Multi-echo fMRI, resting-state connectivity, and high psychometric schizotypy

Abstract

Disrupted striatal functional connectivity is proposed to play a critical role in the development of psychotic symptoms. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies typically reported disrupted striatal connectivity in patients with psychosis and in individuals at clinical and genetic high risk of the disorder relative to healthy controls. This has not been widely studied in healthy individuals with subclinical psychotic-like experiences (schizotypy). Here we applied the emerging technology of multi-echo rs-fMRI to examine corticostriatal connectivity in this group, which is thought to drastically maximize physiological noise removal and increase BOLD contrast-to-noise ratio. Multi-echo rs-fMRI data (echo times, 12, 28, 44, 60 ms) were acquired from healthy individuals with low (LS, n = 20) and high (HS, n = 19) positive schizotypy as determined with the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE). After preprocessing to ensure optimal contrast and removal of non-BOLD signal components, whole-brain functional connectivity from six striatal seeds was compared between the HS and LS groups. Effects were considered significant at cluster-level p < .05 family-wise error correction. Compared to LS, HS subjects showed lower rs-fMRI connectivity between ventromedial prefrontal regions and ventral striatal regions. Lower connectivity was also observed between the dorsal putamen and the hippocampus, occipital regions, as well as the cerebellum. These results demonstrate that subclinical positive psychotic-like experiences in healthy individuals are associated with striatal hypoconnectivity as detected using multi-echo rs-fMRI. Further application of this approach may aid in characterizing functional connectivity abnormalities across the extended psychosis phenotype.

The association of striatal volume and positive schizotypy in healthy subjects: intelligence as a moderating factor

“…Several studies report reduced functional connectivity of striatal and cortical regions in association with (primarily positive) schizotypy, indicating an association of this dimension with striatal hypoconnectivity or cortico-striatal decoupling (Wang et al ., 2018; Waltmann et al ., 2019). Such dysconnectivity might be facilitated by altered striatal dopamine levels, as has been suggested based on results in animal studies (Grace et al ., 2007; Waltmann et al ., 2019). There is, in fact, evidence for striato-cortical decoupling associated with positive schizotypy being induced by altered dopaminergic neurotransmission (Rössler et al ., 2018).…”

“…Further evidence for the notion that brain networks, rather than single structures are involved in the generation of psychotic experiences comes from recent studies analysing resting state connectivity in schizotypy. Several studies report reduced functional connectivity of striatal and cortical regions in association with (primarily positive) schizotypy, indicating an association of this dimension with striatal hypoconnectivity or cortico-striatal decoupling (Wang et al ., 2018; Waltmann et al ., 2019). Such dysconnectivity might be facilitated by altered striatal dopamine levels, as has been suggested based on results in animal studies (Grace et al ., 2007; Waltmann et al ., 2019).…”

“…In addition, highlighting the role of the fronto-striatal network, positive and negative schizotypy have recently been associated with variations in cortico-striatal resting state functional connectivity (Rössler et al ., 2018; Wang et al ., 2018; Waltmann et al ., 2019). SPQ Disorganised has, furthermore, been associated with a higher availability of striatal dopamine (Chen et al ., 2012).…”

Empathy and schizotypy following acquired brain damage

“…The first key finding to emerge was that, irrespective of whether brain damage was localized to frontal or non‐frontal neural structures, schizotypy levels were significantly elevated relative to controls. As noted earlier, this association between brain damage and schizotypy was predicted based on broader literature that has shown schizotypy to be linked to both structural and functional brain abnormalities in psychometrically defined schizotypy, subclinical psychosis, and psychiatric disorders (Asami et al, 2013; Ettinger, Meyhöfer, Steffans, Wagner, & Koutsouleris, 2014; Waltmann et al, 2019; Wang et al, 2015). However, as noted, because of the nature of these groups, these studies could not speak to whether there is a potential neurophysiological basis for schizotypal traits.…”

“…Schizotypy is characterized by the expression of attenuated psychotic‐like symptoms, with people who are higher in schizotypy exhibiting a range of neurocognitive impairments and neural abnormalities that are generally intermediate between individuals with schizophrenia and healthy controls. This includes problems with executive control and memory that are sometimes accompanied by reduced brain activation (Ettinger et al, 2015), functional connectivity abnormalities (Waltmann et al, 2019), and subnormal levels of cortical suppression to specific types of auditory stimuli (Oestreich et al, 2016).…”