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      Thalamic cholinergic innervation makes a specific bottom-up contribution to signal detection: Evidence from Parkinson's disease patients with defined cholinergic losses.

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          Abstract

          Successful behavior depends on the ability to detect and respond to relevant cues, especially under challenging conditions. This essential component of attention has been hypothesized to be mediated by multiple neuromodulator systems, but the contributions of individual systems (e.g., cholinergic, dopaminergic) have remained unclear. The present study addresses this issue by leveraging individual variation in regionally-specific cholinergic denervation in Parkinson's disease (PD) patients, while controlling for variation in dopaminergic denervation. Patients whose dopaminergic and cholinergic nerve terminal integrity had been previously assessed using Positron Emission Tomography (Bohnen et al., 2012) and controls were tested in a signal detection task that manipulates attentional-perceptual challenge and has been used extensively in both rodents and humans to investigate the cholinergic system's role in responding to such challenges (Demeter et al., 2008; McGaughy and Sarter, 1995; see Hasselmo and Sarter 2011 for review). In simple correlation analyses, measures of midbrain dopaminergic, and both cortical and thalamic cholinergic innervation all predicted preserved signal detection under challenge. However, regression analyses also controlling for age, disease severity, and other variables showed that the only significant independent neurotransmitter-related predictor over and above the other variables in the model was thalamic cholinergic integrity. Furthermore, thalamic cholinergic innervation exclusively predicted hits, not correct rejections, indicating a specific contribution to bottom-up salience processing. These results help define regionally-specific contributions of cholinergic function to different aspects of attention and behavior.

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          Author and article information

          Journal
          Neuroimage
          NeuroImage
          Elsevier BV
          1095-9572
          1053-8119
          April 01 2017
          : 149
          Affiliations
          [1 ] Department of Psychology, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: um.kaminkim@gmail.com.
          [2 ] Department of Radiology, University of Michigan, Ann Arbor, MI 48109, United States; University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI 48109, United States.
          [3 ] Department of Radiology, University of Michigan, Ann Arbor, MI 48109, United States; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, United States; University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI 48109, United States; Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48109, United States.
          [4 ] Department of Psychology, University of Michigan, Ann Arbor, MI 48109, United States; Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, United States; University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI 48109, United States.
          [5 ] Department of Psychology, University of Michigan, Ann Arbor, MI 48109, United States; Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, United States; University of Michigan Morris K. Udall Center of Excellence for Parkinson's Disease Research, Ann Arbor, MI 48109, United States. Electronic address: clustig@umich.edu.
          Article
          S1053-8119(17)30110-6 NIHMS851833
          10.1016/j.neuroimage.2017.02.006
          5386784
          28167350

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