川合 謙介

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) suffer from epileptic seizures and memory decline. While focal resection eliminates seizures in 60-70% of patients, surgery carries the risk of further compromising memory. We hypothesized that hippocampal neurofeedback (NF) will induce targeted brain activity associated with memory function. METHODS: Patients with intracranial electrodes implanted in bilateral hippocampi performed a memory NF task, developed specifically for this project. The NF task involved real-time analysis of hippocampal activity using the electrode in the less-affected hippocampus while conducting a memory task. Changes in theta activity and task performance were assessed. RESULTS: The NF task was conducted in seven TLE patients. In five patients, theta activity increased significantly in the targeted hippocampus (Mann-Kendall test; p < 0.05). Mixed linear model analysis across all sessions revealed a significant increase in theta activity in the targeted hippocampus (p = 0.0032), with no significant change contralaterally (p = 0.19). Three additional TLE patients underwent random NF to assess if theta activity was induced merely by the encoding process, but none of them showed significant changes in theta activity. CONCLUSION: Memory NF task effectively induced targeted hippocampal activity in TLE patients. SIGNIFICANCE: Hippocampal NF may enhance memory function in TLE patients prior to focal resection.

BACKGROUND: Redo awake surgery is ideal for recurrent malignant gliomas in the language-dominant hemisphere, but it may not always be optimal because of inadequate awake mapping. In this report, the authors describe a case of recurrent language-dominant frontal glioma in which a super-selective Wada (ssWada) test and super-selective cone-beam CT angiography (ssCBCTA) enabled successful tumor removal under general anesthesia after awake surgery. OBSERVATIONS: A woman in her 30s underwent awake surgery for left frontal glioma recurrence 2 years after the initial resection. Three years after another recurrence, the ssWada test and ssCBCTA revealed that the tumor-supplying artery did not perfuse the functional cortex, allowing safe and maximal resection under general anesthesia. Postoperatively, she had mild motor aphasia but recovered quickly with minimal sequelae. LESSONS: The combined use of the ssWada test and ssCBCTA enables precise preoperative language mapping and safe tumor resection. Originally developed for epilepsy surgery, the ssWada test is valuable for functional mapping and, when paired with ssCBCTA, provides a 3D understanding of the lesions. This combination serves as a critical preoperative tool for tumors in the language-dominant hemisphere. https://thejns.org/doi/10.3171/CASE25384.

Vagus nerve stimulation (VNS) has emerged as a promising therapeutic intervention across various neurological and psychiatric conditions, including epilepsy, depression, and stroke rehabilitation; however, its mechanisms of action on neural circuits remain incompletely understood. Here, we present a novel theoretical framework based on predictive coding that conceptualizes VNS effects through differential modulation of feedforward and feedback neural circuits. Based on recent evidence, we propose that VNS shifts the balance between feedforward and feedback processing through multiple neuromodulatory systems, resulting in enhanced feedforward signal transmission. This framework integrates anatomical pathways, receptor distributions, and physiological responses to explain the influence of the VNS on neural dynamics across different spatial and temporal scales. Vagus nerve stimulation may facilitate neural plasticity and adaptive behavior through acetylcholine and noradrenaline (norepinephrine), which differentially modulate feedforward and feedback signaling. This mechanistic understanding serves as a basis for interpreting the cognitive and therapeutic outcomes across different clinical conditions. Our perspective provides a unified theoretical framework for understanding circuit-specific VNS effects and suggests new directions for investigating their therapeutic mechanisms.

Abstract The brain of a living organism enables stable information processing in response to constantly changing external environments and internal states. As one of such cortical modulation, the present study focused on the effect of vagus nerve stimulation (VNS) therapy on information representation of the auditory cortex. By quantifying sound representation using machine learning, we investigated whether VNS alters cortical information representation in a layer-specific and frequency band-specific manner. A microelectrode array meticulously mapped the band-specific power and phase-locking value of sustained activities in every layer of the rat auditory cortex. Sparse logistic regression was used to decode the test frequency from these neural characteristics. The comparison of decoding accuracy before and after the application of VNS indicated that sound representation of the high-gamma band activity was impaired in the deeper layers, i.e., layers 5 and 6, while it was slightly improved in the superficial layers, i.e., layers 2, 3, and 4. Moreover, there was an improvement of sound representation in theta band activity in the deeper layers, demonstrating the layer-specific and frequency band-specific effect of VNS. Given that the cortical laminar structure and oscillatory activity in multiple frequency bands helps the auditory cortex to act as a hub for feed-forward and feed-back pathways in various information processing, the current findings support the possibility that VNS provide complex effects on brain function by altering the balance of cortical activity between layers and frequency bands.