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

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..

Medienart:

Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:149

Enthalten in:

NeuroImage - 149(2017), Seite 295-304

Sprache:

Englisch

Beteiligte Personen:

Kim, Kamin [VerfasserIn]
Müller, Martijn L.T.M [Sonstige Person]
Bohnen, Nicolaas I [Sonstige Person]
Sarter, Martin [Sonstige Person]
Lustig, Cindy [Sonstige Person]

Links:

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Themen:

Attention
Behavior
Cholinergic nerves
Cholinergic transmission
Correlation analysis
Cortex
Cues
Dementia
Denervation
Disease control
Dopamine
Dopamine receptors
Emission analysis
Emissions control
Hypotheses
Innervation
Integrity
Mesencephalon
Movement disorders
Neurodegenerative diseases
Neuromodulation
Parkinson's disease
Patients
Positron emission
Positron emission tomography
Predictive control
Regression analysis
Rodents
Signal detection
Studies
Thalamus
Young adults

doi:

10.1016/j.neuroimage.2017.02.006

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC1993317406