Thalamic responsive neurostimulation for the treatment of refractory epilepsy: an individual patient data meta-analysis.

OBJECTIVE: In recent years, the treatment of drug-resistant epilepsy (DRE) has made greater use of surgery and expanded options for neurostimulation or neuromodulation. Up to this point, responsive neurostimulation (RNS) has been very promising but has mainly used only the cortex as a target. In this individual patient data meta-analysis (IPDMA), the authors sought to establish if a novel RNS target, the thalamus, can be used to treat DRE. METHODS: The literature regarding the management of DRE by targeting the thalamus with RNS was reviewed per IPDMA guidelines. Five databases were searched with keywords [((Responsive neurostimulation) OR (RNS)) AND ((thalamus) OR (thalamic) OR (Deep-seated) OR (Diencephalon) OR (limbic))] in March 2022. RESULTS: The median (interquartile range) age at implantation was 17 (13.5-27.5) years (n = 42) with an epilepsy duration of 12.1 (5.8-15.3) years. In total, 52.4% of patients had previously undergone epilepsy surgery, 28.6% had prior vagus nerve stimulation, and 2.4% had prior RNS. The median preimplant seizure frequency was 12 per week. The median seizure reduction at last follow-up was 73%. No study in this IPDMA reported complications, although 7 cases (16.3%) did require reoperation. Behavioral improvements and reduced antiepileptic drug dose or quantity were reported for 80% and 28.6% of patients, respectively. CONCLUSIONS: This review indicates that thalamic RNS may be safe and effective for treating DRE. Long-term and controlled studies on thalamic RNS for DRE would further elucidate this technique's potential benefits and complications and help guide clinical judgment in the management of DRE.

Brain network dynamics in the human articulatory loop.

OBJECTIVE: The articulatory loop is a fundamental component of language function, involved in the short-term buffer of auditory information followed by its vocal reproduction. We characterized the network dynamics of the human articulatory loop, using invasive recording and stimulation. METHODS: We measured high-gamma activity70-110 Hz recorded intracranially when patients with epilepsy either only listened to, or listened to and then reproduced two successive tones by humming. We also conducted network analyses, and analyzed behavioral responses to cortical stimulation. RESULTS: Presentation of the initial tone elicited high-gamma augmentation bilaterally in the superior-temporal gyrus (STG) within 40ms, and in the precentral and inferior-frontal gyri (PCG and IFG) within 160ms after sound onset. During presentation of the second tone, high-gamma augmentation was reduced in STG but enhanced in IFG. The task requiring tone reproduction further enhanced high-gamma augmentation in PCG during and after sound presentation. Event-related causality (ERC) analysis revealed dominant flows within STG immediately after sound onset, followed by reciprocal interactions involving PCG and IFG. Measurement of cortico-cortical evoked-potentials (CCEPs) confirmed connectivity between distant high-gamma sites in the articulatory loop. High-frequency stimulation of precentral high-gamma sites in either hemisphere induced speech arrest, inability to control vocalization, or forced vocalization. Vocalization of tones was accompanied by high-gamma augmentation over larger extents of PCG. CONCLUSIONS: Bilateral PCG rapidly and directly receives feed-forward signals from STG, and may promptly initiate motor planning including sub-vocal rehearsal for short-term buffering of auditory stimuli. Enhanced high-gamma augmentation in IFG during presentation of the second tone may reflect high-order processing of the tone sequence. SIGNIFICANCE: The articulatory loop employs sustained reciprocal propagation of neural activity across a network of cortical sites with strong neurophysiological connectivity.

Mapping mental calculation systems with electrocorticography.

OBJECTIVE: We investigated intracranially-recorded gamma activity during calculation tasks to better understand the cortical dynamics of calculation. METHODS: We studied 11 patients with focal epilepsy (age range: 9-28years) who underwent measurement of calculation- and naming-related gamma-augmentation during extraoperative electrocorticography (ECoG). The patients were instructed to overtly verbalize a one-word answer in response to auditorily-delivered calculation and naming questions. The assigned calculation tasks were addition and subtraction involving integers between 1 and 17. RESULTS: Out of the 1001 analyzed cortical electrode sites, 63 showed gamma-augmentation at 50-120Hz elicited by both tasks, 88 specifically during naming, and 7 specifically during calculation. Common gamma-augmentation mainly took place in the Rolandic regions. Calculation-specific gamma-augmentation, involving the period between the question-offset and response-onset, was noted in the middle-temporal, inferior-parietal, inferior post-central, middle-frontal, and premotor regions of the left hemisphere. Calculation-specific gamma-augmentation in the middle-temporal, inferior-parietal, and inferior post-central regions peaked around the question offset, while that in the frontal lobe peaked after the question offset and before the response onset. This study failed to detect a significant difference in calculation-specific gamma amplitude between easy trials and difficult ones requiring multi-digit operations. CONCLUSIONS: Auditorily-delivered stimuli can elicit calculation-specific gamma-augmentation in multiple regions of the left hemisphere including the parietal region. However, the additive diagnostic value of measurement of gamma-augmentation related to a simple calculation task appears modest. SIGNIFICANCE: Further studies are warranted to determine the functional significance of calculation-specific gamma-augmentation in each site, and to establish the optimal protocol for mapping mental calculation.

In vivo animation of auditory-language-induced gamma-oscillations in children with intractable focal epilepsy.

We determined if high-frequency gamma-oscillations (50- to 150-Hz) were induced by simple auditory communication over the language network areas in children with focal epilepsy. Four children (aged 7, 9, 10 and 16 years) with intractable left-hemispheric focal epilepsy underwent extraoperative electrocorticography (ECoG) as well as language mapping using neurostimulation and auditory-language-induced gamma-oscillations on ECoG. The audible communication was recorded concurrently and integrated with ECoG recording to allow for accurate time lock on ECoG analysis. In three children, who successfully completed the auditory-language task, high-frequency gamma-augmentation sequentially involved: i) the posterior superior temporal gyrus when listening to the question, ii) the posterior lateral temporal region and the posterior frontal region in the time interval between question completion and the patient's vocalization, and iii) the pre- and post-central gyri immediately preceding and during the patient's vocalization. The youngest child, with attention deficits, failed to cooperate during the auditory-language task, and high-frequency gamma-augmentation was noted only in the posterior superior temporal gyrus when audible questions were given. The size of language areas suggested by statistically significant high-frequency gamma-augmentation was larger than that defined by neurostimulation. The present method can provide in vivo imaging of electrophysiological activities over the language network areas during language processes. Further studies are warranted to determine whether recording of language-induced gamma-oscillations can supplement language mapping using neurostimulation in presurgical evaluation of children with focal epilepsy.