Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection

Abstract

Neurophysiological studies demonstrated that increases in cholinergic transmission in sensory areas enhance the cortical processing of thalamic inputs. Cholinergic activity also suppresses the retrieval of internal associations, thereby further promoting sensory input processing. Behavioral studies documented the role of cortical cholinergic inputs in attentional functions and capacities by demonstrating, for example, that the integrity of the cortical cholinergic input system is necessary for attentional performance, and that the activity of cortical cholinergic inputs is selectively enhanced during attentional performance. This review aims at integrating the neurophysiological and behavioral evidence on the functions of cortical cholinergic inputs and hypothesizes that the cortical cholinergic input system generally acts to optimize the processing of signals in attention-demanding contexts. Such signals ‘recruit’, via activation of basal forebrain corticopetal cholinergic projections, the cortical attention systems and thereby amplify the processing of attention-demanding signals (termed ‘signal-driven cholinergic modulation of detection’). The activity of corticopetal cholinergic projections is also modulated by direct prefrontal projections to the basal forebrain and, indirectly, to cholinergic terminals elsewhere in the cortex; thus, cortical cholinergic inputs are also involved in the mediation of top-down effects, such as the knowledge-based augmentation of detection (see Footnote 1) of signals and the filtering of irrelevant information (termed ‘cognitive cholinergic modulation of detection’). Thus, depending on the quality of signals and task characteristics, cortical cholinergic activity reflects the combined effects of signal-driven and cognitive modulation of detection. This hypothesis begins to explain signal intensity or duration-dependent performance in attention tasks, the distinct effects of cortex-wide versus prefrontal cholinergic deafferentation on attention performance, and it generates specific predictions concerning cortical acetylcholine (ACh) release in attention task-performing animals. Finally, the consequences of abnormalities in the regulation of cortical cholinergic inputs for the manifestation of the symptoms of major neuropsychiatric disorders are conceptualized in terms of dysregulation in the signal-driven and cognitive cholinergic modulation of detection processes.

Introduction

The basal forebrain corticopetal cholinergic system represents the most rostral of the neuromodulatory cortical input systems, and its anatomical organization reflects its capacity to modulate information processing across the entire cortical mantle [50], [68], [108], [156], [162], [193]. There is now ample experimental evidence in support of the hypothesis that the integrity of cortical cholinergic inputs is necessary for normal attentional performance, and that such performance robustly activates cortical cholinergic inputs [3], [29], [32], [33], [39], [50], [73], [101], [99], [132], [162], [183], [180], [181]. Increases in cholinergic receptor stimulation have also been demonstrated to enhance sensory input processing (below). Thus, questions concerning the contributions of acetylcholine (ACh)-mediated enhancement of sensory input processing to attentional performance have been raised, in part based on the observation that loss of cortical cholinergic inputs primarily affect the animals' ability to respond to cues, signals, or targets in tasks assessing attentional functions [29], [34], [103], [101], [100], [99], [183]. Below, activation of cortical cholinergic inputs is proposed to reflect two interacting mechanisms. In attention-demanding tasks, signals activate the corticopetal cholinergic system and thereby enhance their detection¹ (“signal-driven modulation of detection”). Furthermore, practice- or knowledge-based changes in detection, and requirements for filtering of irrelevant stimuli, are mediated, at least in part, via prefrontal modulation of cortical cholinergic inputs (“cognitive or top-down modulation of detection”). Cortical cholinergic activity reflects the complex interactions between these two recruitment modes and mediates, at the cellular level, enhancement of input processing and, at the behavioral level, attentional performance.