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Objective: To assess executive function in patients with mild cognitive impairment (MCI) and to determine whether task switching ability is associated with transition to Alzheimer’s disease. Methods: Twenty-seven MCI patients and 19 older controls were tested using a cued letter-digit classification switching task. Sixteen patients could perform the task (MCI-able), 6 could not (MCI-unable), and 5 were able only with cognitive support (MCI-cue). Demographic, neuropsychological, event-related potential (ERP), MRI, and genetic data were also collected. Results: The four groups did not differ on age, gender, and APO E4 frequency. Compared to the controls, the MCI-unable group had significantly poorer performance on the Trail Making task ( 2 .430), lower education ( 2 .234), and smaller cortical volume ( 2 .245). Most MCI patients exhibited task-switching deficits but to vastly different degrees and with varying outcomes. The combined pattern of neuropsychological and task switching performance indicates that the MCI-able patients displayed memory retrieval difficulties (F(2,39) 3.6, p .036, MSE 1.44), generally preserved task switching abilities, and had a high probability of remaining dementia-free at follow-up. The MCI-cue patients had increased mixing costs, F(2,39) 11.0, p .001, MSE .07; the MCI-unable patients showed episodic memory deficits, and both groups had a high probability of poor outcome (i.e., developing AD or dying within four years). Conclusion: This study demonstrates that variability in performance on measures of task-switching can highlight important heterogeneity in the MCI population.

A task set may need to be inhibited to facilitate the switch to another task. This event-related potential (ERP) study determined (1) whether backward inhibition (BI) is exerted preferentially in high interference environments, and (2) whether ERPs locked to critical time points reflect BI during cue preparation and/or response stages. High interference (HI) and low interference (LI) were created by manipulating task difficulty. A reaction time (RT) BI effect (i.e., BI>control trials) was shown only during HI tasks. Cue-locked ERPs on LI tasks suggest increased attentional resources were allocated during the reactivation of a recently inhibited task. For HI tasks, BI versus control trial differences were reflected in a response-locked ERP negativity only after response selection (indexed by the response-locked lateralized readiness potential), indicating that BI is a lateral inhibition mechanism exerted during response preparation.

In order to understand how the brain prepares for and executes a switch in task demand, we measured reaction time (RT), accuracy, and event-related brain potentials associated with performance in single and mixed-task blocks using a cued design. Our results show that trials which repeat in a mixed-task block (repeat trials) were more demanding than trials which repeated in a single-task block, as reflected by the presence of a RT mixing cost and by the presence of a smaller target-locked positivity (P3b) on repeat trials. Within a mixed-task block, repeat and switch trials also differed, where repeat trials showed evidence of greater preparation (larger cue-locked negativity), more efficient target processing (larger target-locked P3b), and shorter RTs. In addition, the cue-locked negativity difference remained despite equating repeat and switch trials on RT, suggesting that this negativity difference is specific to the switching process. Our results are discussed in light of existing models of task switching.

Theta-frequency (4-12 Hz) electroencephalographic activity is thought to play a role in mechanisms mediating sensory and mnemonic processing in the entorhinal cortex and hippocampus, but the effects of acetylcholine on excitatory synaptic inputs to the entorhinal cortex are not well understood. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the piriform (olfactory) cortex were recorded in the medial entorhinal cortex during behaviors associated with theta activity (active mobility) and were compared with those recorded during nontheta behaviors (awake immobility and slow wave sleep). Synaptic responses were smaller during behavioral activity than during awake immobility and sleep, and responses recorded during movement were largest during the negative phase of the theta rhythm. Systemic administration of cholinergic agonists reduced the amplitude of fEPSPs, and the muscarinic receptor blocker scopolamine strongly enhanced fEPSPs, suggesting that the theta-related suppression of fEPSPs is mediated in part by cholinergic inputs. The reduction in fEPSPs was investigated using in vitro intracellular recordings of EPSPs in Layer II neurons evoked by stimulation of Layer I afferents. Constant bath application of the muscarinic agonist carbachol depolarized membrane potential and suppressed EPSP amplitude in Layer II neurons. The suppression of EPSPs was not associated with a substantial change in input resistance, and could not be accounted for by a depolarization-induced reduction in driving force on the EPSP. The GABA(A) receptor-blocker bicuculline (50 microM) did not prevent the cholinergic suppression of EPSPs, suggesting that the suppression is not dependent on inhibitory mechanisms. Paired-pulse facilitation of field and intracellular EPSPs were enhanced by carbachol, indicating that the suppression is likely due to inhibition of presynaptic glutamate release. These results indicate that, in addition to well known effects on postsynaptic conductances that increase cellular excitability, cholinergic activation in the entorhinal cortex results in a strong reduction in strength of excitatory synaptic inputs from the piriform cortex.

We investigated age-related differences in task-switching performance by using behavioral measures and event-related brain potentials. We tested younger and older adults, and we separated older adults into groups with high and low working memory (WM); that is, we separated them into old-high-WM and old-low-WM groups. On average, all participants responded more slowly in mixed-task than in single-task blocks (i.e., reaction time or RT mixing cost). Younger adults and old-high-WM participants had equivalent RT mixing costs and showed larger posterior negative slow-wave activity when preparing for mixed trials than for single-task trials, suggesting that mixed-task trials required trial-to-trial preparation. Old-high-WM participants also showed frontally distributed activity on mixed-task trials, suggesting their use of executive control to offset age-related differences in mixed-task preparation. In contrast, old-low-WM participants had large RT mixing costs and large posterior event-related brain potential negativities during single-task trials, suggesting that they prepare during single- and mixed-task blocks. High WM, therefore, may help older adults offset the age-related difficulties often observed when they are task switching.