Biomedical subjects

Katharina Henke

Publications and source records attributed to Katharina Henke.

17 recordsLinked to original sources

PubMed2006

Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers.

The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.

Adult↗

PubMed2006

Common Kibra alleles are associated with human memory performance.

Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.

Adolescent↗

PubMed2006

Enhanced brain activity may precede the diagnosis of Alzheimer's disease by 30 years.

Presenilin 1 (PSEN1) mutations cause autosomal dominant familial Alzheimer's disease (FAD). PSEN1 mutation carriers undergo the course of cognitive deterioration, which is typical for sporadic Alzheimer's disease but disease onset is earlier and disease progression is faster. Here, we sought to detect signs of FAD in presymptomatic carriers of the PSEN1 mutation (C410Y) by use of a neuropsychological examination, functional MRI during learning and memory tasks and MRI volumetry. We examined five non-demented members of a FAD family and 21 non-related controls. Two of the five family members were carrying the mutation; one was 20 years old and the other 45 years old. The age of clinical manifestation of FAD in the family studied here is approximately 48 years. Neuropsychological assessments suggested subtle problems with episodic memory in the 20-year-old mutation carrier. The middle-aged mutation carrier fulfilled criteria for amnestic mild cognitive impairment. The 20-year-old mutation carrier exhibited increased, while the middle-aged mutation carrier exhibited decreased brain activity compared to controls within memory-related neural networks during episodic learning and retrieval, but not during a working-memory task. The increased memory-related brain activity in the young mutation carrier might reflect a compensatory effort to overcome preclinical neural dysfunction caused by first pathological changes. The activity reductions in the middle-aged mutation carrier might reflect gross neural dysfunction in a more advanced stage of neuropathology. These data suggest that functional neuroimaging along with tasks that challenge specifically those brain areas which are initial targets of Alzheimer's disease pathology may reveal activity alterations on a single-subject level decades before the clinical manifestation of Alzheimer's disease.

Adult↗

PubMed2005

Memory-related hippocampal dysfunction in poly-drug ecstasy (3,4-methylenedioxymethamphetamine) users.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic in animal studies and its use has been associated with cognitive impairments in humans. OBJECTIVE: To study hippocampal activation during the retrieval from episodic memory in polyvalent users of ecstasy. METHODS: Twelve polyvalent ecstasy users and twelve matched controls were examined by means of functional magnetic resonance imaging (fMRI) while they retrieved face-profession associations from episodic memory. RESULTS: Ecstasy users had a normal structural MRI scan without focal brain lesions or anatomical abnormalities. They exhibited equal retrieval accuracy during memory retrieval to that of the matched controls. Yet, their retrieval-related activity was lower and more spatially restricted in the left anterior hippocampus than that of the controls. CONCLUSIONS: These results provide evidence for abnormal hippocampal functioning in MDMA users even at the presence of normal memory performance. This finding may be linked to MDMA-induced neurotoxicity and suggests that diminished hippocampal activation during memory retrieval might be a more sensitive or earlier index of MDMA-related neurotoxicity than neuropsychological performance.

Adult↗

PubMed2005

Age-dependent effects of the 5-hydroxytryptamine-2a-receptor polymorphism (His452Tyr) on human memory.

A polymorphism (His452Tyr) of the 5-hydroxytryptamine (5-HT)2a receptor is associated with episodic memory in healthy young humans. Because 5-HT2a-receptor density decreases with increasing age, we tested whether the 5-HT2a receptor genotype effect on memory is influenced by age. We investigated the association of the His452Tyr genotype with memory performance in 622 healthy study participants aged from 18 to 90 years. In young to middle-aged participants, age significantly influenced genotype effects on episodic memory: the His452Tyr genotype exerted a significant influence on memory only in young participants. In the group of elderly cognitively healthy participants, the His452Tyr genotype did not affect memory performance. We conclude that age strongly modulates the effect of the 5-HT2a receptor polymorphism at residue 452 on episodic memory.

Adolescent↗

PubMed2005

Implicit associative learning engages the hippocampus and interacts with explicit associative learning.

The hippocampus is crucial for conscious, explicit memory, but whether it is also involved in nonconscious, implicit memory is uncertain. We investigated with functional magnetic resonance imaging whether implicit learning engages the hippocampus and interacts with subsequent explicit learning. The presentation of subliminal faces-written profession pairs for implicit learning was followed by the explicit learning of supraliminal pairs composed of the same faces combined with written professions semantically incongruous to those presented subliminally (experiment 1), semantically congruous professions (experiment 2), or identical professions (experiment 3). We found that implicit face-profession learning interacted with explicit face-profession learning in all experiments, impairing the explicit retrieval of the associations. Hippocampal activity increased during the subliminal presentation of face-profession pairs versus face-nonword pairs and correlated with the later impairment of explicit retrieval. These findings suggest that implicit semantic associative learning engages the hippocampus and influences explicit memory.

Association Learning↗

PubMed2005

Sensitivity-encoded (SENSE) echo planar fMRI at 3T in the medial temporal lobe.

Parallel imaging techniques are useful for fMRI studies in light of the increasing susceptibility effects at high magnetic field strength. Yet, spatially varying noise amplification constitutes a challenge for the application of these techniques. The medial temporal lobe is particularly vulnerable to susceptibility effect with increasingly strong signal reduction. We present two fMRI studies comparing SENSE single-shot (ssh) echo planar imaging (EPI) at acceleration factors of 2.0, 2.4, 2.7, and 3.0 with conventional sshEPI at TE of 22 and 35 ms. Data were acquired during a learning task which activates the medial temporal lobe bilaterally. Susceptibility related image distortion was markedly reduced with increasing SENSE acceleration. Moreover, in the group results, statistical power increased in the whole brain with SENSE compared to conventional imaging and with a TE of 35 ms compared to 22 ms. Higher SENSE acceleration factors further improved image quality and increased statistical power in the occipital lobe and fusiform gyrus, but not in the medial temporal lobe. We therefore conclude that an sshEPI acquisition protocol with a moderate SENSE acceleration factor of R = 2.0 and TE 35 ms is suitable for the detection of medial temporal activation at 3T.

Adult↗

PubMed2005

One month of human memory consolidation enhances retrieval-related hippocampal activity.

We studied the role of the hippocampus in memory retrieval at 1 day and 1 month following associative learning of word pairs. Retrieval-related brain activity was recorded using functional magnetic resonance imaging in 20 healthy students, of which 12 were good learners and eight were poor learners. At the day lag, the poor learners exhibited enhanced neural recruitment in the hippocampus and neocortex to reach a retrieval performance comparable to that of the good learners. Over the 20 subjects, there was a positive correlation between retrieval-related hippocampal activity at the day lag and forgetting over the month retention interval (the greater the activity, the more forgetting). Although the poor learners' retrieval performance declined dramatically from the day to the month lag, the good learners maintained a high retrieval performance, which distinguishes them as good memory consolidators. Their retrieval-related hippocampal and neocortical activity increased from the day to the month lag. This increase was observed both when retrieval performance was matched between the day and the month lag and when the learning procedure for information retrieved at the day and the month lag was matched. This activity increase in the task-specialized neural network from the day lag to the month lag may reflect an increase in task demands or the proliferation of hippocampal-neocortical memory traces during memory consolidation as suggested by the multiple trace theory.

Adult↗

PubMed2005

Effects of memory consolidation on human hippocampal activity during retrieval.

Day-to-day memories undergo transformation from short-term to long-term storage, a process called memory consolidation. Animal studies showed that memory consolidation requires protein synthesis and the growth of new hippocampal synapses within 24 h. To test for effects of memory consolidation in the human, we examined brain activation during the retrieval of information at 10 min and at 24 h following learning using functional magnetic resonance imaging (fMRI), an indirect measure of synaptic activity. Learning instructions were adjusted to yield a comparable retrieval quantity and retrieval quality at 10 min and 24 h after learning. The left hippocampal formation exhibited enhanced activity during the retrieval at the 24 h lag compared to the retrieval at the 10 min lag. Moreover, the activity in the left anterior hippocampal formation showed stronger correlations with retrieval quantity and retrieval quality at the 24 h lag than at the 10 min lag. This suggests that the relation between left anterior hippocampal activity and retrieval success became closer as consolidation progressed. These fMRI results in the human hippocampal formation may correspond to the neurobiological results in the animal hippocampal formation of a strengthening and growth of synaptic connections within 24 h.

Adult↗

PubMed2005

Evidence of a genetic basis of Morgagni-Stewart-Morel syndrome. A case report of identical twins.

We report two 71-year-old female monozygotic twins presenting with advanced hyperostosis frontalis interna, obesity, shortness and cognitive impairment. They both have suffered from generalized seizures since their early adulthood. Moreover, the patients showed some additional conditions only occurring in one individual or the other such as migraine, marked recurrent depressive disorder or polyarthrosis. The symptoms common to both twins appear to correspond to the Morgagni-Stewart-Morel syndrome and indicate a genetic basis of this disorder as these features occur in genetically identical patients.

Aged↗

PubMed2003

A functional genetic variation of the 5-HT2a receptor affects human memory.

Human memory capacity is highly variable across individuals and is influenced by both genetic and environmental factors. A roughly 50% heritability estimate indicates that naturally occurring genetic variations have an important impact on this cognitive ability. Therefore, we investigated a functional variation of a memory-related serotonin receptor in 349 healthy young volunteers, and found 21% poorer memory performance in subjects with the rare variant.

Case-Control Studies↗

PubMed2003

Functional neuroimaging predicts individual memory outcome after amygdalohippocampectomy.

We examined memory-related activity within to-be-resected medial temporal lobe (MTL) structures in 12 epilepsy patients with PET before amygdalohippocampectomy and studied the reallocation of memory functions to the contralateral MTL before and after surgery. Learning tasks were designed to activate predominantly the right or left MTL. Those patients who significantly activated to-be-resected ipsilateral MTL structures during the ipsilateral learning task (i.e. the left MTL during verbal learning or the right MTL during nonverbal learning) experienced a postoperative memory decline. Preoperative activation in the contralateral MTL during the ipsilateral learning task positively correlated with the postoperative outcome for ipsilateral memory. There was no significant postoperative reallocation of ipsilateral memory functions to the contralateral MTL.

Adolescent↗

PubMed2003

Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease.

To test whether antibodies against beta-amyloid are effective in slowing progression of Alzheimer's disease, we assessed cognitive functions in 30 patients who received a prime and a booster immunization of aggregated Abeta(42) over a 1 year period in a placebo-controlled, randomized trial. Twenty patients generated antibodies against beta-amyloid, as determined by tissue amyloid plaque immunoreactivity assay. Patients who generated such antibodies showed significantly slower rates of decline of cognitive functions and activities of daily living, as indicated by the Mini Mental State Examination, the Disability Assessment for Dementia, and the Visual Paired Associates Test of delayed recall from the Wechsler Memory Scale, as compared to patients without such antibodies. These beneficial clinical effects were also present in two of three patients who had experienced transient episodes of immunization-related aseptic meningoencephalitis. Our results establish that antibodies against beta-amyloid plaques can slow cognitive decline in patients with Alzheimer's disease.

Activities of Daily Living↗

PubMed2003

Nonconscious formation and reactivation of semantic associations by way of the medial temporal lobe.

A successful strategy to memorize unrelated items is to associate them semantically. This learning method is typical for declarative memory and depends on the medial temporal lobe (MTL). Yet, only a small fraction of perceived items emerge into conscious awareness and receive the status of representations in declarative memory. This functional magnetic resonance imaging (fMRI) study tackled the mnemonic fate of unrelated item pairs processed without conscious awareness. Stimuli consisted of a face and a written profession (experimental condition) or of a face (control condition) exposed very briefly between pattern masks. Although the participants were unaware of the stimuli, activity in the hippocampus and perirhinal cortex was changed in the experimental versus the control condition; perirhinal activity changes correlated with the reaction time measure of the later nonconscious retrieval. For retrieval, the previously presented faces were shown again, this time for conscious inspection. The task was to guess the professional category of each face. This task was to induce a nonconscious retrieval of previously formed face-profession associations. Remarkably, activity in the hippocampus and perirhinal cortex was enhanced when subjects were confronted with faces from the experimental versus the control condition. The degree of hippocampal and perirhinal activation changes correlated with the reaction time measure of nonconscious retrieval. Together, our findings suggest that new semantic associations can be formed and retrieved by way of the medial temporal lobe without awareness of the associations or its components at encoding or any awareness that one is remembering at retrieval.

Adult↗

PubMed2003

Active hippocampus during nonconscious memories.

The hippocampal formation is known for its importance in conscious, declarative memory. Here, we report neuroimaging evidence in humans for an additional role of the hippocampal formation in nonconscious memory. We maskedly presented combinations of faces and written professions such that subjects were not aware of them. Nevertheless, the masked presentations activated many of the brain regions that unmasked presentations of these stimuli did. To induce a nonconscious retrieval of the faces and face-associated occupational information, subjects were instructed to view the previously masked faces and to guess the professional category of each person--academic, artist, and workman. Guessing the professional category of previously masked versus new faces activated the left and right hippocampal formation and right perirhinal cortex as well as bilateral fusiform areas and fronto-temporal areas known to mediate the retrieval of semantic information. These activations within the semantic processing system suggest that conceptual knowledge acquired during masking was nonconsciously retrieved. Our data provide clues to an analogous role of the hippocampus in conscious and nonconscious memory.

Adult↗

PubMed2003

Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe.

Previous work indicates that stress levels of circulating glucocorticoids can impair retrieval of declarative memory in human subjects. Several studies have reported that declarative memory retrieval relies on the medial temporal lobe. The present study used H(2)(15)O-positron emission tomography to investigate whether acutely elevated glucocorticoid levels affect regional cerebral blood flow in the medial temporal lobe, as well as in other brain regions, during declarative memory retrieval in healthy male human subjects. When measured over four different declarative memory retrieval tasks, a single, stress-level dose of cortisone (25 mg) administered orally 1 h before retention testing, induced a large decrease in regional cerebral blood flow in the right posterior medial temporal lobe, the left visual cortex and the cerebellum. The decrease in the right posterior medial temporal lobe was maximal in the parahippocampal gyrus, a region associated with successful verbal memory retrieval. Cortisone administration also significantly impaired cued recall of word pairs learned 24 h earlier, while drug effects on performance in the other tasks (verbal recognition, semantic generation and categorization) were not significant. The present results provide further evidence that acutely elevated glucocorticoid levels can impair declarative memory retrieval processes and suggest that such impairments may be related to a disturbance of medial temporal lobe function.

Adult↗

PubMed2002

Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease.

Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.

5' Untranslated Regions↗