Medial Temporal Structures Research Articles

High-resolution imaging of medial temporal lobe subfield structure and function in mild cognitive impairment

High-resolution imaging of medial temporal lobe subfield structure and function in mild cognitive impairment

Comparison between brain CT and MRI for voxel‐based morphometry of Alzheimer's disease

The voxel-based morphometry (VBM) technique using brain magnetic resonance imaging (MRI) objectively maps gray matter loss on a voxel-by-voxel basis after anatomic standardization. In patients with Alzheimer's disease (AD), reductions of gray matter volume, mainly in the medial temporal structures, have been reported; however, inhomogeneity and geometric distortion of the field intensity hampers the reproducibility of MRI. In the present study, we developed a novel computed tomography (CT)-based VBM method and used this technique to detect volume loss in AD patients as compared with normal controls. The results were compared with MRI-based VBM using the same subjects. Pittsburgh Compound B (11C-PIB) positron emission tomography (PET)/CT was performed and two experts in neuro-nuclear medicine judged whether regional amyloid β load was consistent with a diagnosis of AD. Before the injection of 11C-PIB, high-quality CT scans were obtained using the same PET/CT equipment. MRI was performed within a mean interval of 25.1 ± 8.2 days before the PET/CT scan. Using statistical parametric mapping 8 (SPM8), the extracted gray matter images from CT and MRI were spatially normalized using a gray matter template and smoothed using a Gaussian kernel. Group comparisons were performed using SPM8 between five 11C-PIB-positive patients with probable AD and seven 11C-PIB-negative age-matched controls with normal cognition. Gray matter volumes in the bilateral medial temporal areas were reduced in the AD group as compared with the cognitively normal group in both CT-based VBM (in the left; P < 0.0001, cluster size 2776 and in the right; P < 0.0001, cluster size 630) and MRI-based VBM (in the left; P < 0.0001, cluster size 381 and in the right, P < 0.0001, cluster size 421). This newly developed CT-based VBM technique can detect significant atrophy in the entorhinal cortex in probable AD patients as previously reported using MRI-based VBM. However, CT-VBM was more sensitive and revealed larger areas of significant atrophy than MR-VBM.

Comparable seizure characteristics in magnetic seizure therapy and electroconvulsive therapy for major depression

Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD); however, its use for less severe forms of depression is somewhat limited by a lack of control over current spreading to medial temporal lobe memory structures, resulting in various cognitive side effects. In contrast, magnetic seizure therapy (MST), which uses high frequency repetitive transcranial magnetic stimulation (rTMS) for local seizure induction, has been associated with reduced cognitive side effects. To assess whether different characteristics of seizures induced by both methods are responsible for the differences in neuropsychological side-effect profile, we studied seven TRD-patients undergoing both MST and ECT in an open-label, within subject, controlled crossover pilot study. Comparison parameters included seizure-related ictal characteristics, including motor activity, electromyogram (EMG), electroencephalogram (EEG), and postictal recovery and reorientation times.Our results showed no differences in motor activity or EMG and EEG characteristics, thus implicating similar electrophysiological processes in seizure induction with MST and ECT. In line with previous studies, we observed shorter postictal recovery and reorientation times following MST.The ictal characteristics of induced seizures were found similar with ECT and MST suggesting that the more focal seizure induction associated with MST may account for the more beneficial neuropsychological side effect profile of MST.

White matter abnormalities associated with Alzheimer’s disease and mild cognitive impairment: a critical review of MRI studies

In this article, the authors aim to present a critical review of recent MRI studies addressing white matter (WM) abnormalities in Alzheimer’s disease (AD) and mild cognitive impairment (MCI), by searching PubMed and reviewing MRI studies evaluating subjects with AD or MCI using WM volumetric methods, diffusion tensor imaging and assessment of WM hyperintensities. Studies have found that, compared with healthy controls, AD and MCI samples display WM volumetric reductions and diffusion tensor imaging findings suggestive of reduced WM integrity. These changes affect complex networks relevant to episodic memory and other cognitive processes, including fiber connections that directly link medial temporal structures and the corpus callosum. Abnormalities in cortico–cortical and cortico–subcortical WM interconnections are associated with an increased risk of progression from MCI to dementia. It can be concluded that WM abnormalities are detectable in early stages of AD and MCI. Degeneration of WM networks causes disconnection among neural cells and the degree of such changes is related to cognitive decline.

High prevalence of brain pathology in violent prisoners: a qualitative CT and MRI scan study

The aim of this study was to determine the frequency and extent of brain anomalies in a large sample of incarcerated violent offenders not previously considered neuropsychiatrically ill, in comparison with non-violent offenders and non-offending controls. MRI and CT brain scans from 287 male prison inmates (162 violent and 125 non-violent) not diagnosed as mentally ill before that were obtained due to headache, vertigo or psychological complaints during imprisonment were assessed and compared to 52 non-criminal controls. Brain scans were rated qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1) or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex and medial temporal structures bilaterally as well as third ventricle. Overall, offenders displayed a significantly higher rate of morphological abnormality, with the violent offenders scoring significantly higher than non-violent offenders and controls. This difference was statistically detectable for frontal/parietal cortex, medial temporal structures, third ventricle and the left but not the right lateral ventricle. The remarkable prevalence of brain pathology in convicted violent prisoners detectable by neuroradiological routine assessment not only highlights the importance of frontal and temporal structures in the control of social, and specifically of violent behaviour, but also raises questions on the legal culpability of violent offenders with brain abnormalities. The high proportion of undetected presence of structural brain damage emphasizes the need that in violent criminals, the comprehensive routine neuropsychiatric assessment usually performed in routine forensic psychiatric expertises should be complemented with brain imaging.

Distinct patterns of medial temporal impairment in degenerative dementia: a brain SPECT perfusion study in Alzheimer’s disease and frontotemporal dementia

Medial temporal impairment can be detected clinically and by morphological imaging during Alzheimer's disease (AD), but the existence of a functional impairment in this area seems to be less well established. Yet such functional impairment is classically found in other degenerative cortical dementias, such as the frontal variant of frontotemporal dementia (fv-FTD). The aim of this study was to characterize and compare brain SPECT perfusion of the medial temporal lobe in AD and fv-FTD. Voxel-based comparisons were performed using SPM8 between cerebral SPECT images from 85 AD patients, 25 fv-FTD patients and 12 healthy controls at the whole-brain level and the medial temporal lobe level using a region of interest approach (p < 0.001, corrected for the cluster). In the free and cued selective reminding test, used to evaluate medial temporal memory function, AD patients had significantly lower scores than the fv-FTD patients (p < 0.005). AD and fv-FTD patients showed hypoperfused medial temporal structures in comparison to normal controls. However, fv-FTD patients had more pronounced hypoperfusion in this area, with a different topography, more anterior and more parahippocampal. These results show that medial temporal hypoperfusion can be detected in degenerative dementias by SPECT. Paradoxically, the hypoperfusion is more severe in fv-FTD than in AD patients, even though the mnesic profile of AD is more altered, suggesting the existence of inefficient compensatory mechanisms.

Epileptic encephalopathy after HHV6 post-transplant acute limbic encephalitis in children: Confirmation of a new epilepsy syndrome

Generalised epilepsy and cognitive deterioration were recently described in three children following human herpesvirus 6 (HHV6)-associated post-transplant acute limbic encephalitis (PALE). Magnetic resonance imaging (MRI) showed bilateral signal change and/or atrophy in the medial temporal structures and there was no evidence of an ongoing viral or immune-mediated process. We report another child who developed this condition after cord blood transplantation for congenital neutropenia at the age of three. He presented with epileptic spasms four months after HHV6-associated PALE. Cognitive regression, prominent electroencephalographic abnormalities and different types of generalised seizures ensued during the following months and proved refractory to antiepileptic and immunomodulating treatment, which included steroids, immunoglobulin and rituximab. MRI was normal at onset of epilepsy but subsequently showed the development of right hippocampal sclerosis. Results from serial blood and cerebrospinal fluid (CSF) analyses were inconclusive, including lack of patient's CSF and serum reactivity with cultures of dissociated rat hippocampal neurons. This report confirms the existence of a new epilepsy syndrome featuring generalised seizures and epileptic encephalopathy after HHV6-associated PALE in children. Presentation with epileptic spasms, lack of CSF and serum reactivity with cultured rat hippocampal neurons, and rituximab inefficacy are novel features that contribute to delineate the syndrome and argue against an immune-mediated basis of this condition.

Event-based prospective memory and everyday forgetting in healthy older adults and individuals with mild cognitive impairment

An event-based nonfocal task was used to evaluate prospective memory (PM) and the relationship between PM, neuropsychological testing data, and everyday forgetting. Twenty-four participants with mild cognitive impairment (MCI) and 24 age- and education-matched cognitively healthy adults responded to a nonfocal PM cue, while completing an ongoing working memory task. Neuropsychological testing data and self- and informant-report of frequency of forgetting were also gathered. Compared to healthy adults, the MCI participants exhibited significantly poorer prospective remembering and ongoing task performance, despite similar self-reported effort directed to the PM task. Both self- and informant-report indicated that the MCI group was experiencing a higher frequency of everyday forgetting than the healthy adult group. Self-report of everyday forgetting was correlated with PM task performance for the healthy adults, but not for the MCI participants. For the healthy adults, correlational analyses also showed significant relationships between PM accuracy and tests of memory and executive functioning, suggesting that both spontaneous retrieval processes and effortful, strategic monitoring may be important in supporting prospective remembering for this nonfocal PM task. The stronger relationships between PM accuracy and memory and language tests for the MCI group suggest that their poorer event-based prospective remembering might be linked to impaired spontaneous retrieval processes, which are thought to be supported by medial temporal structures.

Decrease of theta response in euthymic bipolar patients during an oddball paradigm

Theta oscillations are related to cognitive functions and reflect functional integration of frontal and medial temporal structures into coherent neurocognitive networks. This study assessed event-related theta oscillations in medication-free, euthymic patients with bipolar disorder upon auditory oddball paradigm. Twenty-two DSM-IV euthymic bipolar I (n=19) and II (n=3) patients and twenty-two healthy subjects were included. Patients were euthymic for at least 6months, and psychotropic-free for at least 2weeks. EEG was recorded at 30 electrode sites. Auditory oddball paradigm and sensory stimuli were used. Event-related Oscillations were analyzed using adaptive filtering in two different theta frequency bands (4-6Hz, 6-8Hz). In healthy subjects, slow theta (4-6Hz) responses were significantly higher than those of euthymic patients upon target, non-target and sensory stimuli (p<0.05). Fast theta (6-8Hz) responses of healthy subjects were significantly higher than those of euthymic patients upon target-only stimuli (p<0.05). Reduced theta oscillations during auditory processing provide strong quantitative evidence of activation deficits in related networks in bipolar disorder. Fast theta responses are related to cognitive functions, whereas slow theta responses are related to sensory processes more than cognitive processes.

Application of the VSRAD, a Specific and Sensitive Voxel-Based Morphometry, to Comparison of Entorhinal Cortex Atrophy between Dementia with Lewy Bodies and Alzheimer’s Disease

Background: Previous studies using magnetic resonance imaging (MRI) showed that dementia with Lewy bodies (DLB) had less atrophy in some medial temporal structures than Alzheimer’s disease (AD). However, very few studies have focused on the entorhinal cortex, which is closely related to episodic memory. We compared the degree of entorhinal cortex atrophy between the two types of dementia using the voxel-based specific regional analysis system for AD (VSRAD) targeting this region. Methods: The subjects consisted of 60 patients with DLB and 210 patients with AD. The degree of entorhinal cortex atrophy was quantified by application of the VSRAD to MRI data, and a Z score >2 was defined as significant atrophy. Results: The DLB group had significantly lower Z scores than the AD group (mean ± SD: 2.25 ± 1.10 vs. 2.85 ± 1.33, p < 0.01). The analysis of covariance with possible confounding factors as covariates also showed that Z scores were significantly lower in the DLB group than in the AD group (p < 0.01). The proportion of patients with atrophy was significantly lower in the DLB group than in the AD group (53 vs. 72%, p < 0.01). Conclusions: The present study using the VSRAD suggests that DLB shows less atrophy in the entorhinal cortex than AD.

Volumetric Brain Changes in Thalamus, Corpus Callosum and Medial Temporal Structures: Mild Alzheimer’s Disease Compared with Amnestic Mild Cognitive Impairment

Background: It is widely known that atrophy of medial temporal structures is present in the mild stage of Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, structures such as the thalamus and corpus callosum are much less studied. Methods: We compared the volumes of the entorhinal cortex, hippocampus, thalamus and the corpus callosum in 14 controls, 14 patients with mild AD and 15 with aMCI and correlated these volumes with neuropsychological data. MRI was obtained at 2 T followed by manual segmentation. Results: We found atrophy in hippocampi and thalami of MCI patients compared to controls, and in the bilateral entorhinal cortex of aMCI compared to AD patients. All the structures showed atrophy in AD patients compared to controls, including the corpus callosum. Conclusions: Our study confirms that thalamic areas are atrophied in aMCI, and the corpus callosum might represent a good structural marker for mild AD. Those areas were associated with cognitive functions already described in the literature.

Integrity of medial temporal structures may predict better improvement of spatial neglect with prism adaptation treatment

Prism adaptation treatment (PAT) is a promising rehabilitative method for functional recovery in persons with spatial neglect. Previous research suggests that PAT improves motor-intentional "aiming" deficits that frequently occur with frontal lesions. To test whether presence of frontal lesions predicted better improvement of spatial neglect after PAT, the current study evaluated neglect-specific improvement in functional activities (assessment with the Catherine Bergego Scale) over time in 21 right-brain-damaged stroke survivors with left-sided spatial neglect. The results demonstrated that neglect patients' functional activities improved after two weeks of PAT and continued improving for four weeks. Such functional improvement did not occur equally in all of the participants: Neglect patients with lesions involving the frontal cortex (n = 13) experienced significantly better functional improvement than did those without frontal lesions (n = 8). More importantly, voxel-based lesion-behavior mapping (VLBM) revealed that in comparison to the group of patients without frontal lesions, the frontal-lesioned neglect patients had intact regions in the medial temporal areas, the superior temporal areas, and the inferior longitudinal fasciculus. The medial cortical and subcortical areas in the temporal lobe were especially distinguished in the "frontal lesion" group. The findings suggest that the integrity of medial temporal structures may play an important role in supporting functional improvement after PAT.

Déjà vu in unilateral temporal-lobe epilepsy is associated with selective familiarity impairments on experimental tasks of recognition memory

In déjà vu, a phenomenological impression of familiarity for the current visual environment is experienced with a sense that it should in fact not feel familiar. The fleeting nature of this phenomenon in daily life, and the difficulty in developing experimental paradigms to elicit it, has hindered progress in understanding déjà vu. Some neurological patients with temporal-lobe epilepsy (TLE) consistently experience déjà vu at the onset of their seizures. An investigation of such patients offers a unique opportunity to shed light on its possible underlying mechanisms. In the present study, we sought to determine whether unilateral TLE patients with déjà vu (TLE+) show a unique pattern of interictal memory deficits that selectively affect familiarity assessment. In Experiment 1, we employed a Remember-Know paradigm for categorized visual scenes and found evidence for impairments that were limited to familiarity-based responses. In Experiment 2, we administered an exclusion task for highly similar categorized visual scenes that placed both recognition processes in opposition. TLE+ patients again displayed recognition impairments, and these impairments spared their ability to engage recollective processes so as to counteract familiarity. The selective deficits we observed in TLE+ patients contrasted with the broader pattern of recognition-memory impairments that was present in a control group of unilateral patients without déjà vu (TLE−). MRI volumetry revealed that ipsilateral medial temporal structures were less broadly affected in TLE+ than in TLE− patients, with a trend for more focal volume reductions in the rhinal cortices of the TLE+ group. The current findings establish a first empirical link between déjà vu in TLE and processes of familiarity assessment, as defined and measured in current cognitive models. They also reveal a pattern of selectivity in recognition impairments that is rarely observed and, thus, of significant theoretical interest to the memory literature at large.

P2‐218: Comparison of performance of early diagnostics of Alzheimer's disease between volume and thickness measurements of medial temporal structures using structural MRI

P2‐218: Comparison of performance of early diagnostics of Alzheimer's disease between volume and thickness measurements of medial temporal structures using structural MRI

Symptomatic generalized epilepsy after HHV6 posttransplant acute limbic encephalitis in children

Human herpesvirus 6 (HHV6) is the major cause of posttransplant acute limbic encephalitis (PALE) in immunosuppressed patients following hematopoietic stem cell transplant. Memory impairment and temporal lobe epilepsy following PALE are reported in adults, but sequelae in young children are unknown. We report three children with HHV6-associated PALE 20-23 days after cord blood transplantation for leukemias who developed symptomatic generalized epilepsy. Patients were followed for 2-8 years and underwent magnetic resonance imaging (MRI) and video-electroencephalography (EEG). Two patients underwent viral and autoimmune testing and immunotherapies. Generalized seizures, including tonic seizures, developed 11-18 months after HHV6-associated PALE. Seizures were frequent and resistant to multiple antiepileptic drugs (AEDs). Generalized slow spike-wave and low-voltage fast activity were recorded on interictal and ictal EEGs. The two younger patients regressed in their general abilities, synchronous with seizure evolution, whereas the older patient developed a severe amnestic syndrome that halted intellectual development. Serial MRI studies revealed bilateral signal change and atrophy in the medial temporal structures of all patients. In the two investigated patients, there was no evidence of chronic HHV6 infection, minimal evidence of cerebral inflammation, and no significant improvement with pulse with intravenous methylprednisolone and immunoglobulin. The severe and generalized seizure, cognitive, and EEG sequelae of HHV6-related PALE in these children may be due to a chronic, viral, or immune-mediated inflammatory process or developmental epileptogenesis resulting from bilateral hippocampal injury at an early age, although there was a paucity of evidence for either.

Remediation of information processing following traumatic brain injury: A community-based rehabilitation approach

Traumatic brain injury (TBI) results in disruption of information processing via damage to primary, secondary, and tertiary cortical regions, as well as, subcortical pathways supporting information flow within and between cortical structures. TBI predominantly affects the anterior frontal poles, anterior temporal poles, white matter tracts and medial temporal structures. Fundamental information processing skills such as attention, perceptual processing, categorization and cognitive distance are concentrated within these same regions and are frequently disrupted following injury. Information processing skills improve in accordance with the extent to which residual frontal and temporal neurons can be encouraged to recruit and bias neuronal networks or the degree to which the functional connectivity of neural networks can be re-established and result in re-emergence or regeneration of specific cognitive skills. Higher-order cognitive processes, i.e., memory, reasoning, problem solving and other executive functions, are dependent upon the integrity of attention, perceptual processing, categorization, and cognitive distance. A therapeutic construct for treatment of attention, perceptual processing, categorization and cognitive distance deficits is presented along with an interventional model for encouragement of re-emergence or regeneration of these fundamental information processing skills.

Delayed complication after Gamma Knife surgery for mesial temporal lobe epilepsy

Despite the controversy over the clinical significance of Gamma Knife surgery (GKS) for refractory mesial temporal lobe epilepsy (MTLE), the modality has attracted attention because it is less invasive than resection. The authors report long-term outcomes for 7 patients, focusing in particular on the long-term complications. Between 1996 and 1999, 7 patients with MTLE underwent GKS. The 50% marginal dose covering the medial temporal structures was 18 Gy in 2 patients and 25 Gy in the remaining 5 patients. High-dose treatment abolished the seizures in 2 patients and significantly reduced them in 2 others. One patient in this group was lost to follow-up. However, 2 patients presented with symptomatic radiation necrosis (SRN) necessitating resection after 5 and 10 years. One patient who did not need necrotomy continued to show radiation necrosis on MRI after 10 years. One patient died of drowning while swimming in the sea 1 year after GKS, before seizures had disappeared completely. High-dose treatment resulted in sufficient seizure control but carried a significant risk of SRN after several years. Excessive target volume was considered as a reason for delayed necrosis. Drawbacks such as a delay in seizure control and the risk of SRN should be considered when the clinical significance of this treatment is evaluated.

Episodic memory in frontotemporal dementia: a critical review

This review offers a critical appraisal of the literature on episodic memory performance in frontotemporal dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the frontotemporal dementia syndrome. In particular, patients with the subtypes of behavioural variant frontotemporal dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of frontotemporal dementia, semantic dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for frontotemporal dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early frontotemporal dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in frontotemporal dementia, particularly in behavioural variant frontotemporal dementia. In semantic dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in frontotemporal dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in frontotemporal dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of frontotemporal dementia.

Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area

BackgroundThe medial temporal structures, including the hippocampus and the entorhinal cortex, are critical for the ability to transform daily experience into lasting memories. We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance.MethodsWe implanted intracranial depth electrodes in seven subjects to identify seizure-onset zones for subsequent epilepsy surgery. The subjects completed a spatial learning task during which they learned destinations within virtual environments. During half the learning trials, focal electrical stimulation was given below the threshold that elicits an afterdischarge (i.e., a neuronal discharge that occurs after termination of the stimulus).ResultsEntorhinal stimulation applied while the subjects learned locations of landmarks enhanced their subsequent memory of these locations: the subjects reached these landmarks more quickly and by shorter routes, as compared with locations learned without stimulation. Entorhinal stimulation also resulted in a resetting of the phase of the theta rhythm, as shown on the hippocampal electroencephalogram. Direct hippocampal stimulation was not effective. In this small series, no adverse events associated with the procedure were observed.ConclusionsStimulation of the entorhinal region enhanced memory of spatial information when applied during learning. (Funded by the National Institutes of Health and the Dana Foundation.)

Neuroimaging of Dementia Focused on Alzheimer's Disease

Remarkable progress has been recently achieved in neuroimaging of Alzheimer’s disease prominently in MRI and amyloid PET imaging. We reviewed current morphological and functional MRI and amyloid PET imaging with attention to Pittsburgh compound-B (PiB), the most extensively investigated and validated tracer. Automated voxel-based morphometry of brain MRI has been prevailed in Japan using voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) for the sensitive detection of selective atrophy in medial temporal structures. Arterial spin labeling technique for the evaluation of brain perfusion without any contrast material may replace FDG-PET or brain perfusion SPECT. PiB specifically binds to fibrillar beta-amyloid deposits in such as those found in the cerebral cortex and striatum. PiB-PET imaging is a sensitive and specific biological marker for underlying amyloid deposition that is an early event on the path to dementia. Amyloid imaging in healthy controls and mild cognitive impairment patients may offer the possibility detecting those at high risk of future AD, as so candidates for early preventive measures if and when they become available. (日本医科大学医学会雑誌 2012; 8: 280―284)