BACKGROUND: Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a 'signature' of cortical atrophy in paralimbic and heteromodal association regions measured with MRI.
OBJECTIVE: To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset.
Neuropsychological studies highlight the importance of the prefrontal cortex in abstract reasoning ability. The prefrontal cortex is anatomically connected to the basal ganglia through a series of parallel loops. The dorsolateral prefrontal cortex shares relatively greater connectivity with the caudate head, and it has been proposed that the caudate head may be more sensitive to executive processing. To investigate the frontostriatal circuitry underlying abstract reasoning, we designed a reasoning task in which stimuli varied sequentially across one dimension.
OBJECTIVE: The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD.
Lesions of parahippocampal structures impair performance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working memory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex.
Sequence learning depends on the striatal system, but recent findings also implicate the mediotemporal lobe (MTL) system. Schendan, Searl, Melrose, and Stern (2003) found higher-order associative, learning-related activation in the striatum, dorsolateral prefrontal cortex, and the MTL during the early acquisition phase of both implicit and explicit variants of a serial response time task.
Recent delayed matching studies have demonstrated that maintaining trial-unique stimuli in working memory modulates activity in temporal lobe structures. In contrast, most previous studies that focused on the role of the prefrontal cortex (PFC) used familiar stimuli. We combined fMRI with a delayed-match-to-sample (DMS) task in humans that allowed us to manipulate stimulus pre-exposure (trial-unique vs. familiar objects) and stimulus domain (object vs. location). A visually guided saccade task was used to localize the frontal eye fields (FEF).
Studies of Parkinson's disease (PD) suggest that cognitive deficits accompany the classically recognized motor symptoms, and that these cognitive deficits may result from damage to frontal-basal ganglia circuits. PD patients are impaired on ordering events and action components into coherent sequences. In this study, we examined early-stage, nondemented, medicated PD subjects and matched control subjects during a semantic event sequencing task using functional MRI (fMRI).
Humans encounter and form memories for multiple types of experiences that differ in content, novelty, and memorability. Critical for understanding memory is determining (1) how the brain supports the encoding of events with differing content and (2) whether neural regions that are sensitive to novelty also influence whether stimuli will be subsequently remembered.
During everyday interactions, we continuously monitor and maintain information about different individuals and their changing emotions in memory. Yet to date, working memory (WM) studies have primarily focused on mechanisms for maintaining face identity, but not emotional expression, and studies investigating the neural basis of emotion have focused on transient activity, not delay related activity. The goal of this functional magnetic resonance imaging study was to investigate WM for two critical social cues: identity and emotion.
The importance of the medial temporal lobe in memory has been studied extensively at the neuronal, neural ensemble, and systems level. In this report, we discuss recent systems level neuroimaging results in relation to neurophysiological studies of the hippocampus and related structures within the medial temporal lobe. By combining our knowledge across the cellular and systems levels we sought to gain theoretical insight and a better understanding of the function of the hippocampus and related medial temporal lobe structures.
