DOMAIN-SPECIFIC CHOLINERGIC MODULATION OF COGNITIVE FUNCTIONS IN A PRIMATE TEST BATTERY

In human cognitive research, test batteries are commonly used to obtain a comprehensive evaluation of multiple cognitive domains, whereas preclinical investigations typically rely on individual tasks examined separately. In our study, we implemented a cognitive battery paradigm closely modelled after human protocols and pharmacologically validated this multi-task framework in non-human primates.
Eight adult male rhesus macaques were trained in four touchscreen tasks assessing distinct cognitive functions: object memory (delayed matching to sample, DMTS), spatial memory (self-ordered spatial search, SOSS), associative object–location memory (paired associates learning, PAL), and visual discrimination and attentional set shifting (intra–extra dimensional set shifting, IDED). Additionally, a fifth task was introduced (SOSS-based motivation measurement task, SOMM), consisting of three trials with identical stimuli that disappeared upon touch, to remove mnemonic requirements and selectively measure motivational drive.
Within the multi-task session structure, administration of muscarinic acetylcholine receptor antagonist scopolamine produced comparable transient cognitive disruption in the PAL, SOSS, and DMTS tasks, whereas the IDED task showed weaker impairment. The acetylcholinesterase inhibitor donepezil exhibited a tendency to counteract the amnestic effects; but this effect was again less evident in IDED.
Results indicate domain-dependent pharmacological sensitivity across the paradigm, with memory-related tasks being more affected by cholinergic manipulation than a task emphasizing attention and cognitive flexibility. This supports interpretation of the battery at the level of cognitive domains rather than single tasks. Overall, the paradigm provides a platform for assessing pharmacological efficacy in a preclinical translational context and establishes a foundation for future applications with brain stimulation techniques.