The latter include the basal nucleus of the amygdala,81 innervated by cholinergic projections from basal forebrain structures, and the midline thalamic nuclei, which receive input both from the basal forebrain and from cholinergic peduculopontine projections that form part of the ascending reticular activating system.
Patients with apathy and akinetic mutism are typically Inhibitors,research,lifescience,medical alert, suggesting an intact reticular activating system. However, partial defects in this system may occasionally contribute to akinetic mutism, as exemplified by a patient whose akinetic mutism followed surgical removal of a fourth ventricular astrocytoma and responded well to methylphenidate.104 Apathy is prominent in many neurodegenerative disorders Inhibitors,research,lifescience,medical including frontotemporal dementia, Parkinson’s disease, and progressive supranuclear palsy. Apathy must be distinguished from depression; apathy may occur with or without concomitant depressive symptoms. The orbitofrontal circuit The lateral division of the orbitofrontal circuit originates in the lateral orbital gyrus of Brodmann’s area 11 and the medial inferior frontal gyrus of the areas 10 and 47 in humans.81 These areas send projections to the ventromedial caudate, which projects in turn to the most medial portion of the mediodorsal GPi and to the rostromedial
SNr.105 The ventromedial caudate also sends an indirect loop through the Inhibitors,research,lifescience,medical dorsal GPe to the lateral STN, which then projects to the GPi and SNr.75 Neurons are sent from
the GP and SN to the medial section of the magnocellular division of the ventral ROCK inhibitor anterior thalamus, as well as an inf eromedial sector of the magnocellular division Inhibitors,research,lifescience,medical of the mediodorsal thalamus.35,38 This division of the circuit then closes with projections from this thalamic region to the lateral orbitofrontal cortex.38 A medial division of the orbitofrontal circuit has also been identified, originating in the inf eromedial prefrontal cortex, specifically the gyrus rectus and Inhibitors,research,lifescience,medical the medial orbital gyrus of Brodmann’s area 11 in humans.81 From this area, the medial division has sequential projections to medial aspects of the accumbens, to medial ventral portions of the pallidum, and thence, via the medial magnocellular division of the mediodorsal thalamic nucleus, back to the medial orbitofrontal Cell press cortex.106 The medial orbitofrontal cortex has reciprocal connections with the medial portion of the basal and the magnocellular division of the accessory basal amygdale. Cortical areas that have reciprocal connections with the medial orbitofrontal cortex influence visceral function when stimulated, probably through their shared amygdalar connections.81 Other regions reciprocally connected with the medial orbitofrontal cortex include the rostral insula, ventromedial temporal pole (area 38, and infracallosal cingulate areas 25, 24, and 32,107,108 the latter regions being primarily part of the anterior cingulate circuit.