Direct Cortical Recordings Research Articles

Low-Frequency Oscillations in Mid-rostral Dorsolateral Prefrontal Cortex Support Response Inhibition.

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in the dorsolateral prefrontal cortex (dlPFC)-often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control. We assessed whether cognitive control is topographically organized along this axis and observed that low-frequency power increased prominently in mid-rostral dlPFC when inhibiting and delaying responses. These findings provide evidence for a key role for mid-rostral dlPFC low-frequency oscillations in sculpting motor control.

Signatures of migraine aura in high-density-EEG

ObjectiveCortical spreading depolarization is highly conserved among the species. It is easily detectable in direct cortical surface recordings and has been recorded in the cortex of humans with severe neurological disease. It is considered the pathophysiological correlate of human migraine aura, but direct electrophysiological evidence is still missing. As signatures of cortical spreading depolarization have been recognized in scalp EEG, we investigated typical spontaneous migraine aura, using full band high-density EEG (HD-EEG). MethodsIn this prospective study, patients with migraine with aura were investigated during spontaneous migraine aura and interictally. Time compressed HD-EEG were analyzed for the presence of cortical spreading depolarization characterized by (a) slow potential changes below 0.05 Hz, (b) suppression of faster activity from 0.5 Hz − 45 Hz (c) spreading of these changes to neighboring regions during the aura phase. Further, topographical changes in alpha-power spectral density (8–14 Hz) during aura were analyzed. ResultsIn total, 26 HD-EEGs were recorded in patients with migraine with aura, thereof 10 HD-EEGs during aura. Eight HD-EEGs were recorded in the same subject. During aura, no slow potentials were recorded, but alpha-power was significantly decreased in parieto-occipito-temporal location on the hemisphere contralateral to visual aura, lasting into the headache phase. Interictal alpha-power in patients with migraine with aura did not differ significantly from age- and sex-matched healthy controls. ConclusionsUnequivocal signatures of spreading depolarization were not recorded with EEG on the intact scalp in migraine. The decrease in alpha-power contralateral to predominant visual symptoms is consistent with focal depression of spontaneous brain activity as a consequence of cortical spreading depolarization but is not specific thereof. SignificanceCortical spreading depolarization is relevant in migraine, other paroxysmal neurological disorders and neurointensive care.

Neural control of lexical tone production in human laryngeal motor cortex

In tonal languages, which are spoken by nearly one-third of the world’s population, speakers precisely control the tension of vocal folds in the larynx to modulate pitch in order to distinguish words with completely different meanings. The specific pitch trajectories for a given tonal language are called lexical tones. Here, we used high-density direct cortical recordings to determine the neural basis of lexical tone production in native Mandarin-speaking participants. We found that instead of a tone category-selective coding, local populations in the bilateral laryngeal motor cortex (LMC) encode articulatory kinematic information to generate the pitch dynamics of lexical tones. Using a computational model of tone production, we discovered two distinct patterns of population activity in LMC commanding pitch rising and lowering. Finally, we showed that direct electrocortical stimulation of different local populations in LMC evoked pitch rising and lowering during tone production, respectively. Together, these results reveal the neural basis of vocal pitch control of lexical tones in tonal languages.

Rapid eye movement sleep affects interictal epileptic activity differently in mesiotemporal and neocortical areas.

Rapid eye movement (REM) sleep reduces the rate and extent of interictal epileptiform discharges (IEDs). Breakthrough epileptic activity during REM sleep is therefore thought to best localize the seizure-onset zone (SOZ). We utilized polysomnography combined with direct cortical recordings to investigate the influences of anatomical locations and the time of night on the suppressive effect of REM sleep on IEDs. Forty consecutive patients with drug-resistant focal epilepsy underwent combined polysomnography and stereo-electroencephalography during presurgical evaluation. Ten-minute interictal epochs were selected 2 h prior to sleep onset (wakefulness), and from the first and second half of the night during non-REM (NREM) sleep and REM sleep. IEDs were detected automatically across all channels. Anatomic localization, time of night, and channel type (within or outside the SOZ) were tested as modulating factors. Relative to wakefulness, there was a suppression of IEDs by REM sleep in neocortical regions (median=-27.6%), while mesiotemporal regions showed an increase in IEDs (19.1%) (p=0.01; d=0.39). This effect was reversed when comparing the regional suppression of IEDs by REM sleep relative to NREM sleep (-35.1% in neocortical; -58.7% in mesiotemporal) (p<0.001; d=0.39). Across all patients, no clinically relevant novel IED regions were observed in REM sleep versus NREM or wakefulness based on our predetermined thresholds (4 IEDs/min in REM, 0 IEDs/min in NREM and W). Finally, there was a reduction in IEDs in late (NREM: 1.08/min; REM: 0.61/min) compared to early sleep (NREM: 1.22/min; REM: 0.69/min) for both NREM (p<0.001; d=0.21) and REM (p=0.04; d=0.14). Our results demonstrate a spatiotemporal effect of IED suppression by REM sleep relative to wakefulness in neocortical, but not mesiotemporal regions, and in late versus early sleep. This suggests the importance of considering sleep stage interactions and the potential influences of anatomical locations when using IEDs to define the epileptic focus.

Intraoperative Neuromonitoring of the Visual Pathway in Asleep Neuro-Oncology Surgery.

Brain tumour surgery in visual eloquent areas poses significant challenges to neurosurgeons and has reported inconsistent results. This is a single-centre prospective cohort study of patients admitted for asleep surgery of intra-axial lesions in visual eloquent areas. Demographic and clinical information, data from tractography and visual evoked potentials (VEPs) monitoring were recorded and correlated with visual outcomes. Thirty-nine patients were included (20 females, 19 males; mean age 52.51 ± 14.08 years). Diffuse intrinsic glioma was noted in 61.54% of patients. There was even distribution between the temporal, occipital and parietal lobes, while 55.26% were right hemispheric lesions. Postoperatively, 74.4% remained stable in terms of visual function, 23.1% deteriorated and 2.6% improved. The tumour infiltration of the optic radiation on tractography was significantly related to the visual field deficit after surgery (p = 0.016). Higher N75 (p = 0.036) and P100 (p = 0.023) amplitudes at closure on direct cortical VEP recordings were associated with no new postoperative visual deficit. A threshold of 40% deterioration of the N75 (p = 0.035) and P100 (p = 0.020) amplitudes correlated with a risk of visual field deterioration. To conclude, direct cortical VEP recordings demonstrated a strong correlation with visual outcomes, contrary to transcranial recordings. Invasion of the optic radiation is related to worse visual field outcomes.

SURG-02. INTRAOPERATIVE RADIOTHERAPY FOR BRAIN METASTASES: EVALUATION OF ELECTROCORTICOGRAPHY AND PERI-OPERATIVE SEIZURE RISK

Abstract BACKGROUND Intraoperative radiotherapy (IORT) has emerged as a viable tool for consolidation of surgery and radiation for brain metastases into a single episode of care, but its relative novelty compared to SRS or fractionated radiotherapy warrants evaluation of its safety. While post-operative seizure risk is typically minimal with the use of anti-epileptic drugs during the peri-operative phase, the risk of intra-operative epileptiform discharge remains unknown. METHODS Five consecutive cases of surgically resected brain metastases treated with IORT underwent electrocorticography via direct cortical electrode recordings adjacent to the resection cavity with paddle electrodes used for mapping of phase reversal. Continuous recordings were made before, during, and after radiation delivery and analyzed for evidence of radiation-associated changes. RESULTS No evidence of significant electrophysiological change was noted in any of the cases, nor was there any clinical evidence of seizure in the immediate peri-operative period. These data represent the first direct cortical recordings in human subjects during the delivery of radiation. CONCLUSIONS In this small cohort of IORT treated resected brain metastases, the delivery of intra-operative radiation does not appear to impact cortical activity or precipitate post-operative seizures. Further studies are needed to determine the long-term incidence of treatment associated changes if they exist.

Long-term priors influence visual perception through recruitment of long-range feedback

Perception results from the interplay of sensory input and prior knowledge. Despite behavioral evidence that long-term priors powerfully shape perception, the neural mechanisms underlying these interactions remain poorly understood. We obtained direct cortical recordings in neurosurgical patients as they viewed ambiguous images that elicit constant perceptual switching. We observe top-down influences from the temporal to occipital cortex, during the preferred percept that is congruent with the long-term prior. By contrast, stronger feedforward drive is observed during the non-preferred percept, consistent with a prediction error signal. A computational model based on hierarchical predictive coding and attractor networks reproduces all key experimental findings. These results suggest a pattern of large-scale information flow change underlying long-term priors’ influence on perception and provide constraints on theories about long-term priors’ influence on perception.

Intraoperative mapping and monitoring of the optic pathway

The identification of the visual pathway during surgery for tumors in visual areas is challenging. We present our experience in visual pathway mapping and monitoring, describing the role of direct mapping of the optic radiations and different techniques of VEPs monitoring, employing both Scalp Recording (SR) and the use of strip electrode positioned over the primary visual cortex for Direct Cortical Recording (DCR).

Within-subject reaction time variability: Role of cortical networks and underlying neurophysiological mechanisms

Variations in reaction time are a ubiquitous characteristic of human behavior. Extensively documented, they have been successfully modeled using parameters of the subject or the task, but the neural basis of behavioral reaction time that varies within the same subject and the same task has been minimally studied. In this paper, we investigate behavioral reaction time variance using 28 datasets of direct cortical recordings in humans who engaged in four different types of simple sensory-motor reaction time tasks. Using a previously described technique that can identify the onset of population-level cortical activity and a novel functional connectivity algorithm described herein, we show that the cumulative latency difference of population-level neural activity across the task-related cortical network can explain up to 41% of the trial-by-trial variance in reaction time. Furthermore, we show that reaction time variance may primarily be due to the latencies in specific brain regions and demonstrate that behavioral latency variance is accumulated across the whole task-related cortical network. Our results suggest that population-level neural activity monotonically increases prior to movement execution, and that trial-by-trial changes in that increase are, in part, accounted for by inhibitory activity indexed by low-frequency oscillations. This pre-movement neural activity explains 19% of the measured variance in neural latencies in our data. Thus, our study provides a mechanistic explanation for a sizable fraction of behavioral reaction time when the subject’s task is the same from trial to trial.

Intraoperative thalamocortical tract monitoring via direct cortical recordings during craniotomy

ObjectiveNeuromonitoring of primary motor regions allows preservation of motor strength and is frequently employed during cranial procedures. Less is known about protection of sensory function and ability to modulate movements, both of which rely on integrity of thalamocortical afferents (TCA) to fronto-parietal regions. We describe our experience with TCA monitoring and their cortical relays during brain tumor surgery. MethodologyTo study its feasibility and usefulness, continuous somatosensory evoked potentials (SSEP) recording via a subdural electrode was attempted in 32 consecutive patients. ResultsMedian and posterior tibial SSEP were successfully monitored in 31 and 17 patients respectively. SSEP improved lesion localization and prevented unnecessary cortical stimulation in 9 and 16 cases respectively. A threshold of ≥30% SSEP amplitude decrease influenced management in 10 patients while a decrement of ≥50 % had a sensitivity of 0.89 and specificity of 1 in detecting worsening of sensory function. Simultaneous motor evoked potentials (MEP) and SSEP monitoring were performed in 10 cases, 9 of which showed short-lived fluctuations of the former. ConclusionDirect cortical SSEP monitoring is feasible, informs management and predicts outcome. SignificanceEarly intervention prevents sensory deficit. Concomitant MEP fluctuations may reflect modulation of motor activity by TCA.

Posterior cortex seizures – pediatric challenges

Posterior cortex seizures have a complex semiologic presentation that is especially challenging in the pediatric population. Therefore, using clinical presentation in localizing ictal involvement is not sufficient in children, thus making this type of epilepsy quite under-recognized. As most of the ictal symptoms are subjective and could well be overshadowed by symptoms arising from adjacent cortices, primarily temporal and central ones, it is necessary not to overlook this large source of pharmacoresistant epilepsies. The parietal lobe as part of an extensive synaptic network is a great imitator, thus quite often producing inaccurate localization readings on scalp electroencephalography (EEG) due to very scattered interictal discharges and uninformative ictal recordings. Using direct cortical recordings in delineating the epileptogenic zone is helpful in some cases but even highly experienced epileptologists may erroneously interpret some features as arising from other localizations, especially the frontal lobe. Epilepsy surgery from the posterior quadrant is still quite rare and relatively unsuccessful, especially in non-lesional epilepsies due to elaborate mechanisms of connectivity, misleading semiology, and non-localizing EEG recordings, possibly due to insufficiency of parietal cortex synchronicity. Applying the aforementioned to the pediatric age makes it perhaps the most difficult challenge for a pediatric epileptologist.

How the Human Brain Sleeps: Direct Cortical Recordings of Normal Brain Activity.

Regional variations in oscillatory activity during human sleep remain unknown. Using the unique ability of intracranial electroencephalography to study in situ brain physiology, this study assesses regional variations of electroencephalographic sleep activity and creates the first atlas of human sleep using recordings from the first sleep cycle. Intracerebral electroencephalographic recordings with channels displaying physiological activity from nonlesional tissue were selected from 91 patients of 3 tertiary epilepsy centers. Sections during non-rapid eye movement sleep (stages N2 and N3) and rapid eye movement sleep (stage R) were selected from the first sleep cycle for oscillatory and nonoscillatory signal analysis. Results of 1,468 channels were grouped into 38 regions covering all cortical areas. We found regional differences in the distribution of sleep transients and spectral content during all sleep stages. There was a caudorostral gradient, with more slow frequencies and fewer spindles in temporoparieto-occipital than in frontal cortex. Moreover, deep-seated structures showed spectral peaks differing from the baseline electroencephalogram. The regions with >60% of channels presenting significant rhythmic activity were either mesial or temporal basal structures that contribute minimally to the scalp electroencephalogram. Finally, during deeper sleep stages, electroencephalographic analysis revealed a more homogeneous spatial distribution, with increased coupling between high and low frequencies. This study provides a better understanding of the regional variability of sleep, and establishes a baseline for human sleep in all cortical regions during the first sleep cycle. Furthermore, the open-access atlas will be a unique resource for research (https://mni-open-ieegatlas. mcgill.ca). ANN NEUROL 2020;87:289-301.

BLAST: A short computerized test to measure the ability to stay on task. Normative behavioral data and detailed cortical dynamics.

This article provides an exhaustive description of a new short computerized test to assess on a second-to-second basis the ability of individuals to « stay on task », that is, to apply selectively and repeatedly task-relevant cognitive processes. The task (Bron/Lyon Attention Stability Test, or BLAST) lasts around 1 min, and measures repeatedly the time to find a target letter in a two-by-two letter array, with an update of all letters every new trial across thirty trials. Several innovative psychometric measures of attention stability are proposed based on the instantaneous fluctuations of reaction times throughout the task, and normative data stratified over a wide range of age are provided by a large (>6000) dataset of participants aged 8 to 70. We also detail the large-scale brain dynamics supporting the task from an in-depth study of 32 participants with direct electrophysiological cortical recordings (intracranial EEG) to prove that BLAST involves critically large-scale executive attention networks, with a marked activation of the dorsal attention network and a deactivation of the default-mode network. Accordingly, we show that BLAST performance correlates with scores established by ADHD-questionnaires.

Semantic and perceptual priming activate partially overlapping brain networks as revealed by direct cortical recordings in humans

Facilitation of object processing in the brain due to a related context (priming) can be influenced by both semantic connections and perceptual similarity. It is thus important to discern these two when evaluating the spatio-temporal dynamics of primed object processing. The repetition-priming paradigm frequently used to study perceptual priming is, however, unable to differentiate between the mentioned priming effects, possibly leading to confounded results. In the current study, we recorded brain signals from the scalp and cerebral convexity of nine patients with refractory epilepsy in response to related and unrelated image-pairs, all of which shared perceptual features while only related ones had a semantic connection. While previous studies employing a repetition-priming paradigm observed largely overlapping networks between semantic and perceptual priming effects, our results suggest that this overlap is only partial (both temporally and spatially). These findings stress the importance of controlling for perceptual features when studying semantic priming.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.SIGNIFICANCE STATEMENT Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.

Direct Cortical Recordings Suggest Temporal Order of Task-Evoked Responses in Human Dorsal Attention and Default Networks.

The past decade has seen a large number of neuroimaging studies focused on the anticorrelated functional relationship between the default mode network (DMN) and the dorsal attention network (DAN). Due principally to the low temporal resolution of functional neuroimaging modalities, the fast-neuronal dynamics across these networks remain poorly understood. Here we report novel human intracranial electrophysiology data from six neurosurgical patients (four males) with simultaneous coverage of well characterized nodes of the DMN and DAN. Subjects performed an arithmetic processing task, shown previously to evoke reliable deactivations (below baseline) in the DMN, and activations in the DAN. In this cohort, we show that DMN deactivations lag DAN activations by approximately 200 ms. Our findings suggest a clear temporal order of processing across the two networks during the current task and place the DMN further than the DAN in a plausible information-processing hierarchy.SIGNIFICANCE STATEMENT The human brain contains an intrinsic and strictly organized network architecture. Our understanding of the interplay across association networks has relied primarily on the slow fluctuations of the hemodynamic response, and as such it has lacked essential evidence regarding the temporal dynamics of activity across these networks. The current study presents evidence from high spatiotemporal methods showing that well studied areas of the default mode network display delayed task-induced activity relative to divergent responses in dorsal attention network nodes. This finding provides direct and critical evidence regarding the temporal chronology of neuronal events across opposing brain networks.

Differential Representation of Articulatory Gestures and Phonemes in Precentral and Inferior Frontal Gyri.

Speech is a critical form of human communication and is central to our daily lives. Yet, despite decades of study, an understanding of the fundamental neural control of speech production remains incomplete. Current theories model speech production as a hierarchy from sentences and phrases down to words, syllables, speech sounds (phonemes), and the actions of vocal tract articulators used to produce speech sounds (articulatory gestures). Here, we investigate the cortical representation of articulatory gestures and phonemes in ventral precentral and inferior frontal gyri in men and women. Our results indicate that ventral precentral cortex represents gestures to a greater extent than phonemes, while inferior frontal cortex represents both gestures and phonemes. These findings suggest that speech production shares a common cortical representation with that of other types of movement, such as arm and hand movements. This has important implications both for our understanding of speech production and for the design of brain-machine interfaces to restore communication to people who cannot speak.SIGNIFICANCE STATEMENT Despite being studied for decades, the production of speech by the brain is not fully understood. In particular, the most elemental parts of speech, speech sounds (phonemes) and the movements of vocal tract articulators used to produce these sounds (articulatory gestures), have both been hypothesized to be encoded in motor cortex. Using direct cortical recordings, we found evidence that primary motor and premotor cortices represent gestures to a greater extent than phonemes. Inferior frontal cortex (part of Broca's area) appears to represent both gestures and phonemes. These findings suggest that speech production shares a similar cortical organizational structure with the movement of other body parts.

Encoding of Articulatory Kinematic Trajectories in Human Speech Sensorimotor Cortex

When speaking, we dynamically coordinate movements of our jaw, tongue, lips, and larynx. To investigate the neural mechanisms underlying articulation, we used direct cortical recordings from human sensorimotor cortex while participants spoke natural sentences that included sounds spanning the entire English phonetic inventory. We used deep neural networks to infer speakers' articulator movements from produced speech acoustics. Individual electrodes encoded a diversity of articulatory kinematic trajectories (AKTs), each revealing coordinated articulator movements toward specific vocal tract shapes. AKTs captured a wide range of movement types, yet they could be differentiated by the place of vocal tract constriction. Additionally, AKTs manifested out-and-back trajectories with harmonic oscillator dynamics. While AKTs were functionally stereotyped across different sentences, context-dependent encoding of preceding and following movements during production of the same phoneme demonstrated the cortical representation of coarticulation. Articulatory movements encoded in sensorimotor cortex give rise to the complex kinematics underlying continuous speech production. VIDEO ABSTRACT.

Closed-loop intracranial stimulation alters movement timing in humans

BackgroundA prime objective driving the recent development of human neural prosthetics is to stimulate neural circuits in a manner time-locked to ongoing brain activity. The human supplementary motor area (SMA) is a particularly useful target for this objective because it displays characteristic neural activity just prior to voluntary movement. ObjectiveHere, we tested a method that detected activity in the human SMA related to impending movement and then delivered cortical stimulation with intracranial electrodes to influence the timing of movement. MethodsWe conducted experiments in nine patients with electrodes implanted for epilepsy localization: five patients with SMA electrodes and four control patients with electrodes outside the SMA. In the first experiment, electrocorticographic (ECoG) recordings were used to localize the electrode of interest during a task involving bimanual finger movements. In the second experiment, a real-time sense-and-stimulate (SAS) system was implemented that delivered an electrical stimulus when pre-movement gamma power exceeded a threshold. ResultsStimulation based on real-time detection of this supra-threshold activity resulted in significant slowing of motor behavior in all of the cases where stimulation was carried out in the SMA patients but in none of the patients where stimulation was performed at the control site. ConclusionsThe neurophysiological correlates of impending movement can be used to trigger a closed loop stimulation device and influence ongoing motor behavior in a manner imperceptible to the subject. This is the first report of a human closed loop system designed to alter movement using direct cortical recordings and direct stimulation.

Persistent neuronal activity in human prefrontal cortex links perception and action.

How do humans flexibly respond to changing environmental demands on a sub-second temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behavior, yet the core mechanisms that translate sensory information into behavior remain undefined. Utilizing direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity, indexed by the broadband gamma signal, while sixteen participants performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centered in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behavior.