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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. © 2012 Elsevier Ltd.

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.

BACKGROUND: Of the ~50 million cases of epilepsy worldwide, an estimated 80% originate from cortical areas implicated in language. Although the precise language loci can vary significantly across individuals, electrical stimulation mapping for eloquent areas has become standard of care in resective surgery for frontotemporal epilepsies. Although considerable work has been done to establish the minimum necessary resection distance from these sites to preserve language, no previous work has shown how these representations are affected by proximal resections. METHODS: Between 1967 and 2005, 22 patients [seizure onset (y): 11.5 (0.2–33); age at initial resection (y): 27.7 (10–39); time between operations (y): 8.4 (1–20.3); sex: 14 females; hemisphere: 21 left] underwent repeated perisylvian resective epilepsy surgeries of the language-dominant hemisphere. Each set of operations comprised intraoperative language mapping and cortical photographs. Using this data, a Bayesian hierarchical model was used to estimate the variability of language localization pre-resection Versus post-resection. RESULTS: The statistical model shows the posterior median difference in cortical location of language sites preresection Versus postresection is 0.6 cm, with a posterior 95% CI of 0.4 cm, 0.9 cm. CONCLUSION: This work suggests permanence in cortical language centers following resection of infringing cortex, while providing a reasonable statistical method to impute unobserved sites during the mappings, and confirming the validity of using proximity sites defined by shortest distance in the current literature.

This study reports on the characteristics and distribution of naming errors of patients undergoing cortical stimulation mapping (CSM). During the procedure, electrical stimulation is used to induce temporary functional lesions and locate ‘essential’ language areas for preservation. Under stimulation, patients are shown slides of common objects and asked to name them. Cortical stimulation can lead to a variety of naming errors. In the present study, we aggregate errors across patients to examine the neuroanatomical correlates and linguistic characteristics of six common errors: semantic paraphasias, circumlocutions, phonological paraphasias, neologisms, performance errors, and no-response errors. Aiding analysis, we relied on a suite of web-based querying and imaging tools that enabled the summative mapping of normalized stimulation sites. Errors were visualized and analyzed by type and location. We provide descriptive statistics to characterize the commonality of errors across patients and location. The errors observed suggest a widely distributed and heterogeneous cortical network that gives rise to differential patterning of paraphasic errors. Data are discussed in relation to emerging models of language representation that honor distinctions between frontal, parietal, and posterior temporal dorsal implementation systems and ventral-temporal lexical semantic and phonological storage and assembly regions; the latter of which may participate both in language comprehension and production.

The relationship between changes in functional magnetic resonance imaging and neuronal activity remains controversial. Data collected during awake neurosurgical procedures for the treatment of epilepsy provided a rare opportunity to examine this relationship in human temporal association cortex. We obtained functional magnetic resonance imaging blood oxygen dependent signals, single neuronal activity and local field potentials from 8 to 300 Hz at 13 temporal cortical sites, from nine subjects, during paired associate learning and control measures. The relation between the functional magnetic resonance imaging signal and the electrophysiologic parameters was assessed in two ways: colocalization between significant changes in these signals on the same paired associate-control comparisons and multiple linear regressions of the electrophysiologic measures on the functional magnetic resonance imaging signal, across all tasks. Significant colocalization was present between increased functional magnetic resonance imaging signals and increased local field potentials power in the 50-250 Hz range. Local field potentials power greater than 100 Hz was also a significant regressor for the functional magnetic resonance imaging signal, establishing this local field potentials frequency range as a neuronal correlate of the functional magnetic resonance imaging signal. There was a trend for a relation between power in some low frequency local field potentials frequencies and the functional magnetic resonance imaging signal, for 8-15 Hz increases in the colocalization analysis and 16-23 Hz in the multiple linear regression analysis. Neither analysis provided evidence for an independent relation to frequency of single neuron activity.

OBJECTIVE: The purpose of this investigation was to determine whether clinical speech deficits after brain injury are associated with functional speech reorganization. METHODS: Across an 1 8-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 with 14 matched "control" patients with normal speech who also were undergoing epilepsy surgery. Neuroanatomic data were compared with quantitative language profiles and clinical variables. RESULTS: Cortical lesions were evident near speech areas in all aphasia cases. As expected, aphasic and control patients were distinguished by quantitative language profiles. The groups were further distinguished by the anatomic distribution of their speech sites. A significantly greater proportion of frontal speech sites was found in patients with previous 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 after injury. Significant associations were found between the number of the speech sites, naming fluency, and the lesion proximity in the temporal lobe. CONCLUSION: 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.

✓ The localization of cortical sites essential for language was assessed by stimulation mapping in the left, dominant hemispheres of 117 patients. Sites were related to language when stimulation at a current below the threshold for afterdischarge evoked repeated statistically significant errors in object naming. The language center was highly localized in many patients to form several mosaics of 1 to 2 sq cm, usually one in the frontal and one or more in the temporoparietal lobe. The area of individual mosaics, and the total area related to language was usually much smaller than the traditional Broca-Wernicke areas. There was substantial individual variability in the exact location of language function, some of which correlated with the patient's sex and verbal intelligence. These features were present for patients as young as 4 years and as old as 80 years, and for those with lesions acquired in early life or adulthood. These findings indicate a need for revision of the classical model of language localization. The combination of discrete localization in individual patients but substantial individual variability between patients also has major clinical implications for cortical resections of the dominant hemisphere, for it means that language cannot be reliably localized on anatomic criteria alone. A maximal resection with minimal risk of postoperative aphasia requires individual localization of language with a technique like stimulation mapping.

Eloquent cortex is generally identified using a variety of techniques including direct electrical stimulation to identify motor-sensory, language, and memory cortex and somatosensory evoked potentials to identify motor-sensory cortex. It is important that these areas of cortex be identified so as to prevent damage during the course of neurosurgical procedures. Seventy epilepsy patients undergoing evaluation for epilepsy surgery with chronically implanted subdural grids were retrospectively studied using both somatosensory evoked potentials and direct electrical stimulation. Direct electrical stimulation of motor-sensory cortex elicited responses over a larger area than did somatosensory evoked potentials. A great deal of individual variation was identified using both techniques. The results presented here support previous conclusions that the concept of homunculus somatotopy (point to point representation) of the motor-sensory cortex be abandoned and that of functional mosaicism of the motor-sensory cortex replace the earlier model. The individual variation found in the human motor-sensory cortex will require a continuation of "brain mapping" to identify eloquent cortex so that these vital areas will be spared during neocortical neurosurgical procedures.

The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two. Contrary to the Baddeley model, that activity during verbal working memory maintenance often represented activity specific to working memory rather than speech or language.

Recent studies suggest that benefits obtained from semantic cueing are greater for patient groups experiencing frontal system dysfunction than they are for patients whose cerebral impairment is concentrated in more posterior regions. For example, patients with Huntington’s or Parkinson’s disease, subcortical conditions that are often associated with frontal system dysfunction, were shown to benefit from a cued semantic fluency task more than Alzheimer’s patients (1). It has been posited that the mechanism of impairment underlying limitations in semantic fluency differs on the basis of anterior versus posterior cerebral damage. Restricted semantic fluency among patients with frontal system impairment is thought to have several potential causes, including a retrieval problem resulting from deficits in the executive aspects of searching one’s own semantic memory stores or deficits involving initiation of action or self-monitoring (1–4). In contrast, similar semantic fluency limitations observed among patients with more posterior lesions, particularly those involving the temporal lobes, are thought to be attributable to deficits in semantic memory (3, 5). Growing evidence points to the complementary roles of storage and retrieval respectively played by temporal and frontal regions in the performance of semantic fluency tasks. Lesions in either of these areas have been shown to result in decreased semantic fluency performance (6, 7). In addition, functional neuroimaging studies have demonstrated the importance of these regions in both healthy control subjects and patient groups (8–10). For example, numerous studies using functional magnetic resonance imaging (fMRI) have demonstrated activation of the left inferior frontal gyrus during the generation of semantic exemplars (11–13). Frith and colleagues (8), using PET technology to study cerebral blood flow during a semantic fluency task, found primary activation of the left dorsolateral prefrontal cortex and a bilateral decrease in the temporal cortices. These findings were interpreted as showing an inhibitory modulation of temporal regions by the prefrontal cortex as the basis of word generation. Finally, there are also a number of functional neuroimaging studies that suggest that semantic knowledge may be represented in distributed neural sites in the temporal lobes (14, 15). Taken together, these lesion and functional neuroimaging studies have led to a semantic network model involved with word generation that involves distributed systems involving both the frontal and temporal lobes (16). Given that epilepsy patients with frontal or temporal lobe seizure onset have been shown to be impaired on semantic fluency tasks (6), these groups appear to be natural target populations for examining this differential phenomena. The performance of patients with frontal lobe (FL) seizure onset would be expected to improve when provided with a cued semantic paradigm that gives them additional organizational structure, while the performance of temporal lobe (TL) epilepsy patients would not be expected to show the same benefit. Should this dissociation hold up between these patient groups, standard versus cued semantic fluency performance could be of use in confirming localization of seizure onset. Likewise, with the difficulty involved in developing measures that reliably capture the “control” features of executive processing (17), this differential pattern of semantic fluency performance could also add to the available tools in this seemingly elusive domain of neuropsychological assessment. In the present report, we examined the performance of patients with complex partial seizures of frontal or temporal lobe onset as determined by video-EEG monitoring to determine the robustness of previous findings using a different patient population.

Although non-invasive methods such as functional magnetic resonance imaging, electroencephalograms and magnetoencephalograms provide most of the current data about the human brain, their resolution is insufficient to show physiological processes at the cellular level. Clinical approaches sometimes allow invasive recordings to be taken from the human brain, mainly in patients with epilepsy or with movement disorders, and such recordings can sample neural activity at spatial scales ranging from single cells to distributed cell assemblies. In addition to their clinical relevance, these recordings can provide unique insights into brain functions such as movement control, perception, memory, language and even consciousness.

Object. The aim of this investigation was to address three questions in bilingualism research: 1) are multiple languages functionally separated within the bilingual brain; 2) are these languages similarly organized; and 3) does language organization in bilinguals mirror that in monolinguals? Methods. During awake dominant-hemisphere craniotomy in each of 25 bilingual patients, the authors mapped both languages by using identical object-naming stimuli. Essential sites for primary (L1) and secondary (L2) languages were compared. Sites were photographically recorded and plotted onto an anatomically referenced grid system. Language organization in bilinguals was then compared with that in 117 monolinguals and 11 monolingual children. Conclusions. The authors found distinct language-specific sites as well as shared sites that support both languages. The L1 and L2 representations were similar in total cortical extent but significantly different in anatomical distribution. The L2-specific sites were located exclusively in the posterior temporal and parietal regions, whereas the L1 and shared sites could be found throughout the mapped regions. Bilinguals possessed seven perisylvian language zones, in which L2 sites were significantly underrepresented when compared with the distribution of language sites in monolinguals. These L2-restricted zones overlapped the primary language areas found in monolingual children, indicating that these zones become dedicated to L1 processing. These findings support three conclusions. First, it is necessary to map both languages in bilinguals because L1 and L2 sites are functionally distinct. Second, differences exist in the organization of L1 and L2 sites, with L2-specific sites located exclusively in the posterior temporal and parietal lobes. Third, language organization comparisons in bilingual and monolingual brains demonstrate the presence of L2-restricted zones, which are dedicated to L1.

Object. Intraoperative stimulation mapping of subcortical white matter tracts during the resection of gliomas has become a valuable surgical adjunct that is used to reduce morbidity associated with tumor removal. The purpose of this retrospective analysis was to assess the morbidity and functional outcome associated with this method, thus allowing the surgeon to predict the likelihood of causing a temporary or permanent motor deficit. Methods. In this study, the authors report their experience with intraoperative stimulation mapping to locate subcortical motor pathways in 294 patients who underwent surgery for hemispheric gliomas within or adjacent to the rolandic cortex. Data were collected regarding intraoperative cortical and subcortical stimulation mapping results, along with the patient's neurological status pre- and postoperatively. For patients in whom an additional motor deficit occurred postoperatively, its evolution was examined. Of 294 patients, an additional postoperative motor deficit occurred in 60 (20.4%). Of those 60, 23 (38%) recovered to their preoperative baseline status within the 1st postoperative week. Another 12 (20%) recovered from their postoperative motor deficit by the end of the 4th postoperative week, and 11 more recovered to their baseline status by the end of the 3rd postoperative month. Thus, 46 (76.7%) of 60 patients with postoperative motor deficits regained their baseline function within the first 90 days after surgery. The remaining 14 patients (4.8% of the entire study population of 294) had a persistent motor deficit after 3 months. Patients whose subcortical pathways were identified with stimulation mapping were more prone to develop an additional (temporary or permanent) motor deficit than those in whom subcortical pathways could not be identified (27.5% compared with 13.1%, p = 0.003). This was also true when additional (permanent) motor deficits lasted more than 3 months (7.4% when subcortical pathways were found, compared with 2.1% when they were not found; p = 0.041). Conclusions. In patients with gliomas that are located within or adjacent to the rolandic cortex and, thus, the descending motor tracts, stimulation mapping of subcortical pathways enables the surgeon to identify these descending motor pathways during tumor removal and to achieve an acceptable rate of permanent morbidity in these high-risk functional areas.

Changes in the frequency of neural activity differentiating correct from incorrect responses were identified in extracellular recordings from 113 neurons at 62 sites in temporal lobe of 26 patients undergoing awake neurosurgery, during identification and recent explicit memory for object names, text or auditory words. Activity significantly differentiating correct from incorrect performance was identified in 22 neurons at 16 sites in 12 patients. Different neurons in different regions differentiated identification or memory performance. The 13 neurons differentiating identification performance were overrepresented in medial-basal recordings, the 9 neurons differentiating memory performance in superior temporal gyrus. All memory changes occurred during encoding. For both identification and memory there was separation of neurons showing differentiation early during perception and processing from those showing differentiation late, when output should occur, perhaps reflecting response monitoring. Early differentiating neurons were located more superior-laterally within the different regions related to accuracy of identification or memory.

Do the human cerebral hemispheres process faces differently? Clinical lesion observations and primate studies suggest that the right temporal lobe is critical in face processing. Yet, the nature of this relationship remains unclear. Recording from single neurons during a visuospatial (VS)-matching paradigm, we found that 100% of significantly active neurons discriminated matching from perception, bilaterally. Lateralized differences in the nature and timing of responses revealed that the right hemisphere neurons responded earlier, and with uniform frequency reductions. Additional lateralized differences favoring the right hemisphere neurons were found when subjects matched intact faces compared to scrambled faces or complex objects. We conclude that widely distributed neural ensembles are involved in 'lateralized' behaviors, but cerebral specialization of face processing is as much a function of the nature and timing of neuronal activity as anatomic location.

Summary: Purpose: To determine which patients with evidence of medically refractory bitemporal epilepsy are potentially good candidates for surgical therapy. Methods: We reviewed 42 adults with intractable seizures who were found to have bitemporal ictal onsets, based on scalp video-EEG long-term monitoring (LTM). All underwent invasive LTM before surgery. Surgical outcomes were classified as seizure free, >75% reduction in seizures, or 75% preponderance of interictal scalp EEG discharges to one temporal region; (b) magnetic resonance imaging (MRI) findings; (c) lateralizing deficits on verbal or visual reproduction memory testing; and (d) memory failure with injection contralateral to side of surgery on Wada testing. Results: Twenty-six (62%) of 42 patients had unilateral ictal onsets based on intracranial studies. Seizure freedom (occurring in 64% of this group), or >75% seizure reduction (found in 12% of subjects) occurred only when at least one of the following three factors was concordant with the side of surgery: preponderance of interictal scalp EEG discharges, unilateral temporal lesion on MRI, or lateralizing verbal or visual reproduction memory deficits on neuropsychological tests (p = 0.004). Seven subjects with bilateral ictal onsets based on intracranial studies had resections based on preponderance of seizures to one side, or other lateralizing noninvasive abnormality. Five of these (all of whom had ≥80% of seizures originating from one side) had >75% reduction in seizures. Conclusions: Invasive monitoring to pursue possible surgical therapy for patients with surface EEG evidence of bitemporal epilepsy may be justified only when some lateralizing feature is found in other noninvasive assessments.

Summary: Purpose: To examine the subgroup of patients with medically intractable epilepsy receiving temporal lobectomies who have pathologically verified mesial temporal sclerosis (MTS) and to determine the relation of demographic and clinical factors, results of diagnostic testing, and details of the surgical procedure with prognosis for achieving control of seizures. Methods: All patients receiving surgical treatment for intractable epilepsy between 1991 and 1998 at the University of Washington were reviewed. There were 118 patients who met inclusion criteria of adequate pathological analysis showing MTS without a progressive process and a minimum of 1-year follow-up. Results: Only personal history of status epilepticus demonstrated significant (p = 0.0276) prediction of outcome, increasing the risk of surgical failure. No other factors were significant predictors of outcome, including history of febrile seizures, possible etiologic factors, EEG, magnetic resonance imaging (MRI) or neuropsychological testing results, or extent of resection. Conclusions: Many factors that have been previously described to predict favorable outcome in the overall group of patients receiving temporal lobe resections for intractable epilepsy are, in fact, predictors of MTS and lose their predictive value when the subgroup of patients with confirmed MTS is examined. Neurosurgical treatment of MTS can be very effective even in the presence of significant etiologic factors, or of bilateral or extratemporal abnormalities on EEG or MRI.

Object. Cortical stimulation mapping has traditionally relied on disruption of object naming to define essential language areas. In this study, the authors reviewed the use of a different language task, verb generation, in mapping language. This task has greater use in brain imaging studies and may be used to test aspects of language different from those of object naming. Methods. In 14 patients, cortical stimulation mapping performed using a verb generation task provided a map of language areas in the frontal and temporoparietal cortices. These verb generation maps often overlapped object naming ones and, in many patients, different areas of cortex were found to be involved in the two functions. In three patients, stimulation mapping was performed during the initial performance of the verb generation task and also during learned performance of the task. Parallel to findings of published neuroimaging studies, a larger area of stimulated cortex led to disruption of verb generation in response to stimulation during novel task performance than during learned performance. Conclusions. Results of cortical stimulation mapping closely resemble those of functional neuroimaging when both implement the verb generation task. The precise map of the temporoparietal language cortex depends on the task used for mapping.

We identified functional anatomical subdivisions of human lateral and basal temporal cortex related to recent verbal memory for object names, text and auditory words. Extracellular neuronal activity was recorded during memory encoding compared to identification, during encoding, storage or recall retrieval stages of the memory task, during recognition memory, and during implicit memory as measured by repetition priming. Changes in frequency of activity during encoding were recorded from most neurons. In lateral temporal cortex, these encoding changes in the dominant hemisphere were more likely to be polymodal, whereas those in nondominant hemisphere were unimodal. There was substantial separation of neurons with changes in other aspects of memory, defining additional subdivisions. Inferior lateral and basal cortex were related to memory stages, and superior-posterior lateral cortex was related to implicit and recognition memory.

Reversible side effects of two sulfa-containing antiepileptic drugs (AEDs), topiramate (TPM) and zonisamide (ZNS), are reported. These effects differ from those of other AEDs in that language impairment was the predominant cognitive complaint. Information was available for 42 patients exposed to TPM. Twenty-two (52%) complained of adverse effects; 12, specifically of deficits in language-related functions. Brief neuropsychological testing in four patients on TPM confirmed verbal deficits. These deficits could appear shortly after initiating TPM and disappear variably after drug withdrawal. Similar complaints were seen in a pilot study of ZNS monotherapy, administered in supratherapeutic doses, confirmed by neuropsychological testing. TPM and ZNS both contain a sulfa moiety, suggesting that verbal processing is especially sensitive to these sulfa-containing AEDs.

Electrocorticograms (ECoG) were recorded using subdural grid electrodes in forearm sensorimotor cortex of six human subjects. The subjects performed three visuomotor tasks, tracking a moving visual target with a joystick-controlled cursor; threading pieces of tubing; and pinching the fingers sequentially against the thumb. Control conditions were resting and active wrist extension. ECoGs were recorded at 14 sites in hand- and arm-sensorimotor area, functionally identified with electrical stimulation. For each behavior we computed spectral power of ECoG in each site and coherence in all pair-wise sites. In three out of six subjects, gamma-oscillations were observed when the subjects started the tasks. All subjects showed widespread power decrease in the range of 11-20 Hz and power increase in the 31-60 Hz ranges during performance of the visuomotor tasks. The changes in gamma-range power were more vigorous during the tracking and threading tasks compared with the wrist extension. Coherence analysis also showed similar task-related changes in coherence estimates. In contrast to the power changes, coherence estimates increased not only in gamma-range but also at lower frequencies during the manipulative visuomotor tasks. Paired sites with significant increases in coherence estimates were located within and between sensory and motor areas. These results support the hypothesis that coherent cortical activity may play a role in sensorimotor integration or attention.

The importance of the left hemisphere in language function has been firmly established and current work strives to understand regional specializations within the perisylvian language areas. This paper reports a case study of a deaf user of American Sign Language undergoing an awake cortical stimulation mapping procedure. Patterns of sign errors accompanying electrical stimulation of Broca's area and the supramarginal gyrus (SMG) are reported. Our findings show Broca's area to be involved in the motor execution of sign language. These data demonstrate that the linguistic specificity of Broca's area is not limited to speech behavior. In addition, unusual semantic-phonological errors were observed with stimulation to the SMG; these data may implicate the SMG in the binding of linguistic features in the service of language production. Taken together, these findings provide important insight into the linguistic specificity of Broca's area and the functional role of the supramarginal gyrus in language processing.

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n = 16), non-HS (n = 10), and autopsy hippocampi (n = 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.

Extracellular recordings of human temporal cortical neuronal activity during identification and memory for object names or words were obtained from 31 neurons at 18 sites in 12 left language dominant patients undergoing left (10) or right (2) awake craniotomy for epilepsy under local anesthesia. Frequency of activity during identification was compared with perceptual controls, that during the encoding phase of recent memory to identification of the same material. Statistically significant changes in one or more temporal epoch (p< 0.005) of one or more comparisons were present for 27 of the 31 neurons in either hemisphere. Few neurons changed activity in the same direction for both words and names. The instruction to retain an item in recent memory changed activity in most neurons from that during identification of the same material, although the items presented were identical and overtly identified in each task. Any individual neuron usually changed activity in one direction for only one task. There are separate, widely distributed neural networks for identification or recent memory for each type of material. The majority of nearby neurons recorded through the same extracellular microelectrode were related to the networks for different tasks.The temporal characteristics of these changes were also investigated; 31% of the changes were “phasic”: temporally related to presentation or response to the item. Most of the remaining neuron changes were sustained throughout a task, often for several minutes. These task-specific sustained changes may reflect effects of thalamo-cortical attentional systems. Individual neurons had both sustained and phasic changes to different tasks.

George A. Ojemann was born in Iowa City, and received undergraduate and medical degrees from the University of Iowa, and his neurosurgical training at the University of Washington in Seattle. He has been on the faculty of that school ever since, except for a brief period at the National Institutes of Health in Bethesda, MD. He is presently Professor of Neurological Surgery. His clinical interest is in the surgical treatment of epilepsy. In addition to the research interests that are the subject of this interview, he is past chairman of the neurosurgical certifying board, a present member of the neurosurgical training program accrediting body, a member of the NIH Neurological Institute Advisory Council, and the President-Elect of the American Academy of Neurological Surgery. He is also a recipient of an NIH Javitts Award, a Distinguished Alumni citation from the University of Iowa, and an honorary Doctor of Sciences degree from the Medical College of Ohio. His wife is a neurologist with interests in epilepsy, and his two sons are in neurosurgical training programs, while his daughter is in medical school.

Advances in neuroimaging techniques, particularly high-resolution magnetic resonance imaging (MRI), have proved invaluable in identifying structural brain lesions in patients with epilepsy. The assumption that such focal lesions invariably predict the site of seizure origin may not be correct, however. We report a series of 20 adults with medically intractable partial epilepsy, where high-resolution brain MRI disclosed a unilateral, focal, hippocampal, or neocortical lesion as the only abnormality in each case; nevertheless, based on electroencephalographic (EEG) recordings, ictal onsets arose from a completely different location than that of the MRI lesion. All patients underwent epilepsy surgery, with the operations based on ictal EEG findings, and all were followed at least 2 years after the resection. After the most recent follow-up examination, 50% (10/20) of the patients were completely seizure-free, 35% (7/20) had at least a 75% reduction in the number of seizures, and 15% (3/20) had less than a 75% reduction in the number of seizures. We conclude that the identification of a focal, structural, hippocampal, or neocortical lesion on brain MRI is not always indicative of the site of seizure origin in partial epilepsy. Furthermore, in cases of discordance between MRI and EEG data, a good outcome after epilepsy surgery is possible if EEG ictal onsets are definitive.

The purpose of this study was to determine predictors of probable outcome following reoperation for medically intractable partial epilepsy. We reviewed outcome at least 1 year after reoperation in 21 patients with intractable seizures, for whom an earlier operation had failed. We examined age of onset of epilepsy, duration of seizures, gender, details of the history and clinical examination, pre-operative magnetic resonance (MRI) findings, electroencephalographic (EEG) studies obtained before and after the failed surgery, presence or absence of lateralizing neuro-psychological deficits, sites of operation and pathology of resected tissue to identify the factors associated with outcome. We found two factors that were significantly related to outcome: (1) no individual with a history of central nervous system (CNS) infection which predated the onset of epilepsy had a seizure-free outcome after reoperation (P=0.04). (2) Reoperations that extended previous resections, based on new ictal EEG recordings that were concordant with both EEG ictal onsets and MRI findings obtained before the first, failed surgery resulted in a seizure-free outcome or >95% reduction in seizures for 100% (7/7) of such patients. This compares to 29% (4/14) of the remaining individuals without such concordance who had a similar outcome (P=0.009). Site of operation (temporal or extratemporal) did not, in and of itself, predict outcome. A portion of patients who fail surgery for intractable partial seizures will achieve significant improvement following reoperation. Furthermore, we may be able to identify those individuals most likely to have an excellent result from a second operation.

Objective : We documented changes in spectral power of human electrocorticograms (ECoG) during performance of sensorimotor tasks. Methods : In 6 human subjects, ECoGs were recorded simultaneously from 14 subdural cortical sites in forearm sensorimotor cortex. The subjects performed 3 visuomotor tasks: tracking a moving visual target with a joystick-controlled cursor, threading pieces of tubing, and pinching the fingers sequentially against the thumb. Control conditions consisted of passive resting and active extension of the wrist. For each site the spectral power of the ECoG during these behaviors was computed for 5 10 Hz ranges between 10 and 60 Hz. Results : All subjects showed power decreases in the range of 11–20 Hz and power increases in the 31–60 Hz range during performance of the visuomotor tasks, at sites in forearm sensorimotor cortex and adjacent areas. Simple wrist movements often produced little change in power. Three subjects showed episodes of explicit gamma oscillations during the visuomotor tasks. Different sites showed increases in gamma-range power for different tasks, indicating that the spatial distribution of the gamma activity is specific to the tasks. Cross-spectra showed that gamma activity could become synchronized between separate sites during particular tasks. Conclusions : Synchronized gamma-range activity in human sensorimotor cortex increases with performance of manipulative visuomotor tasks, supporting the hypothesis that coherent gamma oscillations may play a role in sensorimotor integration or attention.

Summary: Purpose: This study was undertaken to determine what changes, if any, occur in the electroencephalogram (EEG) and in neuropsychological test findings of adults with medically intractable complex partial epilepsy over a 10-year period. Methods: We studied 35 adults, with a mean age of 32 years (range, 16–59 years) at time of initial testing. We compared the distribution of epileptiform patterns documented on the initial pair of waking and sleeping EEGs to those observed on another pair obtained 10 years later. During this same 10-year period, we also examined changes in the Wechsler Adult Intelligence Scale (WAIS) and on the tests from the Neuropsychological Battery for Epilepsy. Results: The EEGs of 28 (80%) of patients at the tenth year were identical to those seen initially. Five (14%) of patients demonstrated EEGs after 10 years with either no discharges or only unilateral discharges, where bilateral discharges were seen a decade earlier. Only two (6%) of patients had EEGs at the tenth year that showed bilateral discharges where only unilateral discharges were seen originally. We found no general change in intelligence or neuropsychological functioning after 10 years, although a few subtle losses were noted on several neuropsychological measures. Conclusions: For most adults with medically intractable complex partial epilepsy, the EEG and neuropsychological test scores remain reasonably stable over a decade.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Several special clinical settings provide opportunities for extracellular recording of neuronal activity in the human brain during measures of cognition. The limited experience with recordings obtained from human temporal and frontal cortex, medial temporal lobe, and subcortical structures in association with language, visuospatial processes, memory, learning, and music is reviewed here. The frequency of activity in a high proportion of neurons changes with a specific behavior. These neurons are widely distributed in both hemispheres. Relative inhibition of activity is prominent in cortical recordings made during language measures, particularly in the dominant hemisphere. Widespread excitation is prominent in recordings made during measures of recent explicit memory and learning. However, any individual neuron often has a narrow behavioral repertory, with activation to only one specific behavior in a range of behaviors. Some of the behaviors associated with consistent changes are not intuitively obvious. Nearby neurons often have different behavioral repertories. A few patterns of activity that may represent specific coding for a behavior, in some cases even sparse coding, have been identified. Neuronal recording in humans during cognitive measures provides an additional perspective on the neurobiological substrate of cognition that complements findings from other techniques.

To assess the clinical utility of high-resolution inter-ictal single photon emission tomography (SPET) of regional cerebral perfusion and high-resolution magnetic resonance imaging (MRI) of the brain with a phased-array temporal lobe coil, 35 patients with presumed partial epilepsy were evaluated prospectively by these techniques in addition to prolonged video/electroencephalographic (EEG) monitoring. Twenty of these patients had surgical treatment of partial epilepsy with outcome determinations spanning from 12 months to 3 years at follow-up. There were four categories of imaging findings as compared to scalp/sphenoidal EEG localization. Category I included 12 patients (34% of total) in whom there was complete imaging and EEG concordance. Category II included 4 patients (11 %) in whom MRI and EEG were concordant but SPET was divergent or normal. Category III included 13 patients (37%) in whom SPET and EEG were concordant but MRI was divergent or normal. Category IV included 4 patients (11%) in whom neither SPET nor MRI was concordant with EEG. In this study, the relative sensitivities of SPET and MRI for localization of partial epilepsy based on prolonged scalp/sphenoidal video/EEG recordings were 76% and 49%, respectively. We conclude that these neuroimaging techniques (phased-array MRI and inter-ictal cerebral perfusion SPET) are complementary and useful in the pre-operative evaluation of patients with partial epilepsy.

✓ The authors report the results obtained in 11 patients with tuberous sclerosis (TS) who underwent cortical resection surgery for medically intractable epilepsy. Patients' ages at time of surgery ranged from 3 to 46 years (mean 19.6 years). Preoperative epileptiform electroencephalographic abnormalities were focal spike wave discharges in six patients (55%), multifocal in four patients (36%), and generalized in one patient (9%). In the multifocal and generalized groups, all patients (45%) were evaluated by means of subdural grid and strip electrode recordings, whereas electrophysiological localization in the remaining patients was derived from ictal and interictal scalp recordings. The seizure foci were found to be extratemporal in six patients (55%) and temporal in five patients (45%). Surgical intervention consisted of craniotomy and seizure foci resection guided by electrocorticographic monitoring and functional mapping in five awake (45%) and six asleep (55%) patients. Neuropathological examination of the resected seizure foci revealed cortical tubers in eight patients and diffuse gliosis in three patients. Follow up ranged from 8 to 127 months (mean 35 months). Six patients (55%) were seizure free, half of whom were not receiving antiepileptic drugs (AEDs); three patients (27%) had a greater than 70% reduction in seizure frequency, although they required AEDs; one patient (9%) had a 50% temporary reduction in seizure frequency during the initial 6-month postoperative period; and one patient (9%) was lost to follow-up study. From this small but adequately followed patient population with TS, the authors conclude that cortical resection of seizure foci tailored to electrocorticographic findings and functional mapping is encouraging for this difficult to manage patient population with medically intractable epilepsy.

✓ Valproate (VPA) is associated with a variety of idiosyncratic hematological effects including thrombocytopenia, inhibition of platelet aggregation, and fibrinogen depletion. This has led some investigators to recommend discontinuation of VPA therapy prior to elective surgical procedures. However, administration of VPA therapy is not altered prior to surgery at the authors' center and no VPA-associated bleeding complications have been observed. Therefore, a retrospective chart review was conducted to verify the clinical observations in patients who had undergone cortical resection while receiving antiepileptic drugs (AEDs). Baseline, surgical, and postoperative laboratory data were available for a total of 313 patients, 111 of whom were receiving VPA and 202 of whom were receiving AEDs without VPA (control patients). Eighty-seven percent of the patients receiving VPA were also being treated with at least one other AED. The control group was approximately equally divided between monotherapy (55%) and polytherapy (45%) treatments. Platelet counts were significantly lower in the control polytherapy (284 ± 74 × 109/L) and both VPA groups (279 ± 113 × 109/L) as compared with the control monotherapy group (314 ± 85 × 109/L). Baseline fibrinogen levels were significantly lower in the VPA than in the control groups (223 ± 91 g/dl vs. 278 ± 95 g/dl). Both pre- and postoperatively, the VPA group had lower red blood cells counts, hematocrit, and hemoglobin levels. There was no significant difference between groups in estimated blood loss during surgery or qualitative wound discharge postsurgery. There was only one case of a bleeding complication, which occurred 14 days postoperatively in a patient receiving carbamazepine monotherapy. The results of this study confirm the clinical observations of an absence of bleeding complications in patients receiving VPA therapy at the time of surgery, despite differences in laboratory parameters.

We reviewed outcome at least 1 year after temporal lobectomy in 44 patients with bitemporal, independent, interictal epileptiform patterns on EEG. All 44 underwent preoperative intracranial monitoring. Twenty-two (50%) were seizure-free, 14 (32%) had at a least 75% reduction in seizures, and eight (18%) had less than a 75% reduction in seizures. We analyzed age of seizure onset, duration of epilepsy, gender, side of operation, history and clinical findings, findings on MRI, results of intracranial EEG-video monitoring, presence or absence of lateralizing neuropsychological deficits, and pathology of resected tissue to identify factors associated with outcome. Three factors emerged as independently associated with a good outcome: concordance of MRI abnormality and side of operation (p = 0.01), history of febrile seizures (p = 0.04), and 100% lateralization of intracranially recorded ictal onsets to the side of operation (p = 0.05). A seizure-free outcome was much more likely to occur if more than one of these factors was present: with at least two factors co-existing, 83% (15/18) of patients were seizure-free, while only 35% (7/20) were seizure-free with a single factor present (p = 0.0009). Of the six patients without any of the three factors, none were seizure-free. We conclude that it is possible to predict reasonably which patients with bitemporal epileptiform abnormalities will have a good outcome after surgery.

▪ Abstract Initial management of patients with temporal lobe epilepsy is with antiepileptic drugs, but these control seizures in only half the patients. Patients refractory to drugs should be evaluated for resective surgery. That evaluation requires identification of a focus of onset of seizures, as well as establishing that the focus is in an area of the brain that can be removed with a low risk of new neurologic deficits. Techniques used in that evaluation, including electroencephalography, imaging, recording from intracranial electrodes, use of the intracarotid amobarbitol perfusion test, and the role of specialized studies such as positron emission tomography, are reviewed, along with the correlation of the findings on that evaluation to the control of seizures after surgery. The different surgical techniques for temporal lobe resections are also reviewed, along with the risks of surgery, particularly to recent memory, and the changes in quality of life following surgery.

Some neurosurgeons state that intra-axial tumors may be resected with a low risk of neurological deficit if the tumor removal stays within the confines of the grossly abnormal tissue. This is thought to be so even when the lesion is presumably located in a functional area, providing that the adjacent normal-appearing cortex and subcortical white matter are not disturbed. This retrospective analysis presents evidence that this view is not always correct, because functioning motor, sensory, or language tissue can be located within a grossly obvious tumor or the surrounding infiltrated brain. Intraoperative stimulation mapping techniques identified 28 patients, ranging in age between 22 and 73 years, who showed evidence of functional tissue within the boundaries of infiltrative gliomas, as identified by correlation with computed tomography and magnetic resonance imaging scans, intraoperative ultrasound, gross visualization, and histological confirmation. Direct stimulation mapping of cortical and subcortical portions of the tumor during resections identified motor, sensory, naming, reading, or speech arrest function. Nineteen patients had new or worsened neurological deficits immediately after the operation, but after 3 months, only 6 continued to show new deficits whereas 18 showed no deficits and 2 improved. These results demonstrate that regardless of the degree of tumor infiltration, swelling, apparent necrosis, and gross distortion by the mass, functional cortex and subcortical white matter may be located within the tumor or the adjacent infiltrated brain. Therefore, to safely maximize glioma resection in these functional areas, intraoperative stimulation mapping may be used to identify functional cortical or subcortical tissue within, as well as adjacent to, the tumor, thus avoiding permanent injury.

Neuronal activity was recorded extracellularly from 22 neurons in the right lateral temporal cortex of 12 patients undergoing awake craniotomy for surgical treatment of epilepsy during tests of visuospatial function. These included: measures of short-term visuospatial memory; face, complex figure and line matching; labeling of facial emotional expressions; and a language task, object naming. Six neurons demonstrated significant changes during one or more of the three 1.3-s epochs following test presentation. All 6 of these neurons demonstrated inhibition during short-term visuospatial memory entry, or retrieval, or both. Four of the neurons also showed significant changes during one or more matching tasks; 8 of 10 of these changes were excitatory. One neuron also demonstrated excitation with labeling of facial emotional expression and another with naming. These data demonstrate in human right lateral temporal cortex a pattern of inhibition of neuronal activity during short-term visuospatial memory that contrasts with excitation during other functions, particularly figure matching.

The relation between changes in the blood oxygen dependent metabolic changes imaged by functional magnetic resonance imaging (fMRI) and neural events directly recorded from human cortex from single neurons, local field potentials (LFPs) and electrocorticogram (ECoG) is critically reviewed, based on the published literature including findings from the authors' laboratories. All these data are from special populations, usually patients with medically refractory epilepsy, as this provides the major opportunity for direct cortical neuronal recording in humans. For LFP and ECoG changes are often sought in different frequency bands, for single neurons in frequency of action potentials. Most fMRI studies address issues of functional localization. The relation of those findings to localized changes in neuronal recordings in humans has been established in several ways. Only a few studies have directly compared changes in activity from the same sites in the same individual, using the same behavioral measure. More often the comparison has been between fMRI and electrophysiologic changes in populations recorded from the same functional anatomic system as defined by lesion effects; in a few studies those systems have been defined by fMRI changes such as the "default" network. The fMRI-electrophysiologic relationships have been evaluated empirically by colocalization of significant changes, and by quantitative analyses, often multiple linear regression. There is some evidence that the fMRI-electrophysiology relationships differ in different cortical areas, particularly primary motor and sensory cortices compared to association cortex, but also within areas of association cortex. Although crucial for interpretation of fMRI changes as reflecting neural activity in human cortex, controversy remains as to these relationships. Supported by: Dutch Technology Foundation and University of Utrecht Grant UGT7685, ERC-Advanced grant 320708 (NR) and NIH grant NS065186 (JO).

To identify criteria for selecting pediatric candidates for cortical resection, we compared preoperative standard EEGs, extracranial or intracranial (subdural strip or grid) electrode EEG-video monitoring and imaging studies, and surgical pathology findings with long-term (mean = 6.1 years) seizure outcome. Of 47 children, 83% were either seizure-free or substantially improved. Children with a predominant single interictal focus in standard EEGs over time or with seizures that were mostly well localized (even with equal numbers of bilaterally independent spikes) during monitoring had significantly better outcomes than those who had mostly diffuse or bilaterally independent interictal and ictal discharges. Factors not associated with poor outcomes were some seizures unaccompanied by ictal EEG patterns, spikes in postresection electrocorticograms, extratemporal resection, younger age at surgery, and older age of seizure onset. Significantly more patients with than without tumors were seizure-free. Significantly more preteenagers than teenagers had poorly localized interictal and ictal discharges.