Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults

https://doi.org/10.1016/j.pscychresns.2010.01.001Get rights and content

Abstract

Relationships between prefrontal and temporal lobe grey matter volumes as assessed by magnetic resonance imaging and neurocognitive test results have been reported in schizophrenia. This investigation aimed to localize brain regions where cortical thickness and neurocognitive performance were related, and investigate if such relationships might differ in schizophrenia patients and healthy controls. Sixty-seven patients with schizophrenia and 69 healthy controls were characterized by neurocognitive testing and by brain cortical thickness maps. Putative cortical thickness/cognitive score relationships were investigated with contrast analyses of general linear models for the combined sample. Regions in which relationships were present were further investigated for diagnostic interaction. In the combined sample, significant positive relationships were found between frontal, temporal and occipital regions and tests for verbal IQ, verbal learning and executive functions. Diagnostic interaction was found for the relationships between verbal IQ and the right temporo-occipital junction and the left middle occipital gyrus. In conclusion, the significant relationships between cortical thickness and neurocognitive performances were localized in brain areas known to be involved in cognition. The relationships were similar in patients and controls, except for the right temporo-occipital and left occipital cortical areas, indicating a disrupted structure–function relationship in patients with schizophrenia compared to healthy control subjects.

Introduction

Cognitive impairment is considered a core feature of schizophrenia (Kurtz, 2005) and has been found to be a good predictor of poor functional outcome in this disease (Green et al., 2000). Some of the most prominent cognitive problems include impairment in general intellectual ability, attention, memory and problem solving (Heinrichs and Zakzanis, 1998).

Cognitive abilities are in part related to grey matter in neocortical brain areas (Lezak, 1995). Brain lesion studies have demonstrated highly specific structure–function relationships (Stuss et al., 2000, Stuss et al., 2001), for instance that the labeling of nouns of animals and fruits depends on separate parts of the left temporal lobe (Damasio et al., 1996). In addition, it has been proposed that localized brain areas represent nodes in a distributed neural system underpinning cognitive function (Jung and Haier, 2007). Cognitive deficits in schizophrenia might arise as functional consequences of alterations of central nodes in the neural networks.

Magnetic resonance imaging (MRI) provides a method for in vivo investigations of possible neural substrates for cognitive alterations. Structural MRI studies have shown frontal and temporal grey matter volume reduction (Shenton et al., 2001, Honea et al., 2005) and cortical thinning in schizophrenia (Kuperberg et al., 2003). The latter finding was replicated in a subject sample substantially overlapping with the sample of the present study (Nesvag et al., 2008).

MRI studies have reported specific structure–function relationships in schizophrenia, but the findings are not consistent. Antonova et al. (2004) reviewed region-of-interest (ROI) studies including both healthy controls and patients with schizophrenia, and reported positive relationships between total brain and grey matter volumes and global cognitive ability. Moreover, size of prefrontal cortical volume was related to executive functioning, whereas size of temporal lobe volume was correlated with memory, executive functioning and verbal abilities. Some of the relationships between the medial temporal lobe and cognitive abilities tended to be specific to schizophrenia (Antonova et al., 2004). Interestingly, only a limited number of studies have demonstrated altered relationships between volumes of the superior temporal gyrus (Vita et al., 1995, Gur et al., 2000b, Nestor et al., 2007), which is one of the most consistently reported brain structure alterations in schizophrenia (Shenton et al., 2001, Honea et al., 2005), and cognitive test scores. Consequently, marked brain structure alteration may not necessarily be related to changes in cognitive function, a conclusion that was suggested by a recent study demonstrating grey matter reduction in schizophrenia patients with near intact cognitive skills (Wexler et al., 2009). Thus, these data implicate a need for exploratory studies investigating altered structure–function relationships in areas that are not predefined, as in ROI studies, and not selected on the basis of significant structural case-control differences.

Furthermore, ROI studies often employ relatively gross volume measurements. A study investigating structure–function relationships in both cortical and subcortical grey matter volumes (Lawyer et al., 2006) demonstrated weaker associations between predefined cortical than subcortical volumes in the comparison with neurocognitive test scores. The neural substrates for functional cognitive abnormalities might be localized to subsections within the volume structures that were predefined, indicating a risk that possible structure–function relationships might have been obscured.

Previous studies analyzing cortical thickness of healthy subjects have successfully related localized variations in thickness to scores of intelligence (Shaw et al., 2006, Narr et al., 2007), memory (Walhovd et al., 2006, Dickerson et al., 2008) and set shifting (Dickerson et al., 2008). In schizophrenia however, relationships between localized grey matter areas and neurocognition have only been investigated with volumetric measurements (Antonova et al., 2005, Rusch et al., 2007, Wolf et al., 2008, Bonilha et al., 2008), such as voxel-based morphometry (VBM) methods, which afford a relatively unbiased assessment of grey matter changes across the brain. However, those studies have small sample sizes, lack direct comparisons of relationships between patients and controls, or find few relationships specific to schizophrenia.

In this study we applied a detailed high-resolution method analyzing cortical thickness to localize possible structure–function relationships and, to our knowledge, for the first time extended the search to schizophrenia. Cortical thickness measurements, as opposed to volumetric measurements, may provide additional information regarding possible local cytoarchitectural differences across groups. In order not to restrict the findings to a predefined brain area, an exploratory search was performed.

More specifically, our aim was to identify regions where cortical thickness and neuropsychological performance were statistically related in a combined sample of patients with schizophrenia and healthy controls. Furthermore, in regions with suggested relationships we tested for differences in regression slopes between patients and controls, in order to test for diagnostic interaction. On the basis of previous literature we predicted that localized areas within prefrontal and temporal cortices were associated with cognitive performance. We also predicted some of these relationships to be different in patients with schizophrenia as compared to healthy control subjects.

Section snippets

Subjects

All subjects were unrelated individuals of Caucasian origin recruited in Stockholm, Sweden, between 1999 and 2003, as part of a larger study as previously described (Jonsson et al., 2003, Jonsson et al., 2006). All subjects participated after giving informed written consent. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee at Karolinska Institutet and the Swedish Data Inspection Board (“Datainspektionen”).

Patients diagnosed with

Patient–control differences

Patients were significantly impaired on all selected cognitive domains when compared to healthy control subjects (Table 2). The effect sizes were all in the order of large effect, except for verbal IQ which was moderate (Cohen, 1988).

Significantly thinner cortices in the patients were demonstrated in the temporal pole, superior temporal gyrus, and orbital and inferior frontal gyri in the left hemisphere, and the superior temporal gyrus, insula, orbital frontal, and middle and superior frontal

Discussion

In this study we have shown that relationships between cortical thickness in occipital regions and verbal IQ in both hemispheres were different in patients with schizophrenia than in healthy control subjects. We have also confirmed that localized variations in cortical thickness are related to cognitive performance and extended the findings to schizophrenia patients; thicker frontal, temporal and occipital cortical brain areas were significantly related to better performance in verbal IQ,

Acknowledgements

We thank Monica Hellberg and Kjerstin Lind and the staff at the Neuroimaging Analysis Lab at the Center for the Study of Human Cognition, Institute of Psychology, University of Oslo, for performing processing of MR images using FreeSurfer. This work was supported by the Swedish Medical Research Council [grant numbers 2003-5845, 2007-3687, K2004-21X-15078-01A, 2006-986, 2006-2992], the Karolinska Institutet, the Wallenberg Foundation, the Research Council of Norway [grant number 160181/V50,

References (72)

  • C.R. Genovese et al.

    Thresholding of statistical maps in functional neuroimaging using the false discovery rate

    Neuroimage

    (2002)
  • T.E. Goldberg et al.

    Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia

    Psychiatry Research

    (1994)
  • R.J. Haier et al.

    Structural brain variation and general intelligence

    Neuroimage

    (2004)
  • H. Hokama et al.

    Caudate, putamen, and globus pallidus volume in schizophrenia: a quantitative MRI study

    Psychiatry Research: Neuroimaging

    (1995)
  • M.J. Hoptman et al.

    Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder

    Psychiatry Research: Neuroimaging

    (2005)
  • E.G. Jonsson et al.

    Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study

    Progress in Neuro-Psychopharmacology and Biological Psychiatry

    (2006)
  • M.M. Kurtz

    Neurocognitive impairment across the lifespan in schizophrenia: an update

    Schizophrenia Research

    (2005)
  • B.A. Maher et al.

    Frontal brain volume and context effects in short-term recall in schizophrenia

    Biological Psychiatry

    (1995)
  • D. Mamah et al.

    Structural analysis of the basal ganglia in schizophrenia

    Schizophrenia Research

    (2007)
  • M.A. McDaniel

    Big-brained people are smarter: a meta-analysis of the relationship between in vivo brain volume and intelligence

    Intelligence

    (2005)
  • P.G. Nestor et al.

    A new statistical method for testing hypotheses of neuropsychological/MRI relationships in schizophrenia: partial least squares analysis

    Schizophrenia Research

    (2002)
  • P.G. Nestor et al.

    Dissociable contributions of MRI volume reductions of superior temporal and fusiform gyri to symptoms and neuropsychology in schizophrenia

    Schizophrenia Research

    (2007)
  • R. Nesvag et al.

    Effects of alcohol consumption and antipsychotic medication on brain morphology in schizophrenia

    Schizophrenia Research

    (2007)
  • R. Nesvag et al.

    Regional thinning of the cerebral cortex in schizophrenia: effects of diagnosis, age and antipsychotic medication

    Schizophrenia Research

    (2008)
  • S.D. Newman et al.

    Differential effects of syntactic and semantic processing on the subregions of Broca's area

    Brain Research. Cognitive Brain Research

    (2003)
  • P. Premkumar et al.

    Neuropsychological function–brain structure relationships and stage of illness: an investigation into chronic and first-episode schizophrenia

    Psychiatry Research: Neuroimaging

    (2008)
  • N. Rusch et al.

    Prefrontal–thalamic–cerebellar gray matter networks and executive functioning in schizophrenia

    Schizophrenia Research

    (2007)
  • M. Sanfilipo et al.

    Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms

    Psychiatry Research: Neuroimaging

    (2002)
  • L.J. Seidman et al.

    Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia

    Biological Psychiatry

    (1994)
  • M.E. Shenton et al.

    A review of MRI findings in schizophrenia

    Schizophrenia Research

    (2001)
  • D.T. Stuss et al.

    Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes

    Neuropsychologia

    (2000)
  • E.V. Sullivan et al.

    Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia

    Biological Psychiatry

    (1996)
  • I. Szendi et al.

    Correlations between clinical symptoms, working memory functions and structural brain abnormalities in men with schizophrenia

    Psychiatry Research: Neuroimaging

    (2006)
  • P.R. Szeszko et al.

    Reduced anterior cingulate gyrus volume correlates with executive dysfunction in men with first-episode schizophrenia

    Schizophrenia Research

    (2000)
  • T. Toulopoulou et al.

    The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia

    Biological Psychiatry

    (2004)
  • A. Vita et al.

    Language and thought disorder in schizophrenia: brain morphological correlates

    Schizophrenia Research

    (1995)
  • Cited by (0)

    View full text