Peer Reviewed Articles Occipital Lobe Function and Cortical Blindness

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Research Article

The right occipital lobe and poor insight in outset-episode psychosis

• Diana Tordesillas-Gutierrez,
• Rosa Ayesa-Arriola,
• Manuel Delgado-Alvarado,
• Jennifer L. Robinson,
• Javier Lopez-Morinigo,
• Jesus Pujol,
• M. Encarnación Dominguez-Ballesteros,
• Anthony S. David,
• Benedicto Crespo-Facorro

10

• Published: June 1, 2018
• https://doi.org/10.1371/journal.pone.0197715

Figures

Abstract

Lack of insight is a cadre feature of non-melancholia psychosis and has been associated with poorer outcomes. Brain abnormalities underlying lack of insight have been suggested, mostly in the frontal lobe, although previous research showed mixed results. We used a voxel-based morphometry (VBM) assay in 108 showtime-episode non-melancholia psychosis patients to investigate the pattern of encephalon structural abnormalities related to lack of insight. In addition, 77 healthy volunteers were compared with the patients classified as having poor and good insight. The shortened version of the Scale to Appraise Unawareness of Mental Disorder was used to evaluate insight. Patients with poor insight (n = 68) compared with patients with proficient insight (n = 40) showed a unmarried significant cluster (yard _c = 5834; PcFWE = 0.001) of reduced grey affair volume (GMV) in the right occipital lobe extending to its lateral and medial surfaces, the cuneus, and the middle temporal gyrus. In add-on, GMV at this cluster showed a negative correlation with the score of the SUMD (r = -0.305; p = 0.001). When comparing patients with poor insight with salubrious subjects overall reductions of GMV were found, mainly in frontal and occipital lobes. Hence, poor insight in non-affective psychosis seems to exist associated with specific encephalon abnormalities in the right occipital and temporal cortical regions. Dysfunction in whatever combination of these areas may contribute to lack of insight in not-affective psychosis. Specifically, the 'right' hemisphere dysfunction underlying impaired insight in our sample is consequent with previously reported similarities betwixt lack of insight in psychosis and anosognosia in neurological disorders.

Citation: Tordesillas-Gutierrez D, Ayesa-Arriola R, Delgado-Alvarado K, Robinson JL, Lopez-Morinigo J, Pujol J, et al. (2018) The correct occipital lobe and poor insight in first-episode psychosis. PLoS ONE xiii(6): e0197715. https://doi.org/10.1371/periodical.pone.0197715

Editor: Kim Q. Practice, Universite de Lausanne, SWITZERLAND

Received: January 16, 2018; Accepted: May 2, 2018; Published: June ane, 2018

Copyright: © 2018 Tordesillas-Gutierrez et al. This is an open up access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original writer and source are credited.

Data Availability: The Cantabria Ethics Committee placed data sharing restrictions on the image data because the patient images cannot exist de-identified. The SPM data has been deposited in a public repository (DOI: ten.5281/zenodo.1211475). Interested researchers can request the full data gear up by contacting the The Cantabria Ethics Committee at ceicc@idival.org.

Funding: This work was supported past the Instituto de Salud Carlos 3 (PI020499, PI050427, PI060507, PI14/00639 and PI14/00918) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832, NCT02534363, and API07/011). No pharmaceutical industry has participated in the study. The funders had no role in study pattern, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors take alleged that no competing interests exist.

Abbreviations: FEP, first episode psychosis; GMV, grey thing volume; SUMD, Scale to Appraise Unawareness of Mental Disorder

1. Introduction

Lack of insight is considered to be a cardinal feature of psychoses[1, ii]. Even at the fourth dimension of diagnosis, upwards to 50–fourscore% of offset-episode psychosis (FEP) patients show poor insight into having a mental disease, which remains in some cases after psychosis improvement [3–v]. Importantly, lack of insight has been linked with treatment non-adherence[vi]and poor long-term outcomes [vii].

Little is known about the mechanisms that underlie poor insight in non-affective psychosis. Similarities between lack of insight in schizophrenia and unawareness of neurological deficits, termed anosognosia, has prompted speculation that they might share a common mechanism, which might involve perception and attentional processes. Some authors have linked right hemisphere dysfunction with poor insight [8, 9] in both neurological and psychiatric disorders [ane, 10, xi].Information technology is well established that subjects suffering right perisylvian lesions as a consequence of stroke, for case, are frequently unaware of their left-sided paralysis [12]. Indeed Morgan et al., in one of the first studies using voxel-based morphometry (VBM) in a FEP sample found a cluster of reduced grayness thing volume (GMV) in a correct hemisphere posterior region which correlated with the inability to relabel psychotic symptoms every bit abnormal [eleven].

On the other hand, frontal lobe changes affecting the left or both hemispheres have been found in many neuroimaging studies on insight. Particularly, dorsolateral frontal GMV reduction has been suggested to be critically involved in insight [9, 10]. Furthermore, functional imaging studies showed that the neural network underlying insight involves several regions, encompassing the medial frontal (including cingulate), the parietal, and the temporal cortices [xiii–18].Recent VBM studies investigating patients with chronic schizophrenia have confirmed associations between GMV reductions and poor insight in several brain regions [19–21]. In addition, VBM studies in FEP patients have shown book reductions in the bilateral superior frontal gyri, the right inferior frontal gyrus, the right junior temporal gyrus, the left cerebellum, the left insula, the bilateral superior temporal gyri, the precentralgyrus, the bilateral posterior cingulate gyrus, and the correct cuneus to be associated with poor insight [11, 22].On the other mitt, McFarland et al.[23] constitute excess of GMV in relation to impaired insight in the caudate, the insula, the putamen, the thalamus, and the cerebellum in first-episode affective and non-affective psychosis patients.

Variability amongst studies may be due to the small size of the examined samples and/or their clinical heterogeneity. Besides, about of the previous studies only compare patients with healthy controls. Thus, using a large FEP sample, with more statistical power to compare patients with expert and poor insight while fugitive the effect of some of the confounders associated with chronic illness, may help to clarify the role of cerebral structures specifically associated with lack of insight.

The aim of the present study was to investigate the design of encephalon structural abnormalities related to lack of insight into mental illness in a large homogeneous sample of showtime-episode non-affective psychosis patients. Nosotros hypothesized that psychosis patients unaware of having a mental disease would prove reduced GMV in brain regions associated with self-awareness and, in line with the anosognosia theory, predominantly in the right hemisphere.

ii. Methods

2.1. Report setting and financial support

The studied sample was extracted from a large epidemiological program on first-episode psychosis (PAFIP) at University Hospital Marques de Valdecilla (Santander, Spain). Completemethodological information of this program has been reported elsewhere [24]. Subjects included in the present investigation were part of an on-going longitudinal intervention with a three-year follow-upwardly (clinical trial NCT02305823). The study was approved by the Cantabria ethics committee in accordance with the international standards for research ethics (Announcement of Helsinki, 1964)and written informed consent was obtained from all the patients. Capicity of consent was adamant by the psychiatrist (BC-F) through clinical interview. When minors were included in PAFIP, parents/legal guardians signed a parental permission consent document.

ii.2. Subjects

A total of 264 subjects were included in the PAFIP program from February 2001 to December 2007,The inclusion criteria were: (1) age xv–sixty years; (2) residencein the catchment area; (three) experiencing a FEP; (4) meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, brief psychotic disorder, or schizoaffective disorder(5) no prior treatment with antipsychotic drugsor, if previously treated, a total life time of adequate antipsychotic handling of less than 6 weeks.Patients were excluded if they met DSM-IV criteria for (one) drug dependence (except nicotine dependence), (2) mental retardation, or (3) had a history of neurological disease or head injury. Confirmation of diagnoses were done by using the Structured Clinical Interview for DSM-IV (SCID-I) [25], which was administered by an independent psychiatrist 6 months after the initial contact.

Of the 264 patients who entered the programme, 153 agreed to participate in the MRI study. Of those who took part in this investigation, 22 did not complete the scan and 3 were excluded because of poor quality data. Twenty subjects of age older than 40 were also excluded, resulting in 108 patients, who were included in the terminal analysis (run across Flow-chart). These patients take been randomly assigned to receive treatment with olanzapine (n = 24), risperidone (due north = 22), ziprasidone (n = xvi), quetiapine (north = xvi), aripiprazole (n = 13) or haloperidol (n = 17) equally office of the larger clinical trial. Only two patients had been minimally treated prior to randomization to antipsychotic treatments (one with quetiapine and one with haloperidol). Patients had a baseline structural MRI as before long as they could tolerate the procedure following the initiation of treatment. The mean time between initiation of handling and MRI was four.v weeks (±three.vi SD).

Good for you volunteers (n = 77) were also recruited from the same localarea through advertisements. Exclusion criteria were: (1) current or past history of psychiatric, neurological or general medical illnesses, including substance dependence and significant loss of consciousness, which was determined using an abbreviated version of the Comprehensive Cess of Symptoms and History[26] (2) history of psychosis in first-degree relatives. The choice of healthy controls was performed in lodge to obtain similar distribution in age, gender, laterality index, drug history and years of educational activity equally the patient population.

2.three. Insight assessment

Insight was assessed in the FEP patientsat 6 weeks later on inbound the program with the abbreviated version of the Scale to Assess Unawareness of Mental Disorder (SUMD) [27].

The abbreviated version of SUMD in schizophrenia [28] is a valid and reliable instrument for measuring insight in patients with schizophrenia and may be used past clinicians to accurately appraise insight in clinical settings [29]. A brusk course of a scale is oftentimes associated with better acceptability in clinical practices. The abbreviated version of the SUMD (nine items: SUMD1: Awareness of a mental disorder, SUMD2: Awareness of the consequences of a mental disorder, SUMD3: Sensation of the furnishings of drugs, SUMD4: Sensation of a hallucinatory feel, SUMD5: Sensation of delusional ideas, SUMD6: Awareness of disorganised thoughts, SUMD7: Sensation of blunted affect, SUMD8: Sensation of anhedonia, SUMD9: Sensation of lack of sociability) may announced to be more practical than the long version and could atomic number 82 to the inclusion of insight assessments as a office of routine clinical exercise to offering individualised intendance. Each item was encoded in the aforementioned fashion with respect to the following modalities: not applicable (response of '0' or missing data), aware (response of '1'), slightly enlightened/unaware (response of '3'), and seriously unaware (response of '5').

First dimension, and particularly SUMD1 (Sensation of a mental disorder), which correlation is 0.99 with Awareness of disease, was considered the most representative mensurate of clinical insight, and scores ≤ i are considered as good insight[28, xxx, 31].

2.4. Clinical assessment

The Cursory Psychiatric Rating Scale total[32], the Scale for the Assessment of Negative Symptoms (SANS)[33] and the Scale for the Assessment of Positive Symptoms (SAPS)[34] in their validated Spanish versions were used to appraise clinical symptoms at baseline and at the end of weeks ane, ii, iii, 4, and 6 of antipsychotic treatment. The same trained psychiatrist (BC-F) completed the clinical evaluation of patients. Handedness was evaluated by the Edinburgh Inventory [35], right handednessbeingdefined as an Edinburgh laterality index higher than 0.6.

Duration of untreated illness was defined as the time from the first unspecific symptom related to psychosis (for such symptom to exist considered, there should be no render to previous stable level of functioning) to the engagement of initiation of an adequate dose of antipsychotic drug taken regularly. Elapsing of untreated psychosis was divers as the fourth dimension from the commencement continuous (present most of the fourth dimension) psychotic symptom to initiation of adequate antipsychotic drug treatment. Duration of prodromal menstruum was defined as the menstruation from the first unspecific symptoms related to psychosis (every bit defined in a higher place) to the showtime continuous (present most of the time) psychotic symptom. These affliction-related time intervals were retrospectively evaluated. Age of onset of psychosis was defined equally the historic period of emergence of the first continuous (present most of the fourth dimension) psychotic symptom.

2.five. MRI data conquering and epitome processing

In the start 12 weeks later entering the program patients were offered an MRI browse. Loftier-resolution three-dimensional (3D) T1-weighted images were caused on a ane.5-T whole-body scanner (SIGNA, GE, Milwaukee, WS, United states of america) at the Academy Hospital Marques of Valdecilla, Santander, Spain. Three-dimensional T1-weighted images, using a spoiled gradient-recalled conquering in the steady state (GRASS) (SPGR) sequence, were acquired in the coronal plane with the following parameters: TE = 5 msec, TR = 24 msec, NEX = 2, rotation angle = 45°, FOV = 26 ten xix.v cm, slice thickness = 1.5 mm and a matrix of 256 ten 192.

Voxel Based Morphometry (VBM) [36] was performed using the VBM5 toolbox (http://dbm.neuro.uni-jena.de/vbm/download/), an extension of the SPM5 software package (Statistical Parametric Mapping, Wellcome Department of Imaging Neuroscience, London, Uk). The VBM pre-processing included the following steps. First, inspection for scanner artifacts and gross abnormalities for each bailiwick, then, images were segmented into grey affair (GM), white matter (WM) and cerebrospinal fluid. In gild to ameliorate the quality of sectionalisation a Hidden Markov Random Field (HMRF) model [37] was applied to the segmented tissue. Afterwards, GM and WM images were imported into the DARTEL toolbox to create a population template from the complete dataset using a high-dimensional diffeomorphic registration algorithm DARTEL [38]. The obtained deformation fields were practical to the GM images to annals them to Montreal Neurological Plant (MNI) standard space, followed by modulation in gild to appraise GMV differences and smoothing with a 5mm FWHM Gaussian kernel (voxel size 1x1x1).

2.vi. Statistical analysis

Candy images were analyzed within the framework of the General Linear Model. Several t-test analyses were performed to investigate GMV differences between salubrious controls and both insight psychosis patients groups using pairwise contrasts. Age at scan, gender and total intracranial book were entered every bit covariates of no involvement in the statistical design in order to backslide out possible effects of these parameters on between-grouping volume differences. Commencement, a primary cluster-forming voxel-level threshold of p<0.01 (uncorrected) was practical. And so, a cluster-level inference strategy was employed by evaluating obtained clusters at a cluster-extent threshold of p<0.05 family-wise fault (FWE) corrected. All clusters sizes were adjusted for smoothness non-uniformity by ways of the VBM5 toolbox[39]. Anatomical regions covered by significant clusters were identified using automatic anatomical labeling[xl].Pearson'south chi-square for categorical data and Student's t-tests for continuous variables were used to evaluate differences in sociodemographic characteristics between controls and patients. The Statistical Parcel for Social Science, version nineteen.0 (SPSS Inc.,Chicago, IL, USA), was used for these assay.

3. Results

iii.i. Subjects

First Episode Psychosis (FEP), 40 (37%) individuals presented good insight and 68 (63%) poor insight. The control group included 77 good for you volunteers. Demographic and clinical characteristics of both patientgroups and socio-demographically similar healthy control subjectsare summarized in Table ane. There were no statistically significant differences in relevant socio-demographic characteristics between groups (all p>0.06, cutting off p>0.05).

3.2.VBM assay

Results regarding differences betwixt healthy subjects and the FEP patients grouping have been reported elsewhere[41].

3.2.1. Salubrious controls versus patients with poor insight.

The comparing between healthy controls (HC) (north = 77) and patients with poor disease insight (n = 68) (HC>poor insight) showed an all-encompassing decrease in GMV in five clusters (Tables ii–half dozen):

Cluster 1: kc = 42041; PcFWE<0.001. This large cluster showed bilateral reductions mainly in the occipital and temporal lobes and cerebellum also extended to the parietal lobe and parahippocampalgyrus (Table ii).

Cluster ii: kc = 30893; PcFWE<0.001. This cluster showed bilaterally reduction through the frontal lobe (more in right orbitofrontal cortex) and anterior and medial part of the cingulum (Table 3).

Cluster 3: kc = 16654; PcFWE<0.001. This cluster is located in the correct hemisphere, mainly in the occipital lobe (inferior, middle and superior occipital gyri, Cuneus, lingual gyrus and Calcarine cleft) extending to the heart and inferior temporal gyrus, angular gyrus in the parietal lobe and cerebellum (Table 4).

Cluster four: kc = 3825; PcFW<0.001. 95% of the fourth cluster was located in the right temporal lobe (middle and superior temporal gyri) and extended to the Rolandic operculum and supramarginalgyrus. (Table five).

Cluster five: kc = 3101; PcFWE<0.014. This cluster showed reductions in the left hemisphere, mainly in the temporal lobe (superior temporal and Heschgyrus), Rolandic operculum, insula and limbic lobe (amygdala and putamen)(Table 6).

3.2.2. Good for you controls versus patients with skilful insight.

Whole brain GMV differences between xl patients with goodinsight and 77 HC were identified mainly within cerebellum (tonsil, tuber and culmen), left inferior temporal lobe and fusiform (kc = 4039; PcFWE = 0.001). At p <0.05 cluster-level corrected, onecluster was identified (Table seven and S1 Fig). No GMV increases were observed when comparing both groups.

iii.2.iii. Patients with good versus poor insight.

The contrast revealed just a unmarried significant cluster (thousand _c = 5834; PcFWE = 0.001) for smaller GMV in patients with poor insight (n = 68) compared to patients with proficient insight (n = 40). This was detected in the right occipital lobe, and extended to both its lateral and medial surfaces, and the cuneus. The cluster besides extended into the center temporal gyrus (BA 19 and BA xviii) [10,y,z, coordinates 16, -95, 26] as shown in Table 8, Fig 1 and S2 Fig. In add-on, we extracted gray matter voxels values at this cluster and using SPSS showed a negative correlation with the groups of insight (Pearson r = -0.363; p<0.001) (Fig 1).

Fig one.

(A) In red are shown the results of the VBM contrast FEP patients with good insight vs. FEP with poor insight, cluster extends through the correct center and superior occipital gyri, cuneus and middle temporal gyrus. All results are in MNI space. (B) Correlation analysis: Grey matter values at maximum voxel of the contrast good insight > poor insight and insight.

https://doi.org/10.1371/journal.pone.0197715.g001

iv. Discussion

In the present work the neuroanatomical substrate of poor insight has been studied in a large epidemiological sample of FEP patients. Interestingly, we found a reduction in GMV in the lateral and medial gyrus of the right occipital lobe, the cuneus, and the middle temporal gyrus in patients with poor insight into having a mental illness compared to those with adept insight.

The nowadays results partially agree with some previous neuroimaging studies of insight in FEP subjects [eleven, 20, 22, 41, 42]. It has been previously shown that insight correlated with GMV in correct frontal superior and junior gyri, right frontal inferior operculargyrus, and right junior temporal gyrus[22]. Symptom relabeling, the power to place and aspect the symptoms of psychosis as pathological, has been correlated with GMV decreases in right superior temporal and precentralgyri and correct cuneus, and precuneus[11]. Similarly, Cooke at al.[20] constitute that right superior temporal gyrus GMV had a positive correlation with the ability to recognize experiences equally abnormal. In addition, using surface-based analyses, cortical thickness of the inferior occipital gyrus was negatively correlated with mean awareness of affliction [42]. Decreases of GMV in other areas such as the cerebellum, the left frontal and temporal cortices and the bilateral posterior cingulate and precuneus take as well been related with poor insight [11, 20, 22]. Nonetheless, it seems that in that location is a predominance of abnormalities in correct-sided areas.

Frontal lobe abnormalities have been ane of the near consistent findings in the literature regarding insight in psychosis. In fact, structural changes in several areas of the frontal lobe accept been linked to poor insight, particularly those affecting the prefrontal cortex [nine, 22, 42–45]. And, indeed, frontal lobe mediated cognitive functions have been consistently associated with insight in patients with schizophrenia [8, 46–49]. Prefrontal cortex has been suggested to mediate insight in psychosis through impairment of a meta-representation of the self or deficits in Theory of Mind [l]. In this regard, medial prefrontal cortex has been consistently associated not only with the attribution of mental states to others just too to that of oneself [51]. However, most of the studies addressing insight in not-affective psychosis compared patients in the chronic phase of schizophrenia with healthy volunteers, which might take introduced the effect of the illness as a confounding cistron. For example, a recent report found that schizophrenia patients with poor insight had widespread reductions in GMV as compared to those with preserved insight [52] but this may take been confounded by long-term exposure to neuroleptic drugs[53]. In improver, many of the previous studies adopted a region of involvement arroyo rather than the less constrained whole brain approach. By contrast, our results suggest that differences in GMV due to different insight status are present at the primeval stage of the disease. Using VBM nosotros take shown reductions in GMV in several areas of the frontal lobe when comparing patients with poor insight with healthy controls, but our findings also showed reductions in the temporal and occipital lobes in patients with poor insight compared to those with practiced insight. Taken together, it could be interpreted that reductions in frontal grayness matter may exist linked with the illness per se, while temporal and occipital reductions could be more specifically related to lack of insight into psychological (in addition to physical) change.

The right hemisphere predominance of our findings might be explained by the parallelism betwixt insight and anosognosia for left-sided hemiplegia. Patients showing left hemiplegia, left spatial neglect, and anosognosia in comparison with those with hemiplegia and fail but not anosognosia have lesions specifically associated with anosognosia distributed in correct Brodmann's premotor areas half dozen and 44, right motor area 4, and the right somatosensory cortex, and also, although less frequently, in correct prefrontal areas such as area 46 and the insula [54]. Indeed, several studies have associated anosognosia with damage of the correct hemisphere motor and sensory cortices, the inferior frontal cortex, the insula, and the superior temporal gyrus[55, 56]. It is interesting to note that dumb self-awareness of motor symptoms in Parkinson'due south disease patients has besides been recently associated with correct hemisphere structures[57]. The involvement of right hemisphere structures in anosognosia is complex and information technology has been suggested that, in improver to playing a fundamental function in integrating somatosensory representations of the current state with an expected good for you state, the right hemisphere network plays a function in comparison a broader set of representations that include psychological and social skills.

The role of medial temporal gyrus in insight deserves comment. Previous studies accept shown reductions in this area in patients with poor insight[52] or have correlated its volume with insight in patients with schizophrenia[twenty, 22]. This part of the temporal lobe has been classically associated with semantic and memory processing [58], and multimodal sensory integration [59]. Of note, information technology has been suggested that the medial temporal lobe plays a central function encoding episodic experiences during memory formation. Thus, difficulties in this office might hamper incoming corrective data and thus impair the updating of irrational beliefs [sixty]. In fact, retentivity damage has been associated with poor insight in schizophrenia[61].

Finally, our findings of decreased GMV in the cuneus and medial gyrus of the right occipital lobe, are in keeping with two previous studies. Ane of them showed reduced GMV at the junior occipital gyrus in patients with poor insight as compared to those with preserved insight [52], while another plant an association between poor insight and volume reduction in a cluster extending posteriorly from the precuneus through the cuneus to the medial occipital gyrus[11]. The role of occipital structures in insight has been scarcely considered. Interestingly, Anton's syndrome, visual anosognosia or deprival of loss of vision in the setting of cortical blindness, is derived from bilateral occipital brain damage [62]. Moreover, patients with homonymous hemianopia due to unilateral occipital infarcts, may too be unaware of their visual defect [63]. Thus, occipital cortex might be involved in self-sensation, either in isolation such as in neurological conditions, or in coordination with other correct-sided cortical areas in schizophrenia patients. Nevertheless, further inquiry is warranted to clarify the involvement of this and other herein discussed areas in insight in psychosis.

The primary strength of this study lies on the methodology used, particularly in the sample recruitment and design. To the best of our knowledge, this is the largest VBM study carried out with a FEP sample regarding insight. Of nearly importance, our arroyo comparing not just patients and healthy controls just as well patients with good versus those with poor insight, has allowed the states to exclude the overall upshot of schizophrenia per se on GMV. However, some limitations should exist considered. Although our patients were but treated for a short catamenia of time (mean = 4.53 weeks), the effect of antipsychotic medication on GMV cannot be excluded. In addition, VBM methodology has its own limitations, mainly concerning spatial normalization, smoothing and template[64]. However, a cautious methodological choice of pre-processing parameters and statistical options should lead to more reliable VBM results [65].

In conclusion, lack of insight in not-affective psychosis is associated with specific encephalon anomalies in right occipital and temporal cortical regions. Consequent with anosognosia in neurological disorders, lack of insight does not seem to be caused by harm to a specific brain surface area. Rather, insight in psychosis appears to involve a wider brain network, which includes temporal and occipital, and probably the interactions between these areas. Further research is needed to clarify how these brain regions, the circuitries linking them, or a combination of both underlie lack of insight in psychosis.

Supporting information

S1 Fig. In bluish GMV reduction in patients with skillful insight with respect to healthy controls is overlaid over the contrast HC GMV greater than offset episode of psychosis patients in cherry.

As it can be seen the cluster falls inside the difference betwixt patients and healthy subjects (overlaid area is shown in imperial).

https://doi.org/x.1371/journal.pone.0197715.s001

(TIF)

S2 Fig. In bluish GMV reduction in patients with poor insight with respect patients with skillful insight is overlaid on the red contrast that shows GMV reduction in patients with poor insight with respect healthy subjects (overlaid area is shown in purple).

https://doi.org/10.1371/journal.pone.0197715.s002

(TIF)

Acknowledgments

The authors wish to thank all PAFIP enquiry team and all patients and family members who participated in the study. We wish to acknowledge IDIVAL Neuroimaging Unit for imaging acquirement.

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