Optimizing Electrode Configurations for Wearable EEG Seizure Detection Using Machine Learning.

Epilepsy, a prevalent neurological disorder, profoundly affects patients' quality of life due to the unpredictable nature of seizures. The development of a reliable and user-friendly wearable EEG system capable of detecting and predicting seizures has the potential to revolutionize epilepsy care. However, optimizing electrode configurations for such systems, which is crucial for balancing accuracy and practicality, remains to be explored. This study addresses this gap by developing a systematic approach to optimize electrode configurations for a seizure detection machine-learning algorithm. Our approach was applied to an extensive database of prolonged annotated EEG recordings from 158 epilepsy patients. Multiple electrode configurations ranging from one to eighteen were assessed to determine the optimal number of electrodes. Results indicated that the performance was initially maintained as the number of electrodes decreased, but a drop in performance was found to have occurred at around eight electrodes. Subsequently, a comprehensive analysis of all eight-electrode configurations was conducted using a computationally intensive workflow to identify the optimal configurations. This approach can inform the mechanical design process of an EEG system that balances seizure detection accuracy with the ease of use and portability. Additionally, this framework holds potential for optimizing hardware in other machine learning applications. The study presents a significant step towards the development of an efficient wearable EEG system for seizure detection.

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

A Tradeoff in the Neural Code across Regions and Species.

Many evolutionary years separate humans and macaques, and although the amygdala and cingulate cortex evolved to enable emotion and cognition in both, an evident functional gap exists. Although they were traditionally attributed to differential neuroanatomy, functional differences might also arise from coding mechanisms. Here we find that human neurons better utilize information capacity (efficient coding) than macaque neurons in both regions, and that cingulate neurons are more efficient than amygdala neurons in both species. In contrast, we find more overlap in the neural vocabulary and more synchronized activity (robustness coding) in monkeys in both regions and in the amygdala of both species. Our findings demonstrate a tradeoff between robustness and efficiency across species and regions. We suggest that this tradeoff can contribute to differential cognitive functions between species and underlie the complementary roles of the amygdala and the cingulate cortex. In turn, it can contribute to fragility underlying human psychopathologies.

Noradrenaline Modulates Visual Perception and Late Visually Evoked Activity.

An identical sensory stimulus may or may not be incorporated into perceptual experience, depending on the behavioral and cognitive state of the organism. What determines whether a sensory stimulus will be perceived? While different behavioral and cognitive states may share a similar profile of electrophysiology, metabolism, and early sensory responses, neuromodulation is often different and therefore may constitute a key mechanism enabling perceptual awareness. Specifically, noradrenaline improves sensory responses, correlates with orienting toward behaviorally relevant stimuli, and is markedly reduced during sleep, while experience is largely "disconnected" from external events. Despite correlative evidence hinting at a relationship between noradrenaline and perception, causal evidence remains absent. Here, we pharmacologically down- and upregulated noradrenaline signaling in healthy volunteers using clonidine and reboxetine in double-blind placebo-controlled experiments, testing the effects on perceptual abilities and visually evoked electroencephalography (EEG) and fMRI responses. We found that detection sensitivity, discrimination accuracy, and subjective visibility change in accordance with noradrenaline (NE) levels, whereas decision bias (criterion) is not affected. Similarly, noradrenaline increases the consistency of EEG visually evoked potentials, while lower noradrenaline levels delay response components around 200 ms. Furthermore, blood-oxygen-level-dependent (BOLD) fMRI activations in high-order visual cortex selectively vary along with noradrenaline signaling. Taken together, these results point to noradrenaline as a key factor causally linking visual awareness to external world events. VIDEO ABSTRACT.

Human single neuron activity precedes emergence of conscious perception.

Identifying the neuronal basis of spontaneous changes in conscious experience in the absence of changes in the external environment is a major challenge. Binocular rivalry, in which two stationary monocular images lead to continuously changing perception, provides a unique opportunity to address this issue. We studied the activity of human single neurons in the medial temporal and frontal lobes while patients were engaged in binocular rivalry. Here we report that internal changes in the content of perception are signaled by very early (~-2000 ms) nonselective medial frontal activity, followed by selective activity of medial temporal lobe neurons that precedes the perceptual change by ~1000 ms. Such early activations are not found for externally driven perceptual changes. These results suggest that a medial fronto-temporal network may be involved in the preconscious internal generation of perceptual transitions.

Low-level awareness accompanies "unconscious" high-level processing during continuous flash suppression.

The scope and limits of unconscious processing are a matter of ongoing debate. Lately, continuous flash suppression (CFS), a technique for suppressing visual stimuli, has been widely used to demonstrate surprisingly high-level processing of invisible stimuli. Yet, recent studies showed that CFS might actually allow low-level features of the stimulus to escape suppression and be consciously perceived. The influence of such low-level awareness on high-level processing might easily go unnoticed, as studies usually only probe the visibility of the feature of interest, and not that of lower-level features. For instance, face identity is held to be processed unconsciously since subjects who fail to judge the identity of suppressed faces still show identity priming effects. Here we challenge these results, showing that such high-level priming effects are indeed induced by faces whose identity is invisible, but critically, only when a lower-level feature, such as color or location, is visible. No evidence for identity processing was found when subjects had no conscious access to any feature of the suppressed face. These results suggest that high-level processing of an image might be enabled by-or co-occur with-conscious access to some of its low-level features, even when these features are not relevant to the processed dimension. Accordingly, they call for further investigation of lower-level awareness during CFS, and reevaluation of other unconscious high-level processing findings.

A neural substrate in the human hippocampus for linking successive events.

Memory formation requires the placement of experienced events in the same order in which they appeared. A large body of evidence from human studies indicates that structures in the medial temporal lobe are critically involved in forming and maintaining such memories, and complementing evidence from lesion and electrophysiological work in animals support these findings. However, it remains unclear how single cells and networks of cells can signal this temporal relationship between events. Here we used recordings from single cells in the human brain obtained while subjects viewed repeated presentations of cinematic episodes. We found that neuronal activity in successive time segments became gradually correlated, and, as a result, activity in a given time window became a faithful predictor of the activity to follow. This correlation emerged rapidly, within two to three presentations of an episode and exceeded both context-independent and pure stimulus-driven correlations. The correlation was specific for hippocampal neurons, did not occur in the amygdala and anterior cingulate cortex, and was found for single cells, cell pairs, and triplets of cells, supporting the notion that cell assemblies code for the temporal relationships between sensory events. Importantly, this neuronal measure of temporal binding successfully predicted subjects' ability to recall and verbally report the viewed episodes later. Our findings suggest a neuronal substrate for the formation of memory of the temporal order of events.

Perceptual shape sensitivity to upright and inverted faces is reflected in neuronal adaptation.

Using an fMR-adaptation paradigm for different face morphing levels we have recently demonstrated a narrow neuronal tuning to faces even at the sub-exemplar level which was tightly related to perceptual discrimination (Gilaie-Dotan and Malach, 2007). However, it is unclear whether this relationship is unique to faces or is a general property of object representations including unfamiliar objects, and whether the adaptation tuning is due to physical changes in the stimulus or to changes in perceptual discrimination. Here we compared the same face-morph paradigm for upright and inverted faces, thus modulating familiarity and perceptual discrimination effects while equating all low-level features. We found, as expected, a perceptual "inversion effect", i.e. a significant reduction in inverted face discrimination. Importantly, the fMR-adaptation tuning in the fusiform face area (FFA) changed in accordance with the different perceptual sensitivity both for upright and inverted faces. Additional object selective regions displayed differential tuning widths to the two categories. Our results are compatible with a model by which the ability of human observers to discriminate objects depends on the shape tuning properties of individual neurons.

Internally generated reactivation of single neurons in human hippocampus during free recall.

The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view cinematic episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate for the subjective experience of spontaneous emergence of human recollection.

Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex.

Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40-100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex.

Coupling between neuronal firing rate, gamma LFP, and BOLD fMRI is related to interneuronal correlations.

BACKGROUND: To what extent is activity of individual neurons coupled to the local field potential (LFP) and to blood-oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI)? This issue is of high significance for understanding brain function and for relating animal studies to fMRI, yet it is still under debate. RESULTS: Here we report data from simultaneous recordings of isolated unit activity and LFP by using multiple electrodes in the human auditory cortex. We found a wide range of coupling levels between the activity of individual neurons and gamma LFP. However, this large variability could be predominantly explained (r = 0.66) by the degree of firing-rate correlations between neighboring neurons. Importantly, this phenomenon occurred during both sensory stimulation and spontaneous activity. Concerning the coupling of neuronal activity to BOLD fMRI, we found that gamma LFP was well coupled to BOLD measured across different individuals (r = 0.62). By contrast, the coupling of single units to BOLD was highly variable and, again, tightly related to interneuronal-firing-rate correlations (r = 0.70). CONCLUSIONS: Our results offer a resolution to a central controversy regarding the coupling between neurons, LFP, and BOLD signals by demonstrating, for the first time, that the coupling of single units to the other measures is variable yet it is tightly related to the degree of interneuronal correlations in the human auditory cortex.