Elsevier

Epilepsy & Behavior

Volume 10, Issue 4, June 2007, Pages 553-559
Epilepsy & Behavior

Differential contributions of the hippocampus and rhinal cortices to verbal memory in epilepsy

https://doi.org/10.1016/j.yebeh.2007.03.002Get rights and content

Abstract

The present study explored the left mesial temporal lobe correlates of verbal memory in patients with temporal lobe epilepsy (TLE). An index of structural integrity, T2 relaxation time, was measured bilaterally in three mesial temporal regions of interest, and correlated with measures of verbal memory. The acquisition of verbal arbitrary relational material was most strongly associated with left perirhinal T2 signal. In contrast, verbal memory consolidation was related to T2 signal in the left hippocampus. Our findings suggest a key role for the left perirhinal region in the uptake of arbitrary linkages that underlie new learning. The hippocampus, on the other hand, is important for protecting newly learned information from the effects of interference. This double dissociation provides a neurocognitive account of the left mesial temporal memory syndrome.

Introduction

Over the past 15 years, studies of patients with temporal lobe epilepsy (TLE) have confirmed the nexus between left temporal lobe pathology and verbal memory impairment [1], [2], [3], [4], [5], [6], [7], [8]. There is also evidence suggesting that the medial and lateral aspects of the temporal lobe are differentially involved in the control of verbal memory [2], [7], [9]. Semantic aspects of verbal memory are thought to be more dependent on lateral temporal neocortex. On the other hand, forms of verbal learning and memory that are not facilitated by previously established semantic relationships are more dependent on medial temporal structures [9], [10]. Acquisition of unrelated word pairs (“hard” or arbitrary paired associates) exemplifies the latter form of verbal learning. Arbitrary relational learning is widely regarded as the fundamental building block of the declarative memory system. The role of specific medial structures in arbitrary forms of verbal memory, however, remains unclear.

The most striking evidence for the intratemporal specialization of verbal memory function comes from patients with left mesial temporal lobe epilepsy (mTLE). Left mTLE is associated with a selective impairment in the acquisition of unrelated word pairs (“hard” paired associates) [1], [6], [8], but leaves the ability to learn semantically related word pairs and other forms of semantically based material intact [1], [3], [6], [8]. The selective impairment in arbitrary paired associate learning seen in these studies has been attributed to involvement of the hippocampus proper.

A recent whole-brain positron emission tomography (PET) study [7], however, questions the strength of the relationship between the left hippocampus and verbal arbitrary relational learning in left mTLE. Weintrob et al. correlated out-of-scanner verbal paired associate learning performance with resting glucose uptake [7]. The learning of semantically related word pairs correlated with uptake in the left antero-inferior temporal neocortex, a region known to be associated with semantic function [11]. Semantically unrelated word pair learning, however, mapped onto the inferomedial region of the left temporal lobe. Specifically, a peak correlation between learning and glucose uptake was seen in the perirhinal cortex, but not in the hippocampus. These data raise the possibility that the rhinal cortices make their own functional contribution to arbitrary relational forms of verbal memory in patients with TLE.

The aim of the present study was to test this hypothesis by correlating different aspects of verbal memory with structural integrity in hippocampal as well as rhinal regions of interest, using quantified T2 signal (T2 relaxation time). Structural damage is associated with a nonspecific increment in T2 signal, visualized as a regional T2 hyperintensity on magnetic resonance imaging (MRI). This change can be quantified using the standard technique of T2 relaxometry, which is sensitive to the range of structural changes typically associated with TLE [12], [13], and reflects a regional increase in the ratio of glial cells to neurons [14]. A relationship between left hipppocampal T2 relaxation times and performance on some measures of verbal memory has previously been demonstrated in patients with TLE [6], [15], [16], [17], [18], but these studies have been limited to a single region of interest in the hippocampus, with no specific separation between arbitrary and semantic aspects of verbal learning.

To maximize the range of T2 signal within the mesial temporal region, we studied TLE patients with a variety of epileptogenic lesions, as well as those who were lesion negative on MRI. Patients with right-sided TLE also contribute to variability in left mesial temporal T2 signal: increases in contralateral hippocampal T2 relaxation time are common in patients with TLE [19], reflecting general contralateral mesial temporal damage [20], and in some cases with right TLE the changes can be associated with verbal memory decrements [18]. Although the mechanism underlying this effect is not yet clear, there is some evidence to suggest that the contralateral changes are related to persistent seizure activity [21], [22].

For purposes of comparison, we included a measure of retroactive interference in word list learning. Retroactive interference effects are enhanced in left mTLE [5], [6], presumably reflecting impaired consolidation of the newly learned material. As consolidation processes have long been associated with the functions of the hippocampus proper [23], [24], we hypothesized that susceptibility to the effects of retroactive interference would be more closely related to hippocampal rather than rhinal T2 relaxation times.

Section snippets

Participants

A consecutive series of 22 patients (9 male, 20 right-handed) with a longstanding history (mean duration 14.5 ± 13.1 years, range 3–49 years) of unilateral TLE (left-sided seizure focus or left TLE = 15, right sided seizure focus or right TLE = 7) were retrospectively studied. All patients had been investigated in the Comprehensive Epilepsy Program at Austin Health between April 2002 and November 2004. Diagnosis of TLE and seizure focus lateralization was based on clinical history and ictal

T2 relaxometry

Measurements of T2 relaxation time could not be obtained in all regions of interest in four of the patients because of motion/flow artifacts, or unclear anatomical differentiation. For these participants, data obtained in the remaining regions of interest were included in the analyses.

Hippocampal relaxation times were bilaterally elevated relative to normative values in the left and right TLE groups: left HC—F(2,97) = 44.72, P < 0.001; left TLE > normal: t(91) = 8.95, P < 0.001; right TLE > normal: t(84) = 

Discussion

In this study, an index of structural integrity, derived from three mesial temporal regions of interest, was correlated with measures of verbal learning to investigate the relative contributions of the hippocampus and rhinal cortices to arbitrary relational learning in patients with TLE. Our data provide converging support for the hypothesis that the perirhinal cortex is a key neural substrate for arbitrary relational learning. Specifically, we found a substantial relationship between the

Acknowledgments

The authors gratefully acknowledge the support of the National Health and Medical Research Council, Neurosciences Victoria, and the Brain Imaging Research Foundation, Australia.

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