Quantitative MRI of the prefrontal cortex and executive function in patients with temporal lobe epilepsy

Abstract

We investigated the relationship between prefrontal cortex (PFC) and hippocampal volume and executive functioning in patients with temporal lobe epilepsy (TLE). Prefrontal volume and hippocampal volume were studied using stereology in conjunction with point counting and voxel-based morphometry on MR images. Executive functioning was assessed using tests routinely incorporated into presurgical neuropsychological evaluation. Relative to 30 healthy controls, 43 patients (26 left, 17 right) with TLE had volume atrophy of the ipsilateral hippocampus and bilateral dorsal PFC. Performance on the working memory index of the Wechsler Memory Scale was positively correlated with the volume of all prefrontal regions, and the Controlled Oral Word Association Test with the left dorsal PFC, whole left PFC, and left hippocampus. Stroop Color–Word Interference performance was not related to volume of dorsal PFC. The “extratemporal neuropsychological profile” frequently observed in patients with TLE may be due to extended damage to brain regions remote from the epileptogenic focus. In particular, volume atrophy of the dorsal PFC may account for deficits in executive functioning.

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].