Blunted brain activation in patients with schizophrenia in response to emotional cognitive inhibition: A functional near-infrared spectroscopy study

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Abstract

Introduction

Patients with schizophrenia (SZ) have deficits of facial emotion processing and cognitive inhibition, but the brain pathophysiology underlying these deficits and their interaction are not clearly understood. We tested brain activity during an emotional face go/no-go task that requires rapid executive control affected by emotional stimuli in patients with SZ using functional near-infrared spectroscopy (fNIRS).

Methods

Twenty-five patients with SZ and 28 healthy control subjects were studied. We evaluated behavioral performance and used fNIRS to measure oxygenated hemoglobin concentration changes in fronto-temporal areas during the emotional go/no-go task with emotional and non-emotional blocks.

Results

Patients with SZ made more errors and had longer reaction times in both test blocks compared with healthy subjects. Significantly greater activation in the inferior, superior, middle, and orbital frontal regions were observed in healthy subjects during the emotional go/no-go block compared to the non-emotional go/no-go block, but this difference was not observed in patients with SZ. Relative to healthy subjects, patients with SZ showed less activation in the superior and orbital frontal and middle temporal regions during the emotional go/no-go block.

Discussion

Our results suggest that fronto-temporal dysfunction in patients with SZ is due to an interaction between abnormal processing of emotional facial expressions with negative valence and cognitive inhibition, especially during the rapid selection of rule-based associations that override automatic emotional response tendencies. They indicate that fronto-temporal dysfunction is involved in the pathophysiology of emotional–cognitive deficits in patients with SZ.

Introduction

Patients with schizophrenia (SZ) have been shown to have abnormalities of face perception and emotional face processing in behavioral and neuroimaging studies (Tremeau, 2006, Marwick and Hall, 2008, for review). Emotional processing deficits involving social cognition are associated with poor functional outcomes (Hooker and Park, 2002) and negative symptoms (Chan et al., 2010) in patients with SZ. Behavioral studies suggest that patients with SZ tend to misinterpret neutral faces as negative emotional faces (Kohler et al., 2003, Cohen and Minor, 2010, Habel et al., 2010) and are impaired in processing emotional aspects of facial expressions affected for specificity (correct rejection of a non-target emotion) but not sensitivity (correct identification of a target emotion) (Schneider et al., 2006, Seiferth et al., 2009, Habel et al., 2010).

Several brain regions are thought to be involved in face recognition: the inferior occipital gyrus for early perception of facial features; the superior temporal sulcus for changeable aspects of face-perception; the lateral fusiform gyrus for invariant aspects of face-perception; the amygdala, insula, and limbic system for assessment of emotion; the anterior temporal cortex for personal identity, name, and biographical information (Haxby et al., 2000); and the prefrontal and orbitofrontal cortices for appraising the emotional significance of stimuli and guiding social decisions and behavior (Adolphs et al., 2000, Damasio, 2005). A meta-analysis of functional neuroimaging studies revealed that patients with SZ showed remarkable under-recruitment of the superior frontal gyrus, parahippocampus, amygdala, and middle occipital gyrus in response to emotional faces (Li et al., 2010) and increased activity in the dorsolateral prefrontal cortex, middle orbital gyrus (Habel et al., 2010), amygdala (Holt et al., 2006, Hall et al., 2008) and parahippocampus (Surguladze et al., 2006) in response to neutral faces. Such differences might be a consequence of aberrant attribution of emotional meaning to neutral stimuli (Habel et al., 2010).

Patients with SZ are also less able to control cognitive inhibition. In functional magnetic resonance imaging (fMRI) studies during cognitive inhibition tasks (e.g., go/no-go) patients with SZ showed hypoactivation of the dorsolateral and ventrolateral prefrontal cortices and dorsal anterior cingulate cortex and hyperactivation of the superior parietal lobule compared to healthy subjects (Kiehl et al., 2000, Laurens et al., 2003, Arce et al., 2006, Kaladjian et al., 2007). In a functional near-infrared spectroscopy (fNIRS) study, patients with SZ had greater activation of post-central region compared to healthy subjects during a go/no-go task (Nishimura et al., 2011).

The interaction between emotional processing and cognitive function was impaired in patients with SZ, which contributed to poor social functioning (Park et al., 2008). Prior fMRI studies of emotional–cognitive interaction in patients with SZ employed a Stroop task with emotional pictures or go/no-go task with emotional words and suggested that SZ was characterized by inefficient top-down control and an association of dorsal and ventral frontal brain regions (Park et al., 2008, Vercammen et al., 2012). However, to our knowledge, no neuroimaging study has assessed the interaction between emotional face recognition and cognitive inhibition in patients with SZ. The interaction is useful for evaluating emotional control accompanied by social–cognitive interactions that require the rapid selection of rule-based associations that override automatic emotional response tendencies (Volman et al., 2011). The present study used an emotional go/no-go task with emotional faces combined with cognitive inhibition. This task was also expected to elucidate the subjects' ability to correctly reject irrelevant emotional information that could alter target emotion processing, which has been reported to be affected in patients with SZ (Schneider et al., 2006, Seiferth et al., 2009, Habel et al., 2010).

Near-infrared spectroscopy (NIRS) is a technology that assesses brain function; it measures real-time hemodynamics over the surface of the prefrontal cortex with infrared spectrum light. The signals measured by functional NIRS (fNIRS) correlate strongly with those measured by fMRI (Toronov et al., 2001, Huppert et al., 2006). The fNIRS instrument is small, convenient, noninvasive, is relatively insensitive to motion artifacts, and can be used in a natural seated position without any noise or pain. These advantages make it suitable to assess brain function in adults with psychiatric disorders such as schizophrenia (Takizawa et al., 2008, Takei et al., 2013) and mood disorders (Matsuo et al., 2007, Matsubara et al., 2014). In the content of social cognition, Takei et al. (2013) investigated brain activation during a face-to-face conversation task in patients with SZ and found decreased activation in the temporal lobes and the right inferior frontal gyrus. However, to our knowledge, there are no fNIRS studies that have investigated the interaction between emotional face recognition and cognitive inhibition in patients with SZ.

Here, we examined brain activation in patients with SZ during an emotional go/no-go task using multi-channel fNIRS. Based on the findings of previous neuroimaging studies, we hypothesized that patients with SZ would show inferior behavioral performance and blunted activation of fronto-temporal regions during the task.

Section snippets

Subjects

A total of 53 individuals matched for age, sex, handedness, and premorbid intelligence quotient (IQ) participated in this study, including 25 patients with SZ diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV, Text Revision (DSM-IV-TR) (American Psychiatric Association, 2000) and 28 healthy subjects (Table 1). The patients included outpatients and inpatients being treated at Yamaguchi University Hospital and Katakura Hospital. Healthy subjects were recruited by

Demographics and task performance

There were no significant differences in demographic variables between patients with SZ and healthy subjects except in years of education (Table 1). There was a significant interaction between task and diagnosis for both reaction time (F = 8.56, p = 0.005) and false alarm error rate (F = 8.33, p = 0.006) and a significant effect of task on reaction time (F = 107.7, p < 0.001), omission error rate (F = 31.8, p < 0.001) and false alarm error rate (F = 16.9, p < 0.001) (Table 2).

In patients with SZ, a higher false

Primary results of the study

The results of the current study demonstrate that patients with SZ showed similar fronto-temporal region activations for the non-emotional and emotional go/no-go tasks, whereas healthy subjects exhibited greater activation in the superior, inferior, and orbital frontal regions during the emotional task compared to the non-emotional go/no-go task. Compared to healthy subjects, patients with SZ showed blunted activations during the emotional go/no-go task in the superior and orbital frontal and

Conclusion

This is the first fNIRS study to evaluate brain function during an emotional go/no-go task in patients with SZ. Our results suggest that patients with SZ exhibit blunted fronto-temporal activation in response to the interaction task, suggesting that dysfunction of these brain regions is involved in the pathophysiology of abnormal emotional processing and cognitive inhibition in patients with SZ. These findings may further our understanding of impaired social interaction in patients with SZ.

Role of the funding source

This was supported by JSPS KAKENHI (grant numbers 21591519 and 24591716 [KM], 25861011 [TM], and 25861012 [TW]).

Contributors

Kazuteru Egashira wrote the first draft of the manuscript, collected the data, and analyzed the image data. Koji Matsuo designed the study, wrote the protocol, and supervised the content of the manuscript. Mani Nakashima performed the imaging and performed the statistical analyses. Toshio Watanuki, Kenichiro Harada, Masayuki Nakano, and Toshio Matsubara managed the literature searches and collected data. Yoshifumi Watanabe managed the study and reviewed the draft. All authors contributed to and

Conflict of interests

All authors declare that they have no conflicts of interest.

Acknowledgments

We would like to thank Mr. Masahiro Koike (Department of Radiological Technology, Yamaguchi University Hospital) for programming the NIRS task.

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