Deep brain stimulation of the anterior nuclei of the thalamus in focal epilepsy.

OBJECTIVE: To review the therapeutic effects of deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) and the predictors of its effectiveness, safety, and adverse effects. METHODS: A comprehensive search of the medical literature (PubMed) was conducted to identify relevant articles investigating ANT-DBS therapy for epilepsy. Out of 332 references, 77 focused on focal epilepsies were reviewed. RESULTS: The DBS effect is probably due to decreased synchronization of epileptic activity in the cortex. The potential mechanisms from cellular to brain network levels are presented. The ANT might participate actively in the network elaborating focal seizures. The effects of ANT-DBS differed in various studies; ANT-DBS was linked with a 41% seizure frequency reduction at 1 year, 69% at 5 years, and 75% at 7 years. The most frequently reported adverse effects, depression and memory impairment, were considered non-serious in the long-term follow-up view. ANT-DBS also has been used in a few cases to treat status epilepticus. CONCLUSIONS: We reviewed the clinical literature and identified several factors that may predict seizure outcome following DBS therapy. More large-scale trials are required since there is a need to explore stimulation settings, apply patient-tailored therapy, and identify the presurgical predictors of patient response. SIGNIFICANCE: A critical review of the published literature on ANT-DBS in focal epilepsy is presented. ANT-DBS mechanisms are not fully understood; possible explanations are provided. Biomarkers of ANT-DBS effectiveness may lead to patient-tailored therapy.

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus.

We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of deep brain stimulation (DBS). We analyzed intracerebral electroencephalographic (EEG) recordings from externalized DBS electrodes targeted bilaterally in the anterior nuclei of the thalamus (ANT) in 12 patients (six responders, six nonresponders) with more than 1 year of follow-up care. In the bipolar local field potentials of the EEG, spectral power (PW) and power spectral entropy (PSE) were calculated in the passbands 1-4, 4-8, 8-12, 12-20, 20-45, 65-80, 80-200 and 200-500 Hz. The most significant differences between responders and nonresponders were observed in the BRIDGE area (bipolar recordings with one contact within the ANT and the second contact in adjacent tissue). In responders, PW was significantly decreased in the frequency bands of 65-80, 80-200, and 200-500 Hz (p < .05); PSE was significantly increased in all frequency bands (p < .05) except for 200-500 Hz (p = .06). The local EEG characteristics of ANT recorded after implantation may play a significant role in DBS response prediction.

Resting-State Phase-Amplitude Coupling Between the Human Subthalamic Nucleus and Cortical Activity: A Simultaneous Intracranial and Scalp EEG Study.

It has been suggested that slow oscillations in the subthalamic nucleus (STN) reflect top-down inputs from the medial prefrontal cortex, thus implementing behavior control. It is unclear, however, whether the STN oscillations are related to cortical activity in a bottom-up manner. To assess resting-state subcortico-cortical interactions, we recorded simultaneous scalp electroencephalographic activity and local field potentials in the STN (LFP-STN) in 11 patients with Parkinson's disease implanted with deep brain stimulation electrodes in the on-medication state during rest. We assessed the cross-structural phase-amplitude coupling (PAC) between the STN and cortical activity within a wide frequency range of 1 to 100 Hz. The PAC was dominant between the δ/θ STN phase and ß/γ cortical amplitude in most investigated scalp regions and between the δ cortical phase and θ/α STN amplitude in the frontal and temporal regions. The cross-frequency linkage between the slow oscillations of the LFP-STN activity and the amplitude of the scalp-recorded cortical activity at rest was demonstrated, and similar involvement of the left and right STNs in the coupling was observed. Our results suggest that the STN plays a role in both bottom-up and top-down processes within the subcortico-cortical circuitries of the human brain during the resting state. A relative left-right symmetry in the STN-cortex functional linkage was suggested. Practical treatment studies would be necessary to assess whether unilateral stimulation of the STN might be sufficient for treatment of Parkinson's disease.