Biology subjects

Richardson, R. M.

Publications and source records attributed to Richardson, R. M..

At least 19 recordsLinked to original sources

bioRxiv2026

Sleep spindles stabilize human thalamocortical networks, inhibiting pathological disruptions

The thalamus coordinates sleep-dependent brain function including memory consolidation, sensory gating, and network stability through spindle oscillations. Thalamocortical circuits are also affected in many neurological and neuropsychiatric disorders. Yet how human thalamocortical circuits respond to pathological disruptions remain poorly understood. Here, we leveraged interictal epileptiform discharges (IEDs) as spontaneous perturbations to probe spindle-generating circuits and thalamocortical dynamics in vivo. Using multi-night intracranial recordings spanning multiple thalamic nuclei and cortical regions in 55 individuals with epilepsy, we investigated interactions between sleep spindles and epileptic activity across timescales from milliseconds to days. Sleep spindles were associated with IED suppression, whereas IEDs increased subsequent spindle probability, revealing bidirectional interactions between physiological and pathological activity. Nights with lower IEDs corresponded to increased spindle occurrence, longer duration, and faster frequency, reflecting a more stable thalamocortical state. These findings propose sleep spindles as potential regulators of thalamocortical networks that actively respond to and regulate pathological activity.

neuroscience↗

bioRxiv2026

Monosynaptic connections link functionally similar regions in human cortex

The functional organization of human cortex has been mapped in considerable detail1-5, yet the axonal connections linking these areas remain largely unknown. This gap precludes inferring either the computational pathways through cortical networks or the principles governing why each area connects to its particular target regions. Here, in patients undergoing intracranial monitoring for epilepsy, we used concurrent electrical stimulation and functional magnetic resonance imaging (es-fMRI), validated previously against tracer studies in nonhuman primates6, to map anatomical connectivity of cortical sites across the whole brain, and combined these maps with task and resting-state fMRI in the same individuals. Es-fMRI revealed four main findings. First, connectivity followed an asymmetric functional-similarity principle: connected sites tended to share similar functional profiles, but, because connectivity is sparse, most pairs of functionally similar sites were not connected. Second, although connectivity also declines with distance7, the functional profile explained three times as much variance in connectivity as distance did, and long-range connections were the most functionally specific. Third, es-fMRI revealed direct monosynaptic links between established functional regions, including between the fusiform face area (FFA)2 and the temporoparietal junction (TPJ)3 for social cognition. Fourth, resting-state functional connectivity (rsFC) of a stimulation site was only weakly correlated with that sites es-fMRI connectivity. Together, these results provide a first principled link between anatomical connectivity and functional organization in the human cortex, and establish es-fMRI as a scalable approach to building a tracer-grade connectome of the human brain.

neuroscience↗

bioRxiv2026

Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy

Mesial (a.k.a., medial) temporal lobe epilepsy (MTLE) is the most common focal epilepsy1,2 and, in drug-resistant cases, is treated by surgical removal of the anterior temporal lobe, which often shows neuronal loss and gliosis consistent with hippocampal sclerosis (HS)2. MTLE with HS has minimal contribution from germline genetic variation3, and is associated with prior precipitating insults such as prolonged childhood seizures and head trauma4-6. Somatic variants in Ras-MAPK pathway genes were recently reported in a few MTLE surgical specimens7,8, but their prevalence, clinical relevance, and underlying biological mechanisms remain unknown. Targeted duplex sequencing of hippocampal DNA from 462 surgical resections revealed significant enrichment of deleterious somatic variants in MTLE versus controls, with >40% of MTLE specimens harboring activating Ras-MAPK variants in PTPN11, NF1, BRAF, KRAS, and twelve genes not previously associated with focal epilepsy. Eight Ras-MAPK genes showed positive clonal selection in MTLE. Increased somatic variant burden predicted worse surgical outcome. Somatic Ras-MAPK variants at ultra-low (<0.5%) variant allele fractions were associated with older seizure onset and HS pathology, supporting a late prenatal or postnatal origin. Ras-MAPK variants in MTLE were enriched in cells derived from hippocampal progenitors--neurons, astrocytes, oligodendrocytes--in line with the known neuronal hyperexcitability and seizures induced by Ras-MAPK overactivation9,10; in contrast, Alzheimer disease hippocampi exhibited microglial enrichment of Ras-MAPK variants, consistent with prior reports11. Single-nucleus RNA sequencing showed increased expression of Ras-MAPK genes in neurons and upregulation of pathways mediating neurogenesis and neural development in MTLE. Functional validation of novel, recurrent PTPN11 variants confirmed gain-of-function, while cellular modeling in induced pluripotent stem cells demonstrated proliferative/survival advantages for mutant cells in mosaic culture. Overall, our data suggest that somatic Ras-MAPK variants and acquired risk factors may converge on clonal competition in the hippocampus to modulate epilepsy risk.

genetics↗

bioRxiv2025

Independent Basal Ganglia Neural Populations Encode Speech Production and Ambient-Noise Levels

The function of the basal ganglia (BG), a set of nuclei deep in the brain, is still under debate despite their clinical relevance. Lines of evidence from non-human primate and human experiments suggest that one key causal contribution of the adult primate BG is invigoration of movement according to environmental and energetic constraints. Previous studies have come to this conclusion using primarily limb motor control tasks. We hypothesized BG are also important for invigorating the respiratory, vocal, and articulatory motor systems during speech production. To test this, we used a rare clinical opportunity to record local field potentials-broadband gamma activity (LFP-BGA) and single unit (SU) activity from human basal ganglia during deep brain stimulation implant surgeries. Participants repeated sentences aloud in the operating room. We modulated environmental and energetic constraints of speech production by inducing the Lombard Effect, wherein people reliably increase the intensity of their voice in the presence of background noise. Participants increased voice intensity, pitch, vowel space size, and respiratory depth in the presence of ambient noise. [~]40% of LFP and SU sites were modulated by speech production. Comparing globus pallidus (GP) LFP-BGA, herein reported for the first time during speech, to subthalamic nucleus (STN) LFP-BGA revealed GP activated after STN. STN was more coincident with the speech preparatory period and GP more coincident with speech onset, suggesting differential roles in speech production. We found only weak evidence that STN or GP activity encodes the level of produced speech intensity. Instead, we found that LFP-BGA and SU-FR robustly track the ambient background noise levels. Linear decoding from SU-firing rate revealed we could infer the background noise levels with >75% accuracy in any given time point in the trial, including baseline. Importantly, the ambient-noise-modulated sites were an independent population from speech-modulated sites. We conclude that human BG encode the energetic constraints of communication. We theorize that the code is leveraged in downstream BG-cortical loop nodes to invigorate speech oro-motor gestures and co-speech manual limb gestures, both of which respond to ambient noise levels to maintain high-fidelity communication.

neuroscience↗

bioRxiv2025

The Effects of Oral Contraceptives on Grip Strength and Neuromuscular Activation During Short-Term Immobilization and Rehabilitation of the Wrist/Hand

Females often experience greater weakness following immobilization compared to males. Hormonal fluctuations from the menstrual cycle or oral contraceptive (OC) use may contribute to sex differences and response variation. We examined differences in peak and rapid force and neuromuscular activation among females using monophasic OC and females not using OC following immobilization and rehabilitation. To examine potential sex differences, a male control group was included. Ten males, 10 OC females, and 10 non-OC females (mean {+/-} SD age = 23 {+/-} 3 years) immobilized their left wrist/hand with a brace for one week, followed by [≥] one week of rehabilitation. Participants completed grip tests to assess peak force and the rate of force development (RFD) before and after immobilization and post-rehabilitation, with electromyographic signals recorded from the extensor carpi radialis brevis (ECBR) and flexor digitorum superficialis (FDS). Grip force declined post-immobilization: males = -17.2 {+/-} 10.3%, non-OC = -22.3 {+/-} 24.7%, OC = -20.7 {+/-} 14.8%. No significant time x group interactions were observed for any dependent variables (p > 0.05, 2p [≤] 0.084). Time effects showed recovery post-rehab. RFD, particularly at 200 ms, declined posttest and rebounded post-rehab. ECBR excitation increased post-rehab; FDS trended upward. Only 5 participants required > one week of rehabilitation (2 males, 2 non-OC, 1 OC). We conclude that males and females exhibit similar declines and recovery in grip force after one week of wrist/hand immobilization, regardless of OC use. OC use does not appear to affect outcomes in female patients undergoing musculoskeletal rehabilitation. NEW & NOTEWORTHYPrevious studies report greater strength losses in females than males after immobilization, yet the underlying mechanisms remain unclear. This is the first study to examine whether monophasic OC use influences neuromuscular responses to disuse and recovery. We found no significant differences in the loss or recovery of peak force, RFD, or sEMG excitation between OC users, non-users, and males. Short-term immobilization and rehabilitation outcomes are not meaningfully affected by OC use in healthy, young females.

physiology↗

bioRxiv2025

Decoding semantics from natural speech using human intracranial EEG

Brain-computer interfaces (BCIs) hold promise for restoring natural language production capabilities in patients with speech impairments, potentially enabling smooth conversation that conveys meaningful information via synthesized words. While considerable progress has been made in decoding phonetic features of speech, our ability to extract lexical semantic information (i.e. the meaning of individual words) from neural activity remains largely unexplored. Moreover, most existing BCI research has relied on controlled experimental paradigms rather than natural conversation, limiting our understanding of semantic decoding in ecological contexts. Here, we investigated the feasibility of decoding lexical semantic information from stereo-electroencephalography (sEEG) recordings in 14 participants during spontaneous conversation. Using multivariate pattern analysis, we were able to decode word level semantic features during language production with an average accuracy of 21% across all participants compared to a chance level of 10%. This semantic decoding remained robust across different semantic representations while maintaining specificity to semantic features. Further, we identified a distributed left-lateralized network spanning precentral gyrus, pars triangularis, and middle temporal cortex, with low-frequency oscillations showing stronger contributions. Together, our results establish the feasibility of extracting word meanings from neural activity during natural speech production and demonstrate the potential for decoding semantic content from unconstrained speech.

neuroscience↗

bioRxiv2024

Movement-related activity in the internal globus pallidus of the parkinsonian macaque

Although the basal ganglia (BG) plays a central role in the motor symptoms of Parkinsons disease, few studies have investigated the influence of parkinsonism on movement-related activity in the BG. Here, we studied the perimovement activity of neurons in globus pallidus internus (GPi) of non-human primates during performance of a choice reaction time reaching task before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal responses, including increases or decreases in firing rate, were equally common in the parkinsonian brain as seen prior to MPTP and the distribution of different response types was largely unchanged. The slowing of behavioral reaction times and movement durations following the induction of parkinsonism was accompanied by a prolongation of the time interval between neuronal response onset and movement initiation. Neuronal responses were also reduced in magnitude and prolonged in duration after the induction of parkinsonism. Importantly, those two effects were more pronounced among decrease-type responses, and they persisted after controlling for MPTP-induced changes in the between-trial variability in response timing. Following MPTP the trial-to-trial timing of neuronal responses also became uncoupled from the time of movement onset and more variable in general. Overall, the effects of MPTP on temporal features of GPi responses were related to the severity of parkinsonian motor impairments whereas changes in response magnitude and duration did not reflect symptom severity consistently. These findings point to a previously underappreciated potential role for abnormalities in the timing of GPi task-related activity in the generation of parkinsonian motor signs. New & NoteworthyAlthough the globus pallidus internus (GPi) plays a central role in the cardinal symptoms of Parkinsons disease (PD), how parkinsonism alters the movement-related activity of GPi neurons remains understudied. Using a monkey model of PD, we found that: 1) the timing of GPi responses became uncoupled from movement onset. And 2) responses, especially decrease-type responses, became attenuated and prolonged. These abnormalities in GPi perimovement activity may contribute to the generation of parkinsonian motor signs.

neuroscience↗

bioRxiv2024

Photothrombosis induced cortical stroke produces electrographic epileptic biomarkers in mice

ObjectiveInterictal epileptiform spikes, high-frequency ripple oscillations, and their co-occurrence (spike ripples) in human scalp or intracranial voltage recordings are well-established epileptic biomarkers. While clinically significant, the neural mechanisms generating these electrographic biomarkers remain unclear. To reduce this knowledge gap, we introduce a novel photothrombotic stroke model in mice that reproduces focal interictal electrographic biomarkers observed in human epilepsy. MethodsWe induced a stroke in the motor cortex of C57BL/6 mice unilaterally (N=7) using a photothrombotic procedure previously established in rats. We then implanted intracranial electrodes (2 ipsilateral and 2 contralateral) and obtained intermittent local field potential (LFP) recordings over several weeks in awake, behaving mice. We evaluated the LFP for focal slowing and epileptic biomarkers - spikes, ripples, and spike ripples - using both automated and semi-automated procedures. ResultsDelta power (1-4 Hz) was higher in the stroke hemisphere than the non-stroke hemisphere in all mice (p<0.001). Automated detection procedures indicated that compared to the non-stroke hemisphere, the stroke hemisphere had an increased spike ripple (p=0.006) and spike rates (p=0.039), but no change in ripple rate (p=0.98). Expert validation confirmed the observation of elevated spike ripple rates (p=0.008) and a trend of elevated spike rate (p=0.055) in the stroke hemisphere. Interestingly, the validated ripple rate in the stroke hemisphere was higher than the non-stroke hemisphere (p=0.031), highlighting the difficulty of automatically detecting ripples. Finally, using optimal performance thresholds, automatically detected spike ripples classified the stroke hemisphere with the best accuracy (sensitivity 0.94, specificity 0.94). SignificanceCortical photothrombosis-induced stroke in commonly used C57BL/6 mice produces electrographic biomarkers as observed in human epilepsy. This model represents a new translational cortical epilepsy model with a defined irritative zone, which can be broadly applied in transgenic mice for cell type specific analysis of the cellular and circuit mechanisms of pathologic interictal activity. Key PointsO_LICortical photothrombosis in mice produces stroke with characteristic intermittent focal delta slowing. C_LIO_LICortical photothrombosis stroke in mice produces the epileptic biomarkers spikes, ripples, and spike ripples. C_LIO_LIAll biomarkers share morphological features with the corresponding human correlate. C_LIO_LISpike ripples better lateralize to the lesional cortex than spikes or ripples. C_LIO_LIThis cortical model can be applied in transgenic mice for mechanistic studies. C_LI

neuroscience↗

bioRxiv2023

Speech induces spatiotemporal and frequency specific subthalamic-cortical spike-phase coupling events

Speech provides a rich context for understanding how cortical interactions with the basal ganglia contribute to unique human behaviors, but opportunities for direct intracranial recordings across cortical-basal ganglia networks are rare. We recorded electrocorticographic signals in the cortex synchronously with single units in the basal ganglia during awake neurosurgeries where subjects spoke syllable repetitions. We discovered that individual STN neurons have transient (200ms) spike-phase coupling (SPC) events with multiple cortical regions. The spike timing of STN neurons was coordinated with the phase of theta-alpha oscillations in the posterior supramarginal and superior temporal gyrus during speech planning and production. Speech sound errors occurred when this STN-cortical interaction was delayed. Our results suggest that the STN supports mechanisms of speech planning and auditory-sensorimotor integration during speech production that are required to achieve high fidelity of the phonological and articulatory representation of the target phoneme. These findings establish a framework for understanding cortical-basal ganglia interaction in other human behaviors, and additionally indicate that firing-rate based models are insufficient for explaining basal ganglia circuit behavior.

neuroscience↗

bioRxiv2022

Interacting cortical gradients of neural timescales and functional connectivity and their relationship to perceptual behavior

Cognitive acts take place over a large range of temporal scales. Numerous corresponding gradients in neurodynamic timescales and long-range cortical interactions are believed to provide organizational constraints to the brain and influence neural populations roles in cognition. However, it is unclear if gradients in various types of neural timescales and functional connectivity arise from related or distinct neurophysiological processes and if they influence behavior. Here, intracranial recordings from 4,090 electrode contacts in 35 individuals were used to systematically map gradients of multiple aspects of neurodynamics, neural timescales, and functional connectivity, and assess their interactions along category-selective ventral temporal cortex. Opposing functional connectivity gradients, with decreasing connectivity to visually responsive regions and increasing connectivity to regions that were not visually responsive, were observed along the ventral visual hierarchy. Endogenous neural timescales were correlated with functional connectivity to visually responsive regions after removing the effects of shared anatomical gradients, suggesting that these properties influence one another. Different stimulus evoked and endogenous timescales exhibited gradients with longer dynamics along the ventral visual hierarchy, but none of these timescales were significantly correlated with one another. This suggests that local neural timescales depend on neural and cognitive context and different timescales may arise through distinct neurophysiological processes. Furthermore, activity from neural populations with faster endogenous timescales and stronger functional connectivity to visually responsive regions was more predictive of perceptual behavior during a visual repeat detection task. These results reveal interrelationships and key distinctions among neural timescale and functional connectivity gradients that together can influence behavior.

neuroscience↗

bioRxiv2022

Characterizing ketamine-induced dissociation using human intracranial neurophysiology: brain dynamics, network activity, and interactions with propofol

Subanesthetic doses of ketamine produce rapid and sustained anti-depressant effects in patients with treatment-resistant depression. Unfortunately, the usefulness of ketamine as a treatment is limited by its potential for abuse because of psychotropic side effects such as dissociation. Understanding the brain dynamics and the neural circuits involved in ketamines effects could lend insight into improved therapies for depression with fewer adverse effects. It is believed that ketamine acts via NMDA receptor and hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels to produce changes in oscillatory brain dynamics. Here we show, in humans, a detailed description of the principal oscillatory changes in cortical and subcortical structures by administration of a subanesthetic dose of ketamine. Using recordings from intracranial electrodes, we found that ketamine increased gamma oscillations within prefrontal cortical areas and the hippocampus--structures previously implicated in ketamines antidepressant effects. Furthermore, our studies provide direct evidence of a ketamine-induced 3 Hz oscillation in posteromedial cortex that has been proposed as a mechanism for its dissociative effects. By analyzing changes in neural oscillations after the addition of propofol, whose GABAergic activity antagonizes ketamines NMDA-mediated disinhibition alongside a shared HCN1 inhibitory effect, we identified brain dynamics that could be attributed to NMDA-mediated disinhibition versus HCN1 inhibition. Overall, our results imply that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of novel brain dynamic biomarkers and therapeutics for depression.

neuroscience↗

bioRxiv2021

Brain networks in human conscious visual perception

Consciousness is not explained by a single mechanism, rather it involves multiple specialized neural systems overlapping in space and time. We hypothesize that synergistic, large-scale subcortical and cortical attention and signal processing networks encode conscious experiences. To identify brain activity in conscious perception without overt report, we classified visual stimuli as perceived or not using eye measurements. Report-independent event-related potentials and functional magnetic resonance imaging (fMRI) signals both occurred at early times after stimuli. Direct recordings revealed a novel thalamic awareness potential linked to conscious visual perception based on report. fMRI showed thalamic and cortical detection, arousal, attentional salience, task-positive, and default mode networks were involved independent of overt report. These findings identify a specific sequence of neural mechanisms in human conscious visual perception. One-Sentence SummaryHuman conscious visual perception engages large-scale subcortical and cortical networks even without overt report.

neuroscience↗

bioRxiv2021

Hyperdirect connectivity of opercular speech network to the subthalamic nucleus

The importance of the basal ganglia in modulating cognitive and motor behaviors is well known, yet how the basal ganglia participate in the uniquely human behavior of speech is poorly understood. The subthalamic nucleus (STN) is well positioned to facilitate two basal ganglia functions critical for speech: motor learning and gain modulation. Using a novel paradigm to study cortical-subcortical interactions during speech in patients undergoing awake DBS surgery, we found evidence for a left opercular hyperdirect pathway in humans by stimulating in the STN and examining antidromic evoked activity in the left temporal, parietal and frontal opercular cortex. These high resolution cortical and subcortical mapping data provided evidence for hyperdirect connectivity between Brocas area (typically corresponding to pars triangularis and pars opercularis of the inferior frontal gyrus) and the STN. In addition, we observed evoked potentials consistent with the presence of monosynaptic projections from areas of opercular speech cortex that are primarily sensory, including auditory cortex, to the STN. These connections may be unique to humans, evolving alongside the ability for speech. SIGNIFICANCEUsing intracranial recordings from the basal ganglia and cortex in subjects undergoing deep brain stimulation, this study provides evidence for monosynaptic cortical inputs from motor planning, motor sensory, and auditory sensory cortices to the subthalamic nucleus. These observations suggest that in humans, the cortical-basal ganglia hyperdirect pathway is uniquely positioned to participate in speech production. Moreover, the existence of a monosynaptic connection between human sensory cortical areas and the subthalamic nucleus indicates a need to update traditional models of information transfer within cortical-basal ganglia-thalamocortical circuitry, which has significant implications for understanding other human cognitive behavior or dysfunction.

neuroscience↗

bioRxiv2021

A spatio-spectral approach for movement decoding from cortical and subcortical recordings in patients with Parkinson's disease

The application of machine learning to intracranial signal analysis has the potential to revolutionize deep brain stimulation (DBS) by personalizing therapy to dynamic brain states, specific to symptoms and behaviors. Most decoding pipelines for movement decoding in the context of adaptive DBS are based on single channel frequency domain features, neglecting spatial information available in multichannel recordings. Such features are extracted either from DBS lead recordings in the subcortical target and/or from electrocorticography (ECoG). To optimize the simultaneous use of both types of signals, we developed a supervised online-compatible movement decoding pipeline based on multichannel and multiple site recordings. We found that adding spatial information to the model has the potential to improve decoding. In addition, we demonstrate movement decoding from spatio-spectral features derived from cortical and subcortical oscillations. We demonstrate between-patients variability of the spatial neural maps and its relationship to feature decoding performance. This application of spatial filters to decode movement from combined cortical and subcortical recordings is an important step in developing machine learning approaches for intelligent DBS systems.

neuroscience↗

bioRxiv2021

The sensitivity of ECG contamination to surgical implantation site in adaptive closed-loop neurostimulation systems

BackgroundBrain sensing devices are approved today for Parkinsons, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. ObjectivesInvestigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. MethodsElectric field modelling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination.a ResultsThe impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. ConclusionsGiven the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration. HighlightsO_LIChronic embedded brain sensing promises algorithm-based neurostimulation C_LIO_LIAlgorithms for closed-loop stimulation can be impaired by artifacts C_LIO_LIThe relationship of implant location to cardiac dipole has relevant impact on neural signal fidelity; simple models can provide guidance on the sensitivity C_LIO_LIECG artifacts are present in up to 50% of neural signals from left subclavicular DBS systems C_LIO_LIImplanting DBS in a right subclavicular location significantly reduces frequency of ECG artifacts C_LIO_LICranial-mounted implants are relatively immune to artifacts C_LI

neuroscience↗

bioRxiv2020

Quantifying a Frequency Modulation Response Biomarker in Responsive Neurostimulation

ObjectiveResponsive Neurostimulation (RNS) is an effective treatment for controlling seizures in patients with drug-resistant focal epilepsy who are not suitable candidates for resection surgery. A lack of tools for detecting and characterizing potential response biomarkers, however, contributes to a limited understanding of mechanisms by which RNS improves seizure control. We developed a method to quantify ictal frequency modulation, previously identified as a biomarker of clinical responsiveness to RNS. ApproachFrequency modulation is characterized by shifts in power across spectral bands during ictal events, over several months of neurostimulation. This effect was quantified by partitioning each seizure pattern into segments with distinct spectral content and measuring the extent change from the baseline distribution of spectral content using the squared Earthmovers distance. Main resultsWe analyzed intracranial electroencephalography data from 13 patients who received RNS therapy, six of whom exhibited frequency modulation on expert evaluation. Subjects in the frequency modulation group had, on average, significantly larger and more sustained changes in their Earthmovers distances (mean = 13.97x10-3 {+/-} 1.197x10-3). In contrast, those subjects without expert-identified frequency modulation exhibited statistically insignificant or negligible distances (mean = 4.994x10-3 {+/-} 0.732x10-3). SignificanceThis method is the first step towards a quantitative, feedback-driven system for systematically optimizing RNS stimulation parameters, with an ultimate goal of truly personalized closed-loop therapy for epilepsy.

neuroscience↗

bioRxiv2020

Dynamic Domain Specificity In Human Ventral Temporal Cortex

An enduring neuroscientific debate concerns the extent to which neural representation is restricted to neural populations specialized for particular domains of perceptual input, or distributed outside of highly selective populations as well. A critical level for this debate is the neural representation of the identity of individual images, such as individual-level face or written word recognition. Here, intracranial recordings throughout ventral temporal cortex across 17 human subjects were used to assess the spatiotemporal dynamics of individual word and face processing within and outside regions strongly selective for these categories of visual information. Individual faces and words were first discriminable primarily only in strongly selective areas, beginning at about 150 milliseconds after word or face onset, and then discriminable both within and outside strongly selective areas approximately 170 milliseconds later. Regions of ventral temporal cortex that were and were not strongly selective both contributed non-redundant information to the discrimination of individual images. These results can reconcile previous results endorsing disparate poles of the domain specificity debate by highlighting the temporally segregated contributions of different functionally defined cortical areas to individual level representations. This work supports a dynamic model of neural representation characterized by successive domain-specific and distributed processing stages.

neuroscience↗

bioRxiv2020

Thalamic encoding of lexical status is lateralized during reading aloud

To explore whether the thalamus participates in lexical status encoding, local field potentials were recorded in patients undergoing deep brain stimulation lead implantation while they read aloud single-syllable words and nonwords. Bilateral decreases in thalamic beta (12-30Hz) activity were preferentially locked to stimulus presentation, and these decreases were greater when nonwords were read. Increased broadband gamma (70-150Hz) activity also was locked preferentially to speech onset bilaterally, but greater nonword-related increases in this activity were observed only on the left, demonstrating lateralization of thalamic gamma selectivity for lexical status. In addition, this lexical status effect was strongest in more anterior thalamic locations, regions which are more likely to receive pallidal than cerebellar afferents. These results provide evidence from intracranial thalamic recordings for the lateralization and topography of subcortical lexical status processing.

neuroscience↗