A model of effects of ketamine, a NMDA glutamatergic antagonist, on
executive control in monkeys

G. Stoet and L.H. Snyder
Anatomy and Neurobiology, Washington University in St.Louis, MO, USA

Executive control is the mental capacity to plan, coordinate, and
regulate how we respond to stimuli.  The capacity to switch between
different tasks is an important index of executive control commonly
used in psychiatric tests.  We studied an animal model of executive
control.

Monkeys performed trials of two visual discrimination tasks, which
were randomly interleaved.  On each trial, the monkey was presented a
task cue, which informed him to perform either a color or a shape
discrimination on the following stimulus.  The animal responded with a
left or right button press to the subsequent stimulus.  We measured
response time as a function of whether a trial followed the same task
(repeat trial) or a different task (switch trial), and whether stimuli
required a low or a high level of selective attention.

Monkeys are not slower on switch trials, unless the intertrial
interval (ITI) is extremely short.  This is different from humans, who
reliably show switch costs.

Some human studies have reported that ketamine administration
lengthens switch times.  Although our data show a dose-related
increase in reaction time, we found no specific impairment on the
ability to switch between tasks.

There are a number of differences between task-switching studies that
report increased task-switching costs and ours.  The animals in our
study were highly trained before we measured the effect of ketamine on
behavior.  Another difference is methodological.  Many of the human
studies required subjects to use short-term memory to detect the
occurrence and type of task switch (e.g., Wisconsin Card Sorting Task,
WCST), while we directly instructed the task to be performed on each
trial.  Thus it is possible that the effect of ketamine on switch
times in human studies was mediated by an effect on short-term memory
and not on executive control per se.

In conclusion, the capacity to switch between tasks is unaffected by
ketamine in monkeys.  Factors other than executive control might
contribute to task switching problems in humans tested using WCST or a
related paradigm.  Finally, our results suggest that ketamine may be
of limited use for understanding executive disorders in animal models.