Functional alterations in brain activation and deactivation in mild cognitive impairment in response to a graded working memory challenge.
OBJECTIVE
To investigate dynamic changes in functional brain activity in mild cognitive impairment (MCI) in response to a graded working memory (WM) challenge with increasing memory load.


METHODS
In an event-related functional magnetic resonance imaging (fMRI) study, 35 MCI and 22 cognitively normal subjects performed a visuospatial associative WM task with 3 load levels. Potential performance differences were controlled for by individually calibrating the number of items presented at each load.


RESULTS
An interaction between group and WM load was observed during stimulus encoding. At lower loads, greater activity in the right anterior cingulate and right precuneus was observed in MCI subjects. As the load increased to higher levels, reduced activation in these regions and greater deactivation in the posterior cingulate-medial precuneus were observed in MCI compared to control subjects. Stronger expression of load-related patterns of activation and deactivation in MCI subjects was associated with greater clinical severity and a more abnormal pattern of performance variability.


CONCLUSIONS
Patterns of overactivation, underactivation and deactivation during successful encoding in MCI subjects were dependent on WM load. This type of graded cognitive challenge may operate like a 'memory stress test' in MCI and may be a useful biomarker of disease at the pre-dementia stage.
Brain and Ageing Research Program, School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia. n.kochan@unsw.edu.au
N A
NA
Kochan
M
M
Breakspear
M J
MJ
Slavin
M
M
Valenzuela
S
S
McCraw
H
H
Brodaty
P S
PS
Sachdev
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002138:Calibration; D003072:Cognition Disorders / Q000145:classification / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D010775:Photic Stimulation; D011930:Reaction Time / Q000502:physiology; D012959:Socioeconomic Factors