The effects of epilepsy and its treatments have contributed significantly to language models. The setting of epilepsy surgery, which allows for careful pre- and postsurgical evaluation of patients with cognitive testing and neuroimaging, has produced a wealth of language findings. Moreover, a new wave of surgical interventions, including stereotactic laser ablation and radio frequency ablation, have contributed new insights and corrections to language models as they can make extremely precise, focal lesions. This review covers the common language deficits observed in focal dyscognitive seizure syndromes. It also addresses the effects of surgical interventions on language, and highlights insights gained from unique epilepsy assessment methods (e.g., cortical stimulation mapping, Wada evaluation). Emergent findings are covered including a lack of involvement of the hippocampus in confrontation word retrieval, possible roles for key white matter tracts in language, and the often-overlooked basal temporal language area. The relationship between language and semantic memory networks is also explored, with brief consideration given to the prevailing models of semantic processing, including the amodal Hub and distributed, multi-modal processing models.

We present data on a 10-year-old patient with drug-resistant epilepsy who was treated with methylphenidate for symptoms of attention deficit hyperactivity disorder (ADHD) that developed after she underwent surgical resection of a left frontal cortical dysplasia.. The patient's parents reported methylphenidate was helpful in improving their child's reading performance. Based on parents’ report, we examined benefits of methylphenidate on our patient's cognitive problems in a controlled setting. The patient underwent a neuropsychological evaluation completed in three sessions over a five-day period. Methylphenidate was administered prior to the second testing session only and was associated with improvements in the patient's attention, executive function, processing speed, and short-term memory performances. In comparison, word-reading performance, a task less susceptible to neurological impairment, was stable over the three sessions. The patient remained seizure-free after surgery and use of methylphenidate did not reduce seizure threshold. These findings support the use of methylphenidate in treating targeted cognitive problems associated with ADHD emerging after epilepsy surgery in children.

Purpose Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed with such patients, as most undergo non-dominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathological process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Further, these data confirm the Wada test findings of atypical dominance. Methods Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our Center between 1974 and 2006. Out of 1209 interpretable Wada procedures, 89 (7.4%) patients had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients (Ojemann et al., 1989). Key Findings Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus; all of which were common zones where language was identified in the left hemisphere dominant comparison sample. Significance Results suggest: 1) the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding RH language sites), and 2) the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization.

We present a 56 year-old, right-handed, congenitally deaf, female who exhibited a partial Balint's syndrome accompanied by positive visual phenomena restricted to her lower right visual quadrant (e.g., color band, transient unformed visual hallucinations). Balint's syndrome is characterized by a triad of visuo-ocular symptoms that typically occur following bilateral parieto-occipital lobe lesions. These symptoms include the inability to perceive simultaneous events in one's visual field (simultanagnosia), an inability to fixate and follow an object with one's eyes (optic apraxia), and an impairment of target pointing under visual guidance (optic ataxia). Our patient exhibited simultanagnosia, optic ataxia, left visual-field neglect, and impairment of all complex visual-spatial tasks, yet demonstrated normal visual acuity, intact visual-fields, and an otherwise normal neurocognitive profile. The patient's visuo-ocular symptoms were noticed while she was participating in rehabilitation for a small right pontine stroke. White matter changes involving both occipital lobes had been incidentally noted on the CT scan revealing the pontine infarction. As the patient relied upon sign language and reading ability for communication, these visuo-perceptual limitations hindered her ability to interact with others and gave the appearance of aphasia. We discuss the technical challenges of assessing a patient with significant barriers to communication (e.g., the need for a non-standardized approach, a lack of normative data for such special populations), while pointing out the substantial contributions that can be made by going beyond the standard neuropsychological test batteries.

BACKGROUND:: Surgery is indicated for cerebral cavernous malformations (CCMs) that cause medically refractory epilepsy. Real-time magnetic resonance thermography (MRT)-guided stereotactic laser ablation (SLA) is a minimally invasive approach to treating focal brain lesions. SLA of CCM has not previously been described. OBJECTIVE:: To describe MRT-guided SLA, a novel approach to treating CCM-related epilepsy, with respect to feasibility, safety, imaging, and seizure control in 5 consecutive patients. METHODS:: Five patients with medically refractory epilepsy undergoing standard presurgical evaluation were found to have corresponding lesions fulfilling imaging characteristics of CCM and were prospectively enrolled. Each underwent stereotactic placement of a saline-cooled cannula containing an optical fiber to deliver 980-nm diode laser energy via twist drill craniostomy. MR anatomic imaging was used to evaluate targeting before ablation. MR imaging provided evaluation of targeting and near real-time feedback regarding the extent of tissue thermocoagulation. Patients maintained seizure diaries, and remote imaging (6-21 months postablation) was obtained in all patients. RESULTS:: Imaging revealed no evidence of acute hemorrhage following fiber placement within presumed CCM. MRT during treatment and immediate postprocedure imaging confirmed the desired extent of ablation. We identified no adverse events or neurological deficits. Four of 5 (80%) patients achieved freedom from disabling seizures after SLA alone (Engel class 1 outcome), with follow-up ranging 12 to 28 months. Reimaging of all subjects (6-21 months) indicated lesion diminution with surrounding liquefactive necrosis, consistent with the surgical goal of extended lesionotomy. CONCLUSION:: Minimally invasive MRT-guided SLA of epileptogenic CCM is a potentially safe and effective alternative to open resection. Additional experience and longer follow-up are needed. ABBREVIATIONS:: CCM, cerebral cavernous malformationsGRE, gradient recalled echoMRT, magnetic resonance thermographySLA, stereotactic laser ablation

Stereotactic laser amygdalohippocampotomy (SLAH) uses laser interstitial thermal therapy guided by magnetic resonance thermography. This novel intervention can achieve seizure freedom while minimizing collateral damage compared to traditional open surgery, in patients with mesial temporal lobe epilepsy. An algorithm is presented to guide treatment decisions for initial and repeat procedures in patients with and without mesial temporal sclerosis. SLAH may improve access by medication-refractory patients to effective surgical treatments and thereby decrease medical complications, increase productivity, and minimize socioeconomic consequences in patients with chronic epilepsy.

Objective: The distributed white matter network underlying language leads to difficulties in extracting clinically meaningful summaries of neural alterations leading to language impairment. Here we determine the predictive ability of the structural connectome (SC), compared with global measures of white matter tract microstructure and clinical data, to discriminate language impaired patients with temporal lobe epilepsy (TLE) from TLE patients without language impairment. Methods: T1- and diffusion-MRI, clinical variables (CVs), and neuropsychological measures of naming and verbal fluency were available for 82 TLE patients. Prediction of language impairment was performed using a robust tree-based classifier (XGBoost) for three models: (1) a CV-model which included demographic and epilepsy-related clinical features, (2) an atlas-based tract-model, including four frontotemporal white matter association tracts implicated in language (i.e., the bilateral arcuate fasciculus, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus), and (3) a SC-model based on diffusion MRI. For the association tracts, mean fractional anisotropy was calculated as a measure of white matter microstructure for each tract using a diffusion tensor atlas (i.e., AtlasTrack). The SC-model used measurement of cortical-cortical connections arising from a temporal lobe subnetwork derived using probabilistic tractography. Dimensionality reduction of the SC was performed with principal components analysis (PCA). Each model was trained on 49 patients from one epilepsy center and tested on 33 patients from a different center (i.e., an independent dataset). Randomization was performed to test the stability of the results. Results: The SC-model yielded a greater area under the curve (AUC;.73) and accuracy (79%) compared to both the tract-model (AUC:.54, p <.001; accuracy: 70%, p <.001) and the CV-model (AUC:.59, p <.001; accuracy: 64%, p <.001). Within the SC-model, lateral temporal connections had the highest importance to model performance, including connections similar to language association tracts such as links between the superior temporal gyrus to pars opercularis. However, in addition to these connections many additional connections that were widely distributed, bilateral and interhemispheric in nature were identified as contributing to SC-model performance. Conclusion: The SC revealed a white matter network contributing to language impairment that was widely distributed, bilateral, and lateral temporal in nature. The distributed network underlying language may be why the SC-model has an advantage in identifying sub-components of the complex fiber networks most relevant for aspects of language performance.

Summary Objectives Patients with temporal lobe epilepsy (TLE) experience significant deficits in category-related object recognition and naming following standard surgical approaches. These deficits may result from a decoupling of core processing modules (e.g., language, visual processing, and semantic memory), due to "collateral damage" to temporal regions outside the hippocampus following open surgical approaches. We predicted that stereotactic laser amygdalohippocampotomy (SLAH) would minimize such deficits because it preserves white matter pathways and neocortical regions that are critical for these cognitive processes. Methods Tests of naming and recognition of common nouns (Boston Naming Test) and famous persons were compared with nonparametric analyses using exact tests between a group of 19 patients with medically intractable mesial TLE undergoing SLAH (10 dominant, 9 nondominant), and a comparable series of TLE patients undergoing standard surgical approaches (n = 39) using a prospective, nonrandomized, nonblinded, parallel-group design. Results Performance declines were significantly greater for the patients with dominant TLE who were undergoing open resection versus SLAH for naming famous faces and common nouns (F = 24.3, p < 0.0001, η2 = 0.57, and F = 11.2, p < 0.001, η2 = 0.39, respectively), and for the patients with nondominant TLE undergoing open resection versus SLAH for recognizing famous faces (F = 3.9, p < 0.02, η2 = 0.19). When examined on an individual subject basis, no SLAH patients experienced any performance declines on these measures. In contrast, 32 of the 39 patients undergoing standard surgical approaches declined on one or more measures for both object types (p < 0.001, Fisher's exact test). Twenty-one of 22 left (dominant) TLE patients declined on one or both naming tasks after open resection, while 11 of 17 right (nondominant) TLE patients declined on face recognition. Significance Preliminary results suggest (1) naming and recognition functions can be spared in TLE patients undergoing SLAH, and (2) the hippocampus does not appear to be an essential component of neural networks underlying name retrieval or recognition of common objects or famous faces.

Both animal research and human research suggest that interictal epileptiform discharges (IEDs) may affect cognition, although the significance of such findings remains controversial. We review a wide range of literature with bearing on this topic and present relevant epilepsy surgery cases, which suggest that the effects of IEDs may be substantial and informative for surgical planning. In the first case, we present a patient with epilepsy with left anterior temporal lobe (TL) seizure onset who experienced frequent IEDs during preoperative neuropsychological assessment. Cognitive results strongly lateralized to the left TL. Because the patient failed performance validity tests and appeared amnestic for verbal materials inconsistent with his work history, selected neuropsychological tests were repeated 6 weeks later. Scores improved one to two standard deviations over the initial evaluation and because of this improvement, were only mildly suggestive of left TL impairment. The second case involves another patient with documented left TL epilepsy who experienced epileptiform activity while undergoing neurocognitive testing and simultaneous ambulatory EEG recording. This patient's verbal memory performance was impaired during the period that IEDs were present but near normal when such activity was absent. Overall, although the presence of IEDs may be helpful in confirming laterality of seizure onset, frequent IEDs might disrupt focal cognitive functions and distort accurate measurement of neuropsychological ability, interfering with accurate characterization of surgical risks and benefits. Such transient effects on daily performance may also contribute to significant functional compromise. We include a discussion of the manner in which IED effects during presurgical assessment can hinder individual patient presurgical planning as well as distort outcome research (e.g., IEDs occurring during presurgical assessment may lead to an underestimation of postoperative neuropsychological decline).

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in the era of combination antiretroviral therapies, but there are no validated psychological interventions aimed at improving cognitive outcomes. This study sought to determine the potential benefit of semantic cueing on category fluency deficits, which are prevalent in HIV and affect daily functioning. A group of 86 HIV-infected individuals and 87 demographically-matched seronegative participants were administered a standard (i.e., uncued) and a cued category fluency task. Results revealed significant improvements in cued versus uncued performance in HIV, particularly for persons with lower levels of education. The cueing benefit observed may inform rehabilitation efforts aimed at ameliorating HAND.