Age-related differences in the functional connectivity of the hippocampus during memory encoding

The purpose of the current experiment was to examine the functional connectivity of the hippocampus during encoding in young and old adults, and the way in which this connectivity was related to recognition performance. Functional connectivity was defined as the correlation between activity in the hippocampus and activity in the rest of the brain, as measured by neuroimaging. During encoding of words and pictures of objects in young adults, hippocampal activity was correlated with activity in the ventral prefrontal and extrastriate regions, and increased activity in all these regions was associated with better recognition. In contrast, older adults showed correlations between hippocampal activity and the dorsolateral prefrontal and parietal regions, and positive correlations between activity in these regions and better memory performance. This ventral/dorsal distinction suggests a shift in the cognitive resources used with age from more perceptually based processes to those involved in executive and organizational functions. The results of this study provide evidence that aging is associated with alterations in hippocampal function, including how it is functionally connected with prefrontal cortex, and that these alterations have an impact on memory performance.     

Entorhinal cortex modules of the human brain

Much is known about modular organization in the cerebral cortex, but this knowledge is skewed markedly toward primary sensory areas, and in fact, it has been difficult to demonstrate elsewhere. In this report, we test the hypothesis that a unique form of modules exists in the entorhinal area of the human cortex (Brodmann's area 28). We examined this issue using classic cyto- and myeloarchitectonic stains, immunolabeling for various neurochemicals, and histochemistry for certain enzymes. The findings reveal that the entorhinal cortex in the human is formed by a mosaic of cellular aggregates whose most conspicuous elements are the cell islands of layer II and myelinated fibers around the cell islands, the disposition of glutamic acid decarboxylase-positive neurons and processes, cytochrome oxidase staining, and the pattern of cholinergic afferent fibers. The neuropathology of Alzheimer's disease cases highlights the modules, but inversely so, by destroying their features. The findings are of interest because 1) anatomically defined modules are shown to be present in areas other than the sensory and motor cortices, 2) the modules are morphological entities likely to reflect functions of the entorhinal cortex, and 3) the destruction of entorhinal cortex modules may account disproportionately for the severity of memory impairments in Alzheimer's disease. © 1996 Wiley-Liss, Inc.     

A medial temporal lobe division of labor: Insights from memory in aging and early Alzheimer disease

Dual process theories of recognition memory posit that recollection and familiarity represent dissociable processes. Animal studies and human functional imaging experiments support an anatomic dissociation of these processes in the medial temporal lobes (MTL). By this hypothesis, recollection may be dependent on the hippocampus, while familiarity appears to rely on extrahippocampal MTL (ehMTL) structures, particularly perirhinal and lateral entorhinal cortices. Despite these findings, the dual process model and these anatomic mappings remain controversial, in part because the study of patients with lesions to the MTL has been limited and has revealed predominantly single dissociations. We examined measures of recollection and familiarity in three groups (normal older adults, amnesic‐mild cognitive impairment, Alzheimer's disease) in which these memory measures and the relative integrity of MTL structures are variable, thus enhancing our power to detect MTL‐memory relationships. Recollection and familiarity and volumes of hippocampus and ehMTL, defined as a region including entorhinal/perirhinal cortices and parahippocampus, were measured. Regression analyses revealed a stronger relationship of recollection with the hippocampus compared to ehMTL, while familiarity was more highly related to ehMTL compared to hippocampus. These results are consistent with a division of labor in the MTL and the dual process model. © 2010 Wiley‐Liss, Inc.     

Temporal lobe-oriented CT scanning and dementia in Down's syndrome

BACKGROUND: Although individuals with Down's syndrome (DS) are uniquely at risk of developing Alzheimer's disease, the diagnosis of dementia in DS is problematic because of the difficulty in detecting cognitive decline in individuals with pre-existing learning disability. AIM: To determine if dementia in DS is associated with Medial Temporal Lobe (MTL) atrophy as measured by temporal lobe-oriented CT scanning. METHOD: Ten individuals with DS who were experiencing functional decline had CT scans with temporal lobe-oriented views. All individuals were assessed for the presence of dementia according to modified DSM-IIIR criteria. The minimal thickness of the MTL, corrected for age-related atrophy was measured using a computer calipers at the level of the mid-brainstem by a radiologist blind to the dementia diagnosis. RESULTS: All six individuals who met modified DSM-IIIR criteria for dementia showed significant MTL atrophy. CONCLUSIONS: The utility of temporal lobe-oriented CT scanning as an adjunct to the diagnosis of dementia in DS appears promising and warrants further study.     

Medial temporal lobe atrophy and memory deficits in elderly stroke patients

Medial temporal lobe atrophy (MTA) and its role in memory deficits have been studied extensively in patients with various dementias and non-degenerative neurologic diseases. In stroke patients MTA is a significant risk factor for dementia. However, its role in memory decline in non-demented stroke patients is not yet known. Our aim was to evaluate the relationship between MTA and cognitive functions in a large cohort of elderly patients, who underwent a comprehensive neuropsychologic examination and magnetic resonance imaging 3 months after an ischemic stroke. The study sample (n = 260) was divided into three groups according to the severity of MTA. After adjusting for age, volume of infarcts and cortical atrophy, we found that patients with moderate to severe MTA performed significantly worse in tests of learning, story recall, visual reproduction, block design and mental speed. In contrast, the groups did not differ in tests of digit span, flexibility, verbal fluency and conceptualization. Our conclusion is that in aged stroke patients, MTA is associated with poor performance in specific cognitive domains. The most vulnerable domains are memory and visuospatial functions, whereas verbal and executive functions seem to be unrelated to MTA.     

Quantitative EEG and medial temporal lobe atrophy in Alzheimer's dementia: Preliminary study

Backgrounds:

The electroencephalogram (EEG) abnormalities in Alzheimer''s disease (AD) have been widely reported, and medial temporal lobe atrophy (MTLA) is one of the hallmarks in early stage of AD. We aimed to assess the relationship between EEG abnormalities and MTLA and its clinical validity.

Materials and Methods:

A total of 18 patients with AD were recruited (the mean age: 77.83 years). Baseline EEGs were analyzed with quantitative spectral analysis. MTLA was assessed by a T1-axial visual rating scale (VRS).

Results:

In relative power spectrum analysis according to the right MTLA severity, the power of theta waves in C4, T4, F4, F8, and T5 increased significantly and the power of beta waves in T6, C4, T4, F8, T5, P3, T3, and F7 decreased significantly in severe atrophy group. In relative power spectrum analysis according to the left MTLA severity, the power of theta waves in T3 increased significantly and that of beta waves in P4, T6, C4, F4, F8, T5, P3, C3, T3, F3, and F7 decreased significantly in severe atrophy group.

Conclusion:

The severe MTLA group, regardless of laterality, showed more severe quantitative EEG alterations. These results suggest that quantitative EEG abnormalities are correlated with the MTLA, which may play an important role in AD process.     

Entorhinal cortex pathology in Alzheimer's disease.

The anatomical distribution of pathological changes in Alzheimer's disease, although highly selective for only certain brain areas, can be widespread at the endstage of the illness and can affect many neural systems. Propriety for onset among these is a question of importance for clues to the etiology of the disease, but one that is formidable without an experimental animal model. The entorhinal cortex (Brodmann's area 28) of the ventromedial temporal lobe is an invariant focus of pathology in all cases of Alzheimer's disease with selective changes that alter some layers more than others. The authors' findings reveal that it is the most heavily damaged cortex in Alzheimer's disease. Neuroanatomical studies in higher mammals reveal that the entorhinal cortex gives rise to axons that interconnect the hippocampal formation bidirectionally with the rest of the cortex. Their destruction in Alzheimer's disease could play a prominent role in the memory deficits that herald the onset of Alzheimer's disease and that characterize it throughout its course.     

Default network connectivity during a working memory task

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task‐related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task‐related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task‐positive networks at rest. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and alzheimer's disease

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel‐based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age‐ and education‐matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole‐brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Hum Brain Mapp 35:1422–1435, 2014. © 201 Wiley Periodicals, Inc.     

MRI Temporal Lobe Volume Measures and Neuropsychologic Function in Alzheimer's Disease

The authors performed quantitation of the temporal lobes using magnetic resonance imaging in 20 patients with mild-tomoderate Alzheimer's disease, 20 age-matched aged control subjects, and 26 healthy young volunteers. Compared to young subjects, aged controls showed volume reductions in amygdala (17%, p=0.02), hippocampus (15%, p=0.0001) and temporal lobe (22%, p=0.0001). Compared to aged controls, Alzheimer's subjects showed further volume reductions in amygdala (33%, p=0.0001) and hippocampus (20%, p=0.006) but not temporal lobe (7%, p=0.15). In Alzheimer's subjects, left temporal lobe volume correlated strongly with the Mini Mental State (MMSE) score (adjusted r² =0.46, p=0.0006) whereas right amygdala volume correlated inversely with the noncognitive ADAS score (adjusted r²=0.46, p=0.0006). The authors conclude that significant volume changes occur in the temporal lobe in aging and in Alzheimer's disease, with the greatest percentage reductions in the amygdala in Alzheimer's disease. Temporal neocortical atrophy and temporal limbic atrophy might be associated with different patterns of performance and behavior in Alzheimer's patients.     

Accuracy of CT scan measurements of the medial temporal lobe in routine dementia diagnostics

BACKGROUND: Atrophy of the medial part of the temporal lobe is seen in Alzheimer's disease (AD). We studied the usefulness of CT scan measurements of the medial temporal lobe (MTL) in elderly with suspected dementia. METHODS: MTL measurements were done with callipers by three raters, blinded to the diagnosis and to each other, on scans from 110 subjects with suspected dementia from a memory clinic in Oslo, Norway and 36 participants included in the OPTIMA study, Oxford, England. RESULTS: The correlation between the MTL and the Mini-Mental State Examination (MMSE) was very low, and there was a marked overlap between Alzheimer and cognitively unimpaired subjects. The inter-rater reliability was lower on the Norwegian than on the OPTIMA scans (R = 0.48 vs R = 0.68), but this was partly explained by larger MTL readings (4.5 mm after adjustment for age, gender and MMSE sumscore) on the OPTIMA scans as the reliability was confounded by MTL width and was higher at larger MTLs. A wider scan width (3 mm vs 2 mm in the OPTIMA scans) can also contribute to differences in reliability. CONCLUSIONS: The published threshold values regarding the CT scan MTL measurements for the diagnosis of AD may be invalid when applied by other radiology departments without a local standardisation and validation.     

The human perirhinal cortex and recognition memory

The importance of the perirhinal cortex for visual recognition memory performance is undisputed. However, it has not been clear whether its contribution to performance is mainly perceptual, or mainly mnemonic, or whether the perirhinal cortex contributes to both perception and memory. We determined the effects of medial temporal lobe damage that includes complete damage to the perirhinal cortex in two amnesic patients by assessing recognition memory for complex visual stimuli across delays from 0 to 40 s. These patients, as well as six other amnesic patients with damage limited to the hippocampal formation or diencephalic structures, exhibited intact recognition memory at delays of 0–2 s and a delay-dependent memory impairment at delays of 6 s and longer. Additionally, the patients with damage to the perirhinal cortex performed worse than the other amnesic patients at delays of 25 s and longer. The findings suggest that the perirhinal cortex is not important for visual perception or immediate memory. In this respect, the findings for perirhinal cortex resemble the findings for other medial temporal lobe structures, including the hippocampus. Hippocampus 1998;8:330–339. © 1998 Wiley-Liss, Inc.     

Impaired associative memory in temporal lobe epilepsy subjects after lesions of hippocampus, parahippocampal gyrus, and amygdala

There has been growing interest in the differential role of medial temporal lobe structures in learning and memory. The goal of the present study was to clarify how lesions of hippocampus, parahippocampal gyrus, and amygdala interfere with associative learning and memory. Thirty subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 30 matched healthy control subjects. A set of neuropsychological test measures and an associative learning task requiring the learning and recall of objects and faces were administered. The lesions of hippocampus, parahippocampal gyrus, amygdala, and fusiform gyrus of TLE subjects were determined by three-dimensional magnetic resonance imaging (3-D MRI) volumetric assessment. The results indicate that TLE subjects with combined large hippocampal lesions, large parahippocampal gyrus (i.e., perirhinal/entorhinal) lesions, and large amygdala lesions learned and recalled the associative task significantly worse than control subjects or subjects with small lesions of the hippocampus, parahippocampal gyrus, and amygdala. Regression analysis revealed that larger lesions of the parahippocampal gyrus (i.e., perirhinal/entorhinal cortices) were significantly related to increasing deficits on the task, and that hippocampal and amygdala lesion size did not significantly improve the prediction. Our results suggest that perirhinal and entorhinal cortices may contribute predominantly to the associative learning and recall of objects and faces.     

Functional response in ventral temporal cortex differentiates mild cognitive impairment from normal aging

This study sought to identify altered brain activation patterns in amnestic mild cognitive impairment (MCI) that could precede frank task impairment and neocortical atrophy. A high‐accuracy lexical decision (LD) task was therefore employed. Both MCI and normal seniors (NS) groups completed the LD task while functional magnetic resonance imaging (fMRI) was performed. Accuracy on the LD task was high (≥89% correct for both groups), and both groups activated a network of occipitotemporal regions and inferior frontal cortex. However, compared with the NS group, the MCI group showed reduced fMRI activation in these regions and increased activation in bilateral portions of anterior cingluate cortex. The results from a voxel‐based morphometry analysis indicated that altered activations in the MCI group were not within regions of atrophy. Receiver operating characteristic curves demonstrated that reduced fMRI response in the left and right midfusiform gyri accurately discriminated MCI from NS. When activation magnitude in both fusiform gyri were included in a single logistic regression model, group classification accuracy was very high (area under the curve = 0.93). These results showed that a disrupted functional response in the ventral temporal lobe accurately distinguishes individuals with MCI from NS, a finding which may have implications for identifying seniors at risk for cognitive decline. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Temporo‐frontal functional connectivity during auditory change detection is altered in Alzheimer's disease

Cortico‐cortical connections might be disturbed in patients with Alzheimer's disease (AD). This study aimed to investigate the alterations of functional connectivity in AD during auditory change detection processing by measuring the local neuronal activation and functional connectivity between cortical regions. Magnetoencephalographic responses to deviant and standard sounds were recorded in 16 AD patients, 18 young controls and 16 elderly controls. Larger source amplitudes and shorter peak latencies were found in the right temporal magnetic mismatch responses of young controls compared with elderly controls and AD patients. During deviant stimuli, the right theta temporal‐frontal phase synchrony was significantly smaller in AD than in young controls and elderly controls. Moreover, the left temporal‐frontal synchronization at theta and alpha bands was reduced in AD and elderly controls compared with young controls. In conclusion, the loss in temporo‐frontal theta synchronization might be an electrophysiological hallmark of AD. Hum Brain Mapp 35:5565–5577, 2014. © 2014 Wiley Periodicals, Inc.     

Direct comparison between regional cerebral metabolism in progressive supranuclear palsy and Parkinson's disease.

The differentiation between progressive supranuclear palsy (PSP) and Parkinson's disease (PD) may be difficult, especially in the early stages of disease. Positron emission tomography potentially provides a tool for making such a distinction. To identify key features in the spatial distributions of cerebral glucose metabolism, 18F-fluorodeoxyglucose (FDG) measurements of 10 patients with probable or possible PSP were directly compared with those of 9 PD patients. This analysis was done with statistic parametric mapping. After normalization of global brain uptake, in PSP, relative uptake of FDG was reduced in the caudal (motor) part of the anterior cingulate gyrus (Brodmann's area BA 24; P < 0.05, corrected for multiple comparisons). At a lower threshold, an additional decrease was present in the dorsal mesencephalon. In PD, relative hypometabolism was seen in extrastriate visual, ventrolateral temporal, posterior parietal, and orbitofrontal regions. Only reduction in the right fusiform gyrus and the lateral extrastriate visual cortex reached statistical significance. We concluded that particularly the reduction of medial frontal metabolism may be a valuable diagnostic imaging parameter in distinguishing PSP from PD. For PD, a possible association between occipitotemporal FDG decrease and vulnerability to hallucinations is suggested.     

Functional connectivity during recognition memory in individuals genetically at risk for Alzheimer's disease

The medial temporal lobes (MTL) and frontal cortex have been shown to subserve memory processes. Neurodegenerative diseases, such as Alzheimer's disease (AD), disrupt the neuronal networks that underlie memory processing. The ε4 allele of the apolipoprotein E gene is a genetic risk factor for AD and is associated with decrements in memory and in olfactory function. The present study utilized EQS, a structural equation modeling software program, to examine differences in the neuronal networks between non‐demented ε4 carriers and ε4 noncarriers during a cross‐modal olfactory recognition memory paradigm. Prior to fMRI scanning, participants were presented with 16 odors. During two scans, participants discriminated between names of odors presented before scanning (targets) or not presented (foils). The results indicate significant connections between bilateral frontal lobes and MTL for ε4 carriers when they misidentified a foil as a target. When ε4 noncarriers correctly identified a target, there were greater associations between the amygdala, MTL, and right frontal lobe; these associations also modeled the brain's response when ε4 noncarriers misidentified a foil as a target. During memory retrieval, affective cues may facilitate retrieval in ε4 noncarriers relative to ε4 carriers. Last, no model was found that best represented the functional network used by ε4 carriers when they correctly identified a target, which may reflect variability of neuronal recruitment within this population. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.