Inhibition of Action, Thought, and Emotion: A Selective Neurobiological Review

Abstract

The neural bases of inhibitory function are reviewed, covering data from paradigms assessing inhibition of motor responses (antisaccade, go/nogo, stop-signal), cognitive sets (e.g., Wisconsin Card Sort Test), and emotion (fear extinction). The frontal cortex supports performance on these paradigms, but the specific neural circuitry varies: response inhibition depends upon fronto-basal ganglia networks, inhibition of cognitive sets is supported by orbitofrontal cortex, and retention of fear extinction reflects ventromedial prefrontal cortexamygdala interactions. Inhibition is thus neurobiologically heterogeneous, although right ventrolateral prefrontal cortex may support a general inhibitory process. Dysfunctions in these circuits may contribute to psychopathological conditions marked by inhibitory deficits.

Figure 1

Regions of prefrontal cortex (PFC) implicated in inhibition. a) Dorsolateral PFC (blue) and ventrolateral PFC (orange). b) Ventromedial PFC (red) and orbitofrontal cortex (green). Reprinted with permission from Davidson, Pizzagalli, Nitschke, & Putman (2002). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)

Figure 2

Neural bases of antisaccades. Simplified fronto-basal ganglia-collicular loop underlying saccade generation and inhibition (adapted from Munoz & Everling, 2004). Saccades are controlled by the midbrain reticular formation, which receives projections from the superior colliculus, SEF, and FEF. In addition, the DLPFC, SEF, FEF, and basal ganglia can influence eye movements via their projections to the superior colliculus. Note that many structures and connections have been omitted for simplicity.

Figure 3

Neural basis of response inhibition in the go/nogo and stop-signal tasks (adapted from Band & van Boxtel, 1999). Manual responses are under the influence of two neural loops. The primary loop (black lines) involves connections between cortical structures (including the DLPFC and VLPFC), the basal ganglia, and the thalamus. This loop is directly implicated in response selection and response inhibition. The secondary loop (gray lines) involves connections between more restricted cortical regions, the cerebellum, and the thalamus, and is thought to fine-tune activity in the first loop. Output from these loops is integrated at the level of primary motor cortex, which projects to the spinal cord (heavy black line). Several connections and cortical regions have been omitted for simplicity. DLPFC: dorsolateral prefrontal cortex; SMA: supplementary motor area; VLPFC: ventrolateral prefrontal cortex.

Figure 4

Example trials from the test of dimensional shifts and discrimination reversals (adapted from Dias et al., 1996). Trials feature two compound stimuli consisting of line exemplars overlaid on polygon exemplars. Correct choices are indicated by a plus (+), incorrect choices are indicated by a minus (−). a) Compound discrimination: The participant must first identify the correct exemplar (e.g., the triangle) from the correct dimension (e.g., the polygons). b) Correct performance requires retaining the selection rule across trials. c) Intra-dimensional shift: A new exemplar (diamond) in the same dimension (polygons) becomes the correct stimulus. d) Extra-dimensional shift: An exemplar from the other dimension (lines) becomes correct. e) Discrimination reversal: Stimuli from the previous trial are retained, but the previously correct stimulus becomes incorrect and vice-versa.

Figure 5

Neural mechanisms involved in the acquisition and extinction of conditioned fear. During fear acquisition, sensory information regarding the CS+ and US enters the basolateral amgydaloid (BLA) complex via the cortex and thalamus; the BLA is where CS-US associations are formed. The BLA sends excitatory projections to the central nucleus (CE) of the amygdala. The central nucleus controls fear expression via its projections to a number of effector sites. These include the lateral hypothalamus (LH), periaqueductal gray (PAG), and reticularis pontis caudalis (RPC), which are important for autonomic components of the fear response, freezing behavior, and startle-potentiation, respectively. The VMPFC mediates extinction of conditioned fear, possibly through its connections with intercalated cell masses (ITC). The VMPFC sends excitatory projections (+) to the ITC, which in turn send inhibitory projections (−) to the CE. Thus, the net effect of vmPFC activity is inhibition of both CE activity and the fear response. The hippocampus also sends projections to the amygdala, and has been implicated in contextual control of extinction.