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We will demonstrate that FIRDA (frontal intermittent rhythmic delta activity) - otherwise related to systemic disorders and encephalopathy - has a role as an epileptic biomarker of deep seated midline SOZ. Its abolishment following SEEG guided radiofrequency of such SOZ correlates with clinical improvement, suggests its role as a non-invasive biomarker of otherwise inaccessible SOZs.We report the case of AK who was admitted with "psychiatric and gastrointestinal complaints". AK's complaints were further associated with FIRDA during VEEG. His previous refractoriness to AEDs, the clinico-electroencephalographic correlation, MRI showing bilateral hippocampal atrophy (more to the left) and severe memory deficits prompted us to suggest a left temporo-mesial SOZ, for which SEEG was done. Dual SEEG and scalp electrodes was used primarily for diagnostic purpose but taking into account an option for a therapeutic action by RF ablation.The dual array demonstrated a clear association between left hippocampal high voltage spikes and HFO's on SEEG recordings with FIRDA on concomitant scalp EEG parallel to behavioral changes, as suspected on our preliminary hypothesis. A further RF ablation eliminated the epileptiform activity (Spikes, HFO's and FIRDA) followed by clinical improvement.This is the first report showing the clinical significance of FIRDA associated with behavioral changes as a marker for latent refractory mesial epilepsy. SEEG exploration has the potential to uncover deep sources which are manifested as FIRDA on scalp EEG. These abnormalities and clinical symptoms can be eliminated by RF ablation.

Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery., This work was funded by K23NS104252 (A.A.L.) R01 MH117777 (E.B., J.W.R.) Whitehall Foundation (KH) 5F31NS120783-02 (Z.L.) 1U19NS104590 (A.L.) R01NS106611-02 (J.S., M.K.) MTEC-20-06-MOM013 (J.S., M.K.) 1U19NS107609-01 (I.S., J.L.) 1U19NS104590 (A.L., J.S.F., I.S.) 1U19NS107609 (E.A.B., J.W.R., J.J.L., I.S.) La Caixa LCF/PR/HR21/52410030 (A.N.O., L.dl.P) European Research Council Consolidator Grant 101001121 (B.P.S.) U.S.-Israel BSF grant 2017015 (RM)U01-NS113198 (J.J.) NSF CAREER IOS-1844935 (M.vdM.) 1R01NS121764-01 (B.L.M.) R01 MH122391 (G.B.) 30MH126483 (J.A.G.) Fondation pour la Recherche Médicale EQU202103012768 (M.Z.) 1R16-NS131108-01 (L.L.).

The magnitude of neuronal activation is commonly considered a critical factor for conscious perception of visual content. However, this dogma contrasts with the phenomenon of rapid adaptation, in which the magnitude of neuronal activation drops dramatically in a rapid manner, while the visual stimulus and the conscious experience it elicits remain stable. Here we report that the profiles of multi-site activation patterns and their relational geometry –i.e. the similarity distances between activation patterns, as revealed using iEEG recordings, are sustained during extended stimulation despite the major magnitude decrease. These results are compatible with the hypothesis that conscious perceptual content is associated with the neuronal pattern profiles and their similarity distances, rather than by the overall activation magnitude, in human visual cortex.

Research in functional neuroimaging has suggested that category-selective regions of visual cortex, including the ventral temporal cortex (VTC), can be reactivated endogenously through imagery and recall. Face representation in the monkey face-patch system has been well studied and is an attractive domain in which to explore these processes in humans. The VTCs of 8 human subjects (4 female) undergoing invasive monitoring for epilepsy surgery were implanted with microelectrodes. Most (26 of 33) category-selective units showed specificity for face stimuli. Different face exemplars evoked consistent and discriminable responses in the population of units sampled. During free recall, face-selective units preferentially reactivated in the absence of visual stimulation during a 2 s window preceding face recall events. Furthermore, we show that in at least 1 subject, the identity of the recalled face could be predicted by comparing activity preceding recall events to activity evoked by visual stimulation. We show that face-selective units in the human VTC are reactivated endogenously, and present initial evidence that consistent representations of individual face exemplars are specifically reactivated in this manner.SIGNIFICANCE STATEMENTThe role of “top-down” endogenous reactivation of native representations in higher sensory areas is poorly understood in humans. We conducted the first detailed single-unit survey of ventral temporal cortex (VTC) in human subjects, showing that, similarly to nonhuman primates, humans encode different faces using different rate codes. Then, we demonstrated that, when subjects recalled and imagined a given face, VTC neurons reactivated with the same rate codes as when subjects initially viewed that face. This suggests that the VTC units not only carry durable representations of faces, but that those representations can be endogenously reactivated via “top-down” mechanisms.

While controlled experiments form the core of human brain research – a fundamental, yet far less studied, domain concerns the neuronal mechanism underlying freely-generated, spontaneous behavior. Intracranial recordings in conscious human patients offer an invaluable window into this question. Here we review relevant iEEG findings highlighting a universal mechanism underlying human free behavior: internally generated ultra-slow fluctuations in neuronal activity. These spontaneous firing dynamics are ubiquitous across the brain and appear at various scales – from functionally-specialized local sub-populations, to brain wide networks. Crucially, signatures of these slow fluctuations appear in every free behavior studied so far. Focusing on free recall as a paradigmatic example, we demonstrate that spontaneous activity fluctuations – manifested as slow anticipatory waves in cortico-hippocampal circuits – tend to precede spontaneous recollections by 1-2 seconds. Moreover, when patients attempt to constrain their spontaneous recollections to a particular category, intracranial recordings in the cortex reveal a category-specific “baseline shift”, i.e., steady enhancement in the excitability of neuronal populations encoding the targeted category. Such top-down modulation can bias the free recall process by pushing the spontaneous fluctuations of the relevant neuronal subpopulations closer to the behavioral threshold. Along with evidence derived from fMRI studies, these iEEG experiments demonstrate that slow spontaneous fluctuations within the appropriate brain circuits may serve as a driving force behind the emergence of spontaneous thoughts and free human behavior.

Hippocampal ripples are prominent synchronization events generated by hippocampal neuronal assemblies. To date, ripples have been primarily associated with navigational memory in rodents and short-term episodic recollections in humans. Here, we uncover different profiles of ripple activity in the human hippocampus during the retrieval of recent and remote autobiographical events and semantic facts. We found that the ripple rate increased significantly before reported recall compared to control conditions. Patterns of ripple activity across multiple hippocampal sites demonstrated remarkable specificity for memory type. Intriguingly, these ripple patterns revealed a semantization dimension, in which patterns associated with autobiographical contents become similar to those of semantic memory as a function of memory age. Finally, widely distributed sites across the neocortex exhibited ripple-coupled activations during recollection, with the strongest activation found within the default mode network. Our results thus reveal a key role for hippocampal ripples in orchestrating hippocampal-cortical communication across large-scale networks involved in conscious recollection.

Asked to freely recall items from a predefined set (e.g., animals), we rarely recall a wrong exemplar (e.g., a vegetable). This capability is so powerful and effortless that it is essentially taken for granted, yet, surprisingly, the underlying neuronal mechanisms are unknown. Here we investigate this boundary setting mechanism using intracranial recordings (ECoG), in 12 patients undergoing epilepsy monitoring engaged in episodic free recall. After viewing vivid photographs from two categories (famous faces and places), patients were asked to freely recall these items, targeting each category in separate blocks. Our results reveal a rapid and sustained rise in neuronal activity (“baseline shift”) in high-order visual areas that persists throughout the free recall period and reflects the targeted category. We further show a more transient reactivation linked to individual recall events. The results point to baseline shift as a flexible top−down mechanism that biases spontaneous recall to remain within the required categorical boundaries., Though people are easily able to recall items in a category without mentioning a wrong exemplar, the mechanism underlying this ability is unknown. Here, authors use intracranial recordings to show that this ability is likely due to a selective increase in baseline neuronal activity in category-specific regions.

Sharp-wave ripples in the hippocampus What are the brain mechanisms responsible for episodic memory retrieval? Norman et al. investigated epilepsy patients who had electrodes implanted in the hippocampus and a variety of cortical areas. Using a visual learning paradigm, they examined the temporal relationship between the incidence of hippocampal sharp-wave ripples and recall. Effective encoding of visual information was associated with higher incidence of ripples. Successful recall was preceded by an increased probability of ripples, which were also associated with transient reemergence of activation patterns in higher visual cortical areas. Hippocampal ripples may thus boost recollections during episodic memory retrieval. Science , this issue p. eaax1030