High and low frequency anterior nucleus of thalamus deep brain stimulation: Impact on memory and mood in five patients with treatment resistant temporal lobe epilepsy

High frequency anterior nucleus of the thalamus deep brain stimulation (ANT DBS) is an established therapy for treatment resistant focal epilepsies. Although high frequency-ANT DBS is well tolerated, patients are rarely seizure free and the efficacy of other DBS parameters and their impact on comorbidities of epilepsy such as depression and memory dysfunction remain unclear. The purpose of this study was to assess the impact of low vs high frequency ANT DBS on verbal memory and self-reported anxiety and depression symptoms. Five patients with treatment resistant temporal lobe epilepsy were implanted with an investigational brain stimulation and sensing device capable of ANT DBS and ambulatory intracranial electroencephalographic (iEEG) monitoring, enabling long-term detection of electrographic seizures. While patients received therapeutic high frequency (100 and 145 Hz continuous and cycling) and low frequency (2 and 7 Hz continuous) stimulation, they completed weekly free recall verbal memory tasks and thrice weekly self-reports of anxiety and depression symptom severity. Mixed effects models were then used to evaluate associations between memory scores, anxiety and depression self-reports, seizure counts, and stimulation frequency. Memory score was significantly associated with stimulation frequency, with higher free recall verbal memory scores during low frequency ANT DBS. Self-reported anxiety and depression symptom severity was not significantly associated with stimulation frequency. These findings suggest the choice of ANT DBS stimulation parameter may impact patients cognitive function, independently of its impact on seizure rates.