Substantia innominata: a notion which impedes clinical–anatomical correlations in neuropsychiatric disorders

Abstract

Comparative neuroanatomical investigations in primates and non-primates have helped disentangle the anatomy of the basal forebrain region known as the substantia innominata. The most striking aspect of this region is its subdivision into two major parts. This reflects the fundamental organizational scheme for this portion of the forebrain. According to this scheme, two major subcortical telencephalic structures, i.e. the striatopallidal complex and extended amygdala, form large diagonally oriented bands. The rostroventral extension of the pallidum accounts for a large part of the rostral subcommissural substantia innominata, while the sublenticular substantia innominata is primarily occupied by elements of the extended amygdala. Also dispersed across this region is the basal nucleus of Meynert, which is part of a more or less continuous collection of cholinergic and non-cholinergic corticopetal and thalamopetal cells, which stretches from the septum–diagonal band rostrally to the caudal globus pallidus. The basal nucleus of Meynert is especially prominent in the primate, where it is sometimes inappropriately applied as a synonym for the substantia innominata, thereby tacitly ignoring the remaining components.In most mammals, the extended amygdala presents itself as a ring of neurons encircling the internal capsule and basal ganglia. The extended amygdala may be further subdivided, i.e. into the central extended amygdala (related to the central amygdaloid nucleus) and the medial extended amygdala (related to the medial amygdaloid nucleus), which generally form separate corridors both in the sublenticular region and along the supracapsular course of the stria terminalis. The extended amygdala is directly continuous with the caudomedial shell of the accumbens, and to some extent appears to merge with it. Together the accumbens shell and extended amygdala form an extensive forebrain continuum, which establishes specific neuronal circuits with the medial prefrontal–orbitofrontal cortex and medial temporal lobe. This continuum is particularly characterized by a prominent system of long intrinsic association fibers, and a variety of highly differentiated downstream projections to the hypothalamus and brainstem.The various components of the extended amygdala, together with the shell of the accumbens, are ideally structured to generate endocrine, autonomic and somatomotor aspects of emotional and motivational states. Behavioral observations support this proposition and demonstrate the relevance of these structures to a variety of functions, ranging from the various elements of the reproductive cycle to drug-seeking behavior. The neurochemical and connectional features common to the accumbens shell and the extended amygdala are especially relevant to understanding the etiology and treatment of neuropsychiatric disorders. This is discussed in general terms, and also in specific relation to the neurodevelopmental theory of schizophrenia and to the neurosurgical treatment of neuropsychiatric disorders.