Relationships between spike-free local field potentials and spike timing in human temporal cortex.

Intracortical recordings comprise both fast events, action potentials (APs), and slower events, known as local field potentials (LFPs). Although it is believed that LFPs mostly reflect local synaptic activity, it is unclear which of their signal components are most closely related to synaptic potentials and would therefore be causally related to the occurrence of individual APs. This issue is complicated by the significant contribution from AP waveforms, especially at higher LFP frequencies. In recordings of single-cell activity and LFPs from the human temporal cortex, we computed quantitative, nonlinear, causal dynamic models for the prediction of AP timing from LFPs, at millisecond resolution, before and after removing AP contributions to the LFP. In many cases, the timing of a significant number of single APs could be predicted from spike-free LFPs at different frequencies. Not surprisingly, model performance was superior when spikes were not removed. Cells whose activity was predicted by the spike-free LFP models generally fell into one of two groups: in the first group, neuronal spike activity was associated with specific phases of low LFP frequencies, lower spike activity at high LFP frequencies, and a stronger linear component in the spike-LFP model; in the second group, neuronal spike activity was associated with larger amplitude of high LFP frequencies, less frequent phase locking, and a stronger nonlinear model component. Spike timing in the first group was better predicted by the sign and level of the LFP preceding the spike, whereas spike timing in the second group was better predicted by LFP power during a certain time window before the spike.

Cortical stimulation mapping and Wada results demonstrate a normal variant of right hemisphere language organization.

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 in such patients, as most undergo nondominant 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 pathologic 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. Furthermore, 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. Of 1,209 interpretable Wada procedures, 89 patients (7.4%) 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. 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 that 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 right hemisphere language sites), and that 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.

Long-term outcome of extratemporal resection in posttraumatic epilepsy.

OBJECT: Posttraumatic epilepsy (PTE) is a common cause of medically intractable epilepsy. While much of PTE is extratemporal, little is known about factors associated with good outcomes in extratemporal resections in medically intractable PTE. The authors investigated and characterized the long-term outcome and patient factors associated with outcome in this population. METHODS: A single-institution retrospective query of all epilepsy surgeries at Regional Epilepsy Center at the University of Washington was performed for a 17-year time span with search terms indicative of trauma or brain injury. The query was limited to adult patients who underwent an extratemporal resection (with or without temporal lobectomy), in whom no other cause of epilepsy could be identified, and for whom minimum 1-year follow-up data were available. Surgical outcomes (in terms of seizure reduction) and clinical data were analyzed and compared. RESULTS: Twenty-one patients met inclusion and exclusion criteria. In long-term follow-up 6 patients (28%) were seizure-free and an additional 6 (28%) had a good outcome of 2 or fewer seizures per year. Another 5 patients (24%) experienced a reduction in seizures, while only 4 (19%) did not attain significant benefit. The presence of focal encephalomalacia on imaging was associated with good or excellent outcomes in 83%. In 8 patients with the combination of encephalomalacia and invasive intracranial EEG, 5 (62.5%) were found to be seizure free. Normal MRI examinations preoperatively were associated with worse outcomes, particularly when combined with multifocal or poorly localized EEG findings. Two patients suffered complications but none were life threatening or disabling. CONCLUSIONS: Many patients with extratemporal PTE can achieve good to excellent seizure control with epilepsy surgery. The risks of complications are acceptably low. Patients with focal encephalomalacia on MRI generally do well. Excellent outcomes can be achieved when extratemporal resection is guided by intracranial EEG electrodes defining the extent of resection.

Neuronal correlates of functional magnetic resonance imaging in human temporal cortex.

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.

The roles of human lateral temporal cortical neuronal activity in recent verbal memory encoding.

Activity of 98 single neurons in human lateral temporal cortex was measured during memory encoding for auditory words, text, or pictures and compared with identification of material of the same modality in extracellular recordings during awake neurosurgery for epilepsy. Frequency of activity was divided into early or late epochs or activity sustained throughout both; 44 neurons had significant changes in one or more categories. Polymodal and sustained changes lateralized to dominant hemisphere and late changes to nondominant. The majority of polymodal neurons shifted categories for different modalities. In dominant hemisphere, the timing and nature of changes in activity provide the basis for a model of the roles of temporal cortex in encoding. Superior temporal gyrus excitatory activity was related to the early epoch, when perception and processing occur, and middle gyrus to the late epoch, when semantic labeling occurs. The superior two-thirds of middle gyrus also demonstrated sustained inhibition. In a subset of lateral temporal neurons, memory-encoding activity reflected simultaneous convergence of sustained attentional and early perceptual inputs.

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.

Category-specific naming and recognition deficits in temporal lobe epilepsy surgical patients.

OBJECTIVE: 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. METHODS: We assessed epilepsy patients with unilateral seizure onset of anterior TL or other origin (n=22), pre- or post-operatively, using a set of category-specific items and a conventional measure of visual naming (Boston Naming Test: BNT). RESULTS: 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. INTERPRETATION: 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 post-surgical 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.

Unobtrusive integration of data management with fMRI analysis.

This note describes a software utility, called X-batch which addresses two pressing issues typically faced by functional magnetic resonance imaging (fMRI) neuroimaging laboratories (1) analysis automation and (2) data management. The first issue is addressed by providing a simple batch mode processing tool for the popular SPM software package (http://www.fil.ion. ucl.ac.uk/spm/; Welcome Department of Imaging Neuroscience, London, UK). The second is addressed by transparently recording metadata describing all aspects of the batch job (e.g., subject demographics, analysis parameters, locations and names of created files, date and time of analysis, and so on). These metadata are recorded as instances of an extended version of the Protégé-based Experiment Lab Book ontology created by the Dartmouth fMRI Data Center. The resulting instantiated ontology provides a detailed record of all fMRI analyses performed, and as such can be part of larger systems for neuroimaging data management, sharing, and visualization. The X-batch system is in use in our own fMRI research, and is available for download at http://X-batch.sourceforge.net/.

Study of the human visual cortex: direct cortical evoked potentials and stimulation.

The authors studied the visual cortex of 15 patients undergoing studies for medically intractable epilepsy. Although the subdural and strip electrode placement varied in each of these patients, there were enough electrodes over the visual cortex to complete studies involving evoked potentials and direct cortical stimulation. Visual evoked potentials were elicited using two check sizes (50 and 16 min) for pattern reversal studies, 50 min checks for on-off stimulation, 50 min checks for horizontal and vertical hemifields and simple flash for the VEP. These studies demonstrated that the pattern reversal and on-off stimuli caused very complex, multipotential waveforms in striate and vision associational cortex that do not resemble the response obtained at the scalp. Different volumes of visual cortex are activated by stimulation with 16 min checks, 50 min checks and simple flash. Flash activates the largest volume of visual cortex and it is likely that this finding is what makes this test of so little value clinically. Direct cortical stimulation shows that colored responses are generated primarily in the posterior striate cortex and inferior occipital lobe, while movement is primarily generated by the visual association cortex. No complex visual images were obtained by stimulation of either the striate cortex or visual association cortex. The brain mechanisms that lead to formed visual images remain to be identified.

Individual variation in human motor-sensory (rolandic) cortex.

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.

Different neurons in different regions of human temporal lobe distinguish correct from incorrect identification or memory.

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.

A direct measure of human lateral temporal lobe neurons responsive to face matching.

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.

Cortical stimulation mapping of language cortex by using a verb generation task: effects of learning and comparison to mapping based on object naming.

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.

Functional separation of languages in the bilingual brain: a comparison of electrical stimulation language mapping in 25 bilingual patients and 117 monolingual control patients.

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? 9: 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.

Localization of language function in children: results of electrical stimulation mapping.

OBJECT: The authors examined the localization of language sites and the frequency of naming errors at these sites in a population of children undergoing electrical stimulation mapping during surgeries in which epileptic foci and dominant hemisphere neoplasms were resected. The frequency with which essential language sites were found (that is, "the frequency of language sites") in children was compared with that of a population of adults who had undergone this procedure, to assess the relationship of age to the distribution of essential areas for language. METHODS: The results of electrical stimulation mapping to determine sites of naming and speech arrest in 26 children ranging in ages from 4 to 16 years are presented in this report. Mapping was performed in the intraoperative setting in eight patients and in the extraoperative setting, by stimulation across a subdural grid, in 18 patients. The frequency and distribution of essential language areas were analyzed in populations of different ages and according to the method used to obtain the map. Considerable variability was found in the localization of language sites. When the language site distribution in pediatric patients was compared with the language site distribution found previously in a population of patients older than 16 years of age, a relative paucity of language sites was found in all perisylvian cortices in the younger age group. This relationship was also found within the group of patients 16 years of age and younger, when segregated into two groups: those patients 8 years of age or younger, and those patients between 9 and 16 years of age. These findings are relevant to theories of the intrahemispheric organization of the cortex devoted to language function. CONCLUSIONS: The differences found between groups of younger and older patients in the frequencies of sites where stimulation produces naming errors was identified suggests the possibility that, with advancing age, maturational processes contribute new foci of cortex essential for language.

Language Disturbances as Side Effects of Topiramate and Zonisamide Therapy.

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.

The neurobiology of language and verbal memory: observations from awake neurosurgery.

Neurosurgical operations under local anesthesia provide a unique opportunity to investigate the neurobiology of human cognition. We have studied the cortical organization of language and verbal memory in this setting, using two different techniques: electrical stimulation mapping and extracellular microelectrode recording of activity of individual neurons. The two techniques provide very different perspectives. Stimulation mapping identifies brain areas that are essential for a behavior, while changes in neuronal activity can occur in non-essential regions. Stimulation mapping identifies multiple discrete areas in perisylvian cortex of the dominant hemisphere as essential for a function, with separation of areas for different aspects of language including naming in two languages, different semantic classes, naming compared to reading, and language from verbal memory. There is substantial individual variation in the location of these essential areas, variability that in part relates to subjects age, gender and verbal abilities. Neurons changing activity with language or verbal memory are widely distributed, in both hemispheres. However, individual neurons usually change activity with only one function, including naming in only one of two languages, only naming or reading, or with recent verbal memory encoding but not identification of similar items. A few lateralized changes in neuronal activity have been identified, including a predominance of inhibition in dominant hemisphere with naming, and polymodal memory responses in dominant hemisphere, unimodal in nondominant. Specific neuronal populations have been identified that are related to different aspects of memory, that differentiate correct from incorrect identification or memory performance and differentiate learned from unlearned associations, with some evidence of differences in neuronal activity related to subjects' ability.

Human Temporal Cortical Single Neuron Activity during Language: A Review.

Findings from recordings of human temporal cortical single neuron activity during several measures of language, including object naming and word reading are reviewed and related to changes in activity in the same neurons during recent verbal memory and verbal associative learning measures, in studies conducted during awake neurosurgery for the treatment of epilepsy. The proportion of neurons changing activity with language tasks was similar in either hemisphere. Dominant hemisphere activity was characterized by relative inhibition, some of which occurred during overt speech, possibly to block perception of one's own voice. However, the majority seems to represent a dynamic network becoming active with verbal memory encoding and especially verbal learning, but inhibited during performance of overlearned language tasks. Individual neurons are involved in different networks for different aspects of language, including naming or reading and naming in different languages. The majority of the changes in activity were tonic sustained shifts in firing. Patterned phasic activity for specific language items was very infrequently recorded. Human single neuron recordings provide a unique perspective on the biologic substrate for language, for these findings are in contrast to many of the findings from other techniques for investigating this.

The thalamus and language revisited.

Regionalization of language function within the left thalamus has been established with language and verbal memory effects of thalamic stimulation during surgery for movement disorders. Three distinct language effects of thalamic stimulation were established: anomia from posterior ventrolateral (VL) and pulvinar regions; perseveration from mid-VL regions; and, a memory and acceleratory effect from anterior VL, described as a "specific alerting response" (SAR). These studies are reviewed in context of pertinent contemporary and recent literature on the thalamic role in memory and language. An explicit mechanistic model for the anomia and SAR effect is proposed. The suggested model for the SAR effect involves secondary switching in the striatum by the activation of thalamostriatal projections, whereas the anomia effect implicates the disruption of the cortical synchronization action of pulvinar via the cortico-pulvinar-cortical projection system. Further experimental data is required to firmly establish these mechanisms.