Teresa A. Blaxton

FUNCTIONAL MAPPING OF HUMAN MEMORY USING PET : COMPARISONS OF CONCEPTUAL AND PERCEPTUAL TASKS

An experiment is reported in which regional cerebral blood flow (rCBF) as measured using positron emission tomography (PET) as participants performed conceptual and perceptual memory tasks. Blood flow during two conceptual tests of semantic cued recall and semantic association was compared to a control condition in which participants made semantic associations to nonstudied words. Analogously, rCBF during two perceptual tasks of word fragment cued recall and word fragment completion was compared to a word fragment nonstudied control condition. A direct comparison of conceptual and perceptual tasks showed that conceptual tasks activated medial and lateral left hemisphere in frontal and temporal regions as well as the lateral aspect of bilateral inferior parietal lobule. Perceptual tasks, in contrast, produced relatively greater activation in right frontal and temporal cortex as well as bilateral activation in more posterior regions. Comparisons of the memory tasks with their control conditions revealed memory-specific deactivations in left medial and superior temporal cortex as well as left frontal cortex for both conceptual tasks. In contrast, memory-specific deactivations for both perceptual fragment completion tests were localized in posterior regions including occipital cortex. Results from this and other functional imaging experiments provide evidence that conceptual and perceptual memory processes are subserved, at least in part, by different neurological structures in the human brain.

A direct comparison of PET activation and electrocortical stimulation mapping for language localization

Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET. We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation. Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion.

Activation of language cortex with automatic speech tasks.

Objective: To identify automatic speech tasks that reliably demonstrate increased regional cerebral blood flow (rCBF) in Broca’s and Wernicke’s areas of the cortex using PET. Background: Localizing language with direct cortical stimulation mapping requires that patients have a stable baseline on tests that engage eloquent cortex. For dysphasic patients or younger children, automatic speech tasks such as counting are often used in lieu of more complex language tests. Evidence from both lesion and neuroimaging studies suggests that these tasks may not adequately engage language cortices. In this study, we examined rCBF during automatic oromotor and speech tasks of varying complexity to identify those eliciting increased CBF in Broca’s and Wernicke’s areas. Methods: Eight normal volunteers underwent PET during rest, tongue movements, and three automatic speech tasks: repeating a phoneme sequence, repeating the months of the year, and reciting a memorized prose passage. Images were averaged across subjects and compared across tasks for regional localization and laterality. Results: Whereas all activation tasks produced increased relative CBF in brain regions that correlated with articulation and auditory processing, only the two tasks that used real words (versus phonemes) showed left-lateralized rCBF increases in posterior superior temporal lobe (Wernicke’s area), and only the prose repetition task produced left lateralized activity in Broca’s area. Conclusions: Whereas automatic speech typically does not engage language cortex, repeating a memorized prose passage showed unambiguous activation in both Broca’s and Wernicke’s areas. These results caution against the use of common automatic speech tasks for mapping eloquent cortex and suggest an alternative task for those with poor language abilities or acquired dysphasia who cannot perform standardized language tests reliably.

Regional cerebral blood flow during auditory responsive naming : evidence for cross-modality neural activation

ONE issue of continuing debate in language research concerns whether the brain holds separate representations for semantic information through the auditory vs visual modalities. Regardless of whether we hear, see or read meaningful information, our brains automatically activate both auditory and visual semantic associations to the sensory input. The prominent models for how the brain makes these cross-modality associations holds that semantic information conveyed through either sensory input modality is represented in a shared semantic system comprising the traditionally identified language areas in the brain. A few recent case reports as well as activation imaging studies, have challenged this notion by demonstrating category-specific organization within the semantic system in spatially discrete brain regions. Neither view posits a role for primary sensory cortices in semantic processing. We obtained positron emission tomographic (PET) images while subjects performed an auditory responsive naming task, an auditory analog to visual object naming. Subjects heard and responded to descriptions of concrete objects while blindfolded to prevent visual stimulation. Our results showed that, in addition to traditional language centres, auditory language input produced reciprocal activation in primary and secondary visual brain regions, just as if the language stimuli had entered in the visual modality. These findings provide evidence for a distributed semantic system in which sensory-specific semantic modules are mutually interactive, operating directly onto early sensory processing centers.

Cortical Stimulation Elicits Regional Distinctions in Auditory and Visual Naming

We used electrical stimulation mapping to compare performance on auditory and visual naming tasks in inferotemporal, lateral temporal, frontal, and parietal cortex in 8 temporal lobe epilepsy (TLE) patients with subdural electrodes placed for preoperative language localization. Performance on auditory responsive naming (ARN) and visual confrontation naming (VCN) was best during stimulation of parietal cortex and was equally impaired during stimulation of inferotemporal and frontal cortex. In contrast, ARN performance was significantly poorer than VCN performance during stimulation of anterior and posterior lateral temporal cortex. In most patients, stimulation of inferotemporal cortex at relatively low stimulus intensities (≥ 5 mA) during either ARN or VCN elicited reproducible errors in which patients could describe, gesture, spell, or draw, but not name, in response to auditory or visual cues. Inferotemporal and frontal cortex appear to be multimodality language regions distinct from lateral temporal cortex.

Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia

Recent neuroimaging studies of patients with schizophrenia have suggested structural and functional abnormalities of mesial temporal lobe structures. We compared the intelligence and memory test performance of 70 patients with schizophrenia and 72 patients with focal, lateralized temporal lobe epilepsy (30 left, 42 right temporal lobe) in order to examine the adequacy of a temporal lobe model of schizophrenic cognitive deficits. The groups did not differ in age, education, or Full Scale IQ. The right temporal lobe group had better overall memory performance than either the left temporal or schizophrenic patients. Unlike the schizophrenic patients, the memory impairment of the left temporal group was most evident with verbal materials and was amplified by delayed testing. Both epilepsy groups had better visual memory than the schizophrenic group. The clear differences in performance pattern between groups suggests that lateralized temporal lobe dysfunction does not by itself provide an adequate model of schizophrenic cognitive impairment.

Carbamazepine withdrawal: Effects of taper rate on seizure frequency

We prospectively investigated the effects of rate of carbamazepine (CBZ) withdrawal and CBZ level on seizure type and frequency in 12 epilepsy patients withdrawn completely from antiepileptic drugs prior to entering an investigational monotherapy trial. Patients withdrawn from CBZ rapidly (over 4 days) experienced significantly more generalized tonic-clonic seizures (GTCSs) and GTCS clusters than did those withdrawn slowly (over 10 days). Complex partial seizure (CPS) frequency did not differ between the two groups. CPSs preceded GTCSs, with GTCSs occurring in the majority of patients after CBZ had been discontinued, at subtherapeutic or absent CBZ levels. Two of six patients who had been tapered rapidly and all six patients who had been tapered slowly were able to enter the investigational monotherapy trial.

Retrieval inhibition in anomia

Reading latencies for anomic temporal lobe epileptics, nonanomic epileptic patient controls, and normal controls were measured in semantic priming paradigms. Both the epileptic controls and the normal controls showed typical semantic facilitation with faster response times following related than unrelated primes. The anomic subjects, on the other hand, were much slower to read targets following presentation of semantically related items than following unrelated primes. This inhibition effect was seen to increase as the number of related primes increased. These patterns were observed both when picture primes (Experiment 1) and word primes (Experiment 2) were used. These findings were interpreted as evidence for a category-specific retrieval inhibition in the anomic epileptic subjects.

Relationship of Carbamazepine Reduction Rate to Seizure Frequency During Inpatient Telemetry

Summary: To establish guidelines for medication reduction during inpatient telemetry, the records of 18 children and young adults with refractory partial seizures undergoing carbamazepine (CBZ) reductions during continuous video/EEG telemetry were reviewed. Six patients were receiving CBZ monotherapy, and 12 patients were treated with an additional antiepileptic drug (AED) maintained at baseline dosage during CBZ taper. Despite relatively rapid mean reductions in dosage of 44% by day 2 of taper, no patients experienced frequent repetitive seizures or status epilepticus (SE). Seizure rate during the entire CBZ reduction period correlated significantly with rate of drug reduction. Linear regression analysis showed drug reduction rate to be a good predictor of seizure rate. Fourteen patients experienced at least three seizures during CBZ taper. On the average, the third seizure occurred on day 5 of taper at a percentage of dose seduction of 79%. In 8 patients, CBZ concentrations were measured both before taper and ≤24 h after the third seizure. For these patients, seizure rate also correlated significantly with reduction in CBZ level. We conclude that manipulation of CBZ dose reduction rate is important in maximizing seizure frequency during telemetry and, in our patients, a relatively rapid rate of dose reduction was safe and effective in promoting seizure recordings.

Hematoma‐Related Seizures Detected During Subdural Electrode Monitoring

Summary: A 28‐year‐old woman with epilepsy developed the new onset of paroxysmal tongue tingling during subdural electrode monitoring. Her symptoms coincided with electrographic seizure activity arising from an area of the perisylvian region that had not previously been involved in her habitual seizures. At electrode removal, a focal 2x2 cm hematoma was detected and evacuated from beneath these electrode contacts. Unexpected episodic events may represent nonhabitual seizure activity related to the surgical procedure.