Prediction and detection of seizures from simultaneous thalamic and scalp electroencephalography recordings.

OBJECTIVE The authors explored the feasibility of seizure detection and prediction using signals recorded from the anterior thalamic nucleus, a major target for deep brain stimulation (DBS) in the treatment of epilepsy. METHODS Using data from 5 patients (13 seizures in total), the authors performed a feasibility study and analyzed the performance of a seizure prediction and detection algorithm applied to simultaneously acquired scalp and thalamic electroencephalography (EEG). The thalamic signal was obtained from DBS electrodes. The applied algorithm used the similarity index as a nonlinear measure for seizure identification, with patient-specific channel and threshold selection. Receiver operating characteristic (ROC) curves were calculated using data from all patients and channels to compare the performance between DBS and EEG recordings. RESULTS Thalamic DBS recordings were associated with a mean prediction rate of 84%, detection rate of 97%, and false-alarm rate of 0.79/hr. In comparison, scalp EEG recordings were associated with a mean prediction rate of 71%, detection rate of 100%, and false-alarm rate of 1.01/hr. From the ROC curves, when considering all channels, DBS outperformed EEG for both detection and prediction of seizures. CONCLUSIONS This is the first study to compare automated seizure detection and prediction from simultaneous thalamic and scalp EEG recordings. The authors have demonstrated that signals recorded from DBS leads are more robust than EEG recordings and can be used to predict and detect seizures. These results indicate feasibility for future designs of closed-loop anterior nucleus DBS systems for the treatment of epilepsy.

Memory enhancement induced by hypothalamic/fornix deep brain stimulation.

Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded "on" versus "off" manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions.

Mesial temporal inhibition in a patient with deep brain stimulation of the anterior thalamus for epilepsy.

We investigated the electrophysiological effects of high-frequency anterior thalamic deep brain stimulation using intracerebral mesial and lateral temporal depth electrodes in a patient with intractable focal epilepsy. Monopolar and bipolar stimulation delivered to the thalamic anterior nucleus using the programmable ITREL II stimulation device led to a significant decrease of cross power spectral density and a nonsignificant decrease of coherence in ipsilateral hippocampal structures. No such effect was found in lateral temporal or contralateral sites. The hippocampal inhibition was clearly related to the voltage (> or =7 V) and frequency (> or =70 Hz) of the thalamic stimulus and occurred with a delay of approximately 60 s after stimulus onset.

Rhythmic cortical EEG synchronization with low frequency stimulation of the anterior and medial thalamus for epilepsy.

OBJECTIVE: To investigate the neurophysiological characteristics and prognostic impact of EEG synchronization with low frequency thalamic stimulation in patients with intractable epilepsy. METHODS: Electrical stimuli were delivered through deep brain stimulating (DBS) electrodes at 2, 5 or 10Hz to the anterior nucleus (AN) and the dorsomedial nucleus (DM) of six patients using the implanted programmable stimulation device. EEGs were recorded from 27 scalp electrodes. "Modeled" responses for 5 and 10Hz stimulation were computed based on the cerebral responses (CRs) evoked by "single pulse" (2Hz) stimulation and compared with the recorded EEG results. RESULTS: Rhythmic cortical 5Hz EEG synchronization occurred in 4/6 patients, with stimulation at 6/11 AN and 5/11 DM sites. Three of four patients with synchronization, but neither of the two patients without, had a significant reduction in seizure frequency. The magnitude of 5 and 10Hz EEG synchronization was positively related to the amplitudes of "single pulse" CRs. Simple temporal superposition of "single pulse" CRs resulted in "modeled" responses with strikingly similar morphology and scalp voltage distribution. CONCLUSIONS: Rhythmic EEG synchronization with low frequency stimulation primarily reflects spatiotemporal summation (interference) of "single pulse" CRs. SIGNIFICANCE: Rhythmic EEG synchronization might not serve as a physiologic verification of optimal localization of DBS electrodes. Its usefulness for the prediction of clinical efficacy is questionable.

Cortical activation with deep brain stimulation of the anterior thalamus for epilepsy.

OBJECTIVE: We studied the relation between thalamic stimulation parameters and the morphology, topographic distribution and cortical sources of the cerebral responses in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Bipolar and monopolar stimuli were delivered at a rate of 2 Hz to the anterior (AN, four patients), the dorsomedian (DM, four patients), and the centromedian nucleus (CM, one patient) using the programmable stimulation device (Medtronic ITREL II). Source modeling was carried out by using statistical non-parametric mapping of low-resolution electromagnetic tomography (LORETA) values. RESULTS: All patients demonstrated reproducible time-locked cortical responses (CRs) consisting of a sequence of components with latencies between 20 and 320 ms. The morphology of these CRs, however, was very heterogeneous, depending primarily on the site of stimulation. Following AN stimulation, cortical activation was most prominent in ipsilateral cingulate gyrus, insular cortex and lateral neocortical temporal structures. Stimulation of the DM mainly showed activation of the ipsilateral orbitofrontal and mesial and lateral frontal areas, but also involvement of mesial temporal structures. Stimulation of the CM showed a rather diffuse (though still mainly ipsilateral) increase of cortical activity. The magnitude of cortical activation was positively related to the strength of the stimulus and inversely related to the impedance of the electrode. CONCLUSIONS: The pattern of cortical activation corresponded with the hodology of the involved structures and may underscore the importance of optimal localization of DBS electrodes in patients with epilepsy. SIGNIFICANCE: The method of analyzing sources of CRs could potentially be a useful tool for titration of DBS parameters in patients with electrode contacts in clinically silent areas. Furthermore, the inverse relation of the cortical activation and the impedance of the electrode contacts might suggest that these impedance measurements should be taken into consideration when adjusting DBS parameters in patients with epilepsy.

Intracranial volume conduction of cortical spikes and sleep potentials recorded with deep brain stimulating electrodes.

OBJECTIVE: To examine interictal epileptiform and sleep potentials recorded intracranially from deep brain stimulation (DBS) electrodes in patients treated with DBS for epilepsy. Specifically, this study sought to determine whether the DBS-recorded potentials represent: (a) volume conduction from surface neocortical discharges or (b) transsynaptic propagation along cortical-subcortical pathways with local generation of the subcortical potentials near the DBS targets. METHODS: Six patients with intractable epilepsy treated with thalamic DBS of the central median nucleus (CM; one patient) or anterior thalamus (5 patients) who had focal interictal spikes were studied. Sleep potentials were also studied in a 7th patient with Parkinson disease treated with DBS of the subthalamic nucleus (STN). RESULTS: Focal interictal cortical spikes recorded by scalp electroencephalography (EEG) were recorded synchronously, but with opposite polarity, from the DBS electrodes in CM as well as the more superficial anterior thalamic contacts situated in the anterior nucleus (AN) and dorsal medial nucleus (DM). In referential montages, the subcortical potentials were of highest amplitude ipsilateral to the focal cortical spikes, with a small but reproducible amplitude decrement present at each electrode contact more distant from the cortical source, irrespective of the specific DBS target. Subcortical sleep potentials (K-complexes and sleep spindles) were also recorded synchronously and with inverse polarity compared to the corresponding scalp potentials, and appeared in a similar fashion at all subcortical sites sampled by the DBS electrodes. Amplitude attenuation in the thalamus of intracranial volume conducted potentials with increasing distance from their cortical spike sources was measured at approximately 5-10 microV/mm. DISCUSSION: Recent reports on scalp-CM or scalp-STN EEG recordings in patients treated with DBS for epilepsy have interpreted the intracranial waveforms as evidence of transsynaptic cortical-subcortical transmission across neuroanatomical pathways presumed to be involved in the generation of sleep potentials (Clin. Neurophysiol. 113 (2002) 25) and epileptiform activity (Clin. Neurophysiol. 113 (2002) 1391). However, our results show that the intracranial spikes recorded from DBS electrodes in various regions of the thalamus (CM, AN and DM) represent subcortical volume conduction of the synchronous cortical spikes recorded with scalp EEG. The same is true for the intracranial reflections of scalp EEG sleep potentials recorded from DBS electrodes in CM, AN, DM and STN. These interictal DBS waveforms thus cannot be used to support hypotheses of specific cortical-subcortical pathways of neural propagation or subcortical generation of the DBS-recorded potentials associated with scalp EEG interictal spikes and sleep potentials. SIGNIFICANCE: Detailed analysis of the intracranial potentials recorded from DBS electrodes in association with scalp EEG spikes and sleep discharges shows that the intracranial waveforms represent volume conduction from discharges generated in the neocortex and not, as has been suggested, locally generated activity resulting from cortical-subcortical neural propagation.

Chronic anterior thalamus stimulation for intractable epilepsy.

PURPOSE: A significant number of patients with epilepsy remain poorly controlled despite antiepileptic medication (AED) treatment and are not eligible for resective surgery. Novel therapeutic methods are required to decrease seizure burden in this population. Several observations have indicated that the anterior thalamic region plays an important role in the maintenance and propagation of seizures. We investigated neuromodulation of the anterior thalamus by using deep-brain stimulation (DBS) in patients with intractable seizures. METHODS: Five patients with medically refractory epilepsy underwent stereotactic placement of and received stimulation through bilateral DBS electrodes in the anterior thalamus. RESULTS: Treatment showed a statistically significant decrease in seizure frequency, with a mean reduction of 54% (mean follow-up, 15 months). Two of the patients had a seizure reduction of > or =75%. No adverse effects were observed after DBS electrode insertion or stimulation. Unexpectedly, the observed benefits did not differ between stimulation-on and stimulation-off periods. CONCLUSIONS: DBS of the anterior thalamus is a safe procedure and possibly effective in patients with medically resistant seizures.