Saliency, switching, attention and control: a network model of insula function

Abstract

The insula is a brain structure implicated in disparate cognitive, affective, and regulatory functions, including interoceptive awareness, emotional responses, and empathic processes. While classically considered a limbic region, recent evidence from network analysis suggests a critical role for the insula, particularly the anterior division, in high-level cognitive control and attentional processes. The crucial insight and view we present here is of the anterior insula as an integral hub in mediating dynamic interactions between other large-scale brain networks involved in externally oriented attention and internally oriented or self-related cognition. The model we present postulates that the insula is sensitive to salient events, and that its core function is to mark such events for additional processing and initiate appropriate control signals. The anterior insula and the anterior cingulate cortex form a "salience network" that functions to segregate the most relevant among internal and extrapersonal stimuli in order to guide behavior. Within the framework of our network model, the disparate functions ascribed to the insula can be conceptualized by a few basic mechanisms: (1) bottom-up detection of salient events, (2) switching between other large-scale networks to facilitate access to attention and working memory resources when a salient event is detected, (3) interaction of the anterior and posterior insula to modulate autonomic reactivity to salient stimuli, and (4) strong functional coupling with the anterior cingulate cortex that facilitates rapid access to the motor system. In this manner, with the insula as its integral hub, the salience network assists target brain regions in the generation of appropriate behavioral responses to salient stimuli. We suggest that this framework provides a parsimonious account of insula function in neurotypical adults, and may provide novel insights into the neural basis of disorders of affective and social cognition.

Fig. 1

Three major brain networks identified during cognition. Activations in the central executive and salience networks and deactivations in the default mode network during auditory event segmentation. a Analysis with the general linear model revealed regional activations (left) in the right AI and ACC (blue circles); DLPFC and PPC (green circles) and deactivations (right) in the VMPFC and PCC. b Independent component analysis provided converging evidence for spatially distinct networks. From left to right: salience network (rAI and ACC), central executive network (rDLPFC and rPPC), and default mode network (VMPFC and PCC) (adapted from Sridharan et al. 2008)

Fig. 2

Two independent control networks identified using intrinsic physiological coupling in fMRI data. The salience network (shown in red) is important for monitoring the saliency of external inputs and internal brain events, and the central executive network (shown in blue) is engaged in higher-order cognitive and attentional control. The salience network is anchored in anterior insular and anterior cingulate cortices and features extensive connectivity with subcortical and limbic structures involved in reward and motivation. Central executive network links the dorsolateral frontal and parietal neocortices, with subcortical coupling that is distinct from that of the salience network (adapted from Seeley et al. 2007)

Fig. 3

Net causal outflow of major nodes of the salience, central executive, and default mode networks. a Dynamical systems analysis revealed that the right anterior insula (rAI) has a significantly higher net causal outflow than any of the nodes of the central executive or default mode networks. b Granger causal analysis of connectivity showed significant causal outflow from the rAI to major nodes of the two other networks. These analyses, together with latency analyses, suggest that the rAI may function as a causal outflow hub for salient events (adapted from Sridharan et al. 2008)

Fig. 4

Network model of anterior insula function. The anterior insula is part of a salience network, which serves to initiate dynamic switching between the central executive and default mode networks. In our model, sensory and limbic inputs are processed by the anterior insula (AI), which detects salient events and initiates appropriate control signals to regulate behavior and homeostatic state (adapted from Uddin and Menon 2009)

Fig. 5

Schematic model of dynamic bottom–up and top–down interactions underlying attentional control. Stage 1 About 150 ms post-stimulus primary sensory areas detect a deviant stimulus as indexed by the mismatch negativity (MMN) component of the evoked potential. Stage 2 This “bottom–up” MMN signal is transmitted to other brain regions, including the anterior insula (AI). The anterior insula provides selective amplification of salient events and triggers a strong response in the anterior cingulate cortex (ACC). Stage 3 About 200–300 ms post-stimulus, the ACC generates a “top–down” control signal as indexed by the N2b/P3a component of the evoked potential. This signal is simultaneously transmitted to primary sensory and association cortex, as well the central executive network. Stage 4 About 300–400 ms post-stimulus, neocortical regions, notably the premotor cortex and temporo-parietal areas, respond to the attentional shift with a signal that is indexed by the time-average P3b evoked potential. Stage 5 The ACC also facilitates response selection and motor response via its links to the midcingulate cortex, supplementary motor cortex, and other motor areas (adapted from Crottaz-Herbette and Menon 2006)

Fig. 6

DTI tractography between parietal cortex and insula. DTI tractography and density of fibers between three subdivisions in human intraparietal sulcus (hIP2, hIP1, and hIP3) and insula. hIP1 shows greater structural connectivity than hIP2 and hIP3 with insula (*p < 0.05, **p < 0.01) (adapted from Uddin et al. 2010)