**5. From aberrant salience to schizophrenic psychosis**

Salience attribution is the process of events and thoughts that come to grab attention, drive the actions and determine behaviour because of their associations with reward or punishment [84]. This corresponds very well to the role of the amygdaloid complex described in a few pages above: playing an essential role in fear and anger control by perception and paying attention to relevant sensory input (including, e.g. facial expression in order to allow adequate social functioning), by validating this input with respect to their significance for reward-seeking and misery-fleeing behaviour. As until mammals the neocortex was not capable of playing its input-processing and output-organising role as in humans, salience attribution was taken care of by the pallium of our anamniote and turtle-like ancestors. As described above this ancient pallium essentially corresponds with the superficial and deep corticoid amygdala and associated hippocampal areas. Later during evolution the interaction of the corticoid amygdala with neocortical areas became involved in the process, and in humans probably no part of the neocortex can be excluded from participating.

At the beginning of this century, Shitij Kapur [8, 85–88] proposed a model for the development of delusional systems in psychiatric disorders due to aberrant attribution of salience to objects and associations, which would normally be meaningless, but now are interpreted as being significant and to be dealt with considerable carefulness. Due to a dysregulated, hyperdopaminergic state this theory holds, environmental events and internal representations become associated with important elements of one's experiences and induce the creation of a cognitive construct (the delusion) to explain these strange occurrences. Hallucinations are believed to reflect the direct observation of these salient internal representations [85]. Antipsychotics decrease the salience of the abnormal experiences by blocking dopamine transmission and allow their resolution by making them unimportant. Howes and Kapur integrated vast experimental findings to this pathophysiological context of causing psychosis by inducing aberrant salience [88].

The model may correspond to the observation that delusions and hallucinations are not uncommon in the general population and not always result in a full-blown psychosis [89]. Substantial evidence suggests that psychotic-like experiences exist along a continuum in the general population [90]. Moreover, stress from life hassles can provoke delusional ideation [90]. In line with this, Jim van Os has suggested to replace the concept of schizophrenia being an illness with the model that it is a salience dysregulation syndrome [91–93].

An important limitation of the model is that the corticoid amygdala is integrated within at least four cortical networks regulating salience-involving processes [61, 84]. Within this context, especially, the interaction between the ventromedial prefrontal cortex and the corticoid amygdala may be essential. Therefore, the corticoid amygdala cannot be considered to be a separate salience-attributing structure, but is having this role in interaction with other cortical structures participating in the network [61].
