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.

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.

Optimally targeting the centromedian nucleus of the thalamus for generalized epilepsy: A meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) of the centromedian nucleus (CM) is an effective therapeutic option for select patients with generalized epilepsy. However, several studies suggest that success varies with active contact location within the CM and the exact target remains undefined. OBJECTIVE: To quantify the association between active contact location and outcomes across all published series of CM DBS. METHODS: A literature search using PRISMA criteria was performed to identify all studies that reported active contact locations PLUS outcomes following DBS of the CM for epilepsy. Patient, disease, treatment, and outcome data were extracted for statistical analysis. Active contact locations were analyzed on a common reference frame and weighted by percent seizure reduction at last follow-up. RESULTS: From 184 studies that were screened for review, 3 studies comprising 47 patients met criteria for inclusion and were analyzed. At time of surgery, mean duration of epilepsy was 18 years. Pooled rates of atonic, atypical absence, generalized tonic-clonic, myoclonic, and tonic epilepsies were 38%, 74%, 68%, 14%, and 60%, respectively. Indirect targeting was used in all these studies. After a mean follow-up duration of 2.3 years, 87% of patients were deemed to be responders with mean seizure reduction of 73% (95% CI: [64%-81%]). Optimal location of the active contact was found to be at the dorsal border of the CM. CONCLUSIONS: Success following DBS of the CM for epilepsy varies by active contact location, even within the CM. Our findings suggest that stimulation within the dorsal region of the CM improves outcomes. Additional studies are needed to further refine these findings.

Optimal targeting of the anterior nucleus of the thalamus for epilepsy: a meta-analysis.

OBJECTIVE: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has been shown to be an effective therapeutic option for select patients with limbic epilepsy. However, the optimal target and electrode position for this indication remains undefined. Therefore, the objective of this systematic review and meta-analysis is to quantify the association between active contact location and outcomes across all published series of ANT DBS. METHODS: A literature search using PRISMA criteria was performed to identify all studies that reported both active contact locations and outcomes of DBS in the ANT for epilepsy. Patient, disease, treatment, and outcome data were extracted for statistical analysis. Contact locations of responders (defined as ≥ 50% seizure reduction at last follow-up) versus nonresponders to DBS were analyzed on a common reference frame. Centers of mass, weighted by clinical response, were computed for the contacts in each cohort. RESULTS: From 555 studies that were screened for review, a total of 7 studies comprising 162 patients met criteria for inclusion and were analyzed. Across the cohort, the mean duration of epilepsy was 23 years and the mean pre-DBS seizure frequency was 56 seizures per month. DBS electrodes were implanted using direct targeting in 5 studies (n = 62, 38% of patient cohort) via a transventricular electrode trajectory in 4 studies (n = 123, 76%). At the mean follow-up duration of 2.3 years, 56% of patients were considered responders. Active contacts of responders were 1.6 mm anterior (95% CI 1.5-1.6 mm, p < 0.001) compared to those of nonresponders and were adjacent to the mammillothalamic tract (MTT). CONCLUSIONS: Accurate targeting of the ANT is crucial to successful DBS outcomes in epilepsy. These findings suggest that stimulation within the ANT subregions adjacent to the MTT improves outcomes.

Intraoperative localization and preservation of reading in ventral occipitotemporal cortex.

OBJECTIVE: Resective surgery in language-dominant ventral occipitotemporal cortex (vOTC) carries the risk of causing impairment to reading. Because it is not on the lateral surface, it is not easily accessible for intraoperative mapping, and extensive stimulation mapping can be time-consuming. Here the authors assess the feasibility of using task-based electrocorticography (ECoG) recordings intraoperatively to help guide stimulation mapping of reading in vOTC. METHODS: In 11 patients undergoing extraoperative, intracranial seizure mapping, the authors recorded induced broadband gamma activation (70-150 Hz) during a visual category localizer. In 2 additional patients, whose pathologies necessitated resections in language-dominant vOTC, task-based functional mapping was performed intraoperatively using subdural ECoG alongside direct cortical stimulation. RESULTS: Word-responsive cortex localized using ECoG showed a high sensitivity (72%) to stimulation-induced reading deficits, and the confluence of ECoG and stimulation-positive sites appears to demarcate the visual word form area. Intraoperative task-based ECoG mapping was possible in < 3 minutes, providing a high signal quality, and initial intraoperative data analysis took < 3 minutes, allowing for rapid assessment of broad areas of cortex. Cortical areas critical for reading were mapped and successfully preserved, while also enabling pathological tissue to be completely removed. CONCLUSIONS: Eloquent cortex in ventral visual cortex can be rapidly mapped intraoperatively using ECoG. This method acts to guide high-probability targets for stimulation with limited patient participation and can be used to avoid iatrogenic dyslexia following surgery.