Intracortical recordings reveal vision-to-action cortical gradients driving human exogenous attention.

Exogenous attention, the process that makes external salient stimuli pop-out of a visual scene, is essential for survival. How attention-capturing events modulate human brain processing remains unclear. Here we show how the psychological construct of exogenous attention gradually emerges over large-scale gradients in the human cortex, by analyzing activity from 1,403 intracortical contacts implanted in 28 individuals, while they performed an exogenous attention task. The timing, location and task-relevance of attentional events defined a spatiotemporal gradient of three neural clusters, which mapped onto cortical gradients and presented a hierarchy of timescales. Visual attributes modulated neural activity at one end of the gradient, while at the other end it reflected the upcoming response timing, with attentional effects occurring at the intersection of visual and response signals. These findings challenge multi-step models of attention, and suggest that frontoparietal networks, which process sequential stimuli as separate events sharing the same location, drive exogenous attention phenomena such as inhibition of return.

Memory functioning after hippocampal removal: Does side matter?

To address the memory functioning after medial temporal lobe (MTL) surgery for refractory epilepsy and relationships with the side of the hippocampal removal, 22 patients with pharmaco-resistant epilepsy who had undergone MTL resection (10 right/12 left) at the Salpêtrière Hospital were compared with 21 matched healthy controls. We designed a specific neuropsychological binding memory test that specifically addressed hippocampal cortex functioning, and left-right material-specific lateralization. Our results showed that both left and right mesial temporal lobe removal cause a severe memory impairment, for both verbal and visual material. The removal of left medial temporal lobe causes worse memory impairment than the right removal regardless of the stimuli type (verbal or visual) questioning the theory of the hippocampal material-specific lateralization. The present study provided new evidence for the role of both hippocampus and surrounding cortices in memory-binding whatever the material type and also suggested that a left MTL removal is more deleterious for both verbal and visual episodic memory in comparison with right MTL removal.

Fronto-parietal networks shape human conscious report through attention gain and reorienting.

How do attention and consciousness interact in the human brain? Rival theories of consciousness disagree on the role of fronto-parietal attentional networks in conscious perception. We recorded neural activity from 727 intracerebral contacts in 13 epileptic patients, while they detected near-threshold targets preceded by attentional cues. Clustering revealed three neural patterns: first, attention-enhanced conscious report accompanied sustained right-hemisphere fronto-temporal activity in networks connected by the superior longitudinal fasciculus (SLF) II-III, and late accumulation of activity (>300 ms post-target) in bilateral dorso-prefrontal and right-hemisphere orbitofrontal cortex (SLF I-III). Second, attentional reorienting affected conscious report through early, sustained activity in a right-hemisphere network (SLF III). Third, conscious report accompanied left-hemisphere dorsolateral-prefrontal activity. Task modeling with recurrent neural networks revealed multiple clusters matching the identified brain clusters, elucidating the causal relationship between clusters in conscious perception of near-threshold targets. Thus, distinct, hemisphere-asymmetric fronto-parietal networks support attentional gain and reorienting in shaping human conscious experience.

Gamma amplitude is coupled to opposed hippocampal theta-phase states during the encoding and retrieval of episodic memories in humans.

Computational models and in vivo studies in rodents suggest that the emergence of gamma activity (40-140 Hz) during memory encoding and retrieval is coupled to opposed-phase states of the underlying hippocampal theta rhythm (4-9 Hz).1,2,3,4,5,6,7,8,9,10 However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed-phase states of the ongoing theta rhythm remains elusive. Here, we recorded local field potentials (LFPs) directly from the hippocampus of 10 patients with epilepsy, using depth electrodes. We used a memory encoding and retrieval task whereby trial unique sequences of pictures depicting real-life episodes were presented, and 24 h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. We found theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants' memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, although only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.

Intracranial study in humans: Neural spectral changes during watching comedy movie of Charlie Chaplin.

Humor plays a prominent role in our lives. Thus, understanding the cognitive and neural mechanisms of humor is particularly important. Previous studies that investigated neural substrates of humor used functional MRI and to a lesser extent EEG. In the present study, we conducted intracranial recording in human patients, enabling us to obtain the signal with high temporal precision from within specific brain locations. Our analysis focused on the temporal lobe and the surrounding areas, the temporal lobe was most densely covered in our recording. Thirteen patients watched a fragment of a Charlie Chaplin movie. An independent group of healthy participants rated the same movie fragment, helping us to identify the most funny and the least funny frames of the movie. We compared neural activity occurring during the most funny and least funny frames across frequencies in the range of 1-170 Hz. The most funny compared to least funny parts of the movie were associated with activity modulation in the broadband high-gamma (70-170 Hz; mostly activation) and to a lesser extent gamma band (40-69Hz; activation) and low frequencies (1-12 Hz, delta, theta, alpha bands; mostly deactivation). With regard to regional specificity, we found three types of brain areas: (I) temporal pole, middle and inferior temporal gyrus (both anterior and posterior) in which there was both activation in the high-gamma/gamma bands and deactivation in low frequencies; (II) ventral part of the temporal lobe such as the fusiform gyrus, in which there was mostly deactivation the low frequencies; (III) posterior temporal cortex and its environment, such as the middle occipital and the temporo-parietal junction, in which there was activation in the high-gamma/gamma band. Overall, our results suggest that humor appreciation might be achieved by neural activity across the frequency spectrum.

Daily resting-state intracranial EEG connectivity for seizure risk forecasts.

Forecasting seizure risk aims to detect proictal states in which seizures would be more likely to occur. Classical seizure prediction models are trained over long-term electroencephalographic (EEG) recordings to detect specific preictal changes for each seizure, independently of those induced by shifts in states of vigilance. A daily single measure-during a vigilance-controlled period-to estimate the risk of upcoming seizure(s) would be more convenient. Here, we evaluated whether intracranial EEG connectivity (phase-locking value), estimated from daily vigilance-controlled resting-state recordings, could allow distinguishing interictal (no seizure) from preictal (seizure within the next 24 h) states. We also assessed its relevance for daily forecasts of seizure risk using machine learning models. Connectivity in the theta band was found to provide the best prediction performances (area under the curve ≥ .7 in 80% of patients), with accurate daily and prospective probabilistic forecasts (mean Brier score and Brier skill score of .13 and .72, respectively). More efficient ambulatory clinical application could be considered using mobile EEG or chronic implanted devices.

Description and Outcome of Severe Hypoglycemic Encephalopathy in the Intensive Care Unit.

BACKGROUND: Disorders of consciousness due to severe hypoglycemia are rare but challenging to treat. The aim of this retrospective cohort study was to describe our multimodal neurological assessment of patients with hypoglycemic encephalopathy hospitalized in the intensive care unit and their neurological outcomes. METHODS: Consecutive patients with disorders of consciousness related to hypoglycemia admitted for neuroprognostication from 2010 to 2020 were included. Multimodal neurological assessment included electroencephalography, somatosensory and cognitive event-related potentials, and morphological and quantitative magnetic resonance imaging (MRI) with quantification of fractional anisotropy. Neurological outcomes at 28 days, 3 months, 6 months, 1 year, and 2 years after hypoglycemia were retrieved. RESULTS: Twenty patients were included. After 2 years, 75% of patients had died, 5% remained in a permanent vegetative state, 10% were in a minimally conscious state, and 10% were conscious but with severe disabilities (Glasgow Outcome Scale-Extended scores 3 and 4). All patients showed pathologic electroencephalography findings with heterogenous patterns. Morphological brain MRI revealed abnormalities in 95% of patients, with various localizations including cortical atrophy in 65% of patients. When performed, quantitative MRI showed decreased fractional anisotropy affecting widespread white matter tracts in all patients. CONCLUSIONS: The overall prognosis of patients with severe hypoglycemic encephalopathy was poor, with only a small fraction of patients who slowly improved after intensive care unit discharge. Of note, patients who did not improve during the first 6 months did not recover consciousness. This study suggests that a multimodal approach capitalizing on advanced brain imaging and bedside electrophysiology techniques could improve diagnostic and prognostic performance in severe hypoglycemic encephalopathy.

Older patients with COVID-19 and neuropsychiatric conditions: A study of risk factors for mortality.

BACKGROUND: Little is known about risk factors for mortality in older patients with COVID-19 and neuropsychiatric conditions. METHODS: We conducted a multicentric retrospective observational study at Assistance Publique-Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID-19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID-19. RESULTS: Out of 191 patients included (median age 80 [interquartile range 74-87]), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new-onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), a neutrophil-to-lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69-12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75-11.8) independently increased the risk of mortality (all p < .001). CONCLUSION: Understanding mortality risk factors in older inpatients with COVID-19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice.

Neural modulations in the auditory cortex during internal and external attention tasks: A single-patient intracranial recording study.

Brain sensory processing is not passive, but is rather modulated by our internal state. Different research methods such as non-invasive imaging methods and intracranial recording of the local field potential (LFP) have been used to study to what extent sensory processing and the auditory cortex in particular are modulated by selective attention. However, at the level of the single- or multi-units the selective attention in humans has not been tested. In addition, most previous research on selective attention has explored externally-oriented attention, but attention can be also directed inward (i.e., internal attention), like spontaneous self-generated thoughts and mind-wandering. In the present study we had a rare opportunity to record multi-unit activity (MUA) in the auditory cortex of a patient. To complement, we also analyzed the LFP signal of the macro-contact in the auditory cortex. Our experiment consisted of two conditions with periodic beeping sounds. The participants were asked either to count the beeps (i.e., an "external attention" condition) or to recall the events of the previous day (i.e., an "internal attention" condition). We found that the four out of seven recorded units in the auditory cortex showed increased firing rates in "external attention" compared to "internal attention" condition. The beginning of this attentional modulation varied across multi-units between 30-50 msec and 130-150 msec from stimulus onset, a result that is compatible with an early selection view. The LFP evoked potential and induced high gamma activity both showed attentional modulation starting at about 70-80 msec. As the control, for the same experiment we recorded MUA activity in the amygdala and hippocampus of two additional patients. No major attentional modulation was found in the control regions. Overall, we believe that our results provide new empirical information and support for existing theoretical views on selective attention and spontaneous self-generated cognition.

Human periventricular nodular heterotopia shows several interictal epileptic patterns and hyperexcitability of neuronal firing.

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: (1) Periodic Discharges PLUS Fast activity (PD+F), (2) Sporadic discharges PLUS Fast activity (SD+F), and (3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, the SD+F pattern was found only in the three nodules that were actively involved in seizure generation but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.

Electroencephalogram in the intensive care unit: a focused look at acute brain injury.

Over the past decades, electroencephalography (EEG) has become a widely applied and highly sophisticated brain monitoring tool in a variety of intensive care unit (ICU) settings. The most common indication for EEG monitoring currently is the management of refractory status epilepticus. In addition, a number of studies have associated frequent seizures, including nonconvulsive status epilepticus (NCSE), with worsening secondary brain injury and with worse outcomes. With the widespread utilization of EEG (spot and continuous EEG), rhythmic and periodic patterns that do not fulfill strict seizure criteria have been identified, epidemiologically quantified, and linked to pathophysiological events across a wide spectrum of critical and acute illnesses, including acute brain injury. Increasingly, EEG is not just qualitatively described, but also quantitatively analyzed together with other modalities to generate innovative measurements with possible clinical relevance. In this review, we discuss the current knowledge and emerging applications of EEG in the ICU, including seizure detection, ischemia monitoring, detection of cortical spreading depolarizations, assessment of consciousness and prognostication. We also review some technical aspects and challenges of using EEG in the ICU including the logistics of setting up ICU EEG monitoring in resource-limited settings.

Clinico-biological markers for the prognosis of status epilepticus in adults.

Prediction of mortality, functional outcome and recovery after status epilepticus (SE) is a challenge. Biological and clinical markers have been proposed to reflect the brain injury or to monitor critical ill patients' severity. The aim of this study was to characterize short-term and long-term prognostic factors for SE patients hospitalized in intensive care unit. Patient's outcome was assessed using the modified Rankin Scale at discharge and after 6-12 months. We first assessed the univariate prognosis significance of 51 clinical, demographic or biochemical markers. Next, we built multivariate clinico-biological models by combining most important factors. Statistical models' performances were compared to those of two previous published scales STESS and mSTESS. Eighty-one patients were enrolled. Thirty-five patients showed a steady state while 46 patients clinically worsened at discharge: 14 died, 14 had persistent disability at 6-12 months and 18 recovered. Logistic regression analysis revealed that clinical markers (SE refractoriness, SE duration, de novo SE) were significant independent predictors of worsening while lipids markers and progranulin better predicted mortality. The association of clinico-biological variables allowed to accurately predict worsening at discharge (AUC > 0.72), mortality at discharge (AUC 0.83) and recovery at long-term (AUC 0.89). Previous scales provided lower prediction for worsening (AUC 0.63, STESS; 0.53, mSTESS) and mortality (AUC 0.56, STESS; 0.62, mSTESS) (p < 0.001). We proposed new clinico-biological models with a strong discrimination power for prediction of short- and long-term outcome of hospitalized status epilepticus patients. Their implementation in electronic devices may enhance their clinical liability.

Epilepsy related to focal neuronal lipofuscinosis: extra-frontal localization, EEG signatures and GABA involvement.

Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue.

Long-term deep intracerebral microelectrode recordings in patients with drug-resistant epilepsy: Proposed guidelines based on 10-year experience.

PURPOSE: Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings. RESULTS: During the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis. CONCLUSIONS: We progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.

Face-selective multi-unit activity in the proximity of the FFA modulated by facial expression stimuli.

When we see someone's face, our brain usually effortlessly extracts a variety of information such as facial identity, expression, or gaze direction. While it is widely accepted that dedicated subsystems are responsible for different aspects of face processing, how these subsystems work together is not yet fully understood. To this extent, one of the most explored questions is whether and if so, to what extent facial expression processing interacts with other stages of facial processing. In the present study, we report a rare case of a patient for whom we were able to record multi-unit activity (MUA) in the proximity of the fusiform face area (FFA) while two out of four recorded multi-units were face-selective. In our experiment, the human subject was shown images of neutral and fearful faces as well as everyday objects and frightening images of natural disaster. We found that activity of both face-selective units was modulated by facial expression stimuli, starting at about 150 ms from stimulus onset. For both facial conditions we observed abrupt increase in firing rate with a simultaneous peak, suggesting that this activity and the modulation by facial expression stimuli likely reflected feed-forward processing. Interestingly, while in one multi-unit, the firing rate for fearful faces was higher than for neutral faces, in the other multi-units the polarity was reversed. Finally, modulation in the face-selective units was specific to emotional facial stimuli, but not to emotional stimuli in general. The present multi-unit results, albeit obtained only for several multi-units, nevertheless are potentially valuable for understanding mechanisms of facial processing in humans.

Neuron Specific Enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus.

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure. A rapid diagnosis is fundamental to initiate antiepileptic treatment and to prevent the development of neurological sequels. Several serum and cerebrospinal fluid biomarkers have been proposed to help in the diagnosis of SE. Nevertheless, previous studies were conducted on too small patient cohorts, precluding the utilization of interesting biomarkers for the SE diagnosis. Here, we aimed to assess the ability of Neuron Specific Enolase (NSE), S100-beta protein (S100B) and progranulin to help in the diagnosis of SE in a large cohort of patients (36 control patients, 56 patients with pharmacoresistant epilepsy and 82 SE patients). Blood NSE, S100B and progranulin levels were higher in SE patients when compared with control patients or patients with pharmacoresistant epilepsy. Both NSE and progranulin levels were higher in cerebrospinal fluid from SE patients when compared with control patients. The receiver-operating characteristics curves revealed good accuracy at detecting SE for serum S100B (AUC 0.748) and plasma progranulin (AUC 0.756). The performances were lower for serum NSE (AUC 0.624). Eighty-four percent of patients with serum S100B levels above 0.09 ng/mL presented with a SE, whereas 90% of patients without SE had serum S100B levels lower than 0.09 ng/mL. Serum S100B levels were not significantly different according to SE etiology, SE semiology or SE refractoriness. Our results confirm that NSE, S100B and progranulin levels are increased after SE. We suggest that serum S100B levels might be added to clinical evaluation and electroencephalogram to identify difficult-to-diagnose form of SE.

Serum neuron-specific enolase: a new tool for seizure risk monitoring after status epilepticus.

BACKGROUND AND PURPOSE: There is a need for accurate biomarkers to monitor electroencephalography (EEG) activity and assess seizure risk in patients with acute brain injury. Seizure recurrence may lead to cellular alterations and subsequent neurological sequelae. Whether neuron-specific enolase (NSE) and S100-beta (S100B), brain injury biomarkers, can reflect EEG activity and help to evaluate the seizure risk was investigated. METHODS: Eleven patients, admitted to an intensive care unit for refractory status epilepticus, who underwent a minimum of 3 days of continuous EEG concomitantly with daily serum NSE and S100B assays were included. At 103 days the relationships between serum NSE and S100B levels and two EEG scores able to monitor the seizure risk were investigated. Biochemical biomarker thresholds able to predict seizure recurrence were sought. RESULTS: Only NSE levels positively correlated with EEG scores. Similar temporal dynamics were observed for the time courses of EEG scores and NSE levels. NSE levels above 17 ng/ml were associated with seizure in 71% of patients. An increase of more than 15% of NSE levels was associated with seizure recurrence in 80% of patients. CONCLUSIONS: Our study highlights the potential of NSE as a biomarker of EEG activity and to assess the risk of seizure recurrence.

Comparing stimulus-evoked and spontaneous response of the face-selective multi-units in the human posterior fusiform gyrus.

The stimulus-evoked neural response is a widely explored phenomenon. Conscious awareness is associated in many cases with the corresponding selective stimulus-evoked response. For example, conscious awareness of a face stimulus is associated with or accompanied by stimulus-evoked activity in the fusiform face area (FFA). In addition to the stimulus-evoked response, spontaneous (i.e. task-unrelated) activity in the brain is also abundant. Notably, spontaneous activity is considered unconscious. For example, spontaneous activity in the FFA is not associated with conscious awareness of a face. The question is: what is the difference at the neural level between stimulus-evoked activity in a case that this activity is associated with conscious awareness of some content (e.g. activity in the FFA in response to fully visible face stimuli) and spontaneous activity in that same region of the brain? To answer this question, in the present study, we had a rare opportunity to record two face-selective multi-units in the vicinity of the FFA in a human patient. We compared multi-unit face-selective task-evoked activity with spontaneous prestimulus and a resting-state activity. We found that when activity was examined over relatively long temporal windows (e.g. 100-200 ms), face-selective stimulus-evoked firing in the recorded multi-units was much higher than the spontaneous activity. In contrast, when activity was examined over relatively short windows, we found many cases of high firing rates within the spontaneous activity that were comparable to stimulus-evoked activity. Our results thus indicate that the sustained activity is what might differentiate between stimulus-evoked activity that is associated with conscious awareness and spontaneous activity.

Seizures in autoimmune encephalitis: specific features based on a systematic comparative study.

OBJECTIVE: To highlight specific characteristics of seizure semiology and EEG features associated with different subtypes of autoimmune encephalitis (AE). METHODS: We systematically reviewed the seizure semiology and all the EEG recordings from patients with AE managed in a tertiary referral centre for epilepsy and a neuro-intensive care unit. Each characteristic across the different subtypes of AE was compared by post hoc analysis. RESULTS: We identified 66 patients with anti-neuronal antibody-mediated AE or Rasmussen's encephalitis (RE) experiencing seizures, which were the most frequent symptom at onset. Anti-NMDAR and anti-LGI1 AE accounted for the majority of patients; 41% and 24%, respectively. We isolated specific semiological features, such as early tonic-clonic seizures (TCS) in anti-NMDAR AE, early mesial temporal lobe seizures with emotional symptoms in anti-GAD AE, somatosensory seizures in RE, and a lower frequency of TCS in anti-LGI1 AE. EEG analysis also provided additional insights into distinguishing the subtypes based on: (1) generalized rhythmic delta activity, which was more sensitive than extreme delta brush in identifying anti-NMDAR AE among all subtypes; and (2) temporal interictal epileptiform activity and temporal seizures on EEG in anti-GAD AE. We identified a new EEG pattern consisting of temporal low-voltage and periodic spikes associated with ipsilateral hippocampal abnormalities on MRI, which could be a sign of inflammatory mesial temporal involvement. SIGNIFICANCE: Specific clinical and EEG features can be useful in guiding the diagnosis of a subtype of AE with acute symptomatic seizures, particularly before the results of anti-neuronal antibody testing are available.