Basal forebrain in the context of schizophrenia

The human basal forebrain has been notoriously difficult to analyze, and it was only in the last part of the twentieth Century that its various components came into sharper focus. It has now been demonstrated that the main parts of what was previously referred to as the 'substantia innominata' (a neurological equivalent of the geographer's 'terra incognita') belong to nearby and better defined anatomical systems. These include the ventral aspects of the basal ganglia, i.e. the ventral striatopallidal system, extensions of the centromedial amygdala that links it via subpallidal cell columns to the bed nucleus of stria terminalis, i.e. the extended amygdala, and a more or less continuous collection of aggregated and non-aggregated, predominantly large, hyperchromatic projections neurons referred to as the basal nucleus of Meynert. Following a pictorial survey of the basal forebrain, the anatomy of these three systems are described with special emphasize on clinically relevant details. Sections devoted to clinical-anatomical correlations emphasize the potential significance of the basal forebrain in the context of schizophrenia. The functional-pathological importance of the cortico-subcortical re-entrant circuits through the ventral striatopallidal system is well recognized in the field of neuropsychiatry. Less appreciated is the fact that both the ventral striatum and the extended amygdala contain prominent collections of islands with small neurons, which have collectively been referred to as 'interface islands'. The abundance of neuroactive substances in the interface islands, and the potential for significant postnatal development of the neurons in these islands make them especially intriguing in the context of the developmental hypothesis of schizophrenia. The basal nucleus of Meynert is also of special interest. Involvement of the basal nucleus of Meynert and its related circuits may well be one of the main reasons for attentional dysfunction and cognitive symptoms in this complex disorder. Finally, we emphasize that changes in the neuronal circuits related to the ventral striatopallidal system, extended amygdala and basal nucleus of Meynert in all likelihood provide the anatomical substrate through which pathologic activities in the medial temporal lobe and prefrontal-orbitofrontal structures are translated into disruption of a number of functions ranging from motor activities and basic drives, to personality changes involving stress, mood and higher cognitive functions.