The Emergence of Single Neurons in Clinical Neurology

The Emergence of Single Neurons in Clinical Neurology Cash Hochberg

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The Emergence of Single Neurons in Clinical Neurology 2015 Neuron 10.1016/j.neuron.2015.03.058 Cash2015-the-emergence-of-single-neurons-in-clinical Cash2015-the-emergence-of-single-neurons-in-clinical.txt, the project's staged copy feedc1f1e4478a5da5d835a4c20641a463ef3857 not-redistributable neuroscience

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them the place of single-neuron activity in clinical neurology, neurosurgery and psychiatry Quotation withheld because this record is not cleared for redistribution. why single-neuron activity is missing from clinical practice, and what is now making it available Quotation withheld because this record is not cleared for redistribution. documents an absence in a literature, explains it by the absence of an instrument, and surveys the technologies now removing the constraint Quotation withheld because this record is not cleared for redistribution. prediction Quotation withheld because this record is not cleared for redistribution. single-neuron recording in clinical neurology Quotation withheld because this record is not cleared for redistribution. review review Quotation withheld because this record is not cleared for redistribution. mechanisms Clinical neglect of the single neuron is explained by the prior unavailability of technology able to target or measure small groups of neurons Quotation withheld because this record is not cleared for redistribution. mechanisms Propofol produces unconsciousness by phase-locking cortical neurons to local slow oscillations that are out of phase across regions, fragmenting long-range cortical communication Quotation withheld because this record is not cleared for redistribution. mechanisms Loss of dopamine erodes the separation normally maintained between basal ganglia subcircuits, so circuit elements merge into larger hypersynchronised networks that drive motor cortical synchrony Quotation withheld because this record is not cleared for redistribution. the absence is attributed to instrument resolution: MRI, EEG and MEG cannot resolve activity at the scale of the action potential Quotation withheld because this record is not cleared for redistribution. and to the absence of any intervention that could target small groups of neurons, let alone one Quotation withheld because this record is not cleared for redistribution. and to the nature of the pathology: stroke, trauma, tumours are not diseases of an individual neuron Quotation withheld because this record is not cleared for redistribution. and to the confinement of the relevant physiology to animal models in a small subset of laboratories Quotation withheld because this record is not cleared for redistribution. propofol unconsciousness explained mechanistically: neurons phase-lock to local slow oscillations but fall out of phase with distant cortex, fragmenting the network duplicate of: mechanisms[1] Quotation withheld because this record is not cleared for redistribution. in Parkinson's, dopaminergic loss is hypothesised to erode the separation between basal ganglia subcircuits, which then hypersynchronise Quotation withheld because this record is not cleared for redistribution. single-unit firing patterns mark the boundaries of the STN and globus pallidus as the electrode advances, the one routine clinical use Quotation withheld because this record is not cleared for redistribution. Much relevant work on miniaturised and wireless implanted recording is acknowledged as outside the review's scope. what this limits: the technological coverage of the review: THERE ARE MANY IMPORTANT RESEARCH ENDEAVORS IN THIS FIELD WHICH ARE BEYOND THE SCOPE OF THIS REVIEW Quotation withheld because this record is not cleared for redistribution. The cognitive-neuroscience literature on human single units is only sampled, not covered. what this limits: the cognitive-neuroscience coverage: Quotation withheld Quotation withheld because this record is not cleared for redistribution. The cognitive single-unit findings surveyed are conceded to have no immediate clinical application. what this limits: clinical application specifically: THESE FINDINGS ARE INDEED NOT YET OF IMMEDIATE CLINICAL RELEVANCE Quotation withheld because this record is not cleared for redistribution. the relationship between any animal model of epilepsy and human epilepsy is unclear, unlike the primate-human motor cortex case what this limits: any transfer from animal epilepsy models: UNLIKE THE MOTOR PROSTHESIS APPROACH IN WHICH THE SIMILARITY BETWEEN NONHUMAN PRIMATE M1 AND HUMAN M1 IS EVIDENT, THE RELATIONSHIP BETWEEN ANY GIVEN ANIMAL MODEL and human epilepsy is unclear Quotation withheld because this record is not cleared for redistribution. the details of single-neuron activity in the seizure focus itself remain poorly understood what this limits: claims about the seizure focus itself: THE DETAILS OF SINGLE NEURON ACTIVITY IN THE FOCUS remain poorly understood Quotation withheld because this record is not cleared for redistribution. decades of seizure-prediction work has produced no clinically usable algorithm what this limits: every seizure-prediction method reviewed: NONE HAS LED TO A CLINICALLY USEABLE OR COMMERCIALLY SUCCESSFUL PREDICTIVE ALGORITHM Quotation withheld because this record is not cleared for redistribution. the spiking activity underlying most anaesthetic EEG signatures is simply not known what this limits: the spiking basis of anaesthetic EEG patterns: THE SPIKE (ACTION POTENTIAL) ACTIVITY UNDERLYING MANY OF THESE PATTERNS IS NOT KNOWN, WITH THE EXCEPTION OF SLOW OSCILLATIONS DURING PROPOFOL INDUCED ANESTHESIA Quotation withheld because this record is not cleared for redistribution. animal brains are too small to study large-scale cortical relationships, and human scalp EEG has too little spatial resolution - neither end of the scale is available what this limits: large-scale cortical claims from either source: THE SMALL SIZE OF THE BRAIN IN THE ANIMAL MODELS HAS PREVENTED MUCH ANALYSIS OF LARGE-SCALE RELATIONSHIPS ACROSS THE CORTEX, AND HUMAN STUDIES OF SCALP EEG PROVIDE LITTLE SPATIAL RESOLUTION Quotation withheld because this record is not cleared for redistribution. the cognitive single-unit findings are not yet of immediate clinical relevance, stated plainly what this limits: the same scope as limitations[2] Quotation withheld because this record is not cleared for redistribution. data volumes already exceed what current techniques can extract meaning from what this limits: what can be extracted from the recordings at all: THIS MUCH NEURAL DATA CHALLENGES OUR COMPUTATIONAL CAPABILITIES AND, ESSENTIALLY, OUR TECHNIQUES FOR EXTRACTING MEANINGFUL INFORMATION FROM THIS HIGH DIMENSIONAL DATA SET Quotation withheld because this record is not cleared for redistribution. after forty years single-unit physiology is still a small component of practice what this limits: the clinical uptake claim: SINGLE UNIT PHYSIOLOGY IS STILL A SMALL COMPONENT OF NEUROLOGIC AND PSYCHIATRIC PRACTICE, after A MORE THAN 40-YEAR HISTORY Quotation withheld because this record is not cleared for redistribution. the encoding of movement in M1, transferred to human brain-computer interfaces - the transfer the paper says IS licensed, because the anatomy is evidently similar Quotation withheld because this record is not cleared for redistribution. the transfer the paper says is NOT licensed, because the correspondence to human epilepsy is unclear Quotation withheld because this record is not cleared for redistribution. clustering algorithms, dimensionality reduction and point-process methods, imported to make terabyte-scale spike data tractable Quotation withheld because this record is not cleared for redistribution. single unit here means an isolated action potential train from one neuron, explicitly contrasted with the averaged multineuron signals of EEG and ECoG Quotation withheld because this record is not cleared for redistribution. gold standard is used for single-unit recording in BASIC neurophysiology, in a paper arguing it is absent from clinical practice - the standard and the practice are different communities Quotation withheld because this record is not cleared for redistribution. hypersynchrony, as a framing of epilepsy, is said to be accurate at a superficial level and to break down under finer measurement - a claim whose truth depends on resolution Quotation withheld because this record is not cleared for redistribution. model, for epilepsy, is explicitly weaker than model for motor cortex: the primate-human M1 similarity is evident where the epilepsy correspondence is unclear Quotation withheld because this record is not cleared for redistribution. claim_type: critique a second reading DIFFERING from the recorded value. Recorded: prediction — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: narrative review across motor prosthetics, epilepsy, movement disorders, anaesthesia and cognition, with a textbook search establishing the absence a second reading DIFFERING from the recorded value. Recorded: review — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. phenomenon: single-unit activity as a clinical observable a second reading DIFFERING from the recorded value. Recorded: single-neuron recording in clinical neurology — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. critiques → clinical neurology, neurosurgery and psychiatry, for the absence of single-neuron thinking Quotation withheld because this record is not cleared for redistribution. qualifies → the canonical framing of epilepsy as a disorder of hypersynchrony and imbalanced excitation and inhibition Quotation withheld because this record is not cleared for redistribution. supports → the use of intraoperative single-unit recording to localise DBS electrodes Quotation withheld because this record is not cleared for redistribution. supports → slow-oscillation phase-locking as a mechanism of propofol-induced loss of consciousness Quotation withheld because this record is not cleared for redistribution. cites → Gelbard-Sagiv et al. on hippocampal reactivation during free recall - a paper independently tagged in this corpus Quotation withheld because this record is not cleared for redistribution. single neuron —same-as→ single unit single neuron single unit strength of the relation: 0.9 · note: used interchangeably throughout; the second is the recorded proxy for the first, which is why the weight is not 1.0 Quotation withheld because this record is not cleared for redistribution. electroencephalography —distinct-from→ action potential electroencephalography action potential strength of the relation: 1 · note: the key edge of the paper: EEG, MEG and MRI are NOT capable of resolving activity at the scale of the action potential. an instrument-scale exclusion, not a conceptual one Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but EEG and MEG CANNOT RESOLVE activity at the scale of the action potential; distinct-from is loose. Quotation withheld because this record is not cleared for redistribution. propofol —causes→ slow oscillations propofol slow oscillations strength of the relation: 0.9 · note: RE-GROUNDS another row of this record: the old span named ONE endpoint. Quotation withheld because this record is not cleared for redistribution. Despite being foundational to brain function, single-neuron activity has almost no presence in everyday clinical neurology, neurosurgery or psychiatry. Quotation withheld because this record is not cleared for redistribution. Current clinical measurement modalities cannot resolve neuronal activity at the scale of the action potential. Quotation withheld because this record is not cleared for redistribution. Even after four decades of relevant recordings, single-unit physiology remains a marginal component of neurological and psychiatric practice. Quotation withheld because this record is not cleared for redistribution. Microelectrode and macroelectrode array work has undermined the standard account of epilepsy as purely a disorder of hypersynchrony and excitation-inhibition imbalance. Quotation withheld because this record is not cleared for redistribution. The authors suggest intraoperative single-unit localisation during DBS may be the best example of single-neuron activity used directly in clinical care. Quotation withheld because this record is not cleared for redistribution. Firing rates and patterns are used to identify the boundaries of the subthalamic nucleus and globus pallidus internus as the electrode advances. Quotation withheld because this record is not cleared for redistribution. Intracortical arrays implanted from 2004 onward let people with tetraplegia produce 2D cursor movement and simple robotic control directly from cortical spiking. Quotation withheld because this record is not cleared for redistribution. Multiple studies indicate that individual neurons in higher-order cortex keep tuning or specificity for complex stimuli. Quotation withheld because this record is not cleared for redistribution. discussion of neuronal activity is largely absent from clinical neuroscience Quotation withheld because this record is not cleared for redistribution. the only single-neuron references in classic neurology textbooks concern peripheral nerves Quotation withheld because this record is not cleared for redistribution. existing clinical modalities cannot resolve activity at the scale of the action potential Quotation withheld because this record is not cleared for redistribution. finer measurement challenges the canonical framing of epilepsy as hypersynchrony Quotation withheld because this record is not cleared for redistribution. DBS electrode localisation by firing pattern may be the best example of clinical use of single-neuron activity Quotation withheld because this record is not cleared for redistribution. during loss of consciousness, cortical neurons phase-lock to local slow oscillations but fall out of phase with distant cortex Quotation withheld because this record is not cleared for redistribution. no seizure-prediction method has yet produced a clinically usable or commercially successful algorithm Quotation withheld because this record is not cleared for redistribution. waves often portrayed as homogeneous are more heterogeneous in space and in their involvement of individual neurons Quotation withheld because this record is not cleared for redistribution. after forty years, single-unit physiology remains a small part of clinical practice Quotation withheld because this record is not cleared for redistribution. brain-computer interface (BCI) brain-computer interface (BCI) Quotation withheld because this record is not cleared for redistribution. Utah array Utah array Quotation withheld because this record is not cleared for redistribution. ‘clustering’ algorithms ‘clustering’ algorithms Quotation withheld because this record is not cleared for redistribution. "Jennifer Anniston Neuron" "Jennifer Anniston Neuron" Quotation withheld because this record is not cleared for redistribution. brain-computer interface brain-computer interface Quotation withheld because this record is not cleared for redistribution. single unit single unit Quotation withheld because this record is not cleared for redistribution. 100 probes — number of etched silicon probes in the original Utah array Quotation withheld because this record is not cleared for redistribution. several Tb / 100+ neurons — data volume and neuron count typically obtained from a single 4x4 mm Utah array recording Quotation withheld because this record is not cleared for redistribution. ~500 GB per day — full-bandwidth neural data rate produced by one implanted array at current resolutions Quotation withheld because this record is not cleared for redistribution. 365 Terabytes in one year — storage burden of continuously recording one individual with two implanted arrays for a year Quotation withheld because this record is not cleared for redistribution. mid 1950s — date from which human single-unit recordings have been performed Quotation withheld because this record is not cleared for redistribution. >100 Hz — frequency range of the high frequency oscillations shown to matter in epilepsy Quotation withheld because this record is not cleared for redistribution. <1 Hz / ~10 Hz — slow-oscillation and frontal alpha frequencies that dominate the EEG under propofol anaesthesia Quotation withheld because this record is not cleared for redistribution. about 500 GB per day from one array — full-bandwidth neural data rate Quotation withheld because this record is not cleared for redistribution. 365 terabytes in one year from two arrays — continuous storage for one individual Quotation withheld because this record is not cleared for redistribution. a single 4 x 4 mm Utah array yields several Tb and 100+ neurons — yield per implant Quotation withheld because this record is not cleared for redistribution. at least four high-resolution recording platforms — the available instruments Quotation withheld because this record is not cleared for redistribution. mid 1950s — when human single-unit recording began, against a literature that still omits it Quotation withheld because this record is not cleared for redistribution. 100 years — how long human epilepsy was studied almost entirely by scalp EEG Quotation withheld because this record is not cleared for redistribution. clustering algorithms for spike extraction clustering algorithms for spike extraction Quotation withheld because this record is not cleared for redistribution. dimensionality reduction and point process techniques dimensionality reduction and point process techniques Quotation withheld because this record is not cleared for redistribution. firing rates or patterns firing rates or patterns Quotation withheld because this record is not cleared for redistribution.

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