Safety and Utility of Hybrid Depth Electrodes for Seizure Localization and Single-Unit Neuronal Recording

Background: Invasive electrode monitoring provides more precise localization of epileptogenic foci in patients with medically refractory epilepsy. The use of hybrid depth electrodes that include microwires for simultaneous single-neuron monitoring is becoming more widespread. Objective: To determine the safety and utility of hybrid depth electrodes for intracranial monitoring of medically refractory epilepsy. Methods: We reviewed the medical charts of 53 cases of medically refractory epilepsy operated on from 2006 to 2017, where both non-hybrid and hybrid microwire depth electrodes were used for intracranial monitoring. We assessed the localization accuracy and complications that arose to assess the relative safety and utility of hybrid depth electrodes compared with standard electrodes. Results: A total of 555 electrodes were implanted in 52 patients. The overall per-electrode complication rate was 2.3%, with a per-case complication rate of 20.8%. There were no infections or deaths. Serious or hemorrhagic complications occurred in 2 patients (0.4% per-electrode risk). Complications did not correlate with the use of any particular electrode type, and hybrids were equally as reliable as standard electrodes in localizing seizure onset zones. Conclusions: Hybrid depth electrodes appear to be as safe and effective as standard depth electrodes for intracranial monitoring and provide unique opportunities to study the human brain at single-neuron resolution

Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species

A NWB-based dataset and processing pipeline of human single-neuron activity during a declarative memory task

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory

Spatial selectivity in human ventrolateral prefrontal cortex

The functional organization of lateral prefrontal cortex is not well understood, and there is debate as to whether the dorsal and ventral aspects mediate distinct spatial and non-spatial functions, respectively. We show for the first time that recordings from human ventrolateral prefrontal cortex show spatial selectivity, supporting the idea that ventrolateral prefrontal cortex is involved in spatial processing. Our results also indicate that prefrontal cortex may be a source of control signals for neuroprosthetic applications

Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species

Single-Unit Responses Selective for Whole Faces in the Human Amygdala

The human amygdala is critical for social cognition from faces, as borne out by impairments in recognizing facial emotion following amygdala lesions and differential activation of the amygdala by faces. Single-unit recordings in the primate amygdala have documented responses selective for faces, their identity, or emotional expression, yet how the amygdala represents face information remains unknown. Does it encode specific features of faces that are particularly critical for recognizing emotions (such as the eyes), or does it encode the whole face, a level of representation that might be the proximal substrate for subsequent social cognition? We investigated this question by recording from over 200 single neurons in the amygdalae of seven neurosurgical patients with implanted depth electrodes. We found that approximately half of all neurons responded to faces or parts of faces. Approximately 20% of all neurons responded selectively only to the whole face. Although responding most to whole faces, these neurons paradoxically responded more when only a small part of the face was shown compared to when almost the entire face was shown. We suggest that the human amygdala plays a predominant role in representing global information about faces, possibly achieved through inhibition between individual facial features

Cognitive boundary signals in the human medial temporal lobe shape episodic memory representation

While experience unfolds continuously, memories are organized as a set of discrete events that bind together the “where”, “when”, and “what” of episodic memory. This segmentation of continuous experience is thought to be facilitated by the detection of salient environmental or cognitive events. However, the underlying neural mechanisms and how such segmentation shapes episodic memory representations remain unclear. We recorded from single neurons in the human medial temporal lobe while subjects watched videos with different types of embedded boundaries and were subsequently evaluated for memories of the video contents. Here we show neurons that signal the presence of cognitive boundaries between subevents from the same episode and neurons that detect the abstract separation between different episodes. The firing rate and spike timing of these boundary-responsive neurons were predictive of later memory retrieval accuracy. At the population level, abrupt neural state changes following boundaries predicted enhanced memory strength but impaired order memory, capturing the behavioral tradeoff subjects exhibited when recalling episodic content versus temporal order. Successful retrieval was associated with reinstatement of the neural state present following boundaries, indicating that boundaries structure memory search. These findings reveal a neuronal substrate for detecting cognitive boundaries and show that cognitive boundary signals facilitate the mnemonic organization of continuous experience as a set of discrete episodic events

Tumor-Specific Hsp70 Plasma Membrane Localization Is Enabled by the Glycosphingolipid Gb3

Human tumors differ from normal tissues in their capacity to present Hsp70, the major stress-inducible member of the HSP70 family, on their plasma membrane. Membrane Hsp70 has been found to serve as a prognostic indicator of overall patient survival in leukemia, lower rectal and non small cell lung carcinomas. Why tumors, but not normal cells, present Hsp70 on their cell surface and the impact of membrane Hsp70 on cancer progression remains to be elucidated.Although Hsp70 has been reported to be associated with cholesterol rich microdomains (CRMs), the partner in the plasma membrane with which Hsp70 interacts has yet to be identified. Herein, global lipid profiling demonstrates that Hsp70 membrane-positive tumors differ from their membrane-negative counterparts by containing significantly higher amounts of globotriaoslyceramide (Gb3), but not of other lipids such as lactosylceramide (LacCer), dodecasaccharideceramide (DoCer), galactosylceramide (GalCer), ceramide (Cer), or the ganglioside GM1. Apart from germinal center B cells, normal tissues are Gb3 membrane-negative. Co-localization of Hsp70 and Gb3 was selectively determined in Gb3 membrane-positive tumor cells, and these cells were also shown to bind soluble Hsp70-FITC protein from outside in a concentration-dependent manner. Given that the latter interaction can be blocked by a Gb3-specific antibody, and that the depletion of globotriaosides from tumors reduces the amount of membrane-bound Hsp70, we propose that Gb3 is a binding partner for Hsp70. The in vitro finding that Hsp70 predominantly binds to artificial liposomes containing Gb3 (PC/SM/Chol/Gb3, 17/45/33/5) confirms that Gb3 is an interaction partner for Hsp70.These data indicate that the presence of Gb3 enables anchorage of Hsp70 in the plasma membrane of tumors and thus they might explain tumor-specific membrane localization of Hsp70