Hotspot of human verbal memory encoding in the left anterior prefrontal cortex.

BACKGROUND: Treating memory and cognitive deficits requires knowledge about anatomical sites and neural activities to be targeted with particular therapies. Emerging technologies for local brain stimulation offer attractive therapeutic options but need to be applied to target specific neural activities, at distinct times, and in specific brain regions that are critical for memory formation. METHODS: The areas that are critical for successful encoding of verbal memory as well as the underlying neural activities were determined directly in the human brain with intracranial electrophysiological recordings in epilepsy patients. We recorded a broad range of spectral activities across the cortex of 135 patients as they memorised word lists for subsequent free recall. FINDINGS: The greatest differences in the spectral power between encoding subsequently recalled and forgotten words were found in low theta frequency (3-5 Hz) activities of the left anterior prefrontal cortex. This subsequent memory effect was proportionally greater in the lower frequency bands and in the more anterior cortical regions. We found the peak of this memory signal in a distinct part of the prefrontal cortex at the junction between the Broca's area and the frontal pole. The memory effect in this confined area was significantly higher (Tukey-Kramer test, p<0.05) than in other anatomically distinct areas. INTERPRETATION: Our results suggest a focal hotspot of human verbal memory encoding located in the higher-order processing region of the prefrontal cortex, which presents a prospective target for modulating cognitive functions in the human patients. The memory effect provides an electrophysiological biomarker of low frequency neural activities, at distinct times of memory encoding, and in one hotspot location in the human brain. FUNDING: Open-access datasets were originally collected as part of a BRAIN Initiative project called Restoring Active Memory (RAM) funded by the Defence Advanced Research Project Agency (DARPA). CT, ML, MTK and this research were supported from the First Team grant of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund.

Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry.

Data comprise intracranial EEG (iEEG) brain activity represented by stereo EEG (sEEG) signals, recorded from over 100 electrode channels implanted in any one patient across various brain regions. The iEEG signals were recorded in epilepsy patients (N = 10) undergoing invasive monitoring and localization of seizures when they were performing a battery of four memory tasks lasting approx. 1 hour in total. Gaze tracking on the task computer screen with estimating the pupil size was also recorded together with behavioral performance. Each dataset comes from one patient with anatomical localization of each electrode contact. Metadata contains labels for the recording channels with behavioral events marked from all tasks, including timing of correct and incorrect vocalization of the remembered stimuli. The iEEG and the pupillometric signals are saved in BIDS data structure to facilitate efficient data sharing and analysis.

CyberEye: New Eye-Tracking Interfaces for Assessment and Modulation of Cognitive Functions beyond the Brain.

The emergence of innovative neurotechnologies in global brain projects has accelerated research and clinical applications of BCIs beyond sensory and motor functions. Both invasive and noninvasive sensors are developed to interface with cognitive functions engaged in thinking, communication, or remembering. The detection of eye movements by a camera offers a particularly attractive external sensor for computer interfaces to monitor, assess, and control these higher brain functions without acquiring signals from the brain. Features of gaze position and pupil dilation can be effectively used to track our attention in healthy mental processes, to enable interaction in disorders of consciousness, or to even predict memory performance in various brain diseases. In this perspective article, we propose the term 'CyberEye' to encompass emerging cognitive applications of eye-tracking interfaces for neuroscience research, clinical practice, and the biomedical industry. As CyberEye technologies continue to develop, we expect BCIs to become less dependent on brain activities, to be less invasive, and to thus be more applicable.

Independent dynamics of low, intermediate, and high frequency spectral intracranial EEG activities during human memory formation.

A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various frequency ranges are coordinated across the space of the human cortex and time of memory processing is inconclusive. They can either be coordinated together across the frequency spectrum at the same cortical site and time or induced independently in particular bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated low frequency theta, intermediate frequency alpha and beta, and high frequency gamma power in a mosaic pattern of discrete cortical sites. A majority of the cortical sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and high frequency activities propagated in independent sequences across the visual, temporal and prefrontal cortical areas throughout subsequent phases of memory encoding. Our results provide a holistic, simplified model of the spectral activities engaged in the formation of human memory, suggesting an anatomically and temporally distributed mosaic of coordinated brain rhythms.

Direct Electrical Stimulation of the Human Brain Has Inverse Effects on the Theta and Gamma Neural Activities.

OBJECTIVE: Our goal was to analyze the electrophysiological response to direct electrical stimulation (DES) systematically applied at a wide range of parameters and anatomical sites, with particular focus on neural activities associated with memory and cognition. METHODS: We used a large set of intracranial EEG (iEEG) recordings with DES from 45 subjects with electrodes implanted both subdurally on the cortical surface and subcortically into the brain parenchyma. Subjects were stimulated in blocks of alternating frequency and amplitude parameters during quiet wakefulness. RESULTS: Stimulating at different frequencies and amplitudes of electric current revealed a persistent pattern of response in the slow and the fast neural activities. In particular, amplification of the theta (4-7 Hz) and attenuation of the gamma (29-52 Hz) power-in-band was observed with increasing the stimulation parameters. This opposite effect on the low and high frequency bands was found across a network of selected local and distal sites proportionally to the proximity and magnitude of the electric current. Power increase in the theta and decrease in the gamma band was driven by the total electric charge delivered with either increasing the frequency or amplitude of the stimulation current. This inverse effect on the theta and gamma activities was consistently observed in response to different stimulation frequencies and amplitudes. CONCLUSION: Our results suggest a uniform DES effect of amplifying theta and suppressing gamma neural activities in the human brain. SIGNIFICANCE: These findings reveal the utility of simple power-in-band features for understanding and optimizing the effects of electrical stimulation on brain functions.

Post-comatose patients with minimal consciousness tend to preserve reading comprehension skills but neglect syntax and spelling.

Modern eye tracking technology provides a means for communication with patients suffering from disorders of consciousness (DoC) or remaining in locked-in-state. However, being able to use an eye tracker for controlling text-based contents by such patients requires preserved reading ability in the first place. To our knowledge, this aspect, although of great social importance, so far has seemed to be neglected. In the paper, we presented the possibility of using an eye-tracking technology for assessing reading comprehension skills in post-comatose patients with minimal consciousness. We prepared various syllable-, word- and sentence-based tasks, controlled by gaze, used for assessing the reading comprehension skills. The obtained results showed that people with minimal consciousness preserved the reading comprehension skills, in most cases to a high extent, but had difficulties with recognizing errors in the written text. The ability to maintain attention during performing the tasks was in statistically significant correlation with motivation, and that one was in a statistically significant correlation with the reading ability. The results indicate that post-comatose patients with minimal consciousness can read words and sentences, hence some useful hints may be provided for the development of gaze tracking-based human-computer interfaces for these people.

Human Computer Interface for Tracking Eye Movements Improves Assessment and Diagnosis of Patients With Acquired Brain Injuries.

One of the first clinical signs differentiating the minimally conscious state from the vegetative state is the presence of smooth pursuit eye movements occurring in direct response to moving salient stimuli. Glasgow Coma Scale (GCS) is one of the most commonly used diagnostic tools for acute phase assessment of the level of consciousness, together with a neurological examination. These classic measures are limited to qualitative neurological examination without more quantitative measures provided from e.g., tasks with tracking position of the gaze. Among this and other limitations, it is prone to a relatively high rate of misdiagnosis. Here, we developed an interface for gaze tracking to enhance the assessment of consciousness in 10 patients with acquired brain injuries. According to the acute phase GCS assessment, nine of them were considered unaware and below the minimally conscious state. Chronic neurological examination confirmed six of them below the minimally conscious state. Our new Human Computer Interface (HCI) revealed that six patients were conscious enough to complete at least one of the gaze tracking tasks. Among these six patients, one was originally diagnosed as remaining in a vegetative state and one in coma. The patient diagnosed as remaining in a chronic vegetative state scored six GCS points acutely. Following assessment with our HCI the patient was re-diagnosed with a possible locked-in syndrome. Our HCI method provides a new complementary tool for clinical assessment of patients suffering from disorders of consciousness.