Imaging language networks before and after anterior temporal lobe resection: results of a longitudinal fMRI study

Purpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE‐MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.     

Adaptive visual memory reorganization in right medial temporal lobe epilepsy

Purpose: We investigated functional reorganization mechanisms of the human medial temporal lobe (MTL) for episodic memory, in patients suffering from medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS).
Methods: We used functional magnetic resonance imaging (fMRI) to measure brain activity changes during matched episodic encoding tasks of abstract words (Verbal) and line drawings (Visual), in patients with unilateral right MTLE undergoing presurgical evaluation and healthy controls.
Results: As expected, a significant interaction between material type and the side of MTL activity was present in the control group, with preferential involvement of the left hippocampus in verbal encoding and the right parahippocampal region in visual encoding. When compared with controls, right MTLE patients with intact performance activated a region in the left hippocampus more during visual encoding, which resulted in an interaction between group and hemisphere. Importantly, an effect of memory performance on visual encoding activity was observed in the patients, with greater engagement of the left MTL being associated with higher recognition scores. Interestingly, activity in the left MTL also depended on the epileptic seizure frequency, suggesting a role for this clinical parameter in the recruitment of contralateral regions.
Discussion: Taken together, these results indicate functional reorganization of the MTLs in right HS, through transfer of function from the right to the left hemisphere, and strongly suggest an adaptive role for such reorganization mechanism in supporting preserved visual memory.     

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An fMRI study

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left‐HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left‐HS group recruited more widespread cortical areas, which were even more widespread in the right‐HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right‐HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Impaired gist memory in patients with temporal lobe epilepsy and hippocampal sclerosis

Purpose: Temporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memory functions. We aimed to examine the effect of restricted hippocampal lesions on gist memory function in patients with TLE. Methods: Forty‐five patients with TLE and HS (16 left, 15 right, and 14 bilateral lesions) and 22 control subjects were recruited. Patients with magnetic resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal lesions were excluded. All participants performed a gist‐based recognition task following the Deese‐Roediger‐McDermott paradigm and were tested for verbal IQ and memory functions. We conducted hippocampal volumetry on MRI of all the participants. Results: Patients showed multidomain memory impairments. Gist memory was impaired in patients with bilateral HS and probably in patients with right HS. Hippocampal volumetry supported such findings that total volume of hippocampi and volume of right hippocampus correlated positively with gist memory function. Discussion: HS has a dose effect and a probable right dominance effect on gist memory; good item memory supports gist memory performance; and a disproportionate deficit was noted in tasks with high relational demand but not in tasks with simple association. We should develop memory skills for patients with TLE by enhancing performance of gist memory related to simple association task.     

Behavioral activation of human hippocampal EEG: Relationship to recent memory

Behaviorally activated EEG was recorded from each hippocampus in 17 epilepsy surgery patients with unilateral (11 left, 6 right) mesial temporal lobe (MTL) seizure onset and correlated with preoperative material-specific memory test performances. Whole-band power (1–30 Hz) was recorded and subjected to spectral analysis under three conditions: (a) eyes closed resting, (b) eyes open with a verbal task, and (c) eyes open with a nonverbal task. Significantly less EEG desynchronization was observed in the epileptogenic hippocampus during the verbal activation condition but not during the eyes-open nonverbal task. Decreased EEG reactivity in the left hippocampus during verbal activation was correlated significantly with verbal memory test impairment among patients with left MTL seizure onset. However, similar relationships were not obtained between right seizure focus patients and performance on a visuospatial learning test. Results confirm the association of left MTL structures with verbal memory functions and emphasize the difficulty in demonstrating a consistent relationship between right MTL structures and visuospatial memory performance.     

Abnormalities of lexical and semantic processing in left temporal lobe epilepsy: an fMRI study

Purpose: We examined the efficiency of lexical and semantic processing and associated brain activation using functional magnetic resonance imaging (fMRI) in patients with left temporal lobe epilepsy (TLE). Methods: Twenty patients with left TLE (10 with hippocampal sclerosis, the HS group; and 10 with nonlesional MR scans, the NL group) and 12 healthy controls underwent an event‐related fMRI analysis during a lexical decision task (LDT). Lexical and semantic processing were examined by comparing behavioral and imaging data associated with words and nonwords (lexicality) or with concrete and abstract words (concreteness). Key Findings: Although the control group showed greater activation associated with word stimuli than with nonword stimuli in a bilateral language network, both TLE groups showed greater activation for nonword stimuli than word stimuli, including greater activation of inferior frontal language areas (bilaterally in the HS group and left‐lateralized in the NL group). The TLE groups also exhibited differential activation patterns during the processing of abstract and concrete words compared to controls, and compared to each other. For abstract words, in particular, the HS group showed activation of frontal areas typically associated with executive functions, whereas the NL group showed activation of more posterior semantic processing regions. Significance: These results suggest that left TLE is associated with altered functional organization of cortical networks involved in lexical and semantic processing. In addition, the organization observed varies as a function of hippocampal pathology.     

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.     

Hippocampal formation involvement in a language-activation task in patients with mesial temporal lobe epilepsy

PURPOSE: The study aims to explore the contribution of the hippocampal formation to the retained language-comprehension network in patients with unilateral mesial temporal lobe epilepsy (TLE). METHODS: We performed a functional magnetic resonance (MRI) study based on a language comprehension paradigm in 45 right-handed patients with unilateral mesial TLE and 35 healthy control subjects. Activations in the hippocampal formations in both hemispheres were analyzed for each subject as well as for groups of left TLE, right TLE, and controls. RESULTS: In sum, 82% of TLE patients displayed hippocampal activations. A significant difference in hippocampal activation between left and right TLE was found: Right TLE patients showed increased activity in the left hippocampal formation compared with left TLE patients. In contrast, patients with left TLE did not show increased activity in the right hippocampal formation compared with right TLE patients. In comparison with a healthy control group, right TLE patients activated the left hippocampal formation to a greater extent, whereas patients with left TLE did not activate the right hippocampal formation to a greater degree. These findings point to an increased involvement of the left hippocampal formation during a language-comprehension task in right TLE patients. In contrast, left TLE in right-handed patients seems not associated with an enhanced involvement of the right hippocampal formation in retained language comprehension. CONCLUSIONS: These findings suggest that effective language comprehension in right-handed subjects with TLE depends on the involvement of the left hippocampal formation and underline the risks of postoperative language decline in patients with left TLE.     

Memory fMRI lateralizes temporal lobe epilepsy.

BACKGROUND: The assessment of mesial temporal lobe (MTL) function is important for the diagnosis and treatment of temporal lobe epilepsy (TLE) and other brain diseases. Declarative memory depends on the integrity of the MTL region. OBJECTIVE: To investigate hemispheric asymmetries of MTL activity in patients with symptomatic TLE. METHODS: With use of blood oxygenation level-dependent fMRI, hemispheric asymmetries in MTL activation of 30 individual patients with refractory symptomatic TLE and 17 healthy control subjects were studied. Activation was induced by a task employing mental navigation and recall of landmarks based on the retrieval of individually familiar visuospatial knowledge. RESULTS: The study demonstrated that the memory task used reliably activated MTL structures in individual control subjects and patients with refractory TLE including children, older subjects, and patients with low formal IQ. Interhemispheric differences in MTL activation lateralized the side of seizure onset in 90% of patients with symptomatic unilateral TLE. In contrast, healthy control subjects did not show a systematic asymmetry of MTL activation. Correlations between MTL activation and neuropsychological measures suggest that the fMRI-detectable MTL changes were specifically related to memory rather than to memory-independent visuospatial abilities. CONCLUSION: fMRI of memory-induced MTL activation lateralizes the side of seizure onset in patients with refractory symptomatic TLE and may provide complementary information for presurgical evaluation.     

Resting state functional connectivity of the hippocampus associated with neurocognitive function in left temporal lobe epilepsy

The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans. All LTLE patients underwent neuropsychological testing. Resting state functional connectivity maps to the LH were calculated for each patient, and subsequently used in a multiple regression analysis with verbal memory retention scores as a covariate. The analysis identified brain regions whose connectivity to the LH was linearly related to memory retention scores across the group of patients. In LTLE patients, right sided (contralateral) clusters in the precuneus and inferior parietal lobule (IPL) exhibited increased connectivity to the LH with increased memory retention score; left sided (ipsilateral) regions in the precuneus and IPL showed increased connectivity to the LH with decreased retention score. Patients with high memory retention scores had greater connectivity between the LH–right parietal clusters than between the LH–left parietal clusters; in contrast, control subjects had significantly and consistently greater LH–left hemisphere than LH–right hemisphere connectivity. Our results suggest that increased connectivity in contralateral hippocampal functional pathways within the episodic verbal memory network represents a strengthening of alternative pathways in LTLE patients with strong verbal memory retention abilities. Hum Brain Mapp 35:735–744, 2014. © 2012 Wiley Periodicals, Inc.     

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.     

Accelerated long-term forgetting in temporal lobe epilepsy: Verbal,nonverbal and autobiographical memory

Patients with temporal lobe epilepsy (TLE) often present with memory complaints despite performing within normal limits on standard memory tests. One possible explanation for this phenomenon is accelerated long-term forgetting (ALF). The present study investigated material‐specific ALF in patients with unilateral TLE and also examined whether ALF could be demonstrated on a novel, standardized anterograde autobiographical memory (ABM) task. Fourteen patients with TLE and 17 controls were administered verbal, nonverbal and ABM event memory tasks. The participants were tested for immediate recall, recall and recognition at 30‐minute delay, and recall and recognition after four weeks. The extent of ALF was calculated based on the percentage decay of memory from the 30‐minute delay trial to the four-week delay trial. Patients with left TLE showed significantly greater ALF for verbal material and a trend towards greater forgetting of ABM. Patients with right TLE showed a non-significant trend towards greater ALF for nonverbal material. Patients with unilateral hippocampal abnormalities showed greater ALF compared to patients without hippocampal abnormalities. Patients with seizures that generalize had more global memory deficits and greater ALF. We conclude that patients with unilateral TLE show material‐specific ALF, which appears to be more pronounced with an abnormal hippocampus or seizures that secondarily generalize.     

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis

ObjectiveLittle is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance.MethodsResting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE = 22; right mTLE = 19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS.ResultsConnectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE.ConclusionOur results suggest that right hippocampal–left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal–frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS.     

Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis

ObjectiveWe assessed the cognitive performance of patients with temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis (HS), in comparison with that of matched, healthy controls. We report the relationship between cognitive measures and duration of epilepsy, correlating with hippocampal volumes, and the impact of educational level on cognitive decline.MethodsThis study involved 61 outpatients (40 with ⩽8 years and 21 with >8 years of formal education) with unilateral HS and 61 controls. Volumetric MRI was performed on all patients and 10 controls. The results (mean, SD) of the neuropsychological tests of healthy subjects and patients were compared using the Student t and Mann–Whitney tests.ResultsPatients performed worse than controls in the neuropsychological evaluation. When adjusted z scores were used to calculate the impairment index, patients had a greater percentage of abnormal tests compared with controls. The cognitive decline, assessed through the impairment index, correlated with duration of epilepsy. Higher level of education did not protect against this decline, thus not supporting the hypothesis of cerebral reserve in this population. A significant correlation between hippocampal volumetric measures and duration of epilepsy was observed only in patients with left HS.ConclusionPatients with TLE caused by HS present with cognitive morbidity that extends beyond memory deficits. Cognitive decline is associated with duration of epilepsy, and in patients with left-sided HS, duration may correlate with volumetric hippocampal loss.     

Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study

Background

Impairment of recollection memory is consistently reported in patients with major depressive disorder (MDD) and may reflect underlying functional hippocampal changes, particularly in those with extensive histories of illness. We hypothesized that relative to controls, patients with a protracted course of illness would show diminished hippocampal activation on functional magnetic resonance imaging (fMRI) during a recollection memory task.

Methods

Patients who experienced 3 or more previously treated depressive episodes were compared with age- and sex-matched controls. We acquired fMRI data while participants performed a recollection memory process dissociation task.

Results

Using bilateral regions of interest (ROIs) prescribed for the right and left hippocampal/ parahippocampal complex, we observed increased activation of the right hippocampal and left parahippocampal gyrus in controls compared with patients with MDD during recollection memory trials. Within-group comparisons revealed heightened engagement of the hippocampal head (R/L) for controls during recollection trials, and greater activation of the hippocampal body/tail (R/L) during the learn-list encoding period in both the MDD and control groups. Recollection memory performance was significantly correlated with changes in blood oxygen level–dependent signal during recollection trials in the ROIs of the right hippocampus and right hippocampal head.

Limitations

This study was limited by the inclusion of patients taking antidepressant medication, raising the possibility that the reported findings were treatment effects.

Conclusion

The findings of decreased recruitment of the right hippocampal and left parahippocampal gyrus in patients with MDD suggest that these regions may be sensitive to the impact of disease burden and repeated episodes of MDD. This attenuated activation may represent stable changes in hippocampal function that occur over the course of illness in patients with MDD. The findings from within-group comparisons show that the group differences in the activation of the right hippocampal head were driven by greater engagement of this region among controls during recollection memory performance. These results also associate recollection performance impairments in patients with MDD with diminished hippocampal engagement.     

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

Mesial temporal lobe epilepsy (TLE) is a common neurological disorder affecting the hippocampus and surrounding medial temporal lobe (MTL). Although prior studies have analyzed whole‐brain network distortions in TLE patients, the functional network architecture of the MTL at the subregion level has not been examined. In this study, we utilized high‐resolution 7T T2‐weighted magnetic resonance imaging (MRI) and resting‐state BOLD‐fMRI to characterize volumetric asymmetry and functional network asymmetry of MTL subregions in unilateral medically refractory TLE patients and healthy controls. We subdivided the TLE group into mesial temporal sclerosis patients (TLE‐MTS) and MRI‐negative nonlesional patients (TLE‐NL). Using an automated multi‐atlas segmentation pipeline, we delineated 10 MTL subregions per hemisphere for each subject. We found significantly different patterns of volumetric asymmetry between the two groups, with TLE‐MTS exhibiting volumetric asymmetry corresponding to decreased volumes ipsilaterally in all hippocampal subfields, and TLE‐NL exhibiting no significant volumetric asymmetries other than a mild decrease in whole‐hippocampal volume ipsilaterally. We also found significantly different patterns of functional network asymmetry in the CA1 subfield and whole hippocampus, with TLE‐NL patients exhibiting asymmetry corresponding to increased connectivity ipsilaterally and TLE‐MTS patients exhibiting asymmetry corresponding to decreased connectivity ipsilaterally. Our findings provide initial evidence that functional neuroimaging‐based network properties within the MTL can distinguish between TLE subtypes. High‐resolution MRI has potential to improve localization of underlying brain network disruptions in TLE patients who are candidates for surgical resection.     

Material-specific lateralization of working memory in the medial temporal lobe

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging studies, which have focused primarily on visual and visuospatial WM. In the present study we investigated material-specific lateralization of WM in 96 patients with unilateral damage to MTL stemming from TLE (56 left) and 30 control subjects using a pair of matched verbal and visuospatial supraspan tasks. Patients with unilateral TLE were impaired on both verbal and visuospatial WM tasks irrespective of the affected hemisphere. Patients with unilateral right TLE showed an additional deficit for visuospatial WM capacity when contrasted with patients with left TLE, whereas patients with unilateral left TLE showed increased intrusion errors on the verbal task when compared to patients with right TLE. These findings suggest a material-specific lateralization of WM in the MTL.     

Relating medial temporal lobe volume to frontal fMRI activation for memory encoding in older adults

Neuroimaging research on the brain basis of memory decline in older adults typically has examined age-related changes either in structure or in function. Structural imaging studies have found that smaller medial temporal lobe (MTL) volumes are associated with lower memory performance. Functional imaging studies have found that older adults often exhibit bilateral frontal-lobe activation under conditions where young adults exhibit unilateral frontal activation. As yet, no one has examined whether these MTL structural and frontal-lobe functional findings are associated. In this study, we tested whether these findings were correlated in a population of healthy older adults in whom we previously demonstrated verbal memory performance was positively associated with left entorhinal cortex volume in the MTL (Rosen et al., 2003) and right frontal lobe activation during memory encoding (Rosen et al., 2002). Thirteen, non-demented, community-dwelling older adults participated both in a functional MRI (fMRI) study of verbal memory encoding and structural imaging. MRI-derived left entorhinal volume was measured on structural images and entered as a regressor against fMRI activation during verbal memory encoding. Right frontal activation (Brodmann's Area 47/insula) was positively correlated with left entorhinal cortex volume. These findings indicate a positive association between MTL volume and right frontal-lobe function that may underlie variability in memory performance among the elderly, and also suggest a two-stage model of memory decline in aging.     

Medial temporal lobe function and structure in mild cognitive impairment

Functional magnetic resonance imaging (fMRI) was used to study memory-associated activation of medial temporal lobe (MTL) regions in 32 nondemented elderly individuals with mild cognitive impairment (MCI). Subjects performed a visual encoding task during fMRI scanning and were tested for recognition of stimuli afterward. MTL regions of interest were identified from each individual's structural MRI, and activation was quantified within each region. Greater extent of activation within the hippocampal formation and parahippocampal gyrus (PHG) was correlated with better memory performance. There was, however, a paradoxical relationship between extent of activation and clinical status at both baseline and follow-up evaluations. Subjects with greater clinical impairment, based on the Clinical Dementia Rating Sum of Boxes, recruited a larger extent of the right PHG during encoding, even after accounting for atrophy. Moreover, those who subsequently declined over the 2.5 years of clinical follow-up (44% of the subjects) activated a significantly greater extent of the right PHG during encoding, despite equivalent memory performance. We hypothesize that increased activation in MTL regions reflects a compensatory response to accumulating AD pathology and may serve as a marker for impending clinical decline.