TY - JOUR
T1 - Intermittent stimulation in the nucleus basalis of meynert improves sustained attention in rhesus monkeys
AU - Liu, Ruifeng
AU - Crawford, Jonathan
AU - Callahan, Patrick M.
AU - Terry, Alvin V.
AU - Constantinidis, Christos
AU - Blake, David T.
N1 - Funding Information:
This work was supported by the National Institutes of Health ( R01MH097695 to CC and DTB).
Publisher Copyright:
© 2018
PY - 2018/7/15
Y1 - 2018/7/15
N2 - Sustained attention is essential in important behaviors in daily life. Many neuropsychiatric disorders are characterized by a compromised ability to sustain attention, making this cognitive domain an important therapeutic target. In this study, we tested a novel method of improving sustained attention. Monkeys were engaged in a continuous performance task (CPT) while the nucleus basalis of Meynert (NB), the main source of cholinergic innervation of the neocortex, was stimulated. Intermittent NB stimulation improved the animals' performance by increasing the hit rate and decreasing the false alarm rate. Administration of the cholinesterase inhibitor donepezil or the muscarinic antagonist scopolamine alone impaired performance, whereas the nicotinic antagonist mecamylamine alone improved performance. Applying NB stimulation while mecamylamine or donepezil were administered impaired CPT performance. Methylphenidate, a monoaminergic psychostimulant, was applied in conjunction with intermittent stimulation as a negative control, as it does not directly modulate cholinergic output. Methylphenidate also improved performance, and it produced further improvement when combined with NB stimulation. The additive effect of the combination suggested NB stimulation altered behavior independently from methylphenidate effects. We conclude that basal forebrain projections contribute to sustained attention, and that intermittent NB stimulation is an effective way of improving performance.
AB - Sustained attention is essential in important behaviors in daily life. Many neuropsychiatric disorders are characterized by a compromised ability to sustain attention, making this cognitive domain an important therapeutic target. In this study, we tested a novel method of improving sustained attention. Monkeys were engaged in a continuous performance task (CPT) while the nucleus basalis of Meynert (NB), the main source of cholinergic innervation of the neocortex, was stimulated. Intermittent NB stimulation improved the animals' performance by increasing the hit rate and decreasing the false alarm rate. Administration of the cholinesterase inhibitor donepezil or the muscarinic antagonist scopolamine alone impaired performance, whereas the nicotinic antagonist mecamylamine alone improved performance. Applying NB stimulation while mecamylamine or donepezil were administered impaired CPT performance. Methylphenidate, a monoaminergic psychostimulant, was applied in conjunction with intermittent stimulation as a negative control, as it does not directly modulate cholinergic output. Methylphenidate also improved performance, and it produced further improvement when combined with NB stimulation. The additive effect of the combination suggested NB stimulation altered behavior independently from methylphenidate effects. We conclude that basal forebrain projections contribute to sustained attention, and that intermittent NB stimulation is an effective way of improving performance.
KW - Acetylcholine
KW - Deep brain stimulation
KW - Nonhuman primate
KW - Nucleus basalis of meynert
KW - Sustained attention
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U2 - 10.1016/j.neuropharm.2018.04.026
DO - 10.1016/j.neuropharm.2018.04.026
M3 - Article
C2 - 29704983
AN - SCOPUS:85048732199
SN - 0028-3908
VL - 137
SP - 202
EP - 210
JO - Neuropharmacology
JF - Neuropharmacology
ER -