Alzheimer’s disease (AD) results in a diffuse, but characteristic impairment of
cognitive function, with early involvement of verbal episodic memory. A
prodromal phase of amnestic mild cognitive impairment (MCI) consists of
patients with a mild, isolated impairment of episodic memory. In this thesis, I
have described experiments performed on these patients and healthy
volunteers using functional magnetic resonance imaging (fMRI). I aimed to
investigate changes in neural activity associated with the breakdown in verbal
episodic memory.
Initially, I established the feasibility of using fMRI to investigate spoken
responses in a study of speech production in healthy volunteers. This was
important for investigating spoken retrieval of episodic memory. I also
demonstrated integration of perceptual feedback and motor feedforward
responses during propositional speech production within the medial planum
temporale, associated with suppression of activity in secondary somatosensory
cortex within the parietal operculum.
In the verbal memory study, I demonstrated that successful encoding of heard
sentences was associated with greater activity in cortical regions associated
with semantic processing, but lower activity within early auditory cortex;
implying a “top-down” effect on early perceptual cortex, related to sustained
auditory attention. Patients with AD did not show this top-down effect. In
addition, less activity was observed during encoding in AD patients, compared
to MCI patients or controls, in regions associated with motivation. In the medial temporal lobes, there was less activity in AD compared to controls, but higher
activity in MCI, consistent with previous reports. During retrieval, there was
less activity in frontal executive control systems in AD compared to controls.
This was seen in both performance-matched comparisons and in the neural
response to a reduction in retrieval performance. MCI patients showed early
changes in parietal lobe retrieval performance-related activity.
Overall, the reduced verbal encoding performance in AD was related to
impairments in the function of both MTL memory-related systems and
sustained auditory attention, and was associated with reduced motivation.
During free recall, lower performance in AD was associated with impairment of
frontal cognitive control. Therefore, I have shown that verbal episodic memory
impairment in AD is the consequence of altered activity in multiple cognitive
networks, in addition to the well-recognised impairments in the MTL-memory
network. These results have implications for future therapeutic interventions to
improve memory function in this patient group, highlighting the potential use of
drugs that enhance attention, motivation and frontal executive function.