Neural correlates of global and specific cognitive deficits in schizophrenia

Abstract

Cognitive deficits are a core feature of schizophrenia, but the neural mechanisms that contribute to these characteristics are not fully understood. This study investigated whether volume of the dorsal lateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG), hippocampus, and white matter were associated with impairment in specific cognitive domains, including executive functioning, working memory, verbal memory, verbal fluency, processing speed, versus global functioning. The multi-site data used in this study was collected from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP), and consisted of 206 healthy controls and 247 individuals with either schizophrenia or schizoaffective disorder. The neuroimaging data was segmented based on the Destrieux atlas in FreeSurfer. Linear regression analyses revealed that global cognition, executive functioning, working memory, and processing speed were associated with all brain structures, except the DLPFC was only associated with executive fucntion. When controlling for the global cognitive deficit, executive function was trending significance with white matter, but continued to be associated with the DLPFC and IFG, as did the association between processing speed and the hippocampus. These findings suggest that volumes of the DLPFC, IFG, hippocampus, and white matter are associated with the global cognitive impairment seen in schizophrenia, but some brain structures may also be specifically related to domain-specific deficits (primarily executive function) over-and-beyond the global cognitive deficit.

Relationship between neuropsychological behavior and brain white matter in first-episode psychosis

“…The correlations between regional FA and cognition were stronger in S-FEP than in the whole FEP group, which highlights the importance of population stratification. While we did not observe such relationships in controls, previous studies using other methodologies, elderly populations, and diseases with higher effect size demonstrated similar functionanatomical relations (Aukema et al, 2009;Cacciaglia et al, 2018;Gu et al, 2013;Jirsaraie et al, 2018;Jung et al, 2012;Sasson et al, 2012Sasson et al, , 2013Tartaglia et al, 2012;Turken et al, 2008;Williams et al, 2017). Therefore, although such relations may not be FEP-specific, FEP patients (in particular S-FEP) present a large range of FA and cognition scores that increases the power to detect anatomic-functional links, indirectly pointing to FA as a candidate functional biomarker.…”

Global brain volume reductions in a sub-chronic phencyclidine animal model for schizophrenia and their relationship to recognition memory

“…In the white matter tracts, of these animals, in which both reduced volume and microstructural changes (increased fractional anisotropy) are detectable by MRI, they provide evidence for decreased myelin basic protein immunoreactivity suggestive of demyelination (Wu et al, 2016), as reported previously in this model (Xiu et al, 2014;Xiu et al, 2015). As already indicated, such future studies should also include testing for relationships between not only brain structure, but also function, (Dawson et al, 2010) and other cognitive domains that are impaired in the scPCP model, particularly given that human studies suggest complex relationships between brain anatomy and cognitive performance across different tasks and domains, including studies in patients with schizophrenia (Brandt et al, 2015;Heinrichs et al, 2017;Jirsaraie et al, 2018;Karnik-Henry et al, 2012;Massey et al, 2017,).…”

“…Whilst meta-analyses provide evidence for significant associations between frontal or temporal cortical thinning and positive and negative symptoms, respectively (Walton et al, 2017; Walton et al, 2018), there is evidence both for and against relationships between brain structure and cognitive performance in patients with schizophrenia. This most likely reflects heterogeneity in diagnosis, illness stage and the specific cognitive domains under investigation (Dempster et al, 2017; Heinrichs et al, 2017; Jirsaraie et al, 2018; Karnik-Henry et al, 2012; Massey et al, 2017). As such, efforts to improve our understanding of these associations, have the potential to help uncover the neuronal substrates of impaired cognition and so facilitate the discovery of novel therapeutic targets.…”

Effects of Aerobic Exercise on Metabolic Syndrome, Cardiorespiratory Fitness, and Symptoms in Schizophrenia Include Decreased Mortality

“…Cognitive deficits and negative symptoms are the most important predictors for poor social and functional outcome and are major contributors to disability (11). Cognitive deficits are present in domains such as executive function, episodic memory, attention, and social cognition (11–13), functions that are particularly dependent on the hippocampus and prefrontal cortex (14). In schizophrenia, neurodevelopmental disturbances in vulnerable periods of brain development are thought to lead to hippocampal-prefrontal pathway deficits, resulting in the onset of disease symptoms in young adulthood (15).…”