Thalamo-cortical evoked potentials during stimulation of the dentato-rubro-thalamic tract demonstrate synaptic filtering.

Essential tremor DBS targeting the ventral intermediate nucleus (Vim) of the thalamus and its input, the dentato-rubro-thalamic tract (DRTt), has proven to be an effective treatment strategy. We examined thalamo-cortical evoked potentials (TCEPs) and cortical dynamics during stimulation of the DRTt. We recorded TCEPs in primary motor cortex during clinical and supra-clinical stimulation of the DRTt in ten essential tremor patients. Stimulation was varied over pulse amplitude (2-10 â€‹mA) and pulse width (30-250 â€‹µs) to allow for strength-duration testing. Testing at clinical levels (3 â€‹mA, 60 â€‹µs) for stimulation frequencies of 1-160 â€‹Hz was performed and phase amplitude coupling (PAC) of beta phase and gamma power was calculated. Primary motor cortex TCEPs displayed two responses: early and all-or-none (<20 â€‹ms) or delayed and charge-dependent (>50 â€‹ms). Strength-duration curve approximation indicates that the chronaxie of the neural elements related to the TCEPs is <200 â€‹µs. At the range of clinical stimulation (amplitude 2-5 â€‹mA, pulse width 30-60 â€‹µs), TCEPs were not noted over primary motor cortex. Decreased pathophysiological phase-amplitude coupling was seen above 70 â€‹Hz stimulation without changes in power spectra and below the threshold of TCEPs. Our findings demonstrate that DRTt stimulation within normal clinical bounds does not excite fibers directly connected with primary motor cortex but that supra-clinical stimulation can excite a direct axonal tract. Both clinical efficacy and phase-amplitude coupling were frequency-dependent, favoring a synaptic filtering model as a possible mechanism of action.

The spatiotemporal dynamics of semantic integration in the human brain.

Language depends critically on the integration of lexical information across multiple words to derive semantic concepts. Limitations of spatiotemporal resolution have previously rendered it difficult to isolate processes involved in semantic integration. We utilized intracranial recordings in epilepsy patients (n = 58) who read written word definitions. Descriptions were either referential or non-referential to a common object. Semantically referential sentences enabled high frequency broadband gamma activation (70-150 Hz) of the inferior frontal sulcus (IFS), medial parietal cortex, orbitofrontal cortex (OFC) and medial temporal lobe in the left, language-dominant hemisphere. IFS, OFC and posterior middle temporal gyrus activity was modulated by the semantic coherence of non-referential sentences, exposing semantic effects that were independent of task-based referential status. Components of this network, alongside posterior superior temporal sulcus, were engaged for referential sentences that did not clearly reduce the lexical search space by the final word. These results indicate the existence of complementary cortical mosaics for semantic integration in posterior temporal and inferior frontal cortex.

A cost analysis of MR-guided laser interstitial thermal therapy for adult refractory epilepsy.

OBJECTIVE: MR-guided laser interstitial thermal therapy (LITT) is used increasingly for refractory epilepsy. The goal of this investigation is to directly compare cost and short-term adverse outcomes for adult refractory epilepsy treated with temporal lobectomy and LITT, as well as to identify risk factors for increased costs and adverse outcomes. METHODS: The National Inpatient Sample (NIS) was queried for patients who received LITT between 2012 and 2019. Patients with adult refractory epilepsy were identified. Multivariable mixed-effects models were used to analyze predictors of cost, length of stay (LOS), and complications. RESULTS: LITT was associated with reduced LOS and overall cost relative to temporal lobectomy, with a statistical trend toward lower incidence of postoperative complications. High-volume surgical epilepsy centers had lower LOS overall. Longer LOS was a significant driver of increased cost for LITT, and higher comorbidity was associated with non-routine discharge. SIGNIFICANCE: LITT is an affordable alternative to temporal lobectomy for adult refractory epilepsy with an insignificant reduction in inpatient complications. Patients may benefit from expanded access to this treatment modality for both its reduced LOS and lower cost.

Critical role of the ventral temporal lobe in naming.

OBJECTIVE: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia. METHODS: We performed a multivariate voxel-based lesion-symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface-based mixed-effects multilevel analysis to estimate group-level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and integrated these results with lesion-deficit findings. RESULTS: We observed that ventral temporal regions, centered around the middle fusiform gyrus, were significantly associated with a decline in naming. Furthermore, we found that the ventral aspect of temporal lobectomies was linearly correlated to a decline in naming, with a clinically significant decline occurring once the resection extended 6 cm from the anterior tip of the temporal lobe on the ventral surface. On electrocorticography, the majority of these cortical regions were functionally active following visual processing. These loci coincide with the sites of susceptibility artifacts during echoplanar imaging, which may explain why this region has been previously underappreciated as the locus responsible for postoperative naming deficits. SIGNIFICANCE: Taken together, these data highlight the crucial contribution of the ventral temporal cortex in naming and its important role in the pathophysiology of anomia following temporal lobe resections. As such, surgical strategies should attempt to preserve this region to mitigate postoperative language deficits.

Event-related phase synchronization propagates rapidly across human ventral visual cortex.

Visual inputs to early visual cortex integrate with semantic, linguistic and memory inputs in higher visual cortex, in a manner that is rapid and accurate, and enables complex computations such as face recognition and word reading. This implies the existence of fundamental organizational principles that enable such efficiency. To elaborate on this, we performed intracranial recordings in 82 individuals while they performed tasks of varying visual and cognitive complexity. We discovered that visual inputs induce highly organized posterior-to-anterior propagating patterns of phase modulation across the ventral occipitotemporal cortex. At individual electrodes there was a stereotyped temporal pattern of phase progression following both stimulus onset and offset, consistent across trials and tasks. The phase of low frequency activity in anterior regions was predicted by the prior phase in posterior cortical regions. This spatiotemporal propagation of phase likely serves as a feed-forward organizational influence enabling the integration of information across the ventral visual stream. This phase modulation manifests as the early components of the event related potential; one of the most commonly used measures in human electrophysiology. These findings illuminate fundamental organizational principles of the higher order visual system that enable the rapid recognition and characterization of a variety of inputs.

Dataset of human intracranial recordings during famous landmark identification.

For most people, recalling information about familiar items in a visual scene is an effortless task, but it is one that depends on coordinated interactions of multiple, distributed neural components. We leveraged the high spatiotemporal resolution of direct intracranial recordings to better delineate the network dynamics underpinning visual scene recognition. We present a dataset of recordings from a large cohort of humans while they identified images of famous landmarks (50 individuals, 52 recording sessions, 6,775 electrodes, 6,541 trials). This dataset contains local field potential recordings derived from subdural and penetrating electrodes covering broad areas of cortex across both hemispheres. We provide this pre-processed data with behavioural metrics (correct/incorrect, response times) and electrode localisation in a population-normalised cortical surface space. This rich dataset will allow further investigation into the spatiotemporal progression of multiple neural processes underlying visual processing, scene recognition and cued memory recall.

NetDI: Methodology Elucidating the Role of Power and Dynamical Brain Network Features That Underpin Word Production.

Canonical language models describe eloquent function as the product of a series of cognitive processes, typically characterized by the independent activation profiles of focal brain regions. In contrast, more recent work has suggested that the interactions between these regions, the cortical networks of language, are critical for understanding speech production. We investigated the cortical basis of picture naming (PN) with human intracranial electrocorticography (ECoG) recordings and direct cortical stimulation (DCS), adjudicating between two competing hypotheses: are task-specific cognitive functions discretely computed within well-localized brain regions or rather by distributed networks? The time resolution of ECoG allows direct comparison of intraregional activation measures [high gamma (h γ ) power] with graph theoretic measures of interregional dynamics. We developed an analysis framework, network dynamics using directed information (NetDI), using information and graph theoretic tools to reveal spatiotemporal dynamics at multiple scales: coarse, intermediate, and fine. Our analysis found novel relationships between the power profiles and network measures during the task. Furthermore, validation using DCS indicates that such network parameters combined with hγ power are more predictive than hγ power alone, for identifying critical language regions in the brain. NetDI reveals a high-dimensional space of network dynamics supporting cortical language function, and to account for disruptions to language function observed after neurosurgical resection, traumatic injury, and degenerative disease.

Spatiotemporal dynamics of orthographic and lexical processing in the ventral visual pathway.

Reading is a rapid, distributed process that engages multiple components of the ventral visual stream. To understand the neural constituents and their interactions that allow us to identify written words, we performed direct intra-cranial recordings in a large cohort of humans. This allowed us to isolate the spatiotemporal dynamics of visual word recognition across the entire left ventral occipitotemporal cortex. We found that mid-fusiform cortex is the first brain region sensitive to lexicality, preceding the traditional visual word form area. The magnitude and duration of its activation are driven by the statistics of natural language. Information regarding lexicality and word frequency propagates posteriorly from this region to visual word form regions and to earlier visual cortex, which, while active earlier, show sensitivity to words later. Further, direct electrical stimulation of this region results in reading arrest, further illustrating its crucial role in reading. This unique sensitivity of mid-fusiform cortex to sub-lexical and lexical characteristics points to its central role as the orthographic lexicon-the long-term memory representations of visual word forms.

Category Selectivity for Face and Scene Recognition in Human Medial Parietal Cortex.

The rapid recognition and memory of faces and scenes implies the engagement of category-specific computational hubs in the ventral visual stream with the distributed cortical memory network. To better understand how recognition and identification occur in humans, we performed direct intracranial recordings, in a large cohort of patients (n = 50), from the medial parietal cortex (MPC) and the medial temporal lobe (MTL), structures known to be engaged during face and scene identification. We discovered that the MPC is topologically tuned to face and scene recognition, with clusters in MPC performing scene recognition bilaterally and face recognition in right subparietal sulcus. The MTL displayed a selectivity gradient with anterior, entorhinal cortex showing face selectivity and posterior parahippocampal regions showing scene selectivity. In both MPC and MTL, stimulus-specific identifiable exemplars led to greater activity in these cortical patches. These two regions work in concert for recognition of faces and scenes. Feature selectivity and identity-sensitive activity in the two regions was coincident, and they exhibited theta-phase locking during face and scene recognition. These findings together provide clear evidence for a specific role of subregions in the MPC for the recognition of unique entities.

Uncovering the functional anatomy of the human insula during speech.

The contribution of insular cortex to speech production remains unclear and controversial given diverse findings from functional neuroimaging and lesional data. To create a precise spatiotemporal map of insular activity, we performed a series of experiments: single-word articulations of varying complexity, non-speech orofacial movements and speech listening, in a cohort of 27 patients implanted with penetrating intracranial electrodes. The posterior insula was robustly active bilaterally, but after the onset of articulation, during listening to speech and during production of non-speech mouth movements. Preceding articulation there was very sparse activity, localized primarily to the frontal operculum rather than the insula. Posterior insular was active coincident with superior temporal gyrus but was more active for self-generated speech than external speech, the opposite of the superior temporal gyrus. These findings support the conclusion that the insula does not serve pre-articulatory preparatory roles.

Dynamic Brain Interactions during Picture Naming.

Brain computations involve multiple processes by which sensory information is encoded and transformed to drive behavior. These computations are thought to be mediated by dynamic interactions between populations of neurons. Here, we demonstrate that human brains exhibit a reliable sequence of neural interactions during speech production. We use an autoregressive Hidden Markov Model (ARHMM) to identify dynamical network states exhibited by electrocorticographic signals recorded from human neurosurgical patients. Our method resolves dynamic latent network states on a trial-by-trial basis. We characterize individual network states according to the patterns of directional information flow between cortical regions of interest. These network states occur consistently and in a specific, interpretable sequence across trials and subjects: the data support the hypothesis of a fixed-length visual processing state, followed by a variable-length language state, and then by a terminal articulation state. This empirical evidence validates classical psycholinguistic theories that have posited such intermediate states during speaking. It further reveals these state dynamics are not localized to one brain area or one sequence of areas, but are instead a network phenomenon.

A lexical semantic hub for heteromodal naming in middle fusiform gyrus.

Semantic memory underpins our understanding of objects, people, places, and ideas. Anomia, a disruption of semantic memory access, is the most common residual language disturbance and is seen in dementia and following injury to temporal cortex. While such anomia has been well characterized by lesion symptom mapping studies, its pathophysiology is not well understood. We hypothesize that inputs to the semantic memory system engage a specific heteromodal network hub that integrates lexical retrieval with the appropriate semantic content. Such a network hub has been proposed by others, but has thus far eluded precise spatiotemporal delineation. This limitation in our understanding of semantic memory has impeded progress in the treatment of anomia. We evaluated the cortical structure and dynamics of the lexical semantic network in driving speech production in a large cohort of patients with epilepsy using electrocorticography (n = 64), functional MRI (n = 36), and direct cortical stimulation (n = 30) during two generative language processes that rely on semantic knowledge: visual picture naming and auditory naming to definition. Each task also featured a non-semantic control condition: scrambled pictures and reversed speech, respectively. These large-scale data of the left, language-dominant hemisphere uniquely enable convergent, high-resolution analyses of neural mechanisms characterized by rapid, transient dynamics with strong interactions between distributed cortical substrates. We observed three stages of activity during both visual picture naming and auditory naming to definition that were serially organized: sensory processing, lexical semantic processing, and articulation. Critically, the second stage was absent in both the visual and auditory control conditions. Group activity maps from both electrocorticography and functional MRI identified heteromodal responses in middle fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus; furthermore, the spectrotemporal profiles of these three regions revealed coincident activity preceding articulation. Only in the middle fusiform gyrus did direct cortical stimulation disrupt both naming tasks while still preserving the ability to repeat sentences. These convergent data strongly support a model in which a distinct neuroanatomical substrate in middle fusiform gyrus provides access to object semantic information. This under-appreciated locus of semantic processing is at risk in resections for temporal lobe epilepsy as well as in trauma and strokes that affect the inferior temporal cortex-it may explain the range of anomic states seen in these conditions. Further characterization of brain network behaviour engaging this region in both healthy and diseased states will expand our understanding of semantic memory and further development of therapies directed at anomia.

Development of grouped icEEG for the study of cognitive processing.

Invasive intracranial EEG (icEEG) offers a unique opportunity to study human cognitive networks at an unmatched spatiotemporal resolution. To date, the contributions of icEEG have been limited to the individual-level analyses or cohorts whose data are not integrated in any way. Here we discuss how grouped approaches to icEEG overcome challenges related to sparse-sampling, correct for individual variations in response and provide statistically valid models of brain activity in a population. By the generation of whole-brain activity maps, grouped icEEG enables the study of intra and interregional dynamics between distributed cortical substrates exhibiting task-dependent activity. In this fashion, grouped icEEG analyses can provide significant advances in understanding the mechanisms by which cortical networks give rise to cognitive functions.

Self-contained diffuse optical imaging system for real-time detection and localization of vascular occlusions.

Free flap surgery is a procedure where healthy tissue is transferred from a donor site to a recipient site of the body to fill a defect without maintaining the original blood supply to the flap. The anastomosis of the vascular network of the flap to the blood vessels adjacent to the recipient site has associated risks of arterial and/or venous occlusions that must be promptly detected to avoid temporary or permanent tissue damage. In this work, we present a skin-contact diffusion optical imaging (DOI) system able to continuously provide a three-dimensional representation of the flap oxygenation to promptly detect vascular occlusions potentially occurring in the flap. Multiple near-infrared LEDs and photodetectors were embedded into a self-contained optical sensor for prolonged monitoring of concentration changes of oxygenated (HbO) and deoxygenated hemoglobin (HbR) at multiple locations and depths. A time-efficient algorithm mapped measured oxygenation changes in a three-dimensional volume to allow surgeons and clinical personnel to detect and localize abnormal blood perfusion changes during or after surgery, in time for corrective intervention. The image reconstruction algorithm was validated using computerized flap models in which oxygenation was synthetically altered, whereas the optical system was preliminarily tested on a healthy forearm simulating a flap undergoing arterial and venous occlusions, proving the feasibility of implementing DOI in the form of a wearable patch for prolonged perfusion monitoring.