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1.  Cortical Stimulation Mapping and Wada Results Demonstrate a Normal Variant of Right Hemisphere Language Organization 
Epilepsia  2012;53(10):1790-1798.
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.
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.
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.
PMCID: PMC3463744  PMID: 22780099
atypical language lateralization; epilepsy surgery; Wada; cortical stimulation mapping
2.  Famous face identification in temporal lobe epilepsy: Support for a multimodal integration model of semantic memory 
This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre-and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts.
PMCID: PMC3679345  PMID: 23040175
Famous face naming and recognition; Epilepsy surgery; Models of semantic memory
3.  Category-Specific Naming and Recognition Deficits in Temporal Lobe Epilepsy Surgical Patients 
Neuropsychologia  2007;46(5):1242-1255.
Based upon Damasio's “Convergence Zone” model of semantic memory, we predicted that epilepsy surgical patients with anterior temporal lobe (TL) seizure onset would exhibit a pattern of category-specific naming and recognition deficits not observed in patients with seizures arising elsewhere.
We assessed epilepsy patients with unilateral seizure onset of anterior TL or other origin (n = 22), pre- or postoperatively, using a set of category-specific items and a conventional measure of visual naming (Boston Naming Test: BNT).
Category-specific naming deficits were exhibited by patients with dominant anterior TL seizure onset/resection for famous faces and animals, while category-specific recognition deficits for these same categories were exhibited by patients with nondominant anterior TL onset/resection. Patients with other seizure onset did not exhibit category-specific deficits. Naming and recognition deficits were frequently not detected by the BNT, which samples only a limited range of stimuli.
Consistent with the “convergence zone” framework, results suggest that the nondominant anterior TL plays a major role in binding sensory information into conceptual percepts for certain stimuli, while dominant TL regions function to provide a link to verbal labels for these percepts. Although observed category-specific deficits were striking, they were often missed by the BNT, suggesting that they are more prevalent than recognized in both pre- and postsurgical epilepsy patients. Systematic investigation of these deficits could lead to more refined models of semantic memory, aid in the localization of seizures, and contribute to modifications in surgical technique and patient selection in epilepsy surgery to improve neurocognitive outcome.
PMCID: PMC2474808  PMID: 18206185
semantic memory; temporal lobe epilepsy; category-specific deficits; epilepsy surgery; naming deficits
4.  Category-specific recognition and naming deficits following resection of a right anterior temporal lobe tumor in a patient with atypical language lateralization 
We present a patient with right-hemispheric speech lateralization who exhibited severe recognition and naming deficits for unique objects (famous faces and landmarks) and grossly normal recognition and naming performances for nonunique objects (animals and man-made objects) following an anterior right temporal lobe (TL) resection of a ganglioglioma. While recognition deficits have been reported for famous faces following right temporal pole lesions, and for landmarks and geographic regions following right TL damage in general, this is the first reported case of both recognition and naming deficits for these objects resulting from a single lesion. These results are consistent with research suggesting that the neuroanatomic substrates for the recognition and naming of unique objects lie in the anterior TL regions. Left temporal pole lesions have been associated with naming deficits for unique objects while right temporal pole lesions have been associated with recognition deficits for unique objects. However, these findings suggest that the substrates of naming can be located in homotopic regions of the right hemisphere when language lateralization is atypical. As various object categories appear to have different neuroanatomical representations in the TLs, we discuss the possible benefits of sampling a wider array of objects during cortical stimulation mapping of language.
PMCID: PMC2727923  PMID: 18632095
Semantic memory; Category-specific naming and recognition deficits; Temporal lobes; Tumor resection; Atypical speech lateralization
5.  Better Object Recognition and Naming Outcome With MRI-Guided Stereotactic Laser Amygdalohippocampotomy for Temporal Lobe Epilepsy 
Epilepsia  2014;56(1):101-113.
Temporal lobe epilepsy (TLE) patients 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, semantic memory), due to “collateral damage” to temporal regions outside the hippocampus following open surgical approaches. We predicted stereotactic laser amygdalohippocampotomy (SLAH) would minimize such deficits because it preserves white matter pathways and neocortical regions critical for these cognitive processes.
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 nineteen 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, non-randomized, non-blinded, parallel group design.
Performance declines were significantly greater for the dominant TLE patients undergoing open resection versus SLAH for naming famous faces and common nouns (F=24.3, p<.0001, η2=.57, & F=11.2, p<.001, η2=.39, respectively), and for the nondominant TLE patients undergoing open resection versus SLAH for recognizing famous faces (F=3.9, p<.02, η2=.19). When examined on an individual subject basis, no SLAH patients experienced any performance declines on these measures. In contrast, 32 of the 39 undergoing standard surgical approaches declined on one or more measures for both object types (p<.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 (non-dominant) TLE patients declined on face recognition.
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.
PMCID: PMC4446987  PMID: 25489630
epilepsy surgery; naming and recognition; cognitive outcome; famous faces; laser interstitial thermal therapy; LITT
6.  Real-Time Magnetic Resonance-Guided Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy 
Neurosurgery  2014;74(6):569-585.
Open surgery effectively treats mesial temporal lobe epilepsy (MTLE), but carries risks of neurocognitive deficits, which may be reduced with minimally invasive alternatives.
To describe technical and clinical outcomes of stereotactic laser amygdalohippocampotomy (SLAH) with real-time magnetic resonance thermal imaging (MRTI) guidance.
Under general anesthesia and utilizing standard stereotactic methods, 13 adult patients with intractable MTLE (with and without mesial temporal sclerosis, MTS) prospectively underwent insertion of a saline-cooled fiber-optic laser applicator into amygdalohippocampal structures from an occipital trajectory. Computer-controlled laser ablation was performed during continuous MRTI followed by confirmatory contrast-enhanced anatomic imaging and volumetric reconstruction. Clinical outcomes were determined from seizure diaries.
A mean 60% volume of the amygdalohippocampal complex was ablated in 13 patients (9 with MTS) undergoing 15 procedures. Median hospitalization was one day. With follow-up ranging from 5-26 (median 14) months, 77% (10/13) of patients achieved meaningful seizure reduction, of which 54% (7/13) were free of disabling seizures. Of patients with preoperative MTS, 67% (6/9) achieved seizure freedom. All recurrences were observed by<6 months. Variances in ablation volume and length did not account for individual clinical outcomes. Whereas no complications of laser therapy itself were observed, one significant complication, a visual field defect, resulted from deviated insertion of a stereotactic aligning rod, which was corrected prior to ablation.
Real-time MR-guided SLAH is a technically novel, safe, and effective alternative to open surgery. Further evaluation with larger cohorts over time is warranted.
PMCID: PMC4151501  PMID: 24618797
Epilepsy; laser therapy; magnetic resonance imaging; minimally invasive surgical procedures; stereotactic techniques; temporal lobe; thermometry
7.  Understanding Working Memory Recovery Following Anterior Temporal Lobe Resection 
Epilepsy Currents  2015;15(1):17-19.
PMCID: PMC4320950  PMID: 25678880
8.  Diminished default mode network recruitment of the hippocampus and parahippocampus in temporal lobe epilepsy 
Journal of neurosurgery  2013;119(2):288-300.
Functional neuroimaging has shown that the brain organizes into several independent networks of spontaneously coactivated regions during wakeful rest (resting state). Previous research has suggested that 1 such network, the default mode network (DMN), shows diminished recruitment of the hippocampus with temporal lobe epilepsy (TLE). This work seeks to elucidate how hippocampal recruitment into the DMN varies by hemisphere of epileptogenic focus.
The authors addressed this issue using functional MRI to assess resting-state DMN connectivity in 38 participants (23 control participants, 7 patients with TLE and left-sided epileptogenic foci, and 8 patients with TLE and right-sided foci). Independent component analysis was conducted to identify resting-state brain networks from control participants’ data. The DMN was identified and deconstructed into its individual regions of interest (ROIs). The functional connectivity of these ROIs was analyzed both by hemisphere (left vs right) and by laterality to the epileptogenic focus (ipsilateral vs contralateral).
This attempt to replicate previously published methods with this data set showed that patients with left-sided TLE had reduced connectivity between the posterior cingulate (PCC) and both the left (p = 0.012) and right (p < 0.002) hippocampus, while patients with right-sided TLE showed reduced connectivity between the PCC and right hippocampus (p < 0.004). After recoding ROIs by laterality, significantly diminished functional connectivity was observed between the PCC and hippocampus of both hemispheres (ipsilateral hippocampus, p < 0.001; contralateral hippocampus, p = 0.017) in patients with TLE compared with control participants. Regression analyses showed the reduced DMN recruitment of the ipsilateral hippocampus and parahippocampal gyrus (PHG) to be independent of clinical variables including hippocampal sclerosis, seizure frequency, and duration of illness. The graph theory metric of strength (or mean absolute correlation) showed significantly reduced connectivity of the ipsilateral hippocampus and ipsilateral PHG in patients with TLE compared with controls (hippocampus: p = 0.028; PHG: p = 0.021, after correction for false discovery rate). Finally, these hemispheric asymmetries in strength were observed in patients with TLE that corresponded to hemisphere of epileptogenic focus; 87% of patients with TLE had weaker ipsilateral hippocampus strength (compared with the contralateral hippocampus), and 80% of patients had weaker ipsilateral PHG strength.
This study demonstrated that recoding brain regions by the laterality to their epileptogenic focus increases the power of statistical approaches for finding interhemispheric differences in brain function. Using this approach, the authors showed TLE to selectively diminish connectivity of the hippocampus and parahippocampus in the hemisphere of the epileptogenic focus. This approach may prove to be a useful method for determining the seizure onset zone with TLE, and could be broadly applied to other neurological disorders with a lateralized onset.
PMCID: PMC3924788  PMID: 23706058
individual differences; temporal lobe epilepsy; default mode network; functional magnetic resonance imaging; graph theory; independent component analysis
9.  Development of a Partial Balint's Syndrome in a Congenitally Deaf Patient Presenting as Pseudo-Aphasia 
The Clinical neuropsychologist  2008;23(4):715-728.
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.
PMCID: PMC2836810  PMID: 18923965
Balint's syndrome; Deafness; Simultanagnosia; Optic Apraxia; Optic Ataxia
10.  Structured Cueing on a Semantic Fluency Task Differentiates Patients with Temporal Versus Frontal Lobe Seizure Onset 
Epilepsy & behavior : E&B  2006;9(2):339-344.
Patients with frontal lobe dysfunction (e.g., Huntington’s Disease) reportedly benefit more from cueing on measures of semantic fluency than do patients with damage to temporal lobe structures (e.g., Alzheimer’s disease). This differential benefit from cueing suggests that different neurocognitive functions are impaired in these two groups. Patients with frontal lobe dysfunction are presumed to have difficulty with the executive aspects of this generative fluency task while patients with temporal lobe impairment are limited by deficits in semantic memory. We studied the performance of patients with complex partial seizures of frontal or temporal lobe onset as determined by video-EEG monitoring on standard and cued measures of semantic fluency administered in a counterbalanced sequence across groups. These groups did not differ significantly in terms of age, education, gender, age of seizure onset, total number of antiepileptic drugs, or IQ, and all patients subsequently underwent surgery for intractable epilepsy. FL patients performed significantly worse than TL patients on the standard semantic fluency paradigm (TL M = 18.4, SD = 4.7; FL M = 11.1, SD = 5.3), t (27) = −3.75, p < .001. Nevertheless, results of an ANCOVA demonstrated that the FL patients showed significantly greater performance improvement than the TL patients when provided with a cued semantic fluency format even after controlling for baseline differences in ability on the standard semantic fluency task (TL M = 0.45, SD = 3.8; FL M = 9.4, SD = 5.1), F (1, 29) = 12.37, p = .002. These findings support previous research suggesting that frontal and temporal structures contribute uniquely to semantic generative fluency and suggest that using a combination of standard and cued semantic fluency tasks may help confirm localization of seizure onset in partial epilepsy by localizing the associated cognitive dysfunction
PMCID: PMC2727920  PMID: 16870509
semantic fluency; frontal and temporal lobe epilepsy; localization of seizures
11.  Semantic Cueing Improves Category Verbal Fluency in Persons Living with HIV Infection 
HIV-associated neurocognitive disorders (HAND) remain highly prevalent in the era of cART, 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 impact daily functioning. Eighty-six 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.
PMCID: PMC3396423  PMID: 22772666
infectious disease; verbal fluency; semantic memory; cognitive rehabilitation; executive functions; cognitive neuropsychology
12.  The Oral Trail Making Test: Effects of Age and Concurrent Validity† 
The oral version of the Trail Making Test (OTMT) is a neuropsychological measure that provides an assessment of sequential set-shifting without the motor and visual demands of the written TMT (WTMT). Originally purposed to serve as an oral analog of the WTMT, the OTMT provides a means to evaluate patients with physical restrictions. However, formal validity studies and available normative data remain sparse. In a sample of healthy adults (n = 81), a strong correlation was observed between OTMT-B and its written counterpart (r = .62), but the correlations were weak between OTMT-A and either written version of the TMT. OTMT-B was significantly correlated with age but not with education or gender, whereas OTMT-A was not significantly correlated with demographic factors. The WTMT to OTMT ratios observed in the current study were generally lower than previously reported and varied across age groups, suggesting that the recommended use of a uniform conversion factor to predict one performance based on the other should be cautiously undertaken. Normative data that have been stratified by age are provided as well as suggestions for using both versions of the TMT in tandem to better elucidate the nature of cognitive deficits and to aid in the localization of cerebral dysfunction.
PMCID: PMC2858599  PMID: 20197294
Neuropsychology; Normative data; Cognitive tests; Trail Making Tests; Neuropsychological assessment
13.  Language reorganization in aphasics 
Neurosurgery  2008;63(3):487-497.
The purpose of this investigation was to determine whether clinical speech deficits following brain injury were associated with functional speech reorganization.
Across an 18 year interval, 11 patients with mild to moderate speech deficits underwent language mapping as part of their treatment for intractable epilepsy. These ‘aphasics’ were compared to 14 matched ‘controls’ with normal speech also undergoing epilepsy surgery. Neuroanatomical data were compared to quantitative language profiles and clinical variables.
Cortical lesions were evident near speech areas in all aphasia cases. As expected, aphasics and controls were distinguished by quantitative language profiles. The groups were further distinguished by the anatomical distribution of their speech sites. A significantly higher proportion of frontal speech sites was found in patients with prior brain injury, consistent with frontal site recruitment. The degree of frontal recruitment varied as a function of patient age at the time of initial brain injury—earlier injuries were associated with greater recruitment. The overall number of speech sites remained the same following injury. Significant associations were found between the number of the speech sites, naming fluency and the lesion proximity in the temporal lobe.
Language maps in aphasics demonstrated evidence for age-dependent functional recruitment in the frontal, but not temporal, lobe. The proximity of cortical lesions to temporal speech sites predicted the overall extent of temporal lobe speech representation and performance on naming fluency. These findings have implications for neurosurgical planning in patients with preoperative speech deficits.
PMCID: PMC2700554  PMID: 18812960
language mapping; aphasia; plasticity; dominant hemisphere

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