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Reading a sentence entails integrating the meanings of individual words to infer more complex, higher-order meaning. This highly rapid and complex human behavior is known to engage the inferior frontal gyrus (IFG) and middle temporal gyrus (MTG) in the language-dominant hemisphere, yet whether there are distinct contributions of these regions to sentence reading is still unclear. To probe these neural spatiotemporal dynamics, we used direct intracranial recordings to measure neural activity while reading sentences, meaning-deficient Jabberwocky sentences, and lists of words or pseudowords. We isolated two functionally and spatiotemporally distinct frontotemporal networks, each sensitive to distinct aspects of word and sentence composition. The first distributed network engages the IFG and MTG, with IFG activity preceding MTG. Activity in this network ramps up over the duration of a sentence and is reduced or absent during Jabberwocky and word lists, implying its role in the derivation of sentence-level meaning. The second network engages the superior temporal gyrus and the IFG, with temporal responses leading those in frontal lobe, and shows greater activation for each word in a list than those in sentences, suggesting that sentential context enables greater efficiency in the lexical and/or phonological processing of individual words. These adjacent, yet spatiotemporally dissociable neural mechanisms for word- and sentence-level processes shed light on the richly layered semantic networks that enable us to fluently read. These results imply distributed, dynamic computation across the frontotemporal language network rather than a clear dichotomy between the contributions of frontal and temporal structures.

Speech production is known to engage a distributed network. The brain regions responsible for the initiation of articulation are unclear, and they would be expected to coordinate a distributed network. Using direct intracranial recordings in a large cohort, during stereotyped speech production to eliminate confounds of phonological and semantic complexity, we performed a comprehensive analysis of cortical sites engaged in speech initiation. We found that the supplementary motor area (SMA) was the earliest speech motor region to be active prior to speech onset and was active almost exclusively prior to articulation. Broadband gamma activity in the SMA was predictive of the response time of word production, predicting response time from 250 ms after stimulus onset. Neural activity in SMA began at a highly predictable time after stimulus onset and extended until speech onset. SMA activityoffsetcoincided with ventral premotor cortex and primary motor activityonset. This suggests that the SMA may coordinate the concerted activation of motor execution cortex. Our results support the idea that SMA is a key node in the speech initiation network.Significance statementProducing speech requires coordination across multiple brain regions. One cortical region - the supplementary motor area (SMA) - has long been a candidate region to coordinate across other regions to initiate speech production. In this study, we used human intracranial recordings from patients with epilepsy to investigate the role of the SMA in initiating speech. In a picture-naming task, subjects repeated the word “scrambled” scores of times; using this condition to eliminate any linguistic confounds, we found that the SMA was consistently one of the earliest regions to activate during word production. We also uncovered the SMA’s temporally precise tuning to speech onset at the single-trial level.

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.

Language depends critically on the integration of lexical information to derive semantic concepts. The neurobiology of this fundamental aspect of human cognition remains mostly unknown. Limitations of spatiotemporal resolution have previously rendered it difficult to disentangle processes involved in semantic integration from independent computations such as tracking word meaning and establishing referents. We utilized intracranial recordings (n = 58) during the presentation of orthographic descriptions that were either referential or non-referential to a common object. Referential contexts enabled high frequency broadband gamma activation (70–150 Hz) of a distributed network including the inferior frontal sulcus (IFS), medial parietal cortex (MPC) and medial temporal lobe (MTL) in the left, language-dominant hemisphere. Components of this network (IFS, MPC), alongside posterior superior temporal sulcus, showed greater engagement for trials that did not progressively isolate a limited set of referents, relative to trials that did. IFS and posterior middle temporal gyrus activity was modulated by semantic coherence, regardless of whether the sentence picked out a common object. Centered around IFS and spreading out dorsally towards middle frontal gyrus and ventrally towards anterior/posterior inferior frontal gyrus, we uncovered a cortical mosaic of functional specialization for reference, coherence and semantic narrowing. Early processing windows implicated IFS in all aspects of semantics, and in later windows sub-portions of IFS exposed a clearer functional tessellation with some remaining overlap. This work unveils how lateral fronto-temporal regions make distinctly rich semantic contributions and are involved jointly in semantic integration and conflict resolution, depending on the sub-region and processing stage.

Spoken language, both perception and production, is thought to be facilitated by an ensemble of predictive mechanisms. We obtain intracranial recordings in 37 patients using depth probes implanted along the anteroposterior extent of the supratemporal plane during rhythm listening, speech perception, and speech production. These reveal two predictive mechanisms in early auditory cortex with distinct anatomical and functional characteristics. The first, localized to bilateral Heschl’s gyri and indexed by low-frequency phase, predicts the timing of acoustic events. The second, localized to planum temporale only in language-dominant cortex and indexed by high-gamma power, shows a transient response to acoustic stimuli that is uniquely suppressed during speech production. Chronometric stimulation of Heschl’s gyrus selectively disrupts speech perception, while stimulation of planum temporale selectively disrupts speech production. This work illuminates the fundamental acoustic infrastructure—both architecture and function—for spoken language, grounding cognitive models of speech perception and production in human neurobiology., The human brain fluently parses continuous speech during perception and production. Using direct brain recordings coupled with stimulation, the authors identify separable substrates underlying two distinct predictive mechanisms of “when” in Heschl’s gyrus and “what” in planum temporale.

The ability to comprehend phrases is an essential integrative property of the brain. Here, we evaluate the neural processes that enable the transition from single-word processing to a minimal compositional scheme. Previous research has reported conflicting timing effects of composition, and disagreement persists with respect to inferior frontal and posterior temporal contributions. To address these issues, 19 patients (10 male, 9 female) implanted with penetrating depth or surface subdural intracranial electrodes, heard auditory recordings of adjective-noun, pseudoword-noun, and adjective-pseudoword phrases and judged whether the phrase matched a picture. Stimulus-dependent alterations in broadband gamma activity, low-frequency power, and phase-locking values across the language-dominant left hemisphere were derived. This revealed a mosaic located on the lower bank of the posterior superior temporal sulcus (pSTS), in which closely neighboring cortical sites displayed exclusive sensitivity to either lexicality or phrase structure, but not both. Distinct timings were found for effects of phrase composition (210–300 ms) and pseudoword processing (∼300–700 ms), and these were localized to neighboring electrodes in pSTS. The pars triangularis and temporal pole encoded anticipation of composition in broadband low frequencies, and both regions exhibited greater functional connectivity with pSTS during phrase composition. Our results suggest that the pSTS is a highly specialized region composed of sparsely interwoven heterogeneous constituents that encodes both lower and higher level linguistic features. This hub in pSTS for minimal phrase processing may form the neural basis for the human-specific computational capacity for forming hierarchically organized linguistic structures.SIGNIFICANCE STATEMENTLinguists have claimed that the integration of multiple words into a phrase demands a computational procedure distinct from single-word processing. Here, we provide intracranial recordings from a large patient cohort, with high spatiotemporal resolution, to track the cortical dynamics of phrase composition. Epileptic patients volunteered to participate in a task in which they listened to phrases (red boat), word-pseudoword or pseudoword-word pairs (e.g., red fulg). At the onset of the second word in phrases, greater broadband high gamma activity was found in posterior superior temporal sulcus in electrodes that exclusively indexed phrasal meaning and not lexical meaning. These results provide direct, high-resolution signatures of minimal phrase composition in humans, a potentially species-specific computational capacity.

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans (26 male, 20 female) as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband γ activity varies with multiple word attributes critical to reading speed: lexicality, word frequency, and orthographic neighborhood. We found that lexicality is encoded earliest in mid-fusiform (mFus) cortex, and precentral sulcus, and is represented reliably enough to allow single-trial lexicality decoding. Word frequency is first represented in mFus and later in the inferior frontal gyrus (IFG) and inferior parietal sulcus (IPS), while orthographic neighborhood sensitivity resides solely in IPS. We thus isolate the neural correlates of the distributed reading network involving mFus, IFG, IPS, precentral sulcus, and motor cortex and provide direct evidence for parallel processes via the lexical route from mFus to IFG, and the sublexical route from IPS and precentral sulcus to anterior IFG. SIGNIFICANCE STATEMENT Reading aloud depends on multiple complex cerebral computations: mapping from a written letter string on a page to a sequence of spoken sound representations. Here, we used direct intracranial recordings in a large cohort while they read aloud known and novel words, to track, across space and time, the progression of neural representations of behaviorally relevant factors that govern reading speed. We find, concordant with cognitive models of reading, that known and novel words are differentially processed through a lexical route, sensitive to frequency of occurrence of known words in natural language, and a sublexical route, performing letter-by-letter construction of novel words.

Deficits in word retrieval are a hallmark of a variety of neurological illnesses spanning from dementia to traumatic injuries. The role of the dominant temporal lobe in fluent naming has been characterized by lesional analyses, functional imaging, and intracranial recordings, but limitations of each of these measures preclude a clear assessment of which specific constituent of the temporal lobe is critical for naming. We studied a large cohort of patients undergoing surgical resections or laser ablations of the dominant temporal lobe for medically intractable epilepsy (n=95). These techniques are exceedingly effective for seizure control but often result in language declines, particularly in confrontation naming, which can be socio-economically disabling. We used a multivariate voxel-based lesion symptom mapping analysis to localize brain regions significantly associated with visual object naming deficits. We observed that posterior inferior temporal regions, centered around the middle fusiform gyrus, were significantly associated with a decline in confrontation naming. Furthermore, we found that the posterior margin of anterior temporal lobectomies was linearly correlated to a decline in visual naming with a clinically significant decline occurring once the resection extended 6 cm from the anterior tip of the temporal lobe. We integrated these findings with electrocorticography during naming in a subset of this population and found that the majority of cortical regions whose resection was associated with a significant decline overlapped with regions that were functionally most active prior to articulation. Importantly, these loci coincide with the sites of susceptibility artifacts during echo-planar imaging, which explains why this region has not previously been implicated. Taken together, these data highlight the crucial contribution of the posterior ventral temporal cortex in lexical access and its important role in the pathophysiology of anomia following temporal lobe resections. Surgical strategies, including the use of laser ablation to target the medial temporal lobe as well as microsurgical approaches, should attempt to preserve this region to mitigate postoperative language deficits.

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.

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.

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband gamma activity varies with multiple word attributes critical to reading speed: lexicality, word frequency and orthographic neighborhood. We found that lexicality is encoded earliest in mid-fusiform (mFus) cortex and precentral sulcus, and is represented reliably enough to allow single-trial lexicality decoding. Word frequency is first represented in mFus and later in the inferior frontal gyrus (IFG) and inferior parietal sulcus (IPS), while orthographic neighborhood sensitivity resides solely in IPS. We thus isolate the neural correlates of the distributed reading network involving mFus, IFG, IPS, precentral sulcus and motor cortex and provide direct evidence for dual-route models of reading, with parallel processes via the lexical route from mFus to IFG, and the sub-lexical route from IPS and precentral sulcus to anterior IFG.

The ability to comprehend phrases is an essential integrative property of the brain. Here we evaluate the neural processes that enable the transition from single word processing to a minimal compositional scheme. Previous research has reported conflicting timing effects of composition, and disagreement persists with respect to inferior frontal and posterior temporal contributions. To address these issues, 19 patients (10 male, 19 female) implanted with penetrating depth or surface subdural intracranial electrodes heard auditory recordings of adjective-noun, pseudoword-noun and adjective-pseudoword phrases and judged whether the phrase matched a picture. Stimulus-dependent alterations in broadband gamma activity, low frequency power and phase-locking values across the language-dominant left hemisphere were derived. This revealed a mosaic located in the posterior superior temporal sulcus (pSTS), in which closely neighboring cortical sites displayed exclusive sensitivity to either lexicality or phrase structure, but not both. Distinct timings were found for effects of phrase composition (210–300 ms) and pseudoword processing (approximately 300–700 ms), and these were localized to neighboring electrodes in pSTS. The pars triangularis and temporal pole encode anticipation of composition in broadband low frequencies, and both regions exhibit greater functional connectivity with pSTS during phrase composition. Our results suggest that the pSTS is a highly specialized region comprised of sparsely interwoven heterogeneous constituents that encodes both lower and higher level linguistic features. This hub in pSTS for minimal phrase processing may form the neural basis for the human-specific computational capacity for forming hierarchically organized linguistic structures.SignificanceLinguists have claimed that the integration of multiple words into a phrase demands a computational procedure distinct from single word processing. Here, we provide intracranial recordings from a large patient cohort, with high spatiotemporal resolution, to track the cortical dynamics of phrase composition. Epileptic patients volunteered to participate in a task in which they listened to phrases (“red boat”), word-pseudoword or pseudoword-word pairs (e.g., “red fulg”). At the onset of the second word in phrases, greater broadband high gamma activity was found in posterior superior temporal sulcus in electrodes that exclusively indexed phrasal meaning, and not lexical meaning. These results provide direct, high-resolution signatures of minimal phrase composition in humans, a potentially species-specific computational capacity.

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.

OBJECTIVE Traditional stereo-electroencephalography (sEEG) entails the use of orthogonal trajectories guided by seizure semiology and arteriography. Advances in robotic stereotaxy and computerized neuronavigation have made oblique trajectories more feasible and easier to implement without formal arteriography. Such trajectories provide access to components of seizure networks not readily sampled using orthogonal trajectories. However, the dogma regarding the relative safety and predictability of orthogonal and azimuth-based trajectories persists, given the absence of data regarding the safety and efficacy of oblique sEEG trajectories. In this study, the authors evaluated the relative accuracy and efficacy of both orthogonal and oblique trajectories during robotic implantation of sEEG electrodes to sample seizure networks. METHODS The authors performed a retrospective analysis of 150 consecutive procedures in 134 patients, accounting for 2040 electrode implantations. Of these, 837 (41%) were implanted via oblique trajectories (defined as an entry angle > 30°). Accuracy was calculated by comparing the deviation of each electrode at the entry and the target point from the planned trajectory using postimplantation imaging. RESULTS The mean entry and target deviations were 1.57 mm and 1.89 mm for oblique trajectories compared with 1.38 mm and 1.69 mm for orthogonal trajectories, respectively. Entry point deviation was significantly associated with entry angle, but the impact of this relationship was negligible (−0.015-mm deviation per degree). Deviation at the target point was not significantly affected by the entry angle. No hemorrhagic or infectious complications were observed in the entire cohort, further suggesting that these differences were not meaningful in a clinical context. Of the patients who then underwent definitive procedures after sEEG, 69 patients had a minimum of 12 months of follow-up, of whom 58 (84%) achieved an Engel class I or II outcome during a median follow-up of 27 months. CONCLUSIONS The magnitude of stereotactic errors in this study falls squarely within the range reported in the sEEG literature, which primarily features orthogonal trajectories. The patient outcomes reported in this study suggest that seizure foci are well localized using oblique trajectories. Thus, the selective use of oblique trajectories in the authors’ cohort was associated with excellent safety and efficacy, with no patient incidents, and the findings support the use of oblique trajectories as an effective and safe means of investigating seizure networks.

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.

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.

ObjectiveTo qualify the incidence of and risk factors for visual field deficits (VFD) following laser interstitial thermal ablation (LITT) for mesial temporal lobe epilepsy (MTLE) and to relate this to anterior temporal lobectomy (ATL).MethodsFifty-seven patients underwent LITT of the amygdalo-hippocampal complex (AH) for MTLE. Masks of ablation volumes, laser probe trajectories, and visual radiations (VRs) from individual subject space were transformed into standardized space using nonlinear registration. Voxel-wise statistics were performed to model relationships between VFDs vs ablation volumes, laser trajectories, VRs, and AH asymmetry. A review of VFDs following ATLs was performed.ResultsThe incidence of VFD after LITT is much lower than after ATLs. A total of 37.5% of patients developed a VFD, with the probability of this being much higher after left (50%) vs right hemisphere LITT (10%) (Fisher test, p = 0.05). This laterality effect on VFDs is mirrored but underappreciated in ATL series. The most consistent LITT-VFD occurred in the superior vertical octant. Ablation of Meyer loop as well as the summed probability of VRs within laser trajectories correlated with VFDs (p < 0.05). Left and right hippocampi have significantly distinct orientations in axial and coronal planes, which may be one reason for the variation in VFD probability.ConclusionsLITT results in lower rates of and smaller VFDs—typically an octantanopsia. VRs are at greater risk during surgery for left than right MTLE. Anatomical asymmetries in hippocampal anatomy may explain the hemispheric differences in deficits, and should factor into trajectory planning and also into preoperative patient counseling. Overall the incidence and extent of visual deficits following LITT for MTLE is lower than the reported data following anterior temporal lobectomy. VF tractography incorporated into LITT planning may reduce the occurrence of VFDs.

Summary 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.

Spoken language is thought to be facilitated by an ensemble of predictive mechanisms, yet the neurobiology of prediction for both speech perception and production remains unknown. We used intracranial recordings (31 patients, 6580 electrodes) from depth probes implanted along the anteroposterior extent of the supratemporal plane during rhythm listening, speech perception, and speech production. This revealed a frequency-multiplexed encoding of sublexical features during entrainment and a traveling wave of high-frequency activity across Heschl’s gyrus. Critically, we isolated two predictive mechanisms in early auditory cortex with distinct anatomical and functional characteristics. The first mechanism, localized to bilateral Heschl’s gyrus and indexed by low-frequency phase, predicts the timing of acoustic events (“when”). The second mechanism, localized to planum temporale in the language-dominant hemisphere and indexed by gamma power, predicts the acoustic consequence of speech motor plans (“what”). This work grounds cognitive models of speech perception and production in human neurobiology, illuminating the fundamental acoustic infrastructure – both architecture and function – for spoken language.

Objectives Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique for focal epilepsy. A major appeal of LITT is that it may result in fewer cognitive deficits, especially when targeting dominant hemisphere mesial temporal lobe (MTL) epilepsy. To evaluate this, as well as to determine seizure outcomes following LITT, we evaluated the relationships between ablation volumes and surgical or cognitive outcomes in 43 consecutive patients undergoing LITT for MTL epilepsy. Methods All patients underwent unilateral LITT targeting mesial temporal structures. FreeSurfer software was used to derive cortical and subcortical segmentation of the brain (especially subregions of the MTL) using preoperative magnetic resonance imaging (MRI). Ablation volumes were outlined using a postablation T1-contrasted MRI. The percentages of the amygdala, hippocampus, and entorhinal cortex ablated were quantified objectively. The volumetric measures were regressed against changes in neuropsychological performance before and after surgery, RESULTS: A median of 73.7% of amygdala, 70.9% of hippocampus, and 28.3% of entorhinal cortex was ablated. Engel class I surgical outcome was obtained in 79.5% and 67.4% of the 43 patients at 6 and 20.3 months of follow-up, respectively. No significant differences in surgical outcomes were found across patient subgroups (hemispheric dominance, hippocampal sclerosis, or need for intracranial evaluation). Furthermore, no significant differences in volumes ablated were found between patients with Engel class IA vs Engel class II-IV outcomes. In patients undergoing LITT in the dominant hemisphere, a decline in verbal and narrative memory, but not in naming function was noted. Significance Seizure-free outcomes following LITT may be comparable in carefully selected patients with and without MTS, and these outcomes are comparable with outcomes following microsurgical resection. Failures may result from non-mesial components of the epileptogenic network that are not affected by LITT. Cognitive declines following MTL-LITT are modest, and principally affect memory processes.

Objective Laser interstitial thermal therapy has become increasingly popular for targeting epileptic foci in a minimally invasive fashion. Despite its use in >1000 patients, the long-term effects of photothermal injury on brain physiology remain poorly understood. Methods We prospectively followed clinical and radiographic courses of 13 patients undergoing laser ablation for focal epilepsy by the senior author (N.T.). Only patients with nonenhancing lesions and patients who had a delayed postoperative magnetic resonance imaging (MRI) scan with gadolinium administration approximately 6 months after ablation were considered. Volumetric estimates of the amount of enhancement immediately after ablation and on the delayed MRI scan were made. Results Median interval between surgery and delayed postoperative MRI scan was 6 months (range, 5–8 months). In 12 of 13 cases, persistent enhancement was seen, consistent with prolonged blood-brain barrier dysfunction. Enhancement, when present, was 9%–67% (mean 30%). There was no correlation between the time from surgery and the relative percentage of postoperative enhancement on MRI. The blood-brain barrier remained compromised to gadolinium contrast for up to 8 months after thermal therapy. There were no adverse events from surgical intervention; however, 1 patient developed delayed optic neuritis. Conclusions Prolonged incompetence of the blood-brain barrier produced by thermal ablation may provide a path for delivery of macromolecules into perilesional tissue, which could be exploited for therapeutic benefit, but rarely it may result in autoimmune central nervous system inflammatory conditions.