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1.
Brain ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743817

ABSTRACT

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aß-positive and Aß-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

2.
Hum Brain Mapp ; 44(9): 3586-3609, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37051727

ABSTRACT

The default mode network (DMN) typically exhibits deactivations during demanding tasks compared to periods of relative rest. In functional magnetic resonance imaging (fMRI) studies of episodic memory encoding, increased activity in DMN regions even predicts later forgetting in young healthy adults. This association is attenuated in older adults and, in some instances, increased DMN activity even predicts remembering rather than forgetting. It is yet unclear whether this phenomenon is due to a compensatory mechanism, such as self-referential or schema-dependent encoding, or whether it reflects overall reduced DMN activity modulation in older age. We approached this question by systematically comparing DMN activity during successful encoding and tonic, task-independent, DMN activity at rest in a sample of 106 young (18-35 years) and 111 older (60-80 years) healthy participants. Using voxel-wise multimodal analyses, we assessed the age-dependent relationship between DMN resting-state amplitude (mean percent amplitude of fluctuation, mPerAF) and DMN fMRI signals related to successful memory encoding, as well as their modulation by age-related hippocampal volume loss, while controlling for regional grey matter volume. Older adults showed lower resting-state DMN amplitudes and lower task-related deactivations. However, a negative relationship between resting-state mPerAF and subsequent memory effect within the precuneus was observed only in young, but not older adults. Hippocampal volumes showed no relationship with the DMN subsequent memory effect or mPerAF. Lastly, older adults with higher mPerAF in the DMN at rest tend to show higher memory performance, pointing towards the importance of a maintained ability to modulate DMN activity in old age.


Subject(s)
Brain Mapping , Brain , Humans , Aged , Brain/diagnostic imaging , Default Mode Network , Cognition , Mental Recall , Magnetic Resonance Imaging , Nerve Net
3.
Hum Brain Mapp ; 44(8): 3283-3301, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36972323

ABSTRACT

Memory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy middle-aged and older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and other neuropsychological measures including flexibility. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in other aging-related functions. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.


Subject(s)
Aging , Memory, Episodic , Middle Aged , Young Adult , Humans , Aged , Aging/psychology , Brain/diagnostic imaging , Mental Recall , Brain Mapping , Magnetic Resonance Imaging/methods , Neuropsychological Tests
4.
Brain ; 145(4): 1473-1485, 2022 05 24.
Article in English | MEDLINE | ID: mdl-35352105

ABSTRACT

We investigated whether the impact of tau-pathology on memory performance and on hippocampal/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A-) of amyloid pathology was defined by CSF amyloid-ß42 (Aß42) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A- individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with Aß42 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (>700 pg/ml) and phospho-tau (>100 pg/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and Aß42 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A- groups. After classifying this matched sample for phospho-tau pathology (T-/T+), individuals with A+/T+ were significantly more memory-impaired than A-/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer's disease, did not mediate the relationship between tau pathology and hippocampal function and memory performance. Thus, our data show that the presence of amyloid pathology is associated with a linear relationship between tau pathology, hippocampal dysfunction and memory impairment, although the actual severity of amyloid pathology is uncorrelated. Our data therefore indicate that the presence of amyloid pathology provides a permissive state for tau-related hippocampal dysfunction and hippocampus-dependent recognition and recall impairment. This raises the possibility that in the predementia stage of Alzheimer's disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function.


Subject(s)
Alzheimer Disease , Amyloidosis , Cognitive Dysfunction , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloidogenic Proteins , Apolipoproteins E/genetics , Biomarkers , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/genetics , Cross-Sectional Studies , Hippocampus/metabolism , Humans , tau Proteins/metabolism
5.
Neuroimage ; 230: 117820, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33524573

ABSTRACT

Subsequent memory paradigms allow to identify neural correlates of successful encoding by separating brain responses as a function of memory performance during later retrieval. In functional magnetic resonance imaging (fMRI), the paradigm typically elicits activations of medial temporal lobe, prefrontal and parietal cortical structures in young, healthy participants. This categorical approach is, however, limited by insufficient memory performance in older and particularly memory-impaired individuals. A parametric modulation of encoding-related activations with memory confidence could overcome this limitation. Here, we applied cross-validated Bayesian model selection (cvBMS) for first-level fMRI models to a visual subsequent memory paradigm in young (18-35 years) and older (51-80 years) adults. Nested cvBMS revealed that parametric models, especially with non-linear transformations of memory confidence ratings, outperformed categorical models in explaining the fMRI signal variance during encoding. We thereby provide a framework for improving the modeling of encoding-related activations and for applying subsequent memory paradigms to memory-impaired individuals.


Subject(s)
Brain/diagnostic imaging , Brain/physiology , Magnetic Resonance Imaging/methods , Memory/physiology , Models, Neurological , Photic Stimulation/methods , Adolescent , Adult , Aged , Aged, 80 and over , Bayes Theorem , Cohort Studies , Female , Humans , Male , Middle Aged , Young Adult
6.
Eur J Neurosci ; 53(12): 3942-3959, 2021 06.
Article in English | MEDLINE | ID: mdl-32583466

ABSTRACT

Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the ventrolateral and rostral prefrontal cortex of risk allele carriers. In silico eQTL analysis revealed that rs1064395 SNP is linked not only to increased prefrontal expression of the NCAN gene itself, but also of the neighbouring HAPLN4 gene, suggesting a more complex effect of the SNP on ECM composition. Our results suggest that the NCAN rs1064395 A allele is associated with lower hippocampus-dependent memory function, variation of prefrontal cortex structure and ECM composition. Considering the well-documented hippocampal and prefrontal dysfunction in bipolar disorder and schizophrenia, our results may reflect an intermediate phenotype by which NCAN rs1064395 contributes to disease risk.


Subject(s)
Bipolar Disorder , Hippocampus , Neurocan/genetics , Schizophrenia , Brain Mapping , Chondroitin Sulfate Proteoglycans/genetics , Hippocampus/diagnostic imaging , Hippocampus/physiology , Humans , Lectins, C-Type/genetics , Magnetic Resonance Imaging , Memory , Nerve Tissue Proteins/genetics
7.
Hum Brain Mapp ; 42(14): 4478-4496, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34132437

ABSTRACT

Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Düzel et al., Hippocampus, 2011; 21: 803-814). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE-SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults' activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age-group-related differences for the subsequent memory contrast, and the FADE-SAME score additionally exhibited age-group-related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single-value scores of memory-related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.


Subject(s)
Brain/physiology , Cognitive Aging/physiology , Functional Neuroimaging/methods , Hippocampus/physiology , Memory, Episodic , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Brain/diagnostic imaging , Female , Hippocampus/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
8.
J Neurosci ; 36(29): 7569-79, 2016 07 20.
Article in English | MEDLINE | ID: mdl-27445136

ABSTRACT

UNLABELLED: The hippocampus is proposed to be critical in distinguishing between similar experiences by performing pattern separation computations that create orthogonalized representations for related episodes. Previous neuroimaging studies have provided indirect evidence that the dentate gyrus (DG) and CA3 hippocampal subregions support pattern separation by inferring the nature of underlying representations from the observation of novelty signals. Here, we use ultra-high-resolution fMRI at 7 T and multivariate pattern analysis to provide compelling evidence that the DG subregion specifically sustains representations of similar scenes that are less overlapping than in other hippocampal (e.g., CA3) and medial temporal lobe regions (e.g., entorhinal cortex). Further, we provide evidence that novelty signals within the DG are stimulus specific rather than generic in nature. Our study, in providing a mechanistic link between novelty signals and the underlying representations, constitutes the first demonstration that the human DG performs pattern separation. SIGNIFICANCE STATEMENT: A fundamental property of an episodic memory system is the ability to minimize interference between similar episodes. The dentate gyrus (DG) subregion of the hippocampus is widely viewed to realize this function through a computation referred to as pattern separation, which creates distinct nonoverlapping neural codes for individual events. Here, we leveraged 7 T fMRI to test the hypothesis that this region supports pattern separation. Our results demonstrate that the DG supports representations of similar scenes that are less overlapping than those in neighboring subregions. The current study therefore is the first to offer compelling evidence that the human DG supports pattern separation by obtaining critical empirical data at the representational level: the level where this computation is defined.


Subject(s)
Dentate Gyrus/physiology , Pattern Recognition, Visual/physiology , Recognition, Psychology/physiology , Adult , Analysis of Variance , Brain Mapping , Dentate Gyrus/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Oxygen/blood , Photic Stimulation , Young Adult
9.
Proc Natl Acad Sci U S A ; 108(13): 5408-13, 2011 Mar 29.
Article in English | MEDLINE | ID: mdl-21402920

ABSTRACT

The prefrontal cortex (PFC) is assumed to contribute to goal-directed episodic encoding by exerting cognitive control on medial temporal lobe (MTL) memory processes. However, it is thus far unclear to what extent the contribution of PFC-MTL interactions to memory manifests at a structural anatomical level. We combined functional magnetic resonance imaging and fiber tracking based on diffusion tensor imaging in 28 young, healthy adults to quantify the density of white matter tracts between PFC regions that were activated during the encoding period of a verbal free-recall task and MTL subregions. Across the cohort, the strength of fiber bundles linking activated ventrolateral PFC regions and the rhinal cortex (comprising the peri- and entorhinal cortices) of the MTL correlated positively with free-recall performance. These direct white matter connections provide a basis through which activated regions in the PFC can interact with the MTL and contribute to interindividual differences in human episodic memory.


Subject(s)
Mental Recall/physiology , Neural Pathways/anatomy & histology , Prefrontal Cortex/cytology , Prefrontal Cortex/physiology , Temporal Lobe/cytology , Temporal Lobe/physiology , Adult , Behavior/physiology , Brain Mapping/methods , Diffusion Tensor Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Young Adult
10.
iScience ; 26(10): 107765, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37744028

ABSTRACT

Successful explicit memory encoding is associated with inferior temporal activations and medial parietal deactivations, which are attenuated in aging. Here we used dynamic causal modeling (DCM) of functional magnetic resonance imaging data to elucidate effective connectivity patterns between hippocampus, parahippocampal place area (PPA), and precuneus during encoding of novel visual scenes. In 117 young adults, DCM revealed pronounced activating input from the PPA to the hippocampus and inhibitory connectivity from the PPA to the precuneus during novelty processing, with both being enhanced during successful encoding. This pattern could be replicated in two cohorts (N = 141 and 148) of young and older adults. In both cohorts, older adults selectively exhibited attenuated inhibitory PPA-precuneus connectivity, which correlated negatively with memory performance. Our results provide insight into the network dynamics underlying explicit memory encoding and suggest that age-related differences in memory-related network activity are, at least partly, attributable to altered temporo-parietal neocortical connectivity.

11.
Alzheimers Res Ther ; 15(1): 43, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36855049

ABSTRACT

BACKGROUND: In preclinical Alzheimer's disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions. METHODS: We tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol. RESULTS: In asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Aß42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs. CONCLUSIONS: These data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Cognitive Reserve , Humans , Aged , Alzheimer Disease/diagnostic imaging , Amyloidogenic Proteins , Cerebral Cortex , Cognitive Dysfunction/diagnostic imaging
12.
eNeuro ; 9(6)2022.
Article in English | MEDLINE | ID: mdl-36376083

ABSTRACT

Human cognitive abilities decline with increasing chronological age, with decreased explicit memory performance being most strongly affected. However, some older adults show "successful aging," that is, relatively preserved cognitive ability in old age. One explanation for this could be higher brain-structural integrity in these individuals. Alternatively, the brain might recruit existing resources more efficiently or employ compensatory cognitive strategies. Here, we approached this question by testing multiple candidate variables from structural and functional neuroimaging for their ability to predict chronological age and memory performance, respectively. Prediction was performed using support vector machine (SVM) classification and regression across and within two samples of young (N = 106) and older (N = 153) adults. The candidate variables were (1) behavioral response frequencies in an episodic memory test; (2) recently described functional magnetic resonance imaging (fMRI) scores reflecting preservation of functional memory networks; (3) whole-brain fMRI contrasts for novelty processing and subsequent memory; (4) resting-state fMRI maps quantifying voxel-wise signal fluctuation; and (5) gray matter volume estimated from structural MRIs. While age group could be reliably decoded from all variables, chronological age within young and older subjects was best predicted from gray matter volume. In contrast, memory performance was best predicted from task-based fMRI contrasts and particularly single-value fMRI scores, whereas gray matter volume has no predictive power with respect to memory performance in healthy adults. Our results suggest that superior memory performance in healthy older adults is better explained by efficient recruitment of memory networks rather than by preserved brain structure.


Subject(s)
Magnetic Resonance Imaging , Memory, Episodic , Humans , Aged , Cognition/physiology , Brain/physiology , Brain Mapping , Aging/physiology
13.
Neurology ; 99(8): e775-e788, 2022 08 23.
Article in English | MEDLINE | ID: mdl-35995589

ABSTRACT

BACKGROUND AND OBJECTIVES: We assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy. METHODS: We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of ß-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education. RESULTS: In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers. DISCUSSION: Novelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/diagnosis , Amyloid beta-Peptides , Biomarkers , Cognitive Dysfunction/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Parietal Lobe/diagnostic imaging , Temporal Lobe/diagnostic imaging
14.
Hippocampus ; 21(8): 803-14, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20665594

ABSTRACT

We investigated whether preservation of encoding-related brain activity patterns in older age reflects successful aging in long-term memory. Using a statistical matching technique, we identified groups of healthy older adults with different degrees of Functional Activity Deviation during Encoding (FADE) from young adults in a memory network comprising hippocampal, temporal, occipital, and retrosplenial regions. High FADE scores were associated with impairment in recollection, abnormal activity in the default mode network, and lower gray matter density in bilateral ventral prefrontal cortex and left rhinal cortex; a constellation previously associated with increased risk for dementia. Low FADE scores functionally phenotyped successful aging because recollection was well preserved and there was no evidence for compensatory prefrontal activation. Thus, for some individuals successful aging in long-term memory reflects the preservation of a functionally specific memory network, and can occur in the absence of compensatory brain activity.


Subject(s)
Aging/physiology , Behavior/physiology , Cognition/physiology , Memory, Long-Term/physiology , Recognition, Psychology/physiology , Adult , Aged , Brain Mapping , Frontal Lobe/physiology , Hippocampus/physiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Parietal Lobe/physiology , Prefrontal Cortex/physiology , Temporal Lobe/physiology
15.
Anesthesiology ; 114(5): 1025-35, 2011 May.
Article in English | MEDLINE | ID: mdl-21436678

ABSTRACT

BACKGROUND: The increased tidal volume (V(T)) applied to the ventilated lung during one-lung ventilation (OLV) enhances cyclic alveolar recruitment and mechanical stress. It is unknown whether alveolar recruitment maneuvers (ARMs) and reduced V(T) may influence tidal recruitment and lung density. Therefore, the effects of ARM and OLV with different V(T) on pulmonary gas/tissue distribution are examined. METHODS: Eight anesthetized piglets were mechanically ventilated (V(T) = 10 ml/kg). A defined ARM was applied to the whole lung (40 cm H(2)O for 10 s). Spiral computed tomographic lung scans were acquired before and after ARM. Thereafter, the lungs were separated with an endobronchial blocker. The pigs were randomized to receive OLV in the dependent lung with a V(T) of either 5 or 10 ml/kg. Computed tomography was repeated during and after OLV. The voxels were categorized by density intervals (i.e., atelectasis, poorly aerated, normally aerated, or overaerated). Tidal recruitment was defined as the addition of gas to collapsed lung regions. RESULTS: The dependent lung contained atelectatic (56 ± 10 ml), poorly aerated (183 ± 10 ml), and normally aerated (187 ± 29 ml) regions before ARM. After ARM, lung volume and aeration increased (426 ± 35 vs. 526 ± 69 ml). Respiratory compliance enhanced, and tidal recruitment decreased (95% vs. 79% of the whole end-expiratory lung volume). OLV with 10 ml/kg further increased aeration (atelectasis, 15 ± 2 ml; poorly aerated, 94 ± 24 ml; normally aerated, 580 ± 98 ml) and tidal recruitment (81% of the dependent lung). OLV with 5 ml/kg did not affect tidal recruitment or lung density distribution. (Data are given as mean ± SD.) CONCLUSIONS: The ARM improves aeration and respiratory mechanics. In contrast to OLV with high V(T), OLV with reduced V(T) does not reinforce tidal recruitment, indicating decreased mechanical stress.


Subject(s)
Lung Injury/prevention & control , Pulmonary Alveoli/diagnostic imaging , Pulmonary Atelectasis/diagnostic imaging , Respiration, Artificial/methods , Thoracic Surgical Procedures , Analysis of Variance , Animals , Disease Models, Animal , Image Processing, Computer-Assisted , Lung/diagnostic imaging , Lung Compliance , Lung Volume Measurements , Prospective Studies , Pulmonary Ventilation , Respiratory Mechanics , Swine , Tidal Volume , Tomography, Spiral Computed/methods
16.
Psychiatry Res ; 183(3): 187-94, 2010 Sep 30.
Article in English | MEDLINE | ID: mdl-20702070

ABSTRACT

BACKGROUND: Declarative memory disturbances, known to substantially contribute to cognitive impairment in schizophrenia, have previously been attributed to prefrontal as well as hippocampal dysfunction. AIMS: To characterize the role of prefrontal and mesolimbic/hippocampal dysfunction during memory encoding in schizophrenia. METHOD: Neuronal activation in schizophrenia patients and controls was assessed using functional magnetic resonance imaging (fMRI) during encoding of words in a deep (semantic judgement) and shallow (case judgment) task. A free recall (no delay) and a recognition task (24h delay) were performed. RESULTS: Free recall, but not recognition performance was reduced in patients. Reduced performance was correlated with positive symptoms which in turn were related to increased left hippocampal activity during successful encoding. Furthermore, schizophrenia patients displayed a hippocampal hyperactivity during deep encoding irrespective of encoding success along with a reduced anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (DMPFC) activity in successful encoding but an intact left inferior frontal cortex (LIFC) activity. CONCLUSIONS: This study provides the first evidence directly linking positive symptoms and memory deficits to dysfunctional hippocampal hyperactivity. It thereby underscores the pivotal pathophysiological role of a hyperdopaminergic mesolimbic state in schizophrenia.


Subject(s)
Hippocampus/pathology , Memory Disorders/etiology , Memory Disorders/pathology , Schizophrenia/complications , Adult , Brain Mapping/methods , Female , Functional Laterality/physiology , Hippocampus/blood supply , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Mental Recall/physiology , Neuropsychological Tests , Oxygen/blood , Psychiatric Status Rating Scales , Recognition, Psychology/physiology , Young Adult
17.
Alzheimers Dement (Amst) ; 11: 610-618, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31517023

ABSTRACT

INTRODUCTION: Impaired long-term memory is a defining feature of mild cognitive impairment (MCI). We tested whether this impairment is item specific, limited to some memoranda, whereas some remain consistently memorable. METHODS: We conducted item-based analyses of long-term visual recognition memory. Three hundred ninety-four participants (healthy controls, subjective cognitive decline [SCD], and MCI) in the multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs. RESULTS: We observed consistent memorability for images in healthy controls, SCD, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set. DISCUSSION: Individuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.

18.
Neuropsychologia ; 46(13): 3042-52, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18601938

ABSTRACT

Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR)--a measure of structural integrity--of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus.


Subject(s)
Aging/physiology , Memory/physiology , Substantia Nigra/physiology , Ventral Tegmental Area/physiology , Verbal Learning/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Regression Analysis
19.
Brain ; 130(Pt 9): 2412-24, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17626038

ABSTRACT

The ability to learn stimulus-reward associations on the basis of reward prediction errors critically depends on the mesolimbic dopaminergic system including the dopaminergic midbrain and the ventral striatum. It is known that healthy elderly and patients with Parkinson's disease are less proficient than healthy young adults in learning stimulus-reward contingencies, but it is unclear whether this is due to dysfunctional mesolimbic reward prediction or due to deficiency in processing the rewards per se. We used a well-established event-related fMRI reward-prediction paradigm to address this question. Young adults showed the well-replicated pattern of midbrain and ventral striatal activation for stimuli that predicted monetary reward when compared with stimuli that predicted neutral feedback. Also, as expected, the predicted reward feedback itself did not elicit a mesolimbic response. Healthy elderly subjects and unmedicated early-stage idiopathic Parkinson's disease patients showed the opposite pattern with an absent mesolimbic reward prediction response, but mesolimbic activation to the reward feedback itself. This suggests that the healthy elderly and Parkinson's disease patients were less proficient in learning the predictive value of the reward cues despite preserved mesolimbic processing of reward prediction errors. Parkinson's disease patients additionally displayed a relatively increased response of the anterior cingulate during reward feedback processing and diminished functional connectivity of the midbrain and ventral striatum. Our results are compatible with existing behavioural evidence that both groups exhibit a particularly pronounced deficit in learning from positive feedback and support the view that a tendency to underestimate expected values of reward cues might underlie this deficit. Furthermore, alterations in reward processing in Parkinson's disease extend beyond accelerated ageing effects and include altered connectivity within the mesolimbic system.


Subject(s)
Aging/physiology , Limbic System/physiopathology , Parkinson Disease/physiopathology , Reward , Adult , Aged , Aging/psychology , Association Learning , Brain Mapping/methods , Cues , Female , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Mesencephalon/physiopathology , Middle Aged , Parkinson Disease/psychology , Reaction Time
20.
Cereb Cortex ; 17(12): 2940-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17383999

ABSTRACT

Normal aging is associated with neuronal loss in the dopaminergic midbrain (substantia nigra/ventral tegmental area, SN/VTA), a region that has recently been implicated in processing novel stimuli as part of a mesolimbic network including the hippocampus. Here, we quantified age-related structural degeneration of the mesolimbic system using magnetization transfer ratio (MTR) and correlated it with mesolimbic hemodynamic responses (HRs) to stimulus novelty. Twenty-one healthy older adults between 55 and 77 years performed a visual oddball paradigm allowing to distinguish mesolimbic HRs to novelty from rareness, negative emotional valence, and targetness using functional magnetic resonance imaging. The HRs in the right SN/VTA and the right hippocampus to novelty were positively correlated both with the SN/VTA MTR and hippocampus MTR but not amygdala MTR. However, the HR of the amygdala to negative emotional valence correlated with the amygdala MTR but not with the MTR in SN/VTA or the hippocampus. The results establish a structure-function relationship in support of a hippocampal-SN/VTA loop of mesolimbic novelty processing by showing that the hemodynamic activation in SN/VTA and hippocampus for novelty is selectively affected by age-related degeneration of these structures.


Subject(s)
Aging/physiology , Cognition/physiology , Exploratory Behavior/physiology , Learning/physiology , Limbic System/physiology , Task Performance and Analysis , Aged , Female , Humans , Male , Middle Aged
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