Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum.

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one's own body.SIGNIFICANCE STATEMENT Spatial computations using environmental boundaries are an integral part of the brain's spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to functional neuroimaging studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions, we identified a neural marker of boundary representation in the human subiculum.

Evidence for verbal memory enhancement with electrical brain stimulation in the lateral temporal cortex.

Direct electrical stimulation of the human brain can elicit sensory and motor perceptions as well as recall of memories. Stimulating higher order association areas of the lateral temporal cortex in particular was reported to activate visual and auditory memory representations of past experiences (Penfield and Perot, 1963). We hypothesized that this effect could be used to modulate memory processing. Recent attempts at memory enhancement in the human brain have been focused on the hippocampus and other mesial temporal lobe structures, with a few reports of memory improvement in small studies of individual brain regions. Here, we investigated the effect of stimulation in four brain regions known to support declarative memory: hippocampus, parahippocampal neocortex, prefrontal cortex and temporal cortex. Intracranial electrode recordings with stimulation were used to assess verbal memory performance in a group of 22 patients (nine males). We show enhanced performance with electrical stimulation in the lateral temporal cortex (paired t-test, P = 0.0067), but not in the other brain regions tested. This selective enhancement was observed both on the group level, and for two of the four individual subjects stimulated in the temporal cortex. This study shows that electrical stimulation in specific brain areas can enhance verbal memory performance in humans.awx373media15704855796001.

Dissecting gamma frequency activity during human memory processing.

Gamma frequency activity (30-150 Hz) is induced in cognitive tasks and is thought to reflect underlying neural processes. Gamma frequency activity can be recorded directly from the human brain using intracranial electrodes implanted in patients undergoing treatment for drug-resistant epilepsy. Previous studies have independently explored narrowband oscillations in the local field potential and broadband power increases. It is not clear, however, which processes contribute to human brain gamma frequency activity, or their dynamics and roles during memory processing. Here a large dataset of intracranial recordings obtained during encoding of words from 101 patients was used to detect, characterize and compare induced gamma frequency activity events. Individual bursts of gamma frequency activity were isolated in the time-frequency domain to determine their spectral features, including peak frequency, amplitude, frequency span, and duration. We found two distinct types of gamma frequency activity events that showed either narrowband or broadband frequency spans revealing characteristic spectral properties. Narrowband events, the predominant type, were induced by word presentations following an initial induction of broadband events, which were temporally separated and selectively correlated with evoked response potentials, suggesting that they reflect different neural activities and play different roles during memory encoding. The two gamma frequency activity types were differentially modulated during encoding of subsequently recalled and forgotten words. In conclusion, we found evidence for two distinct activity types induced in the gamma frequency range during cognitive processing. Separating these two gamma frequency activity components contributes to the current understanding of electrophysiological biomarkers, and may prove useful for emerging neurotechnologies targeting, mapping and modulating distinct neurophysiological processes in normal and epileptogenic brain.

Similar patterns of neural activity predict memory function during encoding and retrieval.

Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval.

The Possibility of Eidetic Memory in a Patient Report of Epileptogenic Zone in Right Temporo-Parietal-Occipital Cortex.

Eidetic memory has been reported in children and in patients with synesthesia but is otherwise thought to be a rare phenomenon. Presented herein is a patient with right-sided language dominance, as proven via multiple functional imaging and neuropsychometric methods, who has a seizure onset zone in the right temporo-parietal-occipital cortex. This patient's medically refractory epilepsy and thus hyperactive cortex could possibly contribute to near eidetic ability with paired-associates learning tasks (in both short-term and long-term retention). There are reports of epilepsy negatively affecting memory, but as far as the authors are aware to date, there is limited evidence of any lesion enhancing cognitive functions (whether through direct lesion or via compensatory mechanism) that would be localized to a seizure onset zone in the dominant temporo-parietal-occipital junction.

Creutzfeldt-Jakob Disease May Present Early With Unusual Bulbar Predominance.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a prion protein disorder of significant consequence and currently incurable. Diagnosis can be challenging early in the disease course. CJD can present in many ways but often fits a pattern of cognitive problems, cerebellar disturbance, behavioral/psychological changes, and perhaps myoclonus. CASE REPORT: We herein present the case of a 69-year-old White male with subacute progressive bulbar and limb weakness over ten weeks period. Early on, he was diagnosed with amyotrophic lateral sclerosis versus autoimmune-related bulbar neuropathy and treated as such. However, he continued to deteriorate clinically that prompted another admission, upon readmission, his cerebrospinal fluid RTQuick and 14-3-3 from the National Prion Disease Pathology Surveillance Center (NPDPSC) did eventually return positive. Hence he was diagnosed with CJD. CONCLUSIONS: CJD may present with progressive bulbar symptoms similar to acute inflammatory demyelinating polyradiculoneuropathy (MF variant), motor neuron disease, or autoimmune brainstem encephalitis. It becomes even higher on the differentials especially with no response to immunotherapy.

Developing Strategies for Sustainable Medical Equipment Maintenance in Under-Resourced Settings.

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics. By focusing on the sustainability of donated equipment instead of the equipment itself, this method presented distinguishes itself from other philanthropic endeavors in the field by seeking to establish preventive maintenance habits that can impact clinical outcomes of a community long term. Application of this methodology is reported in the Original Research Article "A Low-Cost Humidity Control System to Protect Microscopes in a Tropical Climate" by Asp et. al.

Author Correction: Pupil size reflects successful encoding and recall of memory in humans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unsupervised machine-learning classification of electrophysiologically active electrodes during human cognitive task performance.

Identification of active electrodes that record task-relevant neurophysiological activity is needed for clinical and industrial applications as well as for investigating brain functions. We developed an unsupervised, fully automated approach to classify active electrodes showing event-related intracranial EEG (iEEG) responses from 115 patients performing a free recall verbal memory task. Our approach employed new interpretable metrics that quantify spectral characteristics of the normalized iEEG signal based on power-in-band and synchrony measures. Unsupervised clustering of the metrics identified distinct sets of active electrodes across different subjects. In the total population of 11,869 electrodes, our method achieved 97% sensitivity and 92.9% specificity with the most efficient metric. We validated our results with anatomical localization revealing significantly greater distribution of active electrodes in brain regions that support verbal memory processing. We propose our machine-learning framework for objective and efficient classification and interpretation of electrophysiological signals of brain activities supporting memory and cognition.

Human Verbal Memory Encoding Is Hierarchically Distributed in a Continuous Processing Stream.

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high γ power during word encoding, and less power before and after the word presentation, was characteristic of successful recall and observed across multiple brain regions. Latencies of the induced power changes and this subsequent memory effect (SME) between the recalled and forgotten words followed an anatomical sequence from visual to prefrontal cortical areas. Finally, the magnitude of the memory effect was unexpectedly found to be the largest in selected brain regions both at the top and at the bottom of the processing stream. These included the language processing areas of the prefrontal cortex and the early visual areas at the junction of the occipital and temporal lobes. Our results provide evidence for distributed encoding of verbal memory organized along a hierarchical posterior-to-anterior processing stream.

Pupil size reflects successful encoding and recall of memory in humans.

Pupil responses are known to indicate brain processes involved in perception, attention and decision-making. They can provide an accessible biomarker of human memory performance and cognitive states in general. Here we investigated changes in the pupil size during encoding and recall of word lists. Consistent patterns in the pupil response were found across and within distinct phases of the free recall task. The pupil was most constricted in the initial fixation phase and was gradually more dilated through the subsequent encoding, distractor and recall phases of the task, as the word items were maintained in memory. Within the final recall phase, retrieving memory for individual words was associated with pupil dilation in absence of visual stimulation. Words that were successfully recalled showed significant differences in pupil response during their encoding compared to those that were forgotten - the pupil was more constricted before and more dilated after the onset of word presentation. Our results suggest pupil size as a potential biomarker for probing and modulation of memory processing.

Spatial variation in high-frequency oscillation rates and amplitudes in intracranial EEG.

OBJECTIVE: To assess the variation in baseline and seizure onset zone interictal high-frequency oscillation (HFO) rates and amplitudes across different anatomic brain regions in a large cohort of patients. METHODS: Seventy patients who had wide-bandwidth (5 kHz) intracranial EEG (iEEG) recordings during surgical evaluation for drug-resistant epilepsy between 2005 and 2014 who had high-resolution MRI and CT imaging were identified. Discrete HFOs were identified in 2-hour segments of high-quality interictal iEEG data with an automated detector. Electrode locations were determined by coregistering the patient's preoperative MRI with an X-ray CT scan acquired immediately after electrode implantation and correcting electrode locations for postimplant brain shift. The anatomic locations of electrodes were determined using the Desikan-Killiany brain atlas via FreeSurfer. HFO rates and mean amplitudes were measured in seizure onset zone (SOZ) and non-SOZ electrodes, as determined by the clinical iEEG seizure recordings. To promote reproducible research, imaging and iEEG data are made freely available (msel.mayo.edu). RESULTS: Baseline (non-SOZ) HFO rates and amplitudes vary significantly in different brain structures, and between homologous structures in left and right hemispheres. While HFO rates and amplitudes were significantly higher in SOZ than non-SOZ electrodes when analyzed regardless of contact location, SOZ and non-SOZ HFO rates and amplitudes were not separable in some lobes and structures (e.g., frontal and temporal neocortex). CONCLUSIONS: The anatomic variation in SOZ and non-SOZ HFO rates and amplitudes suggests the need to assess interictal HFO activity relative to anatomically accurate normative standards when using HFOs for presurgical planning.

Electrical Stimulation Modulates High γ Activity and Human Memory Performance.

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with "poor" memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation.

Seizure Forecasting and the Preictal State in Canine Epilepsy.

The ability to predict seizures may enable patients with epilepsy to better manage their medications and activities, potentially reducing side effects and improving quality of life. Forecasting epileptic seizures remains a challenging problem, but machine learning methods using intracranial electroencephalographic (iEEG) measures have shown promise. A machine-learning-based pipeline was developed to process iEEG recordings and generate seizure warnings. Results support the ability to forecast seizures at rates greater than a Poisson random predictor for all feature sets and machine learning algorithms tested. In addition, subject-specific neurophysiological changes in multiple features are reported preceding lead seizures, providing evidence supporting the existence of a distinct and identifiable preictal state.

Behavioral state classification in epileptic brain using intracranial electrophysiology.

OBJECTIVE: Automated behavioral state classification can benefit next generation implantable epilepsy devices. In this study we explored the feasibility of automated awake (AW) and slow wave sleep (SWS) classification using wide bandwidth intracranial EEG (iEEG) in patients undergoing evaluation for epilepsy surgery. APPROACH: Data from seven patients (age [Formula: see text], 4 women) who underwent intracranial depth electrode implantation for iEEG monitoring were included. Spectral power features (0.1-600 Hz) spanning several frequency bands from a single electrode were used to train and test a support vector machine classifier. MAIN RESULTS: Classification accuracy of 97.8 ± 0.3% (normal tissue) and 89.4 ± 0.8% (epileptic tissue) across seven subjects using multiple spectral power features from a single electrode was achieved. Spectral power features from electrodes placed in normal temporal neocortex were found to be more useful (accuracy 90.8 ± 0.8%) for sleep-wake state classification than electrodes located in normal hippocampus (87.1 ± 1.6%). Spectral power in high frequency band features (Ripple (80-250 Hz), Fast Ripple (250-600 Hz)) showed comparable performance for AW and SWS classification as the best performing Berger bands (Alpha, Beta, low Gamma) with accuracy ⩾90% using a single electrode contact and single spectral feature. SIGNIFICANCE: Automated classification of wake and SWS should prove useful for future implantable epilepsy devices with limited computational power, memory, and number of electrodes. Applications include quantifying patient sleep patterns and behavioral state dependent detection, prediction, and electrical stimulation therapies.