Elsevier

NeuroImage

Volume 40, Issue 1, 1 March 2008, Pages 289-297
NeuroImage

Increased neural response related to neutral faces in individuals at risk for psychosis

https://doi.org/10.1016/j.neuroimage.2007.11.020Get rights and content

Abstract

Objective

The reliable discrimination of emotional expressions in faces is essential for adequate social interaction. Deficits in facial emotion processing are an important impairment in schizophrenia with major consequences for social functioning and subjective well-being. Whether neural circuits underlying emotion processing are already altered before illness onset is yet unclear. Investigating neural correlates of emotion processing in individuals clinically at risk for psychosis offers the possibility to examine neural processes unchanged by the manifest disorder and to study trait aspects of emotion dysfunctions.

Material and methods

Twelve subjects clinically at risk for psychosis and 12 matched control subjects participated in this study. fMRI data were acquired during an emotion discrimination task consisting of standardized photographs of faces displaying different emotions (happiness, sadness, anger, fear) as well as faces with neutral facial expression.

Results

There were no group differences in behavioral performance. Emotion discrimination was associated with hyperactivations in high-risk subjects in the right lingual and fusiform gyrus as well as the left middle occipital gyrus. Further, high-risk compared to control subjects exhibited stronger activation related to neutral faces relative to emotional faces in the inferior and superior frontal gyri, the cuneus, the thalamus and the hippocampus.

Conclusions

The present study indicates that individuals clinically at risk for psychosis show differences in brain activation associated with processing of emotional and – more pronounced – neutral facial expressions despite an adequate behavioral performance. The proneness to attribute salience to neutral stimuli might indicate a biological risk marker for psychosis.

Introduction

The reliable expression and perception of emotions are essential for adequate social interaction and momentous to subjective well-being. Disturbances of emotion expression are key features of schizophrenia, such as flattened affect and parathymia. Several studies have demonstrated that emotion perception – like the discrimination of facial emotions – is also impaired in schizophrenia (e.g., Kohler et al., 2003, Schneider et al., 2006) and that such dysfunctions may have severe consequences for social functioning and functional outcome (Kee et al., 2003). In facial emotion discrimination, particularly specificity – the ability to identify a facial expression as neutral or a non-target emotion – is impaired, while sensitivity to detect the target emotion may be preserved (Schneider et al., 2006).

Deficits in emotion processing were reported to correlate with the severity of psychotic symptoms (Kohler et al., 2000, Schneider et al., 1995), underlining the clinical significance of emotional dysfunctions. They tend to be stable over the course of illness (Kohler et al., 2003) and are already present in healthy individuals with an increased risk to develop schizophrenia due to genetic liability or risk factors like schizotypal personality traits (Kee et al., 2004, van 't Wout et al., 2004). Thus, emotional dysfunctions may represent trait markers or early signs of the disease.

An increasing number of imaging studies dealt with the neurobiological correlates underlying deficits in emotion processing observed in schizophrenia. Structural imaging and neuropathological studies predominantly reported changes in neuronal cell integrity and volume reductions in the amygdala, insula, thalamus and the hippocampus (Wright et al., 2000), which are key regions for emotion processing. Functional neuroimaging studies have demonstrated a failure to activate the amygdala and hippocampal regions in response to emotive stimuli, as well as abnormalities in the prefrontal cortex, the cingulate cortex and the occipital gyri (e.g., Gur et al., 2002a, Hempel et al., 2003, Holt et al., 2006a, Schneider et al., 1998, Taylor et al., 2002). Interestingly, hyperactivations in temporal (hippocampus, amygdala) and frontal regions (e.g., Hempel et al., 2003, Holt et al., 2006a, Kosaka et al., 2002, Russell et al., 2007) have also been observed and are interpreted as compensation for dysfunctions in the underlying neural network.

An important topic currently debated is the question whether alterations in structure and/or function associated with the manifest disorder are already present before its onset, which could point to trait markers and be used as endophenotypes for future genetic studies. Further, the influence of the manifest disorder on brain function could be detected and individuals at risk be further characterized. This issue has been addressed by examining individuals genetically at risk for psychosis as well as clinical high-risk subjects, employing tasks that probe, e.g., working memory and executive functions. Changes in widespread networks underlying these processes have been found, in detail in prefrontal, parietal and temporal regions, the anterior cingulate cortex, the thalamus, the cerebellum and the striatum (e.g., MacDonald et al., 2006, Morey et al., 2005, Seidman et al., 2006, Vink et al., 2006, Whalley et al., 2004; for review see Fusar-Poli et al., 2007).

Although behavioral and neuroimaging findings point to emotion dysfunctions as trait markers of the disorder, the influence of illness onset and course on emotion recognition and its neural correlates have not yet been addressed. Trait markers have been suggested for the neural correlates of emotion experience, manifest in an amygdala hypoactivation in non-affected brothers of schizophrenia patients during mood induction (Habel et al., 2004). Therefore, cerebral dysfunctions in core ‘emotional’ regions were already present in genetic high-risk individuals. Hence, data on subjects with clinical risk factors would add important information in research on emotion processing in early psychosis.

In conclusion, the present study intended to further characterize emotional dysfunctions in psychosis by examining individuals in the putatively prodromal state of the illness. Applying an fMRI facial emotion discrimination paradigm we hypothesized to find altered brain function in areas related to emotion and face processing that have previously been reported to be dysfunctional in schizophrenia patients, such as the amygdala (Gur et al., 2002a, Habel et al., 2004, Hempel et al., 2003, Holt et al., 2006a, Kosaka et al., 2002, Schneider et al., 1998), the insula (Crespo-Facorro et al., 2001), the hippocampus (Gur et al., 2002a, Hempel et al., 2003, Holt et al., 2006a), the prefrontal cortex (Habel et al., 2004, Hempel et al., 2003), the anterior cingulate gyrus (Hempel et al., 2003) and the fusiform gyrus (Taylor et al., 2002).

Section snippets

Subjects

Twelve subjects (10 men, 2 women) clinically at risk for developing psychosis were recruited from an outpatient setting at the Cologne Early Recognition and Intervention Center (German acronym FETZ), Department of Psychiatry and Psychotherapy, University of Cologne, and the Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany. Twelve healthy volunteers were recruited by means of local advertisements, followed by a detailed screening, and were matched pairwise to the

Behavioral data

Analysis of sensitivity revealed a significant main effect for the factor ‘emotion’ (F = 19.41, df = 3, 20; p < .001). No main effect of ‘group’ nor an interaction ’emotion*group’ was observed. Post hoc tests revealed significant differences in sensitivity for happy versus angry faces (t = 5.67, df = 23, p < .001), happy versus fearful faces (t = 6.24, df = 23, p < .001) and sad versus fearful faces (t = 5.42, df = 23, p < .001).

A similar pattern resulted for analysis of specificity (‘emotion’: F = 12.87, df = 3, 20; p < 

Discussion

This study intended to examine the neural correlates of facial emotion discrimination in subjects clinically at risk for psychosis in comparison to control subjects by means of fMRI. In summary, the main findings are that emotion discrimination independent of the specific emotional content was associated with hyperactivations in high-risk subjects in the right lingual and fusiform gyrus as well as the left middle occipital gyrus. Further, high-risk subjects exhibited stronger activation related

Acknowledgments

This work was supported by grants from the Federal Ministry of Education and Research (Brain Imaging Center West, 01GO0204) and the German Research Foundation (Schn 362/13-1/-2). Ms. Seiferth was supported by a fellowship for doctoral students from the German National Academic Foundation. This work is a part of the thesis of Ms. Seiferth.

We thank Volker Backes, Petra Engels, Sabrina Weber, Martina Reske, Kathrin Koch, Tony Stöcker, Barbara Elghahwagi, Gaby Oefler, Bianca Hoppmann and Julia

References (58)

  • H. Kosaka et al.

    Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study

    Schizophr. Res.

    (2002)
  • M.H. Kosmidis et al.

    Impaired emotion perception in schizophrenia: a differential deficit

    Psychiatry Res.

    (2007)
  • A.W. MacDonald et al.

    Functional magnetic resonance imaging study of cognitive control in the healthy relatives of schizophrenia patients

    Biol. Psychiatry

    (2006)
  • R.C. Oldfield

    The assessment and analysis of handedness: the Edinburgh inventory

    Neuropsychologia

    (1971)
  • K.M. Prasad et al.

    Parahippocampal gyrus in first episode psychotic disorders: a structural magnetic resonance imaging study

    Prog. Neuro-psychopharmacol. Biol. Psychiatry

    (2004)
  • T.A. Russell et al.

    Neural responses to dynamic expressions of fear in schizophrenia

    Neuropsychologia

    (2007)
  • F. Schneider et al.

    Emotional processing in schizophrenia: neurobehavioral probes in relation to psychopathology

    Schizophr. Res.

    (1995)
  • F. Schneider et al.

    Differential amygdala activation in schizophrenia during sadness

    Schizophr. Res.

    (1998)
  • L.J. Seidman et al.

    Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: an fMRI study of working memory

    Schizophr. Res.

    (2006)
  • T. Stöcker et al.

    Dependence of amygdala activation on echo time: results from olfactory fMRI experiments

    NeuroImage

    (2006)
  • S.A. Surguladze et al.

    A preferential increase in the extrastriate response to signals of danger

    NeuroImage

    (2003)
  • S. Surguladze et al.

    A reversal of the normal pattern of parahippocampal response to neutral and fearful faces is associated with reality distortion in schizophrenia

    Biol. Psychiatry

    (2006)
  • S.F. Taylor et al.

    A functional anatomic study of emotion in schizophrenia

    Schizophr. Res.

    (2002)
  • N. Tzourio-Mazoyer et al.

    Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain

    NeuroImage

    (2002)
  • M. van 't Wout et al.

    Emotional processing in a non-clinical psychosis-prone sample

    Schizophr. Res.

    (2004)
  • M. Vink et al.

    Striatal dysfunction in schizophrenia and unaffected relatives

    Biol. Psychiatry

    (2006)
  • P. Vuilleumier et al.

    Effects of attention and emotion on face processing in the human brain: an event-related fMRI study

    Neuron

    (2001)
  • J.S. Winston et al.

    Common and distinct neural responses during direct and incidental processing of multiple facial emotions

    NeuroImage

    (2003)
  • J.H. Yoon et al.

    Preserved function of the fusiform face area in schizophrenia as revealed by fMRI

    Psychiatry Res.

    (2006)
  • Cited by (120)

    • Associations between facial affect recognition and neurocognition in subjects at ultra-high risk for psychosis: A case-control study

      2020, Psychiatry Research
      Citation Excerpt :

      It should be noted that the intelligence z-score was only numerically, but not significantly, lower in UHR subjects than in controls. This might be an important issue further supporting the involvement of intelligence in FAR processing in UHR patients, as a concurrent lack of group differences in both intelligence and DFAR performance has been reported previously (Corcoran et al., 2015; Seiferth et al., 2008; Thompson et al., 2012; see however Tseng et al., 2016). In addition, adjusting for intelligence has eliminated otherwise significant FAR impairment in UHR subjects relative to controls (Barbato et al., 2015) as has adjusting for intelligence (in combination with sex) in patients with first-episode schizophrenia relative to UHR subjects (S. Y. Lee et al., 2015).

    • Neural correlates of social cognition in populations at risk of psychosis: A systematic review

      2020, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      In CHR population, Modinos et al. (2015a, 2015b) reported increased activity in the IFG in response to neutral stimuli during an emotional processing task. Similarly, Seiferth (2008) reported increased activity in the IFG and the SFG for neutral relative to emotional stimuli in a facial emotional processing task. All CHR studies included in the current review reported neural hypersensitivity to neutrally valenced stimuli in both temporal and frontal lobe regions.

    View all citing articles on Scopus
    View full text