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. 2022:35:103119.
doi: 10.1016/j.nicl.2022.103119. Epub 2022 Jul 16.

Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect

Paola Fuentes-Claramonte  1 , Núria Ramiro  2 , Llanos Torres  3 , Isabel Argila-Plaza  4 , Pilar Salgado-Pineda  1 , Joan Soler-Vidal  5 , María Ángeles García-León  1 , Auria Albacete  1 , Clara Bosque  6 , Francesco Panicalli  6 , Ester Boix  7 , Josep Munuera  8 , Josep Tristany  9 , Salvador Sarró  1 , Miquel Bernardo  10 , Raymond Salvador  1 , Peter J McKenna  11 , Edith Pomarol-Clotet  1
Affiliations

Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect

Paola Fuentes-Claramonte et al. Neuroimage Clin. 2022.

Abstract

Background: The negative symptoms of schizophrenia have been proposed to reflect prefrontal cortex dysfunction. However, this proposal has not been consistently supported in functional imaging studies, which have also used executive tasks that may not capture key aspects of negative symptoms such as lack of volition.

Method: Twenty-four DSM-5 schizophrenic patients with high negative symptoms (HNS), 25 with absent negative symptoms (ANS) and 30 healthy controls underwent fMRI during performance of the Computerized Multiple Elements Test (CMET), a task designed to measure poor organization of goal directed behaviour or 'goal neglect'. Negative symptoms were rated using the PANSS and the Clinical Assessment Interview for Negative Symptoms (CAINS).

Results: On whole brain analysis, the ANS patients showed no significant clusters of reduced activation compared to the healthy controls. In contrast, the HNS patients showed hypoactivation compared to the healthy controls in the left anterior frontal cortex, the right dorsolateral prefrontal cortex (DLPFC), the anterior insula bilaterally and the bilateral inferior parietal cortex. When compared to the ANS patients, the HNS patients showed reduced activation in the left anterior frontal cortex, the left DLPFC and the left inferior parietal cortex. After controlling for disorganization scores, differences remained in clusters in the left anterior frontal cortex and the bilateral inferior parietal cortex.

Conclusions: This study provides evidence that reduced prefrontal activation, perhaps especially in the left anterior frontal cortex, is a brain functional correlate of negative symptoms in schizophrenia. The simultaneous finding of reduced inferior parietal cortex activation was unexpected, but could reflect this region's involvement in cognitive control, particularly the 'regulative' component of this.

Keywords: Executive function; Frontal lobes; Negative symptoms; Schizophrenia; fMRI.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. The other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic view of the CMET. Participants sequentially play four games during each 48 s block. In the automatic switching condition, the game changes every 12 s without the intervention of the participant. In the voluntary switching condition, the participant has to actively switch games by button press, with approximately the same frequency as in the automatic condition. No time information is shown during either condition.
Fig. 2
Fig. 2
Group mean activation maps. (A) healthy controls, (B) ANS patients, (C) HNS patients. Right side of the image corresponds to right side of the brain. Colour bar shows z values.
Fig. 3
Fig. 3
(A) Clusters of hypoactivation in the HNS group relative to the control group (HNS < HC). (B) Clusters of hypoactivation in the HNS group relative to the ANS group (HNS < ANS); there were no clusters of significant difference in the comparison ANS > HC. (C) Regions of hypoactivation in the HNS group relative to the ANS group (HNS < ANS) after covarying for PANSS disorganization scores. Right side of the image is the right side of the brain. Colour bar depicts z values.
See this image and copyright information in PMC

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