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1.
Proc Natl Acad Sci U S A ; 120(42): e2300255120, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37819985

RESUMEN

Speech production is a complex human function requiring continuous feedforward commands together with reafferent feedback processing. These processes are carried out by distinct frontal and temporal cortical networks, but the degree and timing of their recruitment and dynamics remain poorly understood. We present a deep learning architecture that translates neural signals recorded directly from the cortex to an interpretable representational space that can reconstruct speech. We leverage learned decoding networks to disentangle feedforward vs. feedback processing. Unlike prevailing models, we find a mixed cortical architecture in which frontal and temporal networks each process both feedforward and feedback information in tandem. We elucidate the timing of feedforward and feedback-related processing by quantifying the derived receptive fields. Our approach provides evidence for a surprisingly mixed cortical architecture of speech circuitry together with decoding advances that have important implications for neural prosthetics.


Asunto(s)
Habla , Lóbulo Temporal , Humanos , Retroalimentación , Estimulación Acústica
2.
PLoS Biol ; 20(2): e3001493, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35113857

RESUMEN

Hearing one's own voice is critical for fluent speech production as it allows for the detection and correction of vocalization errors in real time. This behavior known as the auditory feedback control of speech is impaired in various neurological disorders ranging from stuttering to aphasia; however, the underlying neural mechanisms are still poorly understood. Computational models of speech motor control suggest that, during speech production, the brain uses an efference copy of the motor command to generate an internal estimate of the speech output. When actual feedback differs from this internal estimate, an error signal is generated to correct the internal estimate and update necessary motor commands to produce intended speech. We were able to localize the auditory error signal using electrocorticographic recordings from neurosurgical participants during a delayed auditory feedback (DAF) paradigm. In this task, participants hear their voice with a time delay as they produced words and sentences (similar to an echo on a conference call), which is well known to disrupt fluency by causing slow and stutter-like speech in humans. We observed a significant response enhancement in auditory cortex that scaled with the duration of feedback delay, indicating an auditory speech error signal. Immediately following auditory cortex, dorsal precentral gyrus (dPreCG), a region that has not been implicated in auditory feedback processing before, exhibited a markedly similar response enhancement, suggesting a tight coupling between the 2 regions. Critically, response enhancement in dPreCG occurred only during articulation of long utterances due to a continuous mismatch between produced speech and reafferent feedback. These results suggest that dPreCG plays an essential role in processing auditory error signals during speech production to maintain fluency.


Asunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Retroalimentación Sensorial/fisiología , Percepción del Habla/fisiología , Adulto , Electrocorticografía , Epilepsia/cirugía , Femenino , Humanos , Masculino , Corteza Motora/fisiología , Habla/fisiología
3.
PLoS Comput Biol ; 20(5): e1012161, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38815000

RESUMEN

Neural responses in visual cortex adapt to prolonged and repeated stimuli. While adaptation occurs across the visual cortex, it is unclear how adaptation patterns and computational mechanisms differ across the visual hierarchy. Here we characterize two signatures of short-term neural adaptation in time-varying intracranial electroencephalography (iEEG) data collected while participants viewed naturalistic image categories varying in duration and repetition interval. Ventral- and lateral-occipitotemporal cortex exhibit slower and prolonged adaptation to single stimuli and slower recovery from adaptation to repeated stimuli compared to V1-V3. For category-selective electrodes, recovery from adaptation is slower for preferred than non-preferred stimuli. To model neural adaptation we augment our delayed divisive normalization (DN) model by scaling the input strength as a function of stimulus category, enabling the model to accurately predict neural responses across multiple image categories. The model fits suggest that differences in adaptation patterns arise from slower normalization dynamics in higher visual areas interacting with differences in input strength resulting from category selectivity. Our results reveal systematic differences in temporal adaptation of neural population responses between lower and higher visual brain areas and show that a single computational model of history-dependent normalization dynamics, fit with area-specific parameters, accounts for these differences.


Asunto(s)
Adaptación Fisiológica , Modelos Neurológicos , Corteza Visual , Humanos , Corteza Visual/fisiología , Adaptación Fisiológica/fisiología , Adulto , Masculino , Femenino , Estimulación Luminosa , Biología Computacional , Adulto Joven , Electroencefalografía , Percepción Visual/fisiología , Electrocorticografía
4.
Proc Natl Acad Sci U S A ; 118(2)2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33372130

RESUMEN

How do firing patterns in a cortical circuit change when inhibitory neurons are excited? We virally expressed an excitatory designer receptor exclusively activated by a designer drug (Gq-DREADD) in all inhibitory interneuron types of the CA1 region of the hippocampus in the rat. While clozapine N-oxide (CNO) activation of interneurons suppressed firing of pyramidal cells, unexpectedly the majority of interneurons also decreased their activity. CNO-induced inhibition decreased over repeated sessions, which we attribute to long-term synaptic plasticity between interneurons and pyramidal cells. Individual interneurons did not display sustained firing but instead transiently enhanced their activity, interleaved with suppression of others. The power of the local fields in the theta band was unaffected, while power at higher frequencies was attenuated, likely reflecting reduced pyramidal neuron spiking. The incidence of sharp wave ripples decreased but the surviving ripples were associated with stronger population firing compared with the control condition. These findings demonstrate that DREADD activation of interneurons brings about both short-term and long-term circuit reorganization, which should be taken into account in the interpretation of chemogenic effects on behavior.


Asunto(s)
Región CA1 Hipocampal/metabolismo , Interneuronas/fisiología , Células Piramidales/metabolismo , Animales , Región CA1 Hipocampal/efectos de los fármacos , Clozapina/análogos & derivados , Clozapina/farmacología , Femenino , Hipocampo/metabolismo , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Masculino , Inhibición Neural/fisiología , Plasticidad Neuronal/fisiología , Parvalbúminas/metabolismo , Ratas , Ratas Sprague-Dawley , Transmisión Sináptica/fisiología
5.
J Neurosci ; 42(40): 7562-7580, 2022 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-35999054

RESUMEN

Neural responses to visual stimuli exhibit complex temporal dynamics, including subadditive temporal summation, response reduction with repeated or sustained stimuli (adaptation), and slower dynamics at low contrast. These phenomena are often studied independently. Here, we demonstrate these phenomena within the same experiment and model the underlying neural computations with a single computational model. We extracted time-varying responses from electrocorticographic recordings from patients presented with stimuli that varied in duration, interstimulus interval (ISI) and contrast. Aggregating data across patients from both sexes yielded 98 electrodes with robust visual responses, covering both earlier (V1-V3) and higher-order (V3a/b, LO, TO, IPS) retinotopic maps. In all regions, the temporal dynamics of neural responses exhibit several nonlinear features. Peak response amplitude saturates with high contrast and longer stimulus durations, the response to a second stimulus is suppressed for short ISIs and recovers for longer ISIs, and response latency decreases with increasing contrast. These features are accurately captured by a computational model composed of a small set of canonical neuronal operations, that is, linear filtering, rectification, exponentiation, and a delayed divisive normalization. We find that an increased normalization term captures both contrast- and adaptation-related response reductions, suggesting potentially shared underlying mechanisms. We additionally demonstrate both changes and invariance in temporal response dynamics between earlier and higher-order visual areas. Together, our results reveal the presence of a wide range of temporal and contrast-dependent neuronal dynamics in the human visual cortex and demonstrate that a simple model captures these dynamics at millisecond resolution.SIGNIFICANCE STATEMENT Sensory inputs and neural responses change continuously over time. It is especially challenging to understand a system that has both dynamic inputs and outputs. Here, we use a computational modeling approach that specifies computations to convert a time-varying input stimulus to a neural response time course, and we use this to predict neural activity measured in the human visual cortex. We show that this computational model predicts a wide variety of complex neural response shapes, which we induced experimentally by manipulating the duration, repetition, and contrast of visual stimuli. By comparing data and model predictions, we uncover systematic properties of temporal dynamics of neural signals, allowing us to better understand how the brain processes dynamic sensory information.


Asunto(s)
Encéfalo , Corteza Visual , Masculino , Femenino , Humanos , Estimulación Luminosa/métodos , Encéfalo/fisiología , Mapeo Encefálico/métodos , Factores de Tiempo , Corteza Visual/fisiología
6.
Epilepsia ; 64(7): 1910-1924, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37150937

RESUMEN

OBJECTIVE: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (µECoG) arrays, which provide high spatial resolution over large cortical surface areas. METHODS: We used novel liquid crystal polymer thin-film µECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. RESULTS: We found visually delineable subregions of elevated HFO activity within each µECoG recording. Forty-seven percent of HFOs occurred on single 200-µm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our µECoG recordings. SIGNIFICANCE: These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.


Asunto(s)
Ondas Encefálicas , Epilepsia Refractaria , Epilepsia , Humanos , Electroencefalografía/métodos , Epilepsia/cirugía , Epilepsia/diagnóstico , Encéfalo , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/cirugía
7.
PLoS Comput Biol ; 18(8): e1010401, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35939509

RESUMEN

In analyzing the neural correlates of naturalistic and unstructured behaviors, features of neural activity that are ignored in a trial-based experimental paradigm can be more fully studied and investigated. Here, we analyze neural activity from two patients using electrocorticography (ECoG) and stereo-electroencephalography (sEEG) recordings, and reveal that multiple neural signal characteristics exist that discriminate between unstructured and naturalistic behavioral states such as "engaging in dialogue" and "using electronics". Using the high gamma amplitude as an estimate of neuronal firing rate, we demonstrate that behavioral states in a naturalistic setting are discriminable based on long-term mean shifts, variance shifts, and differences in the specific neural activity's covariance structure. Both the rapid and slow changes in high gamma band activity separate unstructured behavioral states. We also use Gaussian process factor analysis (GPFA) to show the existence of salient spatiotemporal features with variable smoothness in time. Further, we demonstrate that both temporally smooth and stochastic spatiotemporal activity can be used to differentiate unstructured behavioral states. This is the first attempt to elucidate how different neural signal features contain information about behavioral states collected outside the conventional experimental paradigm.


Asunto(s)
Electrocorticografía , Electroencefalografía , Mapeo Encefálico , Humanos , Distribución Normal
8.
Neuroimage ; 247: 118746, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-34875382

RESUMEN

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Ongoing fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on intracranial electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input.


Asunto(s)
Ondas Encefálicas/fisiología , Estimulación Luminosa/métodos , Adulto , Percepción Auditiva/fisiología , Encéfalo/fisiología , Discriminación en Psicología/fisiología , Epilepsia Refractaria/fisiopatología , Electroencefalografía , Femenino , Humanos , Estudios Longitudinales , Masculino , Tiempo de Reacción , Percepción Visual/fisiología
9.
Epilepsia ; 63(3): 652-662, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34997577

RESUMEN

OBJECTIVE: Despite the overall success of responsive neurostimulation (RNS) therapy for drug-resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS-ideally before device implantation-are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy. METHODS: We assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy. RESULTS: Ictal measures of synchronizability in the high-γ band (95-105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high-γ synchronizability is inversely associated with the degree of therapeutic response. SIGNIFICANCE: This study provides a proof-of-concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Biomarcadores , Epilepsia Refractaria/terapia , Electrocorticografía , Epilepsia/diagnóstico , Epilepsia/terapia , Humanos , Estudios Retrospectivos
10.
Brain ; 144(5): 1590-1602, 2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-33889945

RESUMEN

We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds of remembering in hippocampus (95% confidence interval 6-23%). Hippocampal interictal epileptiform discharges during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if interictal epileptiform discharges occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal interictal epileptiform discharges were followed by a transient decrease in ripple rate. We hypothesize that interictal epileptiform discharges impair associative memory in a regionally and temporally specific manner by decreasing physiological hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological interictal epileptiform discharge events competing with physiological ripples, interictal epileptiform discharges represent a promising therapeutic target for memory remediation in patients with epilepsy.


Asunto(s)
Epilepsia/fisiopatología , Hipocampo/fisiopatología , Recuerdo Mental/fisiología , Adolescente , Adulto , Electrocorticografía , Epilepsia/complicaciones , Femenino , Humanos , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/fisiopatología , Persona de Mediana Edad , Adulto Joven
11.
Cereb Cortex ; 31(8): 3678-3700, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-33749727

RESUMEN

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.


Asunto(s)
Corteza Cerebral/fisiología , Neuronas/fisiología , Estimulación Acústica , Adulto , Animales , Estimulación Eléctrica , Electroencefalografía , Fenómenos Electrofisiológicos , Epilepsia/fisiopatología , Espacio Extracelular/fisiología , Femenino , Humanos , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Microelectrodos , Persona de Mediana Edad , Corteza Somatosensorial/fisiología , Análisis de Ondículas , Adulto Joven
12.
Proc Natl Acad Sci U S A ; 116(47): 23772-23782, 2019 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-31685634

RESUMEN

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.


Asunto(s)
Ritmo alfa , Corteza Cerebral/fisiología , Electrodos , Electroencefalografía , Humanos , Tálamo/fisiología
13.
J Cogn Neurosci ; 33(11): 2197-2214, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34347873

RESUMEN

Models of reading emphasize that visual (orthographic) processing provides input to phonological as well as lexical-semantic processing. Neurobiological models of reading have mapped these processes to distributed regions across occipital-temporal, temporal-parietal, and frontal cortices. However, the role of the precentral gyrus in these models is ambiguous. Articulatory phonemic representations in the precentral gyrus are obviously involved in reading aloud, but it is unclear if the precentral gyrus is recruited during reading silently in a time window consistent with participation in phonological processing contributions. Here, we recorded intracranial electrophysiology during a speeded semantic decision task from 24 patients to map the spatio-temporal flow of information across the cortex during silent reading. Patients selected animate nouns from a stream of nonanimate words, letter strings, and false-font stimuli. We characterized the distribution and timing of evoked high-gamma power (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus showed a proportion of electrodes responsive to linguistic stimuli (27%) that was at least as high as those of surrounding peri-sylvian regions. These precentral gyrus electrodes had significantly greater high-gamma power for words compared to both false-font and letter-string stimuli. In a patient with word-selective effects in the fusiform, superior temporal, and precentral gyri, there was significant phase-locking between the fusiform and precentral gyri starting at ∼180 msec and between the precentral and superior temporal gyri starting at ∼220 msec. Finally, our large patient cohort allowed exploratory analyses of the spatio-temporal reading network underlying silent reading. The distribution, timing, and connectivity results place the precentral gyrus as an important hub in the silent reading network.


Asunto(s)
Corteza Motora , Lectura , Mapeo Encefálico , Electrofisiología , Humanos , Lenguaje , Imagen por Resonancia Magnética
14.
Epilepsy Behav ; 123: 108209, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34416521

RESUMEN

Interictal epileptiform discharges (IEDs) can impair memory. The properties of IEDs most detrimental to memory, however, are undefined. We studied the impact of temporal and spatial characteristics of IEDs on list learning. Subjects completed a memory task during intracranial EEG recordings including hippocampal depth and temporal neocortical subdural electrodes. Subjects viewed a series of objects, and after a distracting task, recalled the objects from the list. The impacts of IED presence, duration, and propagation to neocortex during encoding of individual stimuli were assessed. The effects of IED total number and duration during maintenance and recall periods on delayed recall performance were also determined. The influence of IEDs during recall was further investigated by comparing the likelihood of IEDs preceding correctly recalled items vs. periods of no verbal response. Across 6 subjects, we analyzed 28 hippocampal and 139 lateral temporal contacts. Recall performance was poor, with a median of 17.2% correct responses (range 10.4-21.9%). Interictal epileptiform discharges during encoding, maintenance, and recall did not significantly impact task performance, and there was no significant difference between the likelihood of IEDs during correct recall vs. periods of no response. No significant effects of discharge duration during encoding, maintenance, or recall were observed. Interictal epileptiform discharges with spread to lateral temporal cortex during encoding did not adversely impact recall. A post hoc analysis refining model assumptions indicated a negative impact of IED count during the maintenance period, but otherwise confirmed the above results. Our findings suggest no major effect of hippocampal IEDs on list learning, but study limitations, such as baseline hippocampal dysfunction, should be considered. The impact of IEDs during the maintenance period may be a focus of future research.


Asunto(s)
Electroencefalografía , Epilepsia del Lóbulo Temporal , Electrocorticografía , Hipocampo , Humanos , Recuerdo Mental
15.
Proc Natl Acad Sci U S A ; 115(31): E7418-E7427, 2018 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-30006465

RESUMEN

Mnemonic decision-making has long been hypothesized to rely on hippocampal dynamics that bias memory processing toward the formation of new memories or the retrieval of old ones. Successful memory encoding may be best optimized by pattern separation, whereby two highly similar experiences can be represented by underlying neural populations in an orthogonal manner. By contrast, successful memory retrieval is thought to be supported by a recovery of the same neural pattern laid down during encoding. Here we examined how hippocampal pattern completion and separation emerge over time during memory decisions. We measured electrocorticography activity in the human hippocampus and posterior occipitotemporal cortex (OTC) while participants performed continuous recognition of items that were new, repeated (old), or highly similar to a prior item (similar). During retrieval decisions of old items, both regions exhibited significant reinstatement of multivariate high-frequency activity (HFA) associated with encoding. Further, the extent of reinstatement of encoding patterns during retrieval was correlated with the strength (HFA power) of hippocampal encoding. Evidence for encoding pattern reinstatement was also seen in OTC on trials requiring fine-grained discrimination of similar items. By contrast, hippocampal activity showed evidence for pattern separation during these trials. Together, these results underscore the critical role of the hippocampus in supporting both reinstatement of overlapping information and separation of similar events.


Asunto(s)
Hipocampo/fisiología , Memoria , Adulto , Toma de Decisiones , Electrocorticografía , Femenino , Humanos , Masculino , Lóbulo Occipital/fisiología , Adulto Joven
16.
Brain ; 142(11): 3502-3513, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31501850

RESUMEN

Dynamic interactions between remote but functionally specialized brain regions enable complex information processing. This intercortical communication is disrupted in the neural networks of patients with focal epilepsy, and epileptic activity can exert widespread effects within the brain. Using large-scale human intracranial electroencephalography recordings, we show that interictal epileptiform discharges (IEDs) are significantly coupled with spindles in discrete, individualized brain regions outside of the epileptic network. We found that a substantial proportion of these localized spindles travel across the cortical surface. Brain regions that participate in this IED-driven oscillatory coupling express spindles that have a broader spatial extent and higher tendency to propagate than spindles occurring in uncoupled regions. These altered spatiotemporal oscillatory properties identify areas that are shaped by epileptic activity independent of IED or seizure detection. Our findings suggest that IED-spindle coupling may be an important mechanism of interictal global network dysfunction that could be targeted to prevent disruption of normal neural activity.


Asunto(s)
Epilepsia/fisiopatología , Convulsiones/fisiopatología , Adulto , Algoritmos , Encéfalo , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Electrocorticografía , Electrodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología
17.
Epilepsy Behav ; 112: 107389, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32890796

RESUMEN

Drug-resistant focal epilepsy (DRFE) in children can impair cognition and behavior, and lead to premature death. Increased pediatric epilepsy surgery numbers reflect the improvements in seizure control and long-term developmental outcomes. Yet, many children with DRFE are not candidates for surgical resection due to overlap of the seizure network with eloquent cortex or multiple seizure-onset zones, making surgery dangerous or ineffective. In adults, responsive neurostimulation (RNS System) therapy is safe and effective treatment for DRFE with one or two seizure foci, especially when the seizure focus is in eloquent cortex. We present six pediatric patients with DRFE who underwent RNS implantation. Our outcomes demonstrate safety, decreased clinical seizure frequency, as well as improved functional status and quality of life. Changes in the clinical seizure semiology and frequency occurred in conjunction with adjustments to the stimulation parameters, supporting the efficacy of responsive neuromodulation in children.


Asunto(s)
Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia , Adulto , Corteza Cerebral , Niño , Epilepsia Refractaria/terapia , Epilepsia/terapia , Humanos , Calidad de Vida
18.
Nature ; 507(7490): 94-8, 2014 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-24429520

RESUMEN

Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception- and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Desempeño Psicomotor/fisiología , Percepción del Habla/fisiología , Habla/fisiología , Mapeo Encefálico , Femenino , Lóbulo Frontal/fisiología , Lateralidad Funcional/fisiología , Audición/fisiología , Humanos , Lenguaje , Masculino , Modelos Neurológicos , Lóbulo Temporal/fisiología
19.
J Neurosci ; 38(12): 3013-3025, 2018 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-29449429

RESUMEN

Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10-16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels. Many spindles were observed in only upper or only middle channels, but approximately half occurred in both. In spindles involving both middle and upper channels, the spindle envelope onset in middle channels led upper by ∼25-50 ms on average. The phase relationship between spindle waves in upper and middle channels varied dynamically within spindle epochs, and across individuals. Current source density analysis demonstrated that upper and middle channel spindles were both generated by an excitatory supragranular current sink while an additional deep source was present for middle channel spindles only. Only middle channel spindles were accompanied by deep low (25-50 Hz) and high (70-170 Hz) gamma activity. These results suggest that upper channel spindles are generated by supragranular pyramids, and middle channel by infragranular. Possibly, middle channel spindles are generated by core thalamocortical afferents, and upper channel by matrix. The concurrence of these patterns could reflect engagement of cortical circuits in the integration of more focal (core) and distributed (matrix) aspects of memory. These results demonstrate that at least two distinct intracortical systems generate human sleep spindles.SIGNIFICANCE STATEMENT Bursts of ∼14 Hz oscillations, lasting ∼1 s, have been recognized for over 80 years as cardinal features of mammalian sleep. Recent findings suggest that they play a key role in organizing cortical activity during memory consolidation. We used linear microelectrode arrays to study their intracortical organization in humans. We found that spindles could be divided into two types. One mainly engages upper layers of the cortex, which are considered to be specialized for associative activity. The other engages both upper and middle layers, including those devoted to sensory input. The interaction of these two spindle types may help organize the interaction of sensory and associative aspects of memory consolidation.


Asunto(s)
Corteza Cerebral/fisiología , Consolidación de la Memoria/fisiología , Sueño/fisiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven
20.
J Neurosci ; 38(40): 8680-8693, 2018 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-30143578

RESUMEN

Using predictions based on environmental regularities is fundamental for adaptive behavior. While it is widely accepted that predictions across different stimulus attributes (e.g., time and content) facilitate sensory processing, it is unknown whether predictions across these attributes rely on the same neural mechanism. Here, to elucidate the neural mechanisms of predictions, we combine invasive electrophysiological recordings (human electrocorticography in 4 females and 2 males) with computational modeling while manipulating predictions about content ("what") and time ("when"). We found that "when" predictions increased evoked activity over motor and prefrontal regions both at early (∼180 ms) and late (430-450 ms) latencies. "What" predictability, however, increased evoked activity only over prefrontal areas late in time (420-460 ms). Beyond these dissociable influences, we found that "what" and "when" predictability interactively modulated the amplitude of early (165 ms) evoked responses in the superior temporal gyrus. We modeled the observed neural responses using biophysically realistic neural mass models, to better understand whether "what" and "when" predictions tap into similar or different neurophysiological mechanisms. Our modeling results suggest that "what" and "when" predictability rely on complementary neural processes: "what" predictions increased short-term plasticity in auditory areas, whereas "when" predictability increased synaptic gain in motor areas. Thus, content and temporal predictions engage complementary neural mechanisms in different regions, suggesting domain-specific prediction signaling along the cortical hierarchy. Encoding predictions through different mechanisms may endow the brain with the flexibility to efficiently signal different sources of predictions, weight them by their reliability, and allow for their encoding without mutual interference.SIGNIFICANCE STATEMENT Predictions of different stimulus features facilitate sensory processing. However, it is unclear whether predictions of different attributes rely on similar or different neural mechanisms. By combining invasive electrophysiological recordings of cortical activity with experimental manipulations of participants' predictions about content and time of acoustic events, we found that the two types of predictions had dissociable influences on cortical activity, both in terms of the regions involved and the timing of the observed effects. Further, our biophysical modeling analysis suggests that predictability of content and time rely on complementary neural processes: short-term plasticity in auditory areas and synaptic gain in motor areas, respectively. This suggests that predictions of different features are encoded with complementary neural mechanisms in different brain regions.


Asunto(s)
Anticipación Psicológica/fisiología , Corteza Auditiva/fisiología , Modelos Neurológicos , Estimulación Acústica , Adulto , Electrocorticografía , Potenciales Evocados Auditivos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiología , Vías Nerviosas/fisiología , Corteza Prefrontal/fisiología , Tiempo de Reacción , Factores de Tiempo , Percepción Visual/fisiología , Adulto Joven
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