Christina Elfgren

A Dynamic Role of the Medial Temporal Lobe during Retrieval of Declarative Memory in Man

Understanding the role of the medial temporal lobe (MTL) in learning and memory is an important problem in cognitive neuroscience. Memory and learning processes that depend on the function of the MTL and related diencephalic structures (e.g., the anterior and mediodorsal thalamic nuclei) are defined as declarative. We have studied the MTL activity as indicated by regional cerebral blood flow with positron emission tomography and statistical parametric mapping during recall of abstract designs in a less practiced memory state as well as in a well-practiced (well-encoded) memory state. The results showed an increased activity of the MTL bilaterally (including parahippocampal gyrus extending into hippocampus proper, as well as anterior lingual and anterior fusiform gyri) during retrieval in the less practiced memory state compared to the well-practiced memory state, indicating a dynamic role of the MTL in retrieval during the learning processes. The results also showed that the activation of the MTL decreases as the subjects learn to draw abstract designs from memory, indicating a changing role of the MTL during recall in the earlier stages of acquisition compared to the well-encoded declarative memory state.

Neuropsychological Findings in Frontal Lobe Dementia

Neuropsychological investigations were performed on 18 patients with a clinical diagnosis of frontal lobe dementia supported by regional cerebral blood flow measurements. Nature and degree of cognitive impairment were examined with a comprehensive test battery. The results of the neuropsychological assessment could be described as three levels of cognitive impairment. The increasing levels of cognitive impairment were accompanied by corresponding levels of reduced cerebral blood flow in frontotemporal areas. No apparent relationship emerged between impairment level and illness duration, indicating a considerable individual variation in the clinical course of frontal lobe dementia.

Dynamic changes in the functional anatomy of the human brain during recall of abstract designs related to practice

In the present PET study we explore some functional aspects of the interaction between attentional/control processes and learning/memory processes. The network of brain regions supporting recall of abstract designs were studied in a less practiced and in a well practiced state. The results indicate that automaticity, i.e., a decreased dependence on attentional and working memory resources, develops as a consequence of practice. This corresponds to the practice related decreases of activity in the prefrontal, anterior cingulate, and posterior parietal regions. In addition, the activity of the medial temporal regions decreased as a function of practice. This indicates an inverse relation between the strength of encoding and the activation of the MTL during retrieval. Furthermore, the pattern of practice related increases in the auditory, posterior insular-opercular extending into perisylvian supramarginal region, and the right mid occipito-temporal region, may reflect a lower degree of inhibitory attentional modulation of task irrelevant processing and more fully developed representations of the abstract designs, respectively. We also suggest that free recall is dependent on bilateral prefrontal processing, in particular non-automatic free recall. The present results confirm previous functional neuroimaging studies of memory retrieval indicating that recall is subserved by a network of interacting brain regions. Furthermore, the results indicate that some components of the neural network subserving free recall may have a dynamic role and that there is a functional restructuring of the information processing networks during the learning process.

Psychiatric symptoms and their psychosocial consequences in frontotemporal dementia.

Based on a retrospective study of 19 neuropathologically verified cases with frontotemporal dementia (FTD), neuropsychiatric symptoms related to behavioral disturbances and their psychosocial consequences were studied. The results indicate that frontotemporal dementia is often misdiagnosed early in the clinical course. Behavioural features with impaired social interactions, impaired personal regulation, and loss of insight were seen in all patients. The psychosocial consequences reported in this paper challenge future research in frontotemporal dementia.

Selective frontal neurodegeneration of the inferior fronto-occipital fasciculus in progressive supranuclear palsy (PSP) demonstrated by diffusion tensor tractography

BackgroundThe clinical presentation in progressive supranuclear palsy (PSP), an atypical parkinsonian disorder, includes varying degrees of frontal dysexecutive symptoms. Using diffusion tensor imaging (DTI) and tractography (DTT), we investigated whether diffusion changes and atrophy of the inferior fronto-occipital fasciculus (IFO) occurs in PSP and if these changes correlate with disease stage and clinical phenotype. The corticospinal tract (CST), which is often involved in PSP, was investigated for comparison.MethodsDTI of the whole brain was performed with a 3 T MR scanner using a single shot-EPI sequence with diffusion encoding in 48 directions. Scans were obtained in patients with PSP (n = 13) and healthy age-matched controls (n = 12). DTT of the IFO and CST was performed with the PRIDE fibre tracking tool (Philips Medical System). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated and correlated with disease stage and clinical phenotype.ResultsIn patients with PSP, significantly decreased FA and increased ADC was found in the frontal part of IFO compared with the medial and occipital parts of IFO, as well as compared to controls. Four of the thirteen patients with PSP showed a marked decrease in the number of tracked voxels in the frontal part of IFO. These findings were most pronounced in patients with severe frontal cognitive symptoms, such as dysexecutive problems, apathy and personality change. There was a strong correlation (r2 = -0.84; p < 0,001) between disease stage and FA and ADC values in the CST.ConclusionsDTT for identification of neuronal tracts with subsequent measurement of FA and ADC is a useful diagnostic tool for demonstrating patterns of neuronal tract involvement in neurodegenerative disease. In selected tracts, FA and ADC values might act as surrogate markers for disease stage.

The tau R406W mutation causes progressive presenile dementia with bitemporal atrophy

Frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are two frequent causes of dementia that share both clinical and neuropathological features. Common to both disorders are the neurofibrillary tangles consisting of aggregations of hyperphosphorylated tau protein. Recently, a number of different pathogenic mutations in the tau gene have been identified in families with FTD and parkinsonism linked to chromosome 17 (FTDP-17). In the present study, a Swedish family with presenile degenerative dementia with bitemporal atrophy was screened for mutations in the tau gene. As a result, the R406W mutation in exon 13 was identified in all affected cases. This mutation has previously been reported in two different FTDP-17 families of Dutch and Midwestern American origin. Common features to these two kindreds and our family are the late age at onset and long duration of the disease. Our pedigree as well as the American one show early memory impairment and pronounced temporal lobar atrophy similar to AD, while the Dutch cases show more FTD features. This further illustrates the large clinical variability among cases with tau mutations and stresses the importance of genetic classification in addition to the traditional clinical classification of neurodegenerative disorders.

Learning-related effects and functional neuroimaging

A fundamental problem in the study of learning is that learning‐related changes may be confounded by nonspecific time effects. There are several strategies for handling this problem. This problem may be of greater significance in functional magnetic resonance imaging (fMRI) compared to positron emission tomography (PET). Using the general linear model, we describe, compare, and discuss two approaches for separating learning‐related from nonspecific time effects. The first approach makes assumptions on the general behavior of nonspecific effects and explicitly models these effects, i.e., nonspecific time effects are incorporated as a linear or nonlinear confounding covariate in the statistical model. The second strategy makes no a priori assumption concerning the form of nonspecific time effects, but implicitly controls for nonspecific effects using an interaction approach, i.e., learning effects are assessed with an interaction contrast. The two approaches depend on specific assumptions and have specific limitations. With certain experimental designs, both approaches may be used and the results compared, lending particular support to effects that are independent of the method used. A third and perhaps better approach that sometimes may be practically unfeasible is to use a completely temporally balanced experimental design. The choice of approach may be of particular importance when learning‐related effects are studied with fMRI. Hum. Brain Mapping 7:234–243, 1999.

Alzheimer's disease (AD) and executive dysfunction. A case-control study on the significance of frontal white matter changes detected by diffusion tensor imaging (DTI).

White matter (WM) changes are frequently seen on structural imaging in AD but the clinical relevance of these changes is uncertain. Frontal WM pathology is often observed upon neuropathological examination in AD. Since frontal cortical/sub-cortical pathology is known to relate to executive dysfunction, the aim was to elucidate if frontal WM changes in AD correlated with executive dysfunction. In all, 15 AD patients and 15 age-matched control cases were investigated in the study, which covered conventional magnetic resonance imaging (MRI), DTI, neuropsychiatric and neuropsychological examinations. Reduced performance on neuropsychological testing of executive function correlated significantly with an increasing degree of frontal WM changes detected by DTI in the AD group, while no such correlation was observed for the controls. Conventional semi-quantitative MRI assessment did not correlate with results on neuropsychological testing of executive function in any of the groups. The structural correlate to certain dimensions of executive dysfunction in AD patients could be related to changes in the deep frontal WM. DTI appears to be more sensitive in the detection of clinically significant WM alterations than conventional semi-quantitative MRI.

Familial Presenile Dementia with Bitemporal Atrophy

This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer’s disease.

Personality characteristics and affective status related to cognitive test performance and gender in patients with memory complaints

The aims are to study personality characteristics of patients with memory complaints and to assess the presence of objective (OMI) versus subjective (SMI) memory impairment, the affective status, as well as potential gender differences. The patients were assessed by means of a neuropsychiatric examination and a neuropsychological test-battery. The Swedish version of the revised NEO Personality Inventory (NEO PI-R) and the Hospital Anxiety and Depression Scale (HADS) were used. The 57 patients (38 women, 19 men, mean age 56.9) differed from the Swedish normative group in three of the five personality factors: neuroticism, extraversion and agreeableness. This was mainly because of the scores of the female patients. Approximately half of the patients had OMI. No differences regarding personality factors or affective status were found between OMI and SMI patients. The female patients scored significantly higher than the male patients on symptoms of anxiety and depression. Neuroticism and symptoms of depression interacted with memory performance and gender. Our findings demonstrate the importance of applying an objective assessment of memory functions and a gender perspective when studying patients with memory complaints.