Catherine L. Leveroni

Empirical Techniques for Determining the Reliability, Magnitude, and Pattern of Neuropsychological Change After Epilepsy Surgery

Summary: Purpose: We assessed test‐retest neuropsychological performance in patients with complex partial seizures to derive reliable change indices (RCIs) and regression‐based norms for change, indices that may be helpful in assessing cognitive outcome after anterior temporal lobectomy.

Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.

The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression-based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed.

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103-2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878-886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age=70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.

Early androgen effects on interest in infants: Evidence from children with congenital adrenal hyperplasia

Early androgens have been shown to facilitate male‐typical behavior in people, but little attention has been paid to androgen effects on female‐typical behavior. We studied the effects of early androgen on human interest in infants, attempting to extend studies in rodents and primates that indicate that exposure to high levels of androgen in the prenatal and early postnatal periods reduces the expression of maternal behavior in juvenile and adult animals. Parents completed a questionnaire about the behavior of children with congenital adrenal hyperplasia (CAH) who had been exposed to high levels of androgens early in life, and their unexposed siblings. As hypothesized, girls with CAH were reported to have less interest in infants than their sisters. These results suggest that early androgens may act to suppress some aspects of female‐typical behavior in people, as in other species, and that sex differences in maternal behavior result, in part, from early hormones.

Early hormones and sex differences in cognitive abilities

Abstract Data from a variety of nonhuman species indicate that early hormones have permanent effects on the sexual differentiation of the brain and behavior, including learning abilities. Hormones also affect the sexual differentiation of human cognitive abilities. Evidence from a variety of human clinical conditions and normal samples suggests that moderate to high levels of androgens in the prenatal and early postnatal periods facilitate the development of spatial ability. There is not enough information to determine whether early hormones influence other aspects of cognition which show sex differences, such as verbal fluency, perceptual speed, and memory. Current research is directed to understanding the behavioral and neural mechanisms underlying hormonal influences on cognition.

The impact of neuropsychological functioning on adherence to HAART in HIV-infected substance abuse patients

This study assessed the frequency of neuropsychological impairment and its relationship to adherence in a sample of HIV-infected injection drug users (IDUs) in treatment. One hundred eight participants recruited between September 2006 and October 2008 completed psychodiagnostic and neuropsychological assessments and monitored HAART adherence over a 2-week period via the use of Medication Event Monitoring System (MEMS) electronic pill caps and self-report. Assessment of concurrent functioning included clinician-rated scales of depression and substance use severity, and a battery of neuropsychological tests. Findings from individual neuropsychological tests were converted to Z scores relative to standard norms and averaged to form a composite score (NPZ). NPZ was generally poor (mean = -1.505, standard deviation = 1.120), with 76.9% of the sample being classified as highly impaired. Self-reported adherence was significantly higher than MEMS cap adherence. In contrast with previous studies, overall neuropsychological functioning was not a significant predictor of electronically monitored or self-reported adherence. However, examiner-rated current global severity of substance use and delayed word list recall emerged as significant predictors of self-reported adherence. Additionally, estimated premorbid verbal intelligence emerged as a significant predictor of the discrepancy between electronically monitored and self-reported adherence. Given the extent of neuropsychological impairment in this sample, future studies should examine the degree to which the impact of neuropsychological impairment may moderate interventions for this population, and the extent to which skills to cope with neuropsychological problems may boost the potential efficacy of such interventions.

Testing neuropsychological hypotheses for cognitive deficits in psychopathic criminals: a study of global-local processing.

Competing hypotheses about neuropsychological mechanisms underlying psychopathy are seldom examined in the same study. We tested the left hemisphere activation hypothesis and the response modulation hypothesis of psychopathy in 172 inmates completing a global-local processing task under local bias, global bias, and neutral conditions. Consistent with the left hemisphere activation hypothesis, planned comparisons showed that psychopathic inmates classified local targets more slowly than nonpsychopathic inmates in a local bias condition and exhibited a trend toward similar deficits for global targets in this condition. However, contrary to the response modulation hypothesis, psychopaths were no slower to respond to local targets in a global bias condition. Because psychopathic inmates were not generally slower to respond to local targets, results are also not consistent with a general left hemisphere dysfunction account. Correlational analyses also indicated deficits specific to conditions presenting most targets at the local level initially. Implications for neuropsychological conceptualizations of psychopathy are considered.

Open trial of nefazodone for combat veterans with posttraumatic stress disorder

Fourteen combat veterans completed a 9-week open trial of nefazodone for treatment of posttraumatic stress disorder (PTSD). Overall PTSD symptoms as measured by the Clinician-Administered PTSD Scale (CAPS) showed a modest but statistically significant decrease with nefazodone treatment. Decreases in CAPS reexperiencing and avoidance, but not hyperarousal symptoms, approached statistical significance. Anxiety decreased significantly, and there were trends toward decreased depression and anger on structured assessments. This study adds to the clinical evidence that nefazodone may be helpful for the management of PTSD symptoms.

Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: a decision analysis.

Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy.

Loss of Resting-State Posterior Cingulate Flexibility Is Associated with Memory Disturbance in Left Temporal Lobe Epilepsy

The association between cognition and resting-state fMRI (rs-fMRI) has been the focus of many recent studies, most of which use stationary connectivity. The dynamics or flexibility of connectivity, however, may be seminal for understanding cognitive functioning. In temporal lobe epilepsy (TLE), stationary connectomic correlates of impaired memory have been reported mainly for the hippocampus and posterior cingulate cortex (PCC). We therefore investigate resting-state and task-based hippocampal and PCC flexibility in addition to stationary connectivity in left TLE (LTLE) patients. Sixteen LTLE patients were analyzed with respect to rs-fMRI and task-based fMRI (t-fMRI), and underwent clinical neuropsychological testing. Flexibility of connectivity was calculated using a sliding-window approach by determining the standard deviation of Fisher-transformed Pearson correlation coefficients over all windows. Stationary connectivity was also calculated. Disturbed memory was operationalized as having at least one memory subtest score equal to or below the 5th percentile compared to normative data. Lower PCC flexibility, particularly in the contralateral (i.e. right) hemisphere, was found in memory-disturbed LTLE patients, who had up to 22% less flexible connectivity. No significant group differences were found with respect to hippocampal flexibility, stationary connectivity during both rs-fMRI and t-fMRI, or flexibility during t-fMRI. Contralateral resting-state PCC flexibility was able to classify all but one patient with respect to their memory status (94% accuracy). Flexibility of the PCC during rest relates to memory functioning in LTLE patients. Loss of flexible connectivity to the rest of the brain originating from the PCC, particularly contralateral to the seizure focus, is able to discern memory disturbed patients from their preserved counterparts. This study indicates that the dynamics of resting-state connectivity are associated with cognitive status of LTLE patients, rather than stationary connectivity.