A New Perspective on Delusional States – Evidence for Claustrum Involvement

Abstract

Delusions are a hallmark positive symptom of schizophrenia, although they are also associated with a wide variety of other psychiatric and neurological disorders. The heterogeneity of clinical presentation and underlying disease, along with a lack of experimental animal models, make delusions exceptionally difficult to study in isolation, either in schizophrenia or other diseases. To date, no detailed studies have focused specifically on the neural mechanisms of delusion, although some studies have reported characteristic activation of specific brain areas or networks associated with them. Here, we present a novel hypothesis and extant supporting evidence implicating the claustrum, a relatively poorly understood forebrain nucleus, as a potential common center for delusional states.

High sensitivity mapping of cortical dopamine D2 receptor expressing neurons

“…Several scenarios may be possible: a) TH positive fibers are dopaminergic fibers from VTA or SN that do not express DAT but use a different monoamine transporter (Morón JA et al 2002;Smith CC and RW Greene 2012;Sesack SR 2014). b) TH positive fibers are noradrenergic fibers from LC that can also co-release dopamine (Cascella NG et al 2011;Patru MC and DH Reser 2015). Hallucinations and delusions are a part of positive symptoms of schizophrenia.…”

Topography of claustrum and insula projections to medial prefrontal and anterior cingulate cortices of the common marmoset (Callithrix jacchus)

“…With respect to our hypothesis that the claustrum may have a role in modulating the asynchrony of cortical functional networks (Reser et al, 2014;Patru and Reser, 2015) a key focus of future studies will be to assess whether the separation of A32 and A24 based on anatomy and claustrum-insula connectivity that we report here is accompanied by changes in functional connectivity, especially in the salience and default mode networks. Both of these networks have been identified in the marmoset (Belcher et al, 2013(Belcher et al, , 2016, and their findings included functional connectivity between the anterior cingulate and the insula-claustrum region (Belcher et al, 2016).…”

“…In recent years, hypotheses surrounding the function of the mammalian claustrum have converged on two main ideas, that this structure has a primary role in polymodal sensory integration and binding (Smythies et al, 2012(Smythies et al, , 2014 and that it is involved primarily in selective attention and/or salience (Remedios et al, 2014;Reser et al, 2014;Goll et al, 2015;Patru and Reser, 2015). Both of these general ideas are underpinned by the widespread connectivity of the claustrum with the cerebral cortex.…”

The functional connectivity of the human claustrum according to the Human Connectome Project database

“…The involvement of the claustrum in such processes is the result of a different research question more than the question of the function of claustrum by itself (Banati et al, 2000;Hadjikhani and Roland, 1998;Naghavi et al, 2007;Lerner et al, 2009). Although it is rarely reported in the medical literature the selective lesion of the claustrum; the claustrum has been involved in disease such as seizures, multiple sclerosis, Parkinson´s diseases and auditory hallucinations and delusions (Wada and Kudo, 1997;Kalaitzakis et al, 2009;Cascella et al, 2011;Cascella & Sawa, 2014;Klaver et al, 2015;Patru & Reser, 2015).…”