Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome

Abstract

The 22q11 deletion syndrome (DS) results in the loss of approximately 30 gene copies and is associated with possible physical anomalies, varied learning disabilities, and a specific cluster of neurocognitive deficits, including primary impairment in working memory, executive visual attention, and sensorimotor processing. Retrospective studies have suggested that children with 22q11DS are at 25 times greater risk of developing schizophrenia, thus specification of early brain network vulnerabilities among children with 22q11DS is critical. Previously, we reported that children with 22q11DS as compared with sibling controls had selective deficits in visual executive attention, and subsequently found lowered prepulse inhibition (PPI) in these same children. Visual executive attention and PPI recruit the same brain pathways linking prefrontal cortex to basal ganglia structures. To test the specificity of brain pathway vulnerability among children with 22q11DS, we examined visual executive attention and PPI paradigm data collected during the same test session from 21 children with 22q11DS and 25 sibling controls. We predicted lower %PPI and less efficient executive attention scores, and a significant inverse correlation between measures. %PPI in children with 22q11DS as compared with sibling controls was 20% lower, and visual executive attention efficiency scores 40% worse. As predicted, %PPI was inversely correlated only with executive attention efficiency scores. The implications of these findings with regard to brain pathway vulnerability in children with 22q11DS are considered. These results suggest that children with 22q11DS have early functional abnormality in pathways linking the prefrontal cortex and basal ganglia. Molecular Psychiatry (2005) 10, 553-562.

Domain specific attentional impairments in children with chromosome 22q11.2 deletion syndrome

“…We (e.g. Bish et al, 2005) and others (notably Sobin et al, 2004, Sobin, Kiley-Brabeck, & Karayiorgou, 2005) have begun to decompose the different kinds of attentional dysfunctions experienced by children with DS22q11.2 and to make inferences about the different neural basis of each one and its possible contribution to other outcomes including the risk for psychosis later in life.…”

Auditory Cortex Electrical Stimulation Suppresses Tinnitus in Rats

“…It can be modulated by both attention and emotion. Several lines of evidence suggest that this early-stage gating is modulated by higher order cognitive processes (Braff et al 2001;Swerdlow et al 2001;Sobin et al 2005;Bjornsson et al 2006). A prepulse presented at short lead intervals reduces the perceived loudness of the probe stimulus, suggesting prepulse-mediated inhibition of auditory cortex processing (Perlstein et al 1993).…”

Associations between TCF4 Gene Polymorphism and Cognitive Functions in Schizophrenia Patients and Healthy Controls

“…A study in humans further suggested that the SCZ risk allele (C) of rs9960767 in this gene was significantly associated with reduced PPI in both healthy controls and patients with SCZ spectrum disorder (Quednow et al, 2011). Reduced PPI is an important intermediate phenotype of SCZ and is believed to be modulated by attention as assessed by the continuous performance test (CPT) (Hazlett et al, 2001(Hazlett et al, , 2008, the attention network test (ANT) (Sobin et al, 2005) and the Stroop test (Molina et al, 2009). However, the role of the TCF4 gene in the etiology of attention function has not been studied.…”