Integrity Of Medial Temporal Lobe Research Articles

Olfactory function reflects episodic memory performance and atrophy in the medial temporal lobe in individuals at risk for Alzheimer’s disease

We examined cognitive domains and brain regions associated with olfactory performance in cognitively unimpaired older adults (CU-OAs) and individuals with or at risk for Alzheimer’s Disease (AD). We compared CU-OAs (N = 55), individuals with subjective cognitive decline (SCD, N = 55), mild cognitive impairment (MCI, N = 101), and AD (N = 45) on measures of olfactory function (Brief Smell Identification Test), cognition (episodic and semantic memory), and medial temporal lobe thickness and volume. Analyses controlled for age, sex, education, and total intracranial volume. Olfactory function decreased from SCD to MCI to AD. CU-OAs outperformed all groups except SCDs on tests of cognition and olfaction. Although these measures did not differ between the CU-OAs and SCDs, olfactory function correlated with episodic memory tests and with entorhinal cortex atrophy only in the SCD group. Olfactory function also correlated with hippocampal volume and right-hemisphere entorhinal cortex thickness in the MCI group. Olfactory dysfunction reflects medial temporal lobe integrity and memory performance in a group at risk for AD with normal cognition and olfaction.

Medial temporal lobe structure, mnemonic and perceptual discrimination in healthy older adults and those at risk for mild cognitive impairment

Cognitive tests sensitive to the integrity of the medial temporal lobe (MTL), such as mnemonic discrimination of perceptually similar stimuli, may be useful early markers of risk for cognitive decline in older populations. Perceptual discrimination of stimuli with overlapping features also relies on MTL but remains relatively unexplored in this context. We assessed mnemonic discrimination in two test formats (Forced Choice, Yes/No) and perceptual discrimination of objects and scenes in 111 community-dwelling older adults at different risk status for cognitive impairment based on neuropsychological screening. We also investigated associations between performance and MTL sub-region volume and thickness. The at-risk group exhibited reduced entorhinal thickness and impaired perceptual and mnemonic discrimination. Perceptual discrimination impairment partially explained group differences in mnemonic discrimination and correlated with entorhinal thickness. Executive dysfunction accounted for Yes/No deficits in at-risk adults, demonstrating the importance of test format for the interpretation of memory decline. These results suggest that perceptual discrimination tasks may be useful tools for detecting incipient cognitive impairment related to reduced MTL integrity in nonclinical populations.

Model of brain maintenance reveals specific change-change association between medial-temporal lobe integrity and episodic memory.

Brain maintenance has been identified as a major determinant of successful memory aging. However, the extent to which brain maintenance in support of successful memory aging is specific to memory-related brain regions or forms part of a brain-wide phenomenon is unresolved. Here, we used longitudinal brain-wide gray matter MRI volumes in 262 healthy participants aged 55 to 80 years at baseline to investigate separable dimensions of brain atrophy, and explored the links of these dimensions to different dimensions of cognitive change. We statistically adjusted for common causes of change in both brain and cognition to reveal a potentially unique signature of brain maintenance related to successful memory aging. Critically, medial temporal lobe (MTL)/hippocampal change and episodic memory change were characterized by unique, residual variance beyond general factors of change in brain and cognition, and a reliable association between these two residualized variables was established (r = 0.36, p < 0.01). The present study is the first to provide solid evidence for a specific association between changes in (MTL)/hippocampus and episodic memory in normal human aging. We conclude that hippocampus-specific brain maintenance relates to the specific preservation of episodic memory in old age, in line with the notion that brain maintenance operates at both general and domain-specific levels.

Does olfactory dysfunction have the same relationship with limbic system integrity in Alzheimer’s and Parkinson’s disease?

AbstractBackgroundWe have demonstrated that olfactory dysfunction is common in Alzheimer’s disease (AD), and is associated with poorer episodic memory performance and medial temporal lobe (MTL) integrity in groups at risk for AD. Olfactory decline is also common in Parkinson’s disease (PD); however, the difference in pathology between these diseases remains poorly understood.MethodUsing data from the Comprehensive Assessment of Neurodegeneration in Aging (COMPASS‐ND) study, we compared older adults with subjective cognitive decline (SCD; N=55, Mage =70.1, %female=78), mild cognitive impairment (MCI; N=100, Mage =71.2, %female=45) and AD (N=47, Mage =74.8, %female=31) with those at risk for (PD‐MCI; N=25, Mage =71.4, %female=20) and with Parkinson’s disease (PD; N=34, Mage =66.5, %female=44) on measures of olfaction (Brief Smell Identification Test), cognition (episodic, working and semantic memory), and structural MRI (volume and cortical thickness of the MTL and orbitofrontal cortex). All analyses controlled for age, sex, and education; MRI analyses also controlled for total intracranial volume.ResultOur analyses revealed that olfactory function was highest in SCD (M=10.33, SD=1.69), and declined in MCI (M=8.84, SD=2.98), and AD groups (M=6.06, SD=2.73) successively. The PD group (M=7.12, SD=2.78) did not differ from PD‐MCI group (M=5.28, SD=3.26), and was in line with the poor performance of the AD participants. These groups had poorer olfactory performance compared to the SCD and MCI groups.ConclusionOlfactory deficits are present in PD participants regardless of MCI. We will also report on whether olfactory function predicts MTL integrity in PD, as it does in individuals at risk for AD.

Brain-behavior investigation of potential cognitive markers of Alzheimer's disease in middle age: a multi-modal imaging study.

Early detection of Alzheimer's disease remains a challenge, and the development and validation of novel cognitive markers of Alzheimer's disease is critical to earlier disease detection. The goal of the present study is to examine brain-behavior relationships of translational cognitive paradigms dependent on the medial temporal lobes and prefrontal cortices, regions that are first to undergo Alzheimer's-associated changes. We employed multi-modal structural and functional MRI to examine brain-behavior relationships in a healthy, middle-aged sample (N = 133; 40-60years). Participants completed two medial temporal lobe-dependent tasks (virtual Morris Water Task and Transverse Patterning Discriminations Task), and a prefrontal cortex-dependent task (Reversal Learning Task). No associations were found between various MRI measures of brain integrity and the Transverse Patterning or Reversal Learning tasks (p's > .05). We report associations between virtual Morris Water Task performance and medial temporal lobe volume, hippocampal microstructural organization, fornix integrity, and functional connectivity within the executive control and frontoparietal control resting state networks (all p's <0.05; did not survive correction for multiple comparisons). This study suggests that virtual Morris Water Task performance is associated with medial temporal lobe integrity in middle age, a critical window for detection and prevention of Alzheimer's disease, and may be useful as an early cognitive marker of Alzheimer's disease risk.

Association between Self-Reported Pain, Cognition, and Neuropathology in Older Adults Admitted to an Outpatient Memory Clinic-A Cross-Sectional Study.

Cognitive impairment has been linked to reduced self-reporting of pain. However, it is unclear whether the various cognitive functions are similarly and/or independently associated with such pain report measures. In the present study, we explored how executive functioning (EF), memory, and global cognition relate to self-reported pain and investigated whether underlying neuropathology partially accounts for these results. We used Lasso categorical regression to analyze data from 179 individuals visiting a memory clinic. The data included the self-reported pain occurrence, intensity, severity and frequency, clinical diagnoses, neuropsychological scores, white matter hyperintensities, medial temporal lobe atrophy, depressive symptoms, and demographics. Our results showed that worse memory and EF performance predicted a lower pain occurrence. In those individuals who did report pain, worse memory predicted lower pain intensity, severity, and frequency levels, but for EF reversed effects were found, with worse EF predicting higher pain scores. These relationships were only partially explained by reductions in white matter and medial temporal lobe integrity. Similar effects were found for depressive symptoms. Our findings highlight the distinct associations of EF and memory with self-reported pain. A similar pattern of relationships found for both self-reported pain and depressive symptoms may reflect shared latent affective components.

Long-term memory and hippocampal function support predictive gaze control during goal-directed search.

Eye movements during visual search change with prior experience for search stimuli. Previous studies measured these gaze effects shortly after initial viewing, typically during free viewing; it remains open whether the effects are preserved across long delays and for goal-directed search, and which memory system guides gaze. In Experiment 1, we analyzed eye movements of healthy adults viewing novel and repeated scenes while searching for a scene-embedded target. The task was performed across different time points to examine the repetition effects in long-term memory, and memory types were grouped based on explicit recall of targets. In Experiment 2, an amnesic person with bilateral extended hippocampal damage and the age-matched control group performed the same task with shorter intervals to determine whether or not the repetition effects depend on hippocampal function. When healthy adults explicitly remembered repeated target-scene pairs, search time and fixation duration decreased, and gaze was directed closer to the target region, than when they forgot targets. These effects were seen even after a one-month delay from their initial viewing, suggesting the effects are associated with long-term, explicit memory. Saccadic amplitude was not strongly modulated by scene repetition or explicit recall of targets. The amnesic person did not show explicit recall or implicit repetition effects, whereas his control group showed similar patterns to those seen in Experiment 1. The results reveal several aspects of gaze control that are influenced by long-term memory. The dependence of gaze effects on medial temporal lobe integrity support a role for this region in predictive gaze control.

Absence of an early hippocampal encoding signal after medial temporal lesions: No consequence for the spacing effect.

Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200-300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements, and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE)-the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL-mediated signal but not the spacing effect. We conclude that the SE does not depend on MTL integrity. We suggest that the early frontal signal at 200-300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's.

Parietal lobe critically supports successful paired immediate and single-item delayed memory for targets

The parietal lobe is important for successful recognition memory, but its role is not yet fully understood. We investigated the parietal lobes’ contribution to immediate paired-associate memory and delayed item-recognition memory separately for hits (targets) and correct rejections (distractors). We compared the behavioral performance of 56 patients with known parietal and medial temporal lobe dysfunction (i.e. early Alzheimer’s Disease) to 56 healthy control participants in an immediate paired and delayed single item object memory task. Additionally, we performed voxel-based morphometry analyses to investigate the functional-neuroanatomic relationships between performance and voxel-based estimates of atrophy in whole-brain analyses. Behaviorally, all participants performed better identifying targets than rejecting distractors. The voxel-based morphometry analyses associated atrophy in the right ventral parietal cortex with fewer correct responses to familiar items (i.e. hits) in the immediate and delayed conditions. Additionally, medial temporal lobe integrity correlated with better performance in rejecting distractors, but not in identifying targets, in the immediate paired-associate task. Our findings suggest that the parietal lobe critically supports successful immediate and delayed target recognition memory, and that the ventral aspect of the parietal cortex and the medial temporal lobe may have complementary preferences for identifying targets and rejecting distractors, respectively, during recognition memory.

Neocortical catastrophic interference in healthy and amnesic adults: a paradoxical matter of time.

The human cortex can accommodate overlapping semantic information, such as synonyms, homonyms, or overlapping concepts. However, neuronal models of cortical networks predict Catastrophic Interference in conditions of overlapping information, obliterating old associations and sometimes preventing formation of new ones. It has been proposed that Catastrophic Interference in declarative memory is never observed in biological systems because of hippocampal pattern separation of competing associations. Here, we tested neocortical Catastrophic Interference during acquisition of overlapping associations through Fast Mapping; an incidental, exclusion based learning mechanism, that can support hippocampal-independent learning. Young adults acquired picture-label associations, either through explicit encoding or through Fast Mapping and were tested after 24 h. Overlapping/competing associations were presented either minutes (Early), or 22 h (Delayed) after learning. Catastrophic Interference was evident only following Fast Mapping, and only in the Delayed competition. In a follow-up experiment, Medial Temporal Lobe (MTL) amnesic patients demonstrated retroactive Catastrophic Interference after the Early competition, despite normal memory for noninterfered Fast Mapping associations. Thus, following Fast Mapping, a biological system demonstrated susceptibility to Catastrophic Interference, as predicted by the neuronal-model. Early retroactive Interference, however, can be prevented by MTL integrity.

Long-lasting effects of prenatal dietary choline availability on object recognition memory ability in adult rats

Choline is an essential nutrient required for early development. Previous studies have shown that prenatal choline availability influences adult memory abilities depending on the medial temporal lobe integrity. The relevance of prenatal choline availability on object recognition memory was assessed in adult Wistar rats. Three groups of pregnant Wistar rats were fed from E12 to E18 with choline-deficient (0 g/kg choline chloride), standard (1.1 g/kg choline chloride), or choline-supplemented (5 g/kg choline chloride) diets. The offspring was cross-fostered to rat dams fed a standard diet during pregnancy and tested at the age of 3 months in an object recognition memory task applying retention tests 24 and 48 hours after acquisition. Although no significant differences have been found in the performance of the three groups during the first retention test, the supplemented group exhibited improved memory compared with both the standard and the deficient group in the second retention test, 48 hours after acquisition. In addition, at the second retention test the deficient group did not differ from chance. Taken together, the results support the notion of a long-lasting beneficial effect of prenatal choline supplementation on object recognition memory which is evident when the rats reach adulthood. The results are discussed in terms of their relevance for improving the understanding of the cholinergic involvement in object recognition memory and the implications of the importance of maternal diet for lifelong cognitive abilities.

Distinct medial temporal contributions to different forms of recognition in amnestic mild cognitive impairment and Alzheimer's disease

The simplest expression of episodic memory is the experience of familiarity, the isolated recognition that something has been encountered previously. Brain structures of the medial temporal lobe (MTL) make essential contributions to episodic memory, but the distinct contributions from each MTL structure to familiarity are debatable. Here we used specialized tests to assess recognition impairments and their relationship to MTL integrity in people with amnestic mild cognitive impairment (aMCI, n=19), people with probable Alzheimer's disease (AD; n=10), and age-matched individuals without any neurological disorder (n=20). Recognition of previously presented silhouette objects was tested in two formats—forced-choice recognition with four concurrent choices (one target and three foils) and yes/no recognition with individually presented targets and foils. Every foil was extremely similar to a corresponding target, such that forced-choice recognition could be based on differential familiarity among the choices, whereas yes/no recognition necessitated additional memory and decision factors. Only yes/no recognition was impaired in the aMCI group, whereas both forced-choice and yes/no recognition were impaired in the AD group. Magnetic resonance imaging showed differential brain atrophy, as MTL volume was reduced in the AD group but not in the aMCI group. Pulsed arterial spin-labeled scans demonstrated that MTL blood flow was abnormally increased in aMCI, which could indicate physiological dysfunction prior to the emergence of significant atrophy. Regression analyses with data from all patients revealed that regional patterns of MTL integrity were differentially related to forced-choice and yes/no recognition. Smaller perirhinal cortex volume was associated with lower forced-choice recognition accuracy, but not with lower yes/no recognition accuracy. Instead, smaller hippocampal volumes were associated with lower yes/no recognition accuracy. In sum, familiarity memory can be specifically assessed using the forced-choice recognition test, it declines later than other MTL-dependent memory functions as AD progresses, and it has distinct anatomical substrates.

The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age

Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 60–87 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 × 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r2 = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE ε4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R2 = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R2 = 0.08) “risk” alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE ε4 carriers with additional TOMM40 “risk” alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.

Decision time and response accuracy in a conditional motor learning task are impaired independently in unilateral temporal lobe-resected patients

Learning and memory of declarative knowledge and relational information are dependent on the integrity of medial temporal lobe (MTL). Numerous studies suggest that left lobectomy impairs verbal memory while right lobectomy impairs non-verbal memory. In order to instrumentally quantify material-specific memory impairment after temporal lobe excision, we compared, using a computerized conditional motor associative learning task, patients with surgically treated drug-resistant temporal lobe epilepsy to age-matched controls.We enrolled seven epileptic patients with left (LTR), seven with right (RTR) temporal lobe resection and fourteen controls. During the task, abstract visual stimuli had to be associated, by trial and error, with a spatially oriented joystick motor response. Response and decision time were analyzed.Statistical analysis disclosed that the learning curve slopes of both RTR and LTR patients were significantly shallower compared to controls, LTR patients needed a number of test trials significantly increased compared to RTR patients and controls, the average probability of success in the test trials was significantly lower in LTR patients compared to RTR patients and controls, and RTR patients' decision times were significantly longer than LTR patients and controls.The results suggest that RTR patients, using the preserved verbalization strategy, achieved higher learning scores than LTR patients, which were forced to use a visuo-spatial representation of the stimuli–response association. Accordingly, RTR patients were significantly slower, compared to LTR patients and controls, indicating that processes involving recall were partially impaired, and non-canonical networks for executing a non-verbal task could be in action.

Structural correlates of prospective memory

Prospective memory (PM) includes the encoding and maintenance of an intention, and the retrieval and execution of this intention at the proper moment in the future. The present study expands upon previous behavioral, electrophysiological, and functional work by examining the association between grey matter volume and PM. Estimates of grey matter volume in theoretically relevant regions of interest (prefrontal, parietal, and medial temporal) were obtained in conjunction with performance on two PM tasks in a sample of 39 cognitively normal and very mildly demented older adults. The first PM task, termed focal in the literature, is supported by spontaneous retrieval of the PM intention whereas the second, termed non-focal, relies on strategic monitoring processes for successful intention retrieval. A positive relationship was observed between medial temporal volume and accuracy on the focal PM task. An examination of medial temporal lobe subregions revealed that this relationship was strongest for the hippocampus, which is considered to support spontaneous memory retrieval. There were no significant structure–behavior associations for the non-focal PM task. These novel results confirm a relationship between behavior and underlying brain structure proposed by the multiprocess theory of PM, and extend findings on cognitive correlates of medial temporal lobe integrity.

A flicker change detection task reveals object-in-scene memory across species

Tests of recognition memory in macaques typically assay memory for objects or isolated images, over time spans of seconds to hours from stimulus presentation, and/or require extensive training. Here, we propose a new application of the flicker change detection task that could measure object-in-scene memory days after single-trial exposures. In three experiments, participants searched for a changing object – or “target” – embedded within a scene as their eye movements were tracked. For new targets-in-scenes, the change is difficult to detect and requires extensive search. Once the target is found, however, the change becomes obvious. We reasoned that the decreased times required to find a target in a repeated scene would indicate memory for the target. In humans, targets were found faster when the targets-and-scenes were explicitly remembered than when they were forgotten, or had never been seen before. This led to faster repeated-trial compared to novel-trial search times. Based solely on repeated-trial search times, we were able to select distributions comprised of predominantly remembered or predominantly forgotten trials. Macaques exhibited the same repetition effects as humans, suggesting that remembered trials could be dissociated from novel or forgotten trials using the same procedures we established in humans. Finally, an anterograde amnesic patient with damage that included the medial temporal lobe (MTL) showed no search time differences, suggesting that memory revealed through search times on this task requires MTL integrity. Together, these findings indicate that the time required to locate a changing object reveals object-in-scene memory over long retention intervals in humans and macaques.

Exercise moderates age-related atrophy of the medial temporal lobe

Regional deterioration of brain structure is a typical feature of aging, but emerging evidence suggests that exercise may mitigate the decline. The purpose of the present investigation was to examine the moderating influence of exercise engagement on cross-sectional estimates of age-related brain atrophy at both global and regional levels. Estimates of exercise engagement over the past 10 years and MRI-based measures of global (gray and white) and regional volumes were obtained in a sample of 52 healthy older adults aged 55-79. Volume estimates were obtained in prefrontal, parietal, temporal, occipital, neostriatal, and medial temporal regions. Higher levels of exercise engagement were related to larger superior frontal volumes. Most critically, exercise engagement selectively moderated age-related medial temporal lobe atrophy. Specifically, significant age-related atrophy was observed for older adults who engaged in low levels of exercise, but not for those who engaged in high levels of exercise. This novel finding extends support for the efficacy of exercise to the potential maintenance of medial temporal lobe integrity in older adults.

Diagnosis and management of patients with heart failure in England

The objective of this postal survey was to assess the services currently accessed by primary care trusts (PCTs) for patients with chronic heart failure. Of the 303 PCTs in England, 225 (74%) responded to the questionnaire. Natriuretic peptides were used by 61 (26%) PCTs, whereas direct access to echocardiography was available to 163 (72%) and heart failure clinics to 95 (42%). Heart failure services were led by a cardiologist in 138 (61%) main referring hospitals, an elderly care physician in 33 (15%), and other physicians in 50 (22%). In total, 138 (62%) PCTs had access to heart failure nurses and 40 (18%) used coronary heart disease nurses; in 13 (5%) PCTs, patients with heart failure were seen by practice nurses. This survey highlights the need for further research on the cost effectiveness of service models for diagnosing and managing heart failure. The evidence base behind heart failure nurses should support their wider availability. The question of who cares for patients with heart failure should be reflected more widely in specialist training programmes in both secondary and primary care.

Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats

Rodent models of cognitive aging routinely use spatial performance on the water maze to characterize medial temporal lobe integrity. Water maze performance is dependent upon this system and, as in the aged human population, individual differences in learning abilities are reliably observed among spatially characterized aged rats. However, unlike human aging in which cognitive deficits rarely occur in isolation, few non-spatial learning deficits have been identified in association with spatial impairment among aged rats. In this study, a subset of male aged Fischer 344 rats was impaired both in water maze and odor discrimination tasks, whereas other aged cohorts performed on par with young adult rats in both settings. The odor discrimination learning deficits were reliable across multiple problems. Moreover, these deficits were not a consequence of anosmia and were specific to olfactory learning, as cognitively impaired aged rats performed normally on an analogous non-olfactory discrimination task. These are among the first data to describe an aging model in which individual variability among aged rat cognition occurs across two independent behavioral domains.

Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment

We examined the dynamic process of encoding novel repeating faces using functional MRI (fMRI) in non-demented elderly volunteers with and without diagnosed memory problems. We hypothesized that adaptation (repetition dependent reduction in activity) would occur in the mesial temporal lobe (MTL), and that this would be associated with cognitive status. Twenty-three right-handed volunteers were studied with an experimental encoding paradigm during fMRI scanning. Twelve participants had the diagnosis of mild cognitive impairment-amnestic type (MCI). The remaining 11 were cognitively healthy. All were diagnosed with a comprehensive neuropsychological battery and neurological evaluation prior to the study; they also received a brief cognitive battery the day of the scan. During the event-related fMRI task, participants viewed unfamiliar faces that repeated on average every 25 s with seven repetitions. The reduction in activation response as a function of repetition of unfamiliar faces was modeled in SPM99. Statistical parametric maps of adaptation slopes reflecting the decrease in activation with stimulus repetition were calculated for each participant, followed by a random-effects group analysis in which slope images were tested for significant group differences. Significant differences in adaptation slopes, with more negative slopes in the controls, were found in the medial temporal search region in the hippocampus and parahippocampal gyrus bilaterally, right more than left. Gray matter density analyses suggest the adaptation difference is not due to atrophy. Results suggest that the medial temporal response over repeated presentation is related to clinical status. Probes of incremental encoding processes over trials may be useful markers of medial temporal lobe integrity.