**Acknowledgement**

the appropriateness of flight, fight, or appetitive responses. Based on attentive salience, it initiates the proper emotional component of behaviour. On the dorsal side of the brain, the caudate nucleus determines the suitability of the available repertoire of skilled behaviours; it selects the proper motor response to achieve the intended goals. The motivation to express these behaviours is regulated by monoaminergic centres within the midbrain. In turn, these monoaminergic centres are regulated by old and new parts of the cerebral cortex through a dorsal connection that travels through the medial and lateral habenula. Of note, the monoaminergic centres are also regulated by the medial prefrontal cortex via a direct ventral con-

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

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].

an illness with the model that it is a salience dysregulation syndrome [91–93].

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

nection, which possibly travels through the medial forebrain bundle [7] (**Figure 9**).

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

126 Schizophrenia Treatment - The New Facets

probably no part of the neocortex can be excluded from participating.

More anatomical details are provided with in Loonen AJM, Ivanova SA. Front Neurosci 2016;10:539. doi: 10.3389/fnins.2016.00539. Part of this work was supported by the Russian Science Foundation [Grant No. 14-15-00480].
