Annett Werner

A meta-analysis of structural brain abnormalities in PTSD.

This series of meta-analyses examined structural abnormalities of the hippocampus and other brain regions in persons with PTSD compared to trauma-exposed and non-exposed control groups. The findings were significantly smaller hippocampal volumes in persons with PTSD compared to controls with and without trauma exposure, but group differences were moderated by MRI methodology, PTSD severity, medication, age and gender. Trauma-exposed persons without PTSD also showed significantly smaller bilateral hippocampal compared to non-exposed controls. Meta-analyses also found significantly smaller left amygdala volumes in adults with PTSD compared to both healthy and trauma-exposed controls, and significantly smaller anterior cingulate cortex compared to trauma-exposed controls. Pediatric samples with PTSD exhibited significantly smaller corpus callosum and frontal lobe volumes compared to controls, but there were no group differences in hippocampal volume. The overall findings suggested a dimensional, developmental psychopathology systems model in which: (1) hippocampal volumetric differences covary with PTSD severity; (2) hippocampal volumetric differences do not become apparent until adulthood; and (3) PTSD is associated with abnormalities in multiple frontal-limbic system structures.

Distinct brain networks in recognition memory share a defined region in the precuneus

Current models of recognition memory performance postulate that there are two fundamentally distinct retrieval processes, i.e. recollection and familiarity. This view has been challenged and little is known from human research about the functional connectivity of the brain areas involved in these processes. In our study we used a Remember‐Know procedure to assess the functional connectivity of brain regions under recognition memory in 30 healthy adults. Using functional magnetic resonance imaging, we analysed the blood oxygen level‐dependent responses during correct Remember, correct Know, correct Rejection and missed responses of the subjects during recognition of non‐emotional nouns. One activation cluster was found in the left precuneus associated with both recollection and familiarity answers. To acquire information about the way in which activity in one brain region modulates activity in another brain region in response to the active task, we performed a psychophysiological interaction analysis with the left precuneus as a seed region. This analysis revealed functionally distinct networks of brain areas underlying recollection and familiarity. Furthermore, we discuss the differential involvement of the hippocampus in a recollection network as compared with a familiarity network. In summary, our results further strengthen the assumptions of a dual‐process view of recognition memory [e.g. H. Eichenbaum et al. (2007) Annual Review of Neuroscience, 30, 123–152; A.P. Yonelinas (2001) Philosophical Transactions of the Royal Society London B Biological Sciences, 356, 1363–1374] and add empirical findings about the functional interconnectivity of brain regions supporting either recollection or familiarity.

The use of proton magnetic resonance spectroscopy in PTSD research—Meta-analyses of findings and methodological review

Different neuroimaging techniques provided evidence for structural and functional brain alterations in posttraumatic stress disorder (PTSD). Due to technical improvements, especially concerning localization techniques and more reliable analysis methods, one technique, proton magnetic resonance spectroscopy ((1)H-MRS), has increasingly become of interest because it allows further insight into metabolic mechanisms that may contribute to these alterations. The aim of this article is, therefore, to review recent studies utilizing (1)H-MRS of the hippocampus and other brain structures in PTSD. Using meta-analytic methods, we attempted to answer the question if PTSD, as compared to different types of control samples, is accompanied by altered neurometabolite ratios and concentrations in the tissue of different brain regions. A second intent was to review methodological aspects to advise on a minimal standard for reliable results with respect to the application of (1)H-MRS in PTSD. Finally, we discussed the implications of the findings with respect to current PTSD models and future research.

Altered neural network supporting declarative long-term memory in mild cognitive impairment

Autobiographical episodic memory represents a subsystem of declarative long-term memory and largely depends on combining information from multiple sources. The purpose of this study was to assess neural correlates of declarative long-term memory in patients with amnestic mild cognitive impairment (MCI) and controls using fMRI and a task requiring autobiographical and semantic memory retrieval. Comparison of the network supporting episodic autobiographical and semantic memory irrespective of remoteness (recent and remote) revealed significant activations in right parietal cortex and precuneus bilaterally in the patients. Autobiographical episodic versus semantic memory retrieval in the controls led to significant bilateral activations of the parietal-temporal junction, left temporal pole, anterior cingulate, retrosplenial cortex and cerebellum. In contrast, MCI patients activated left supplementary motor area, left premotor and superior temporal cortex. In MCI patients compared to controls a dysfunction of the retrosplenial cortex during memory retrieval was revealed by a lack of differential activation in relation to recency of memories and memory type. Our data suggest that MCI leads to a loss of specificity in the neural network supporting declarative long-term memory.

APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging and Alzheimer's disease.

Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimers disease, associated with regionally specific effects on brain morphology and function during the life span. Furthermore, entorhinal and hippocampal hemispheric asymmetry could be modified by pathology during Alzheimers disease development. Using high-resolution magnetic resonance imaging and a cortical unfolding technique we investigated whether carrying the APOE-4 allele influences hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients with Alzheimers disease as well as in middle-aged and older cognitively healthy individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left hemisphere when compared with the right hemisphere across all participants. Non-carriers of the allele showed this asymmetry only in the patient group. Cortical thickness in the hippocampus did not vary between hemispheres among APOE-4 allele carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in entorhinal cortical thickness. Among Alzheimers disease patients, this asymmetry might be less dependent on the APOE genotype and a more general marker of incipient disease pathology.

Age-Dependent Differences in the Neural Mechanisms Supporting Long-Term Declarative Memories

Autobiographical memories enable us to mentally reconstruct and relive past events, which is essential for ones personal identity. Unfortunately, this complex memory system is susceptible to age-related deterioration, possibly changing the way episodic information is being processed in older adults. The aim of this study was to investigate whether age influences the neural activity associated with content (episodic versus semantic) and remoteness (recent versus remote) of memories. Using functional magnetic resonance imaging in healthy older and young adults, we found significant age-dependent differences in the neural networks underlying memory content but not remoteness. Our data suggest an age-associated functional reorganization in the neural networks underlying long-term declarative memory. Relative increase in activity of posterior brain regions could reflect changes in visuospatial processing during episodic memory retrieval in older adults.

Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

Recently, a peak at 1.28 ppm in proton magnetic resonance spectroscopy ((1)H-MRS) of neural stem cells (NSCs) was introduced as a noninterventional biomarker for neurogenesis in vivo. This would be an urgently needed requisite for translational studies in humans regarding the beneficial role of adult neurogenesis for the structural and functional integrity of the brain. However, many concerns have risen about the validity of the proposed signal as a specific marker for NSCs. The peak has also been related to cell-type-independent phenomena such as apoptosis or necrosis. Thus, we compared the 1.28-ppm peak in various immature stem cell populations, including embryonic stem cells, mouse embryonic fibroblasts, embryonic stem cell- and induced pluripotent stem cell-derived NSCs, ex vivo isolated embryonic NSCs, as well as mature and tumor cell types from different germ layers. To correlate the integral peak intensity with cell death, we induced both apoptosis with camptothecin and necrosis with sodium azide. A peak at 1.28 ppm was found in most cell types, and in most, but not all, NSCH cultures, demonstrating no specificity for NSCs. The intensities of the 1.28-ppm resonance significantly correlated with the rate of apoptosis, but not with the rate of necrosis, cell cycle phase distribution, cell size, or type. Multiple regression analysis displayed a significant predictive value of the peak intensity for apoptosis only. In this context, its specificity for apoptosis as a major selection process during neurogenesis may suggest this resonance as an indirect marker for neurogenesis in vivo.

VISUALIZING NEURONAL STRUCTURES IN THE HUMAN BRAIN VIA DIFFUSION TENSOR MRI

Acquisition, analysis, and visualization of diffusion tensor magnetic resonance imaging (DT-MRI) is still an evolving technology. This article reviews the fundamentals of the data acquisition process and the pipeline leading to visual results that are interpretable by physicians in their clinical practice. The limitations of common approaches for visualizing the retrieved data are discussed and a new statistical method is presented to assess the reliability of the acquired tensor field. A novel visualization method is proposed which is discussed in light of neurophysiological considerations of the perception of colored patterns. It is argued that this method is more accurate for medical data while providing a nearly optimal visual stimulus. The method is evaluated on a patient study with a brain tumor.

Cardiovascular Risk and Hippocampal Thickness in Alzheimer’s Disease

Cardiovascular risk factors influence onset and progression of Alzheimers disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimers disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimers disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimers disease, and age did not influence cortical thickness. Alzheimers disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimers disease.

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment

Background: Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Methods: Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Results: Irrespective of the study participants’ cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Conclusion: Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.