Auditory cortical function during verbal episodic memory encoding in Alzheimer's disease

Abstract

Episodic memory encoding of a verbal message depends upon initial registration, which requires sustained auditory attention followed by deep semantic processing of the message. Motivated by previous data demonstrating modulation of auditory cortical activity during sustained attention to auditory stimuli, we investigated the response of the human auditory cortex during encoding of sentences to episodic memory. Subsequently, we investigated this response in patients with mild cognitive impairment (MCI) and probable Alzheimer's disease (pAD). Using functional magnetic resonance imaging, 31 healthy participants were studied. The response in 18 MCI and 18 pAD patients was then determined, and compared to 18 matched healthy controls. Subjects heard factual sentences, and subsequent retrieval performance indicated successful registration and episodic encoding. The healthy subjects demonstrated that suppression of auditory cortical responses was related to greater success in encoding heard sentences; and that this was also associated with greater activity in the semantic system. In contrast, there was reduced auditory cortical suppression in patients with MCI, and absence of suppression in pAD. Administration of a central cholinesterase inhibitor (ChI) partially restored the suppression in patients with pAD, and this was associated with an improvement in verbal memory. Verbal episodic memory impairment in AD is associated with altered auditory cortical function, reversible with a ChI. Although these results may indicate the direct influence of pathology in auditory cortex, they are also likely to indicate a partially reversible impairment of feedback from neocortical systems responsible for sustained attention and semantic processing.