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 cortex^7,14 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 encephalitis^17–20 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.