What is the Role of the Claustrum in Cortical Function and Neurologic Disease?

The claustrum is a thin, sheet-like structure located between the insular cortex and the putamen and is characterized by its reciprocal connections with all neocortical areas.1–6 This remarkable connectivity led to the proposal that the claustrum may be a nodal structure for conscious perceptual experience.1 The cortical inputs to the claustrum have both anterior–posterior and dorsal–ventral organization, with reciprocal claustral projections back to the cortex.2 The claustrum communicates most densely with medial frontal cortical regions and receives prominent inputs from the amygdala, hippocampus, and mediodorsal nucleus of the thalamus.7 Functions attributed to the claustrum include top-down control of attention by segregating attention between modalities,2,8,9 salience processing,10 allocation of attention to reward-related contextual cues,11 executive control,12 and regulation of impulsivity.13 The claustrum primarily exerts a feedforward inhibitory control over the cortex7,14 and may also orchestrate and integrate cortical activity by boosting synchronized oscillations between cortical areas.13,15 However, the functions of the claustrum remain poorly understood. Experimental studies suggest that the claustrum may be involved in focal seizures associated with altered awareness.16 The claustrum shows reversible MRI changes in disorders associated with severe seizures in the setting of encephalitis17–20 and may potentially be involved in motor and cognitive disorders. The claustrum may thus have a potential role and constitute a therapeutic target in disorders associated with disturbances of cognition, behavior, and cortical excitability.