The Effects of Scopolamine on Changes in Regional Cerebral Blood Flow during Classical Conditioning of the Human Eyeblink Response

Abstract

We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age ± SEM: 26.7 ± 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H₂¹⁵O. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 ± 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system.

Muscarinic Versus Nicotinic Modulation of a Visual Task A PET Study Using Drug Probes

“…In this vein, ACh modulation of brain function at "rest" should be interpreted with caution. Consistent with our findings, several studies have reported scopolamine induced rCBF increases in lateral visual association areas, but during tasks that are primarily non-visual (Grasby et al 1995;Bahro et al 1999). These changes may, nonetheless, reflect modulation of visual perception or visual imagery that occurred while the tasks were performed.…”

“…These changes may, nonetheless, reflect modulation of visual perception or visual imagery that occurred while the tasks were performed. Although rCBF reduction by scopolamine in thalamus was only a trend in our study, significant scopolamineinduced rCBF reduction during various tasks has been reported by others (Cohen et al 1994;Grasby et al 1995;Bahro et al 1999). Cohen and colleagues (Cohen et al 1994) described a scopolamine-induced reduction in thalamic glucose metabolism during an auditory continuous performance task that was interpreted as evidence for muscarinic-dependent increased thalamic function during attention.…”

“…In humans, several studies have suggested that cholinergic modulation occurs within visual brain regions (Grasby et al 1995;Bahro et al 1999;Rosier et al 1999). However, the relative contribution of muscarinic and nicotinic action to cholinergic modulation of visual processing on a regionby-region basis remains unknown.…”

Cerebrovascular Reactivity to Carbon Dioxide in Alzheimer's Disease

“…Although the authors do not list CVR CO2 among the many mechanisms influenced by the cholinergic system, one could argue that it should be included. As supporting evidence, we can cite reports of CBF increases or preservation after treatment with acetylcholinesterase inhibitors in dementia patients [70–74], or the CBF reduction in healthy volunteers after scopolamine administration [75–77]. Furthermore, galantamine normalized CVR CO2 both in patients with AD and patients with vascular dementia [78].…”

Cholinergic modulation of cognition: Insights from human pharmacological functional neuroimaging

“…By comparison with functional imaging data, it is apparent that pro-cholinergic drugs are also often associated with reduced sensory activation magnitude (Bentley et al, 2004) or spread (Silver et al, 2008) (or vice versa for anti-cholinergics, e.g. Bahro et al, 1999), specifically during low-attention or passive stimulation paradigms.…”