Scopolamine impairs human recognition memory: Data and modeling.

Abstract

Eight subjects studied a set of complex visual images after administration of 0.4 mg scopolamine. Another 8 subjects performed the same task without drug administration. On a subsequent item recognition test, subjects rated, on a 5-point scale, their confidence that the studied pictures and an equal number of unstudied lures were actually presented. Results showed that scopolamine affected responses to studied items, but not unstudied lures, demonstrating an unambiguous effect of scopolamine on recognition memory. To describe the scopolamine-injected subjects' data, the authors constructed a new model of 2-process recognition that includes the A. P. Yonelinas (1994) model as a limiting case. The model analysis suggests that scopolamine affected both familiarity and recollection. In particular, scopolamine did not affect the frequency with which recollection took place, but rather, affected the amount of recollected information.

Cholinergic Deafferentation of the Entorhinal Cortex in Rats Impairs Encoding of Novel But Not Familiar Stimuli in a Delayed Nonmatch-to-Sample Task

“…The hypothesized role of sustained spiking for enhancing encoding of stimuli is consistent with behavioral data showing that blockade of muscarinic cholinergic receptors during encoding impairs performance in a later recognition test (Aigner and Mishkin, 1986;Aigner et al, 1991;Sherman et al, 2003). This impairment also occurs with local infusion of scopolamine (Tang et al, 1997) and cholinergic lesions (Turchi et al, 2005) in perirhinal cortex, which is adjacent to entorhinal cortex.…”

“…This effect of acetylcholine could provide a buffer for novel stimuli in the entorhinal cortex that facilitates long-term encoding in the hippocampus (Jensen and Lisman, 1996;Baddeley, 2000;Koene et al, 2003). Consistent with this, blockade of cholinergic receptors impairs encoding of visual stimuli for subsequent recognition performance (Aigner and Mishkin, 1986;Aigner et al, 1991;Sherman et al, 2003), and this impairment occurs selectively with local infusion of scopolamine in the perirhinal (PRh) cortex adjacent to the entorhinal cortex (Tang et al, 1997). Functional magnetic resonance imaging studies show activity in parahippocampal structures during working memory for novel stimuli but not familiar stimuli (Stern et al, 2001), which correlates with subsequent long-term memory for these novel stimuli (Schon et al, 2004), and is reduced by systemic administration of scopolamine (Schon et al, 2005).…”

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

“…At high doses, these drugs cause delirium and hallucinations-a profound breakdown in cognitive processes (see Kopelman, 1986 for review). At lower doses, these antagonists cause impairments in specific cognitive tasks, including encoding of verbal stimuli for subsequent retrieval Ghonheim & Mewaldt, 1977), encoding of visual stimuli for subsequent recognition (Aigner & Mishkin, 1986;Sherman, Atri, Hasselmo, Stern, & Howard, 2003) and response to stimuli in a continuous performance tasks (Wesnes and Warburton, 1983). Selective lesions of cholinergic innervation cause decreases in perceptual discriminability (Linster, Garcia, Hasselmo, & Baxter, 2001) and impairments in continuous performance tasks (McGaughy, Kaiser, & Sarter, 1996;McGaughy & Sarter, 1998).…”

Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans

“…1 B). We have used this scale previously in our laboratory to assess subsequent recognition (Sherman et al, 2003;Schon et al, 2004), and these behavioral procedures are identical to those described by Schon et al (2004).…”

“…Scopolamine is a medication that has been used in a variety of clinical applications, including treatment of gastrointestinal disorders, as a surgical preanesthetic, and as treatment for motion sickness. Scopolamine, at this dosage and higher, has been used in studies to assess the effects of cholinergic blockade on human memory function Mewaldt, 1975, 1977;Sherman et al, 2003;Atri et al, 2004). We selected this relatively low dose to avoid sedation.…”