Quantitative MRI of the prefrontal cortex and executive function in patients with temporal lobe epilepsy
Introduction
Many patients with temporal lobe epilepsy (TLE) experience neurocognitive disturbances classically not associated with temporal lobe function. Some patients are impaired on tasks that require frontal lobe processing in a similar way to patients with frontal lobe epilepsy [1]. As hippocampal sclerosis is the most common neuropathological correlate of TLE, it has been suggested that hippocampal pathology may be the primary cause of executive dysfunction in this patient group. For example, Giovagnoli [1] reported deficits on the Wisconsin Card Sorting Test (WCST), which relies largely on frontal lobe processing, in patients with medial TLE and hippocampal sclerosis, but not in patients with lateral TLE and no hippocampal abnormalities. This is supported by an earlier study that found that patients with TLE with unilateral hippocampal sclerosis performed more poorly than patients with frontal lobe or temporal lobe neocortical lesions on the same task [2]. However, other studies have failed to find a relationship between hippocampal sclerosis and measures of frontal lobe function in patients with TLE [3], [4], [5], [6]. Although recent MRI studies have demonstrated that patients with TLE may have atrophy of prefrontal cortex relative to healthy controls [7], [8], [9], no work to date has prospectively examined the relationship between prefrontal volume and executive functioning in patients with TLE.
During presurgical evaluation for medically intractable TLE, all patients undergo baseline neuropsychological assessment to determine their current cognitive and affective status and to predict postsurgical neurocognitive outcome. The neuropsychological battery used at the Walton Centre for Neurology and Neurosurgery (WCNN) in Liverpool includes assessment of executive functioning using a combination of the Stroop Color–Word Interference task [10], the Controlled Oral Word Association Test (COWAT) [11], and the working memory index of the Wechsler Memory Scale Third Edition (WMS-III) [12]. The present study sought to investigate whether performance on the aforementioned neuropsychological tasks of executive functioning are preferentially related to the structure of the PFC or hippocampus in patients with TLE.
The present study used two complementary quantitative magnetic resonance (MR) image analysis techniques to investigate the neuroanatomical correlates of executive function in patients with TLE: stereological region-of-interest analysis and whole-brain voxel-based morphometry (VBM). Stereological analysis provided unbiased volume estimation of the left and right dorsal and ventral PFC, hippocampus, and cerebral hemispheres, and VBM quantified gray matter concentration (GMC) over the entire brain. There were two primary objectives of the present study. First, we sought to investigate whether patients with unilateral TLE have volume alterations of prefrontal cortical subfields relative to healthy controls, and whether particular volume alterations are dependent on the hemispheric side of seizure onset. Previous VBM studies had shown that patients with unilateral left or right TLE have GMC reduction of right [7] or bilateral [8] dorsal PFC relative to healthy controls. These findings have not been replicated using quantitative MRI region-of-interest analyses. Second, we sought to investigate the relationship between executive functioning using three neuropsychological tasks, and prefrontal and hippocampal volume using stereological analysis and VBM, in patients with TLE. We hypothesized that dorsal prefrontal volume, and not hippocampal volume, would be associated with executive functioning in patients with TLE, based on previous work demonstrating the importance of dorsal prefrontal cortex for executive functions [13], [14], [15], [16], [17].
Section snippets
Participants
Thirty neurologically and psychiatrically healthy individuals were studied as a control population (see Table 1 for information). Forty-three nonconsecutive patients with medically intractable unilateral TLE undergoing presurgical evaluation were retrospectively selected from a large clinical database of patients. Each patient had complete archives of demographic information; clinical history; electroclinical information; volumetric data on the hippocampus, amygdala, temporal lobe, and cerebral
Stereology
In controls, mean left and right hippocampal volumes were found to be 2.5 ml (SD = 0.4) and 2.6 ml (SD = 0.4), respectively. Mean left and right hippocampal volumes in patients with left TLE were 1.5 ml (SD = 0.3) and 2.5 ml (SD = 0.5), and in patients with right TLE, 2.4 ml (SD = 0.4) and 1.8 ml (SD = 0.6). A 3 × 2 mixed ANOVA revealed a significant main effect of group (F(1, 69) = 12.551, P < 0.001), a significant effect of side of hippocampus (F(1, 69) = 33.749, P < 0.001), and a significant group × side interaction (F(2,
Discussion
There were two primary objectives of the present study. First, we sought to investigate whether patients with unilateral TLE have volume alterations of prefrontal cortical subfields relative to healthy controls, and whether particular volume alterations are dependent on the side of seizure onset. We found that patients with unilateral left and right TLE had significant volume reduction of right DPFC relative to controls, and significant volume reduction of left DPFC was obtained only when
Conclusions
Using a stereological region-of-interest approach and whole-brain VBM, we have corroborated the findings from previous VBM studies indicating atrophy of the DPFC in patients with TLE. Importantly and for the first time, we provide evidence indicating that volume changes in the PFC are correlated with impaired executive functioning. These preliminary data may shed light on why many patients with focal TLE show evidence of an extratemporal neuropsychological profile.
Acknowledgments
We thank Helen Jones and James Thompson at the Department of Psychology, University of Liverpool, for assistance with data acquisition. We also thank the radiographers, nursing staff, and Dr. Enis Cezayirli at MARIARC for their roles in acquisition of patient and control MRI data sets.
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Executive function and depressed mood are independently disruptive to health-related quality of life in pediatric temporal lobe epilepsy
2021, Epilepsy and BehaviorCitation Excerpt :The underlying mechanisms that contribute to depression in pediatric TLE are not well understood, but are thought to involve multiple factors, spanning neurocognitive, sociodemographic, and seizure-specific influences. It has been proposed that depression and TLE share a common pathogenic mechanism [12,13] that suggests overlapping disruptions to the hippocampus, amygdala, and frontal lobe projections [14]. In a sample of youth with TLE, Schraegle, Nussbaum, and Titus [15] identified the unique role of executive dysfunction in predicting depressive features.