Frontotemporal Connections in Episodic Memory and Aging: A Diffusion MRI Tractography Study

P8. Relationship of fornix white matter microstructure and memory function in older adults

Through learning and practice, we can acquire numerous skills, ranging from the simple (whistling) to the complex (memorizing operettas in a foreign language). It has been proposed that complex learning requires a network of brain regions that interact with one another via white matter pathways. One candidate white matter pathway, the uncinate fasciculus (UF), has exhibited mixed results for this hypothesis: some studies have shown UF involvement across a range of memory tasks, while other studies report null results. Here, we tested the hypothesis that the UF supports associative memory processes and that this tract can be parcellated into sub-tracts that support specific types of memory. Healthy young adults performed behavioral tasks (two face-name learning tasks, one word pair memory task) and underwent a diffusion-weighted imaging scan. Our results revealed that variation in UF microstructure was significantly associated with individual differences in performance on both face-name tasks, as well as the word association memory task. A UF sub-tract, functionally defined by its connectivity between face-selective regions in the anterior temporal lobe and orbitofrontal cortex, selectively predicted face-name learning. In contrast, connectivity between the fusiform face patch and both anterior face patches had no predictive validity. These findings suggest that there is a robust and replicable relationship between the UF and associative learning and memory. Moreover, this large white matter pathway can be subdivided to reveal discrete functional profiles.

Objective To study the changes of fractional anisotropy (FA) value of white matter of brain and temporal stem in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients as well as normal cognitive (NC) aged people with diffusion tensor imaging (DTI), and explore the damage mechanism of temporal stem and its diagnostic value on AD and aMCI. Methods Ten patients with AD, 10 patients with aMCI and 10 NC volunteers as control group were scanned by routine MRI and DTI. FA values were calculated by post-processing software (DTIstudio) in temporal stem (including anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus), and white matter in anterior frontal, temperal, parietal and occipital lobes. The data were analyzed by SPSS 13.0. If bilateral differences of FA values were not statistically significant (P > 0.05), the average values of bilateral FA were selected and compared among 3 groups. If bilateral differences of FA values were statistically significant (P 0.05, for all). 2) There was significant difference of FA values in anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus between AD and aMCI groups (P 0.05, for all). Conclusions The significant difference of FA values in temporal stem among AD, aMCI and NC groups suggests that temporal stem fiber bundles are of great significance in the white matter damage of AD, and DTI is helpful for the differential diagnosis of AD, aMCI and NC. The abnormal changes of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal and parietal lobes are of great diagnostic value in AD. doi: 10.3969/j.issn.1672-6731.2014.03.011

Early cognitive neuroscientific research revealed that the hippocampus is crucial for spatial navigation in rodents, and for autobiographical episodic memory in humans. Researchers quickly linked these streams to propose that the human hippocampus supports memory through its role in representing space, and research on the link between spatial cognition and episodic memory in humans has proliferated over the past several decades. Different researchers apply the term "spatial" in a variety of contexts, however, and it remains unclear what aspect of space may be critical to memory. Similarly, "episodic" has been defined and tested in different ways. Naturalistic assessment of spatial memory and episodic memory (i.e., episodic autobiographical memory) is required to unify the scale and biological relevance in comparisons of spatial and mnemonic processing. Limitations regarding the translation of rodent to human research, human ontogeny, and inter-individual variability require greater consideration in the interpretation of this literature. In this review, we outline the aspects of space that are (and are not) commonly linked to episodic memory, and then we discuss these dimensions through the lens of individual differences in naturalistic autobiographical memory. Future studies should carefully consider which aspect(s) of space are being linked to memory within the context of naturalistic human cognition. This article is categorized under: Psychology > Memory.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.

What-Where-When (WWW) memory tasks have been used to study episodic(-like) memory in non-human animals. In this study, we investigate whether humans use episodic memory to solve such a WWW memory task. Participants are assigned to one of two treatments, in which they hide different coin types (what) in different locations (where) on two separate occasions (when). In the Active treatment, which mimics the animal situation as closely as possible, participants are instructed to memorize the WWW information; in the Passive treatment, participants are unaware of the fact that memory will be tested. In both groups, the majority of participants report using a mental time travel strategy to solve the task, and performance on a different episodic memory test significantly predicts performance on the WWW memory task. This suggests that the WWW memory task is a good test of episodic memory in humans. Participants remember locations and coins from the first hiding session better than they do those of the second hiding session, suggesting their memories may be reinforced during the second hiding session. We also investigated how well episodic memory performance predicted performance on the three aspects of the WWW memory task separately. In the Passive treatment, episodic memory performance predicts performance on all three aspects of the WWW memory task equally. However, in the Active treatment it only predicts performance on the what component. This could imply that during active encoding a different memory system is used for where and when information than during passive encoding. Encoding of what information seems to rely on episodic memory processing in both conditions.

From structure to function in the lateralized brain: How structural properties of the arcuate and uncinate fasciculus are associated with dichotic listening performance

Two strategies used to uncover neural systems for episodic-like memory in animals are discussed: (i) an attribute of episodic memory (what? when? where?) is examined in order to reveal the neuronal interactions supporting that component of memory; and (ii) the connections of a structure thought to be central to episodic memory in humans are studied at a level of detail not feasible in humans. By focusing on spatial memory (where?) and the hippocampus, it has proved possible to bring the strategies together. A review of lesion, disconnection and immediate early-gene studies in animals reveals the importance of interactions between the hippocampus and specific nuclei in the diencephalon (most notably the anterior thalamic nuclei) for spatial memory. Other parts of this extended hippocampal system include the mammillary bodies and the posterior cingulate (retrosplenial) cortex. Furthermore, by combining lesion and immediate early-gene studies it is possible to show how the loss of one component structure or tract can influence the remaining regions in this group of structures. The validity of this convergent approach is supported by new findings showing that the same set of regions is implicated in anterograde amnesia in humans.

Reduced integrity of the uncinate fasciculus and cingulum in depression: A stem-by-stem analysis

Although the limbic system is closely related to emotion and social behaviors, little is known about the integrity of limbic pathways and how genetics influence the anatomical abnormalities of limbic networks in children with autism spectrum disorder (ASD). Therefore, we used an ASD twin study design to evaluate the microstructural integrity and autism-related differences in limbic pathways of young children with ASD and to estimate the heritability of limbic tracts microstructure variance. We obtained diffusion tensor imaging scans from 33 pairs of twins with ASD aged 2-9 years and 20 age-matched typically developing children. The ACE model was used to estimate the relative effects of additive genetic factors (A), shared environmental factors (C) and specific environmental factors (E) on the variability of diffusivity measurements. We found a significant decrease in fractional anisotropy (FA) in the bilateral fornix and uncinate fasciculus (UF), as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the bilateral fornix and right UF of ASD children. Correlation analysis showed that FA, MD, and lateralization indices of UF were correlated with autism diagnostic observation schedule scores. The ACE model revealed that genetic effects may drive some of the variability of microstructure in the bilateral fornix, cingulum, and left UF. In conclusion, in children with ASD, there are abnormalities in the white matter microstructure of the limbic system, which is related to the core symptoms; these abnormalities may be related to the relative contribution of genetic and environmental effects on specific tracts. LAY SUMMARY: Autism spectrum disorder (ASD) children have abnormal white matter structure in limbic system related to ASD symptoms, and genetic factors play an important role in the development of limbic tracts.

Diffusion tensor imaging (DTI) is a non-invasive technique that can be used to assess the integrity of the white matter in the brain. To investigate the usefulness of DTI in patients with temporal lobe epilepsy (TLE) and to observe its relationship with lateralisation of the epileptogenic focus in these patients. We analysed 11 patients diagnosed with TLE in accordance with the pre-surgical protocol of our epilepsy unit, and who were seizure-free two years after performing a temporal lobectomy plus amygdalohippocampectomy (Spencer technique). As part of their pre-operative study, a 1.5 T magnetic resonance brain scan with diffusion tensor imaging was performed. A voxel-based analysis was then employed to study the differences in connectivity between the hemisphere that underwent surgery and the contralateral hemisphere. Compared with the contralateral hemisphere, a statistically significant reduction in fractional anisotropy (p < 0.05) was observed in the corpus callosum, the cingulate, the superior longitudinal fasciculus, the anterior thalamic radiations, the internal capsule, the ventral lateral and pulvinar nuclei of the thalamus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the inferior longitudinal fasciculus and the parahippocampal gyrus, all ipsilateral to the epileptogenic focus. The characterisation of the abnormalities in the connectivity of the cerebral white matter, by means of DTI in patients with TLE, can be a valuable aid for the lateralisation of the epileptogenic focus in the pre-surgical evaluation of these patients. Further studies with a higher number of patients would be needed to confirm these results.

Material hardship, or difficulty affording basic resources such as food, housing, utilities, and health care, increases children's risk for internalizing problems. The uncinate fasciculus (UNC) and two of the gray matter regions it connects-the orbitofrontal cortex (OFC) and amygdala-may play important roles in the neural mechanisms underlying these associations. We investigated associations among material hardship, UNC microstructure, OFC and amygdala structure, and internalizing symptoms in children. Participants were 5-9-year-old children (N=94, 61% female) from socioeconomically diverse families. Parents completed questionnaires assessing material hardship and children's internalizing symptoms. High-resolution, T1-weighted magnetic resonance imaging (n=51), and diffusion tensor imaging (n=58) data were acquired. UNC fractional anisotropy (FA), medial OFC surface area, and amygdala gray matter volume were extracted. Greater material hardship was significantly associated with lower UNC FA, smaller amygdala volume, and higher internalizing symptoms in children, after controlling for age, sex, and family income-to-needs ratio. Lower UNC FA significantly mediated the association between material hardship and internalizing symptoms in girls but not boys. These findings are consistent with the notion that material hardship may lead to altered white matter microstructure and gray matter structure in neural networks critical to emotion processing and regulation.

Integrity of the uncinate fasciculus is associated with emotional pattern separation-related fMRI signals in the hippocampal dentate and CA3

Segmented brain white matter hyperintensities were compared between subjects with late-life depression and age-matched subjects with similar vascular risk factor scores. Correlations between neuropsychological performance and whole brain-segmented white matter hyperintensities and white and gray matter volumes were also examined. Eighty-three subjects with late-life depression and 32 comparison subjects underwent physical examination, psychiatric evaluation, neuropsychological testing, vascular risk factor assessment, and brain magnetic resonance imaging (MRI). Automated segmentation methods were used to compare the total brain and regional white matter hyperintensity burden between depressed patients and comparison subjects. Depressed patients and comparison subjects did not differ in demographic variables, including vascular risk factor, or whole brain-segmented volumes. However, depressed subjects had seven regions of greater white matter hyperintensities located in the following white matter tracts: the superior longitudinal fasciculus, fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, and inferior longitudinal fasciculus. These white matter tracts underlie brain regions associated with cognitive and emotional function. In depressed patients but not comparison subjects, volumes of three of these regions correlated with executive function; whole brain white matter hyperintensities correlated with executive function; whole brain white matter correlated with episodic memory, processing speed, and executive function; and whole brain gray matter correlated with processing speed. These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.

Abnormal frontal cortex white matter connections in bipolar disorder: A DTI tractography study