

1 Hz stimulation retarded progression of kindling seizures and inhibited chronic spontaneous pilocarpine-induced seizures.

(Han et al. 2014; Zhong et al. 2012)

191 patients with refractory partial-onset seizures. A double-blind, randomized, controlled trial

Open-loop responsive cortical stimulation for 1 month

Reduction in seizure frequency in the treatment group (− 37.9%) than control group (− 17.3%).

(Morrell 2011)

Alpha (2)-adrenoceptor antagonist atipamezole

Treatment started 1 week after SE induction and lasted for 9 weeks.

Lower seizure frequency and severity, and milder cell damage and mossy fiber sprouting in treatment group.

(Pitkanen et al. 2004)

Neuropathic pain

Spared tibial nerve injury and transient spinal cord ischemia models of neuropathic pain in mice

S1 optogenetic stimulation for 1 week, or S1 activity enhancement by bicuculline.

Reduced pain-like behavior in both models and reduced S1 neuronal [80]excitability.

(Xiong et al. 2017).

Eight intractable neuropathic pain patients

TMS (1–50 Hz for 1 h) or electrical stimulation (4–8 Hz) for 1 month.

Significant pain relief in all patients.

(De Ridder et al. 2007)

Tinnitus

43 intractable tinnitus patients

Implanted electrodes in the primary auditory cortex or secondary auditory cortex

67% of patients improved with average tinnitus reduction of 53%. Burst stimulation has better effect than tonic stimulation.

(De Ridder et al. 2011) (Meng et al. 2011).

163 tinnitus patients

rTMS at 1 Hz (2000 stimuli, 110% motor threshold) or sham stimulation

This protocol has no effect.

(Landgrebe et al. 2017)

Ten tinnitus patients

rTMS at 1 Hz on auditory cortex for 5 consecutive days

Improvement was associated with increases intracortical inhibition, intracortical facilitation, and prolongation of cortical silent period.

(Langguth et al. 2007)

Tinnitus induced by tone exposure in rats

Auditory cortex electrical stimulation with electrical array.

Tinnitus is suppressed and hearing is improved at the central level

(Zhang et al. 2011)