Faculty Bibliography

OBJECTIVE: The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging. METHODS: (1)H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. RESULTS: The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. CONCLUSIONS: The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures

Amygdala damage has been associated with impairments in perceiving facial expressions of fear. However, deficits in perceiving other emotions, such as anger, and deficits in perceiving emotion blends have not been definitively established. One possibility is that methods used to index expression perception are susceptible to heuristic use, which may obscure impairments. To examine this, we adapted a task used to examine categorical perception of morphed facial expressions [Etcoff, N. L., & Magee, J. J. (1992). Categorical perception of facial expressions. Cognition, 44(3), 227-240]. In one version of the task, expressions were categorized with unlimited time constraints. In the other, expressions were presented with limited exposure durations to tap more automatic aspects of processing. Three morph progressions were employed: neutral to anger, neutral to fear, and fear to anger. Both tasks were administered to a participant with bilateral amygdala damage (S.P.), age- and education-matched controls, and young controls. The second task was also administered to unilateral temporal lobectomy patients. In the first version, S.P. showed impairments relative to normal controls on the neutral-to-anger and fear-to-anger morphs, but not on the neutral-to-fear morph. However, reaction times suggested that speed-accuracy tradeoffs could account for results. In the second version, S.P. showed impairments on all morph types relative to all other subject groups. A third experiment showed that this deficit did not extend to the perception of morphed identities. These results imply that when heuristics use is discouraged on tasks utilizing subtle emotion transitions, deficits in the perception of anger and anger/fear blends, as well as fear, are evident with bilateral amygdala damage

Epilepsy is a multilayered disorder complicated by numerous comorbid conditions and hormonal changes. More than 1.5 million girls and women with epilepsy face side effects that are compounded at different ages by menstruation, fertility, pregnancy, fetal health, bone health, and other health issues. Changes in hormonal balance during maturation, from menarche through menopause, affect seizure thresholds and antiepileptic drugs, and vice versa. This overview provides physicians with a background on the multiple issues relevant to women of all ages in the reproductive years, including those planning to conceive and those who are pregnant, and beyond the childbearing years

OBJECTIVE: Health-related quality of life (HRQOL) improves after resective epilepsy surgery, but data are limited to short follow-up in mostly retrospective reports, with minimal consideration of other potential factors that might influence HRQOL. METHODS: In a prospective multicenter study, 396 patients underwent resective epilepsy surgery. They completed the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) before surgery, within 6 months, and at approximately yearly intervals after surgery. Seizure outcome was ascertained by phone calls every 3 months, and dates of postoperative seizures were chronicled. Overall HRQOL as measured by the QOLIE-89 was evaluated with respect to seizure outcome using logistic regression. RESULTS: QOLIE-89 scores increased significantly at the first postoperative measurement (within 6 months after surgery) in the cohort overall; subsequent changes over time were sensitive to seizure-free and aura-free status. After adjusting for baseline scores, the corresponding postsurgical QOLIE-89 overall, and four dimension scores, increased as a function of square root of time seizure-free, and independently as a function of square root of time aura free, leveling by 2 years of stable seizure (aura) status. HRQOL was not independently related to duration of epilepsy, duration of intractable epilepsy, or continuation of medications. INTERPRETATION: HRQOL improves early after surgery, regardless of seizure outcome. Subsequent changes parallel length of time seizure free or aura free, stabilize after 2 years, and are unrelated to duration of epilepsy, duration of intractable epilepsy, or continued medication use

Naming is mediated by perisylvian cortex in the left (language-dominant) hemisphere, and thus, left anterior temporal lobe resection for pharmacologically intractable temporal lobe epilepsy (TLE) carries risk for post-operative naming decline. Interestingly, this risk is lower in patients with hippocampal sclerosis (HS) relative to those without HS (non-HS). Although the hippocampus has traditionally been considered a critical structure for memory, without contribution to naming, this pattern might implicate direct hippocampal naming involvement. On the other hand, critical naming sites have been found in anterior, lateral temporal (i.e. extra-hippocampal) neocortex, the region typically removed with 'standard' TLE resection. We, therefore, speculated that the relative preservation of naming in post-operative HS patients might reflect cortical reorganization of language to areas outside this region. Using pre-resection electrical stimulation mapping, we compared the topography of auditory and visual naming sites in 12 patients with HS and 12 patients without structural brain pathology. Consistent with previous work, non-HS patients exhibited post-operative naming decline, whereas HS patients did not. As hypothesized, HS patients had proportionally fewer overall naming sites in anterior temporal cortex, the region typically removed with standard anterior temporal resection, whereas non-HS patients exhibited a more even distribution of naming sites in anterior and posterior temporal regions (P = 0.03). Although both groups exhibited the previously reported pattern of auditory naming sites anterior to visual naming sites, auditory naming sites had a significantly more posterior distribution in HS patients (P = 0.02). Additionally, non-HS patients exhibited a greater proportion of visual naming sites above the superior temporal sulcus, whereas visual naming sites in HS patients were scattered across superior and inferior temporal cortex. Results suggest that preserved naming ability in HS patients following anterior temporal resection might be attributable, at least in part, to intrahemispheric reorganization of language in response to the likely, early development of sclerosis in the medial temporal region. Furthermore, their more posterior distribution of naming sites is consistent with the more anterior propagation of EEG discharges in TLE. These results hold theoretical implications regarding the role of the dominant hippocampus in determining the cortical representation of semantic and lexical information, and raise questions regarding the specific roles of medial and lateral temporal cortex in targeted word retrieval. The different patterns of naming areas identified in patients with and without HS may also carry clinical implications, potentially improving efficiency during the time-constrained process of stimulation mapping

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or 'hypersynchrony' which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation

Changes of cardiovascular function are frequent in temporal lobe epilepsy (TLE). The baroreflex - the most important reflex for cardiovascular stability - has not been studied systematically in TLE. We evaluated cardiovascular variability and baroreflex function in TLE.In 22 TLE patients and 20 controls, we continuously monitored heart rate (HR) and blood pressure (BP). Time-domain parameters were derived from recordings at rest and from standard cardiovascular reflex tests. Spectral analysis determined sympathetic and parasympathetic modulation of HR and BP in the low (LF-power) and high frequency range (HF-power). We calculated the relative LF- and HF-powers of HR in relation to the sum of LF- and HF-powers. LF/HF-ratio of HR was assessed as a parameter of sympatheticovagal balance. LF-transfer function gain between BP and HR determined baroreflex function.Time-domain parameters did not differ between TLE patients and controls. Spectral analysis showed decreased absolute LF- and HF-powers but increased relative LF-power and LF/HF-ratio of HR in TLE. LF-transfer function gain between BP and HR was reduced in TLE (p<0.05).The reduction of absolute LF- and HF-powers indicates decreased total autonomic variability in TLE. However, increased relative LF-power and LF/HF-ratio of HR in TLE show a relative increase of sympathetic tone. Most importantly, we demonstrate an impaired baroreflex function in TLE. These cardiovascular autonomic abnormalities may contribute to cardiac arrhythmia in TLE