CNTRICS final biomarker selection: Control of attention

Abstract

Attention is widely believed to be dysfunctional in schizophrenia. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group previously concluded that the processes involved in the top-down control of attention are particularly impaired in schizophrenia and should be the focus of future research. These processes determine which sources of input should be attended, linking goal representations in prefrontal cortex with more posterior regions that implement the actual selection of attended information. A more recent meeting of the CNTRICS group assessed several paradigms that might be useful for identifying biomarkers of attentional control and that could be used for treatment development and assessment. Two types of paradigms were identified as being particularly promising. In one approach, neural activity is measured (using electroencephalography or functional magnetic resonance imaging) during the period between an attention-directing cue and a target. In a second approach, neural activity is measured under low- and high-distraction conditions. These approaches make it possible to identify the goal representations that guide attention and the interactions between these goal representations and the implementation of selection. Although more basic science research with healthy volunteers and preclinical research with schizophrenia patients is needed before these paradigms will be ready to provide clinically useful biomarkers, they hold substantial promise for aiding in the development and assessment of new treatments.

Fig. 1.

Scheme for subdividing the concept of selective attention.

Fig. 2.

Typical cuing paradigm used to assess neural activity related to top-down attentional control. In this version, the cue could either indicate a spatial location (L for left or R for right) or a color (Y for yellow or B for blue) that is likely to contain a subsequent target stimulus. Sustained activation during the period between the cue and target is observed primarily in prefrontal and parietal areas, presumably reflecting some kind of goal representation or attentional template, and this activity overlaps considerably for attention to spatial and nonspatial features. Data courtesy of Giesbrecht et al.

Fig. 3.

Example of the Theeuwes additional singleton paradigm (A). Subjects search for the item with the unique shape and press one of 2 buttons to indicate whether the line inside this shape is horizontal or vertical. A task-irrelevant color singleton is present on some trials; this singleton captures attention, especially when top-down control is poor, slowing responses to the target. Activity in the left middle frontal gyrus is correlated with the degree of attention capture (B). Data courtesy of Leber.

Fig. 4.

Top: Sustained Attention Task (SAT). Subjects attempt to detect a short signal that appears (signal trials) or does not appear (nonsignal trials) with equal probability after a variable interval of 1, 2, or 3 seconds. Upon hearing a response cue, participants make a button-press response to indicate whether a signal had been perceived. Correct responses elicit a feedback tone signaling a monetary reward. In the distractor version of the SAT (dSAT), the screen flashes between silver and black at 10 Hz. Bottom: Arterial spin labeling results (activation in the dSAT condition after controlling for SAT activation and a passive perceptual control condition), which included activation in right dorsolateral prefrontal cortex as well as bilateral motor, cingulate, and insular regions. The color scale indicates z scores. Reprinted from NeuroImage with permission from Elsevier.