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. Author manuscript; available in PMC: 2020 Nov 1.
Published in final edited form as: Int J Psychophysiol. 2019 Jun 4;145:57–64. doi: 10.1016/j.ijpsycho.2019.06.002

Neutral Face and Complex Object Neurophysiological Processing Deficits in Long-Term Schizophrenia and in First Hospitalized Schizophrenia-Spectrum Individuals

Dean F Salisbury 1,2, Jason W Krompinger 1, Spencer K Lynn 1,3, Toshiaki Onitsuka 1,4, Robert W McCarley 5,6,7
PMCID: PMC6791748  NIHMSID: NIHMS1531885  PMID: 31173768

Abstract

Background:

Face processing is impaired in long-term schizophrenia as indexed by a reduced face-related N170 event-related potential (ERP) that corresponds with volumetric decreases in right fusiform gyrus. Impairment in face processing may constitute an object-specific deficit in schizophrenia that relates to social impairment and misattribution of social signs in the disease, or the face deficit may be part of a more general deficit in complex visual processing. Further, it is not clear the degree to which face and complex object processing deficits are present early in disease course. To that end, the current study investigated face-and object-elicited N170 in long-term schizophrenia and the first hospitalized schizophrenia-spectrum.

Methods:

ERPs were collected from 32 long-term schizophrenia patients and 32 matched controls, and from 31 first hospitalization patients and 31 matched controls. Subjects detected rarely presented butterflies among non-target neutral faces and automobiles.

Results:

For both patient groups, the N170s to all stimuli were significantly attenuated. Despite this overall reduction, the increase in N170 amplitude to faces was intact in both patient samples. Symptoms were not correlated with N170 amplitude or latency to faces.

Conclusions:

Information processing of complex stimuli is fundamentally impaired in schizophrenia, as reflected in attenuated N170 ERPs in both first hospitalized and long-term patients. This suggests the presence of low-level visual complex object processing deficits near disease onset that persist with disease course.

Keywords: schizophrenia, first hospitalization, chronic, face analysis, EEG, event-related potential, N170

Introduction

A wealth of phenomenological and behavioral evidence suggests that individuals with schizophrenia exhibit impairments in face processing and facial affect recognition (Edwards, Jackson, & Pattison, 2002, Hall et al 2004). Such impairments may manifest as positive symptoms, such as delusions and paranoia, or as negative symptoms, such as emotional withdrawal and poor rapport, and likely serve to significantly impede social functioning. Recent neurophysiological investigations trace the root of this dysfunction to structural and functional abnormalities in brain areas thought to subserve face processing. In particular, the fusiform gyrus, hypothesized to be a ‘core’ component of the face perception system involved in identifying invariant facial features (Haxby et al 2000), appears compromised in schizophrenia. Both post-mortem and in-vivo studies reveal reduced cortical volume of the fusiform gyrus in patients (McDonald et al 2000, Lee et al 2002, Onitsuka et al 2003, 2006). Further, functional neuroimaging studies indicate attenuated hemodynamic response in this region during facial identification tasks (Quintana et al 2003, Johnston et al 2005) indicating that patients may not exhibit appropriate neural response when differentiating faces from other stimuli. Given that face processing is a multistaged process, event-related brain potentials (ERPs) with temporal resolution in the millisecond range have been used to dissect such stages, and to more precisely detect where in the information processing stream deficits may lie in schizophrenia. These investigations have generally focused on an ERP thought to index structural face processing: the N170 (e.g., Herrmann et al 2004, Campanella et al 2006, Onitsuka et al 2006, Lynn & Salisbury, 2008).

The N170 is a negative-going ERP typically occurring between 140–200 ms post-stimulus that is larger for faces compared to other complex objects, typically measured at temporal-parietal electrode sites (Itier & Taylor, 2004). Evaluation of the N170 in healthy subjects indicates that its neural generators probably lie in the fusiform gyrus and posterior lateral temporal lobe. The N170 is sensitive to structural encoding of both invariant aspects of facial stimuli (e.g., presence of eyes, nose, mouth) and variable features (e.g., eye and mouth expressions; Allison et al 1999, McCarthy et al 1999, Puce et al 1999). In schizophrenia, N170 amplitude tends to be attenuated. This effect, however, is not uniform across studies. Herrmann and colleagues (2004) and Onitsuka and colleagues (2006) showed attenuations in the difference between the N170 to faces compared to other stimuli in patients with long-term schizophrenia (Onitsuka et al 2006) and illness of unspecified chronicity (Herrmann et al 2004). In a preliminary analysis of the current dataset comparing 22 long-term patients with 9 controls, our group confirmed N170 reductions in long-term schizophrenia, but the attenuation was evident for both faces and cars, and long-term patients showed modulation of N170 by faces (Lynn & Salisbury, 2008). Here we present larger samples of 33 long-term schizophrenia patients and 33 one-to-one matched controls, and also 31 first hospitalized schizophrenia patients and 31 one-to-one matched controls.

N170 has been little studied in first episode schizophrenia. A study by Valkonen-Korhonen and colleagues (2005) showed increased responses in an N170-like face-specific component for a group of patients with acute, first episode schizophrenia compared to controls in a facial emotion identification task. Brennan, Harris, and Williams (2014) reported no significant temporal area N170 differences to neutral faces in first onset schizophrenia, although there were differences in prolonged slow wave activity. In an fMRI study of first episode schizophrenia subjects, Anilkumar et al (2008) showed no significant activation differences in fusiform (or other visual or emotional processing areas) relative to psychiatrically-well comparison subjects. Although studies are scant, extant findings raise the question of the effect that disease course might have on N170-reflected face processing abnormalities in schizophrenia.

To our knowledge, few studies have evaluated the functional integrity of the N170 in long-term schizophrenia and directly compared it with ‘first episode’ patients. There is reason to believe that impairments in face processing may be evident in N170 at the first episode of schizophrenia (typically operationalized as first hospitalization for psychosis). Even first hospitalized patients have impairment of social functioning and misattribute emotions in others as threatening (e.g., paranoia). Lee and colleagues (2002) showed that first hospitalization patients have bilateral reductions in fusiform gyrus gray matter compared to both controls and patients with affective psychosis. Given that such volumetric reductions in fusiform gyrus have been shown to be related to N170 amplitude in schizophrenia (Onitsuka et al 2006), it stands to reason that first hospitalization patients would exhibit attenuations of N170 (although the 2 studies reported above did not detect differences and the fMRI study saw no reductions in the hemodynamic response to faces at first episode).

In the current study, we compared face and car-elicited N170s from patients with long-term schizophrenia or at the first hospitalization for schizophrenia and matched control groups to determine whether complex object visual processing in general and face-modulation of N170 were impaired at both stages of the disorder.

Method

Participants.

Thirty-two chronically-ill schizophrenia subjects (8 female) were compared to 32 control subjects (9 female). Thirty-one first-hospitalized subjects (8 female) were compared to 31 control subjects (10 female). Control participants were matched one-to-one to patients on the basis of age, gender, handedness, WAIS Information scaled scores, and parental socioeconomic status (Table 1). Informed consent was obtained after complete description of the study, and subjects were paid $15 per hour. Recruitment, criteria for enrollment, and diagnostic procedures are described in detail elsewhere (Salisbury et al 2007). Briefly, first hospitalization patients were at or within one year of their first hospitalization for putative schizophrenia or schizoaffective disorder. Initial diagnoses were based on SCID interview and chart review, and were confirmed with a follow up SCID interview (minimum 6 months) or chart review after subsequent admissions when possible (18/31). The first hospitalization sample comprised 19 paranoid, 2 undifferentiated, 1 disorganized schizophrenia subtype patients, 2 schizoaffective disorder depressed subtype, 5 schizoaffective disorder bipolar subtype patients, 1 delusional disorder paranoid subtype subject, and 1 schizophreniform patient. Long-term patients comprised 22 paranoid, 1 undifferentiated, 4 disorganized schizophrenia subtype patients, 2 schizoaffective disorder depressed subtype, and 3 schizoaffective disorder bipolar subtype patients. Patient symptom ratings were obtained using the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Positive and Negative Symptom Scale (PANSS). Two long-term patients were unmedicated at time of testing, and 15 first hospitalization patients were unmedicated. Clinical measures and chlorpromazine-equivalent antipsychotic medication doses are presented in Table 1.

Table 1.

Subject demographic information

Long-term Schizophrenia Older Controls p value First Hospitalization Schizophrenia Younger Controls p value
N 32 32 31 31
Age 38.8 (10.0) 37.3 (10.0) 0.54 24.1 (6.8) 24.5 (7.7) 0.86
Sex (M/F) 24/8 23/9 0.78 23/8 21/10 0.58
WAIS Information (scaled) 11.9(2.3) 13.0 (3.1) 0.13 12.9 (2.1) 13.5 (2.0) 0.30
Parental SES 2.1 (1.2) 1.9 (0.9) 0.47 1.7 (0.9) 1.6 (0.9) 0.86
Handedness 0.75 (0.2) 0.75 (0.3) 0.97 0.66 (0.4) 0.71 (0.29) 0.59
PANSS
Total		 65.8 (17.7) 75.9 (15.2)
PANSS
Positive		 19.0 (5.5) 20.6 (4.6)
PANSS
Negative		 16.3 (6.4) 18.5 (7.4)
SAPS 8.3 (4.6) 9.5 (4.1)
SANS 10.4 (6.3) 12.6 (11.4)
Meds* 523.1 (408.3) 302.2 (246.9)
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Note: Values are means (sd). N = Number of subjects. Age in years. Parental SES = Parental Socioeconomic Status. Handedness = Edinburgh inventory scores (1 = right-handed, −1 = left-handed. Oldfield, 1971). PANSS = Positive and Negative Syndrome Scale. SAPS = Scale for the Assessment of Positive Symptoms. SANS = Scale for the Assessment of Negative Symptoms. Meds = chlorpromazine equivalents.

*

Medication means do not include zero for unmedicated participants.

Stimuli and Procedures.

Subjects viewed experimental stimuli serially on a computer screen from 1.3 m. Stimuli subtended approximately 6° visual angle. Stimulus presentation and button press responding were accomplished with SuperLab Pro 2 (Cedrus Corp.). Stimuli were preceded by a 200 ms fixation cross at the center of the screen followed by a 200 ms blank screen. Stimuli were shown in the center of the screen for 500 ms and followed by a 1000 ms blank screen.

The stimulus set comprised images of faces, cars, and butterflies. Face stimuli comprised 32 faces (16 male, 16 female faces, half Asian, half Caucasian). Thirty-two images showed cars from a 3/4-profile view, and 10 images were of butterflies shown in a “pinned” perspective. Subjects pressed a button with their right forefinger when they saw a butterfly.

Psychophysiological Recording, Data Reduction and Analysis.

EEG activity was recorded with using 60 silver-silver chloride electrodes embedded in preconfigured caps (ElectroCap International, Eaton, Ohio). The electrode sites were Fp1/2, F7/8, F5/6, F3/4, F1/z/2, FT9/10, FT7/8, FC5/6, FC3/4, FC1/2, T9/10, T7/8, C5/6, C3/4, C1/z/2, TP7/8, CP5/6, CP3/4, CP1/2, P9/10, P7/8, P5/6, P3/4, P1/z/2, PO9/10, PO7/8, PO1/2, and O1/z/2. M1 and the nosetip were also recorded. All sites were referenced to the right mastoid, with the forehead as ground. The vertical electro-oculogram (EOG) was recorded from two electrodes located medially to the right eye, one above and one below the eye. The horizontal EOG was recorded at the outer canthi. Electrode impedances were <5kΩ. Activity was passed from 0.15 (12 dB/octave) to 100 Hz (24 dB/octave) with 500 Hz sampling rate using Neuroscan Synamps, and recorded using Neuroscan Acquire. Digital triggers were embedded using Superlab. Data processing was accomplished with EEGLab and BrainVision Analyzer2. In EEGLab, bad channels were interpolated and eye blink and movement artifact were removed using adaptive mixture independent components analysis (AMICA). In BrainVision Analyzer2, activity was digitally filtered off-line using a Butterworth zero-phase filter with a high cutoff of 32 Hz (24 db/octave). Recordings were rereferenced to the average reference as computed from all scalp electrodes. Epochs were 1150 ms duration, including a 100 ms prestimulus baseline. Individual trials were baseline corrected and any trial containing voltage ±100 μV was rejected. Averages were computed separately for cars and faces. To visualize face modulation, the averaged ERP to cars was subtracted from the averaged ERP to faces.

The N170 ERP was examined at four bilateral posterior electrode sites (P7/8, P9/10, PO7/8, PO9/10). Amplitude and latency of the N170 ERP were measured for each subject using automated peak detection, searched separately on each channel, with subsequent visual confirmation. N170 amplitude was quantified as the mean voltage over a 10 ms interval centered on the individual peak latency for each site. ERP amplitude was analyzed separately for long-term and first hospitalized patients using mixed design ANOVAs with diagnosis as the between subjects factor and object (face, car), hemisphere (left, right), electrode chain (P and PO), and electrode site (2 in each chain, one superior (7/8) and one inferior (9/10)) as within-subject factors. Effect sizes are reported as partial eta squared (pη2). Exploratory correlational analyses utilized Spearman’s rank ordered rho, and were limited to PO10, the right ventral site where N170 is typically largest. Results were considered significant at p <.05. Trend-level interactions are not reported.

Results

Chronically Ill Patients vs. Controls.

Long-term patients and controls performed the butterfly detection task accurately (Table 2). Comparison of hits and false alarms revealed no significant differences between the groups. Further, comparisons of mean reaction times revealed no significant differences.

Table 2.

Butterfly target detection performance.

Long-term Schizophrenia Older Controls p value First Hospitalization Schizophrenia Younger Controls p value
Hits 9.90 (0.30) 9.90 (0.54) 0.98 9.90 (0.40) 9.94 (0.25) 0.70
False Alarms 0.09 (0.30) 0.06 (0.25) 0.67 0.16 (0.37) 0.0 (0.0) 0.02
Reaction Time 468.8 (60.0) 455.7 (77.3) 0.46 470.1 (98.8) 418.0(43.3) .009
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Averaged ERP waveforms for faces and cars in each group are presented in Figure 1. Mean N170 amplitudes at each site for each object are presented in Table 3. The control group exhibited larger N170s than the patient group (Group: −7.1 μV vs −4.8 μV, F(1,62)=4.96, p=.030, pη2=.074, Fig. 1 A & B). The analysis further revealed that N170 amplitudes were larger for faces compared to cars (Object: −6.8 μV vs −5.1 μV, F(1,62)=24.37, p<.0001, pη2=.282), and face modulation did not differ significantly between groups (Group × Object:p=.830, pη2=.001, Fig 1 C). N170 was larger over the right than left hemisphere (Hemisphere: −6.7 μV vs −5.2 μV, F(1,62)=34.90, p<.0001, pη2=.360), which did not differ between groups (Group × Hemisphere: p =.536, pη2=.006). The greater right than left N170 was also unaffected by object (Hemisphere × Object: p =.79, pη2=.001), and this did not differ between groups (Group × Hemisphere × Object: p =.417, pη2=.011). The more posterior PO chain was more negative (−6.5 μV) than the P chain (−5.4 μV; Chain: F(1,62)=23.21, p<.0001, pη2=.272), and this did not differ between groups (Group × Chain: p=.249, pη2=.021). However, the difference between chains was smaller for faces (0.8 μV) than for cars (1.3 μV; Chain × Object: F(1,62)=6.78, p=.012, pη2=.099), and this was the same for both groups (Group × Chain × Object: p=.908, pη2<.001). Similarly, the difference between inferior sites and superior sites was smaller for faces (0.2 μV) than for cars (0.8 μV; Site: F(1,62)=24.72, p<.001, pη2=.285), and this was the same for both groups (Group × Site: p=.989, pη2<.001). These interactions are consistent with the overall larger N170 to faces than to cars. The difference between inferior and superior sites was larger for the PO chain (0.5 μV) than the P chain (Chain × Site: 0.2 μV; F(1,62)=6.22, p=.015, pη2=.091), similarly for both groups (Group × Chain × Site: p=.184, pη2=.028). Finally, there was an interaction between object, hemisphere, chain, and site, (F(1,62)=7.42, p=.008, pη2=.107) driven by markedly larger face-modulation of N170 at the right hemisphere inferior parietal site (P10; see Fig 1, Table 3).

Figure 1.

Figure 1.

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ERP waveforms to faces and cars for long-term schizophrenia and matched controls. Panel A. Responses to cars. Panel B. Responses to faces. Panel C. Face-modulation of ERPs (Face - Car ERP waveforms). Voltage is in μV. Time is in msec.

Table 3.

Mean N170 amplitudes.

P7 P9 PO7 PO9 P8 P10 PO8 PO10
Long-term Schizophrenia
Face −3.9 (4.4) −4.6 (3.6) −5.1 (5.5) −4.9 (5.1) −5.4 (4.9) −4.7 (4.4) −6.7 (5.6) −6.2 (4.8)
Car −3.3 (3.1) −2.7 (3.2) −4.4 (3.9) −4.1 (3.7) −4.6 (3.9) −4.1 (3.9) −5.8 (4.9) −5.3 (4.4)
Older Controls
Face −7.2 (5.2) −6.4 (6.3) −9.5 (7.2) −8.0 (7.4) −7.7 (4.9) −7.4 (5.3) −10.2 (6.3) −8.6 (7.5)
Car −4.9 (4.3) −4.1 (5.2) −6.8 (7.1) −5.6 (6.8) −6.1 (4.4) −5.3 (5.3) −7.7 (6.5) −6.4 (7.5)
First Hospitalization Schizophrenia
Face −4.8 (4.3) −4.4 (3.5) −5.6 (5.0) −5.2 (3.9) −5.9 (4.5) −4.9 (3.8) −7.4 (6.4) −5.9 (4.6)
Car −3.4 (3.6) −2.7 (3.5) −4.1 (4.1) −3.2 (3.9) −5.2 (4.6) −4.3 (4.0) −6.5 (5.9) −4.9 (4.4)
Younger Controls
Face −5.7 (4.5) −4.9 (4.0) −8.1 (5.0) −7.2 (3.3) −9.1 (6.3) −7.3 (4.7) −10.0 (6.6) −8.5 (4.6)
Car −4.9 (3.6) −3.7 (2.9) −6.6 (5.4) −4.7 (4.2) −7.7 (5.5) −6.0 (4.3) −8.2 (5.4) −6.6 (4.0)
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Note: Values are mean (SD) μV.

Correlations.

Face N170 amplitude and latency at P010 (where face N170 was largest) were not associated total, positive, or negative symptoms, WAIS Information scaled scores, or Socio-economic status in long term schizophrenia participants.

First hospitalization Patients vs. Controls.

First hospitalization patients and controls both performed the task accurately (See Table 2). Comparison of hits revealed no significant differences between the groups. First hospitalization patients made significantly more false alarms (t57 =2.28, p =.026), but note that no younger control made a false alarm, suggesting this difference is trivial. Comparisons of mean reaction times showed first hospitalization patients to be slower at butterfly detection than controls (t57 =2.65, p =.010). (Note: Behavioral data were lost for 3 young healthy participants.)

Averaged ERP waveforms for faces and cars in each group are presented in Figure 2. Mean N170 amplitudes at each site for each object are presented in Table 3. The control group exhibited larger N170s than the first hospitalized schizophrenia-spectrum group (Group: −6.4 μV vs −4.4 μV, F(1,60)=7.28, p=.009, pη2=.108,Fig 2 A & B). N170 amplitudes were larger for faces compared to cars (Object: −5.8 μV vs −4.9 μV, F(1,60)=8.44, p=.001, pη2=.123), and face modulation did not differ significantly between groups (Group × Object: p=.291, pη2=.019, Fig 2 C). N170 was larger over the right than left hemisphere (Hemisphere: −6.4 μV vs −4.4 μV; F(1,60)=31.75, p<.0001, pη2=.346), which did not differ between groups (Group × Hemisphere: p =.344, pη2=.015). The more posterior PO chain was more negative (−5.7 μV) than the P chain (−5.1 μV; Chain: F(1,60)=16.11, p<.0001, pη2=.212), and this did not differ between groups (Group × Chain: p=.564, pη2=.006). N170 was larger at inferior sites (−5.8 μV) than superior sites (−5.0 μV; Site: F(1,60)=19.56, p<.001, pη2=.246), and did not differ significantly between groups (Group × Site: p=.083, pη2=.049). This site effect was greater for cars (1.3 μV) than faces (0.5 μV; Object × Site: F(1,60)=13.29, p=.001, pη2=.181), similarly in both groups (Group × Object × Site” p=.974, pη2<.001). There was a significant interaction between hemisphere, chain, and group (F(1,60)=4.33, p=.042, pη2=.067), with healthy individuals showing more difference between P and PO chains in the left hemisphere, whereas first hospitalized individuals showed greater differences between chains in the right hemisphere (see Table 3). Finally, there was an interaction between object, hemisphere, chain, and site, and group (F(1,60)=18.51, p<.001, pη2=.236) driven by a larger face N170 at the left hemisphere superior parietal site (P7) versus marked right hemisphere (P8) reduction in first hospitalized schizophrenia-spectrum individuals (see Fig 2 C and Table 3).

Figure 2.

Figure 2.

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ERP waveforms to faces and cars for first hospitalization schizophrenia and matched controls. Panel A. Responses to cars. Panel B. Responses to faces. Panel C. Face-modulation of ERPs (Face - Car ERP waveforms). Voltage is in μV. Time is in msec.

Correlations.

Face N170 amplitude and latency at P010 (where face N170 was largest) were not associated total, positive, or negative symptoms, WAIS Information scaled scores, or Socio-economic status in first hospitalization schizophrenia participants.

Discussion

The current study sought to identify N170-indicated disturbances in face processing in patients with long-term schizophrenia and in first hospitalized schizophrenia-spectrum patients. In both groups, N170 amplitude was significantly reduced across both stimulus types when compared to control groups. Both long-term patients and first hospitalized patient groups exhibited appropriate modulation of N170 by faces.

The finding of impaired N170 amplitude to faces in long-term schizophrenia is generally consistent with the literature. However, our data suggest this occurs within the context of overall N170 deficits. Not all studies that reported reduced face N170 in schizophrenia compared faces to other complex objects. For example, in their meta-analysis of the face N170 effect, McCleery et al (2015) reported 9 faces-only studies, 11 comparing faces to complex objects, and one comparing faces to words. Of those studies, 15 reported a reduced face N170 in schizophrenia, and 6 did not. In terms of the face N170 itself, our data are in agreement with reductions, present at both first hospitalization for psychosis within the schizophrenia spectrum and in long term illness. However, both our samples increased N170 appropriately to faces within the context of a generalized N170 reduction. Of the 11 studies using complex non-face stimuli, 3 did not examine the non-face N170 (Streit et al 2001, Kirihara et al 2012, Akbarfahimi, Tehrani-Doost & Ghassemi 2013). One of the 9 reports that compared N170 to faces and complex objects was the preliminary report of this now larger dataset (Lynn & Salisbury, 2008). For the remaining 8 studies that examined N170 to faces and other complex objects, Onitsuka et al (2006) reported an interaction between item (face, car) and group, indicating impaired face-modulation in long-term illness. Tsunoda et al (2012) likewise showed an interaction indicative of impaired face-modulation of N170. Obayashi et al (2009) showed impaired N170 face-modulation in schizophrenia without an overall N170 reduction. Herrmann, Ellgring, and Fallgatter (2004) showed reduced face-modulation of N170 within the context of a trend-level reduction in right hemisphere N170 to buildings in long-term illness. Komlósi et al (2013) reported intact N170 face-modulation in schizophrenia, and no overall N170 reduction. Wynn et al (2008) also reported intact overall N170 and N170 face-modulation in schizophrenia. However, Wynn et al (2013) reported a smaller N170 difference wave (Face minus building) in schizophrenia, which implies less N170 face-modulation, but might also (at least partially) reflect an overall N170 reduction. A recent report using face-like and tree-like degraded line drawings (Maher et al 2016) suggested a specific lack of face-modulation of N170 in schizophrenia, but did not use actual faces which may confound the results with feature extraction capabilities. Thus, while the majority of studies comparing the N170s elicited by faces and complex objects in schizophrenia find impaired face-modulation, there is some variability, with reports of both overall impairments and no impairments. It is not known why these empirical differences exist. Our study, which detected overall N170 reductions and intact N170 face-modulation in long term schizophrenia, tested 32 participants per group. In general (and with the notable exception of the Wynn et al studies) our sample size was generally twice that of extant studies. It is possible that power issues at least partially allowed us to detect overall N170 visual processing reductions in long-term schizophrenia, although task differences and patient symptom profiles, chronicity, and functioning all likely play a role that deserve further examination.

To our knowledge, this is the first study to show impairments in N170 in schizophrenia at first hospitalization. However, face specific N170 modulation appeared intact. This suggests a general complex visual object information processing deficit evident at first hospitalization. Structural imaging studies generally indicate widespread volumetric decreases already evident at first episode schizophrenia, with extant studies indicating notable decrements at aforementioned face-processing regions but also the superior temporal gyrus, parahipppocampal gyrus, cingulate gyrus, insular cortex, temporal pole, and cerebellum, as well as whole-brain volumetric decreases (Kasai et al 2003, Takahashi et al 2006, Koo et al 2008, Bangalore et al 2009, for a review: Steen et al 2006). Given that an intact visual processing stream reflected in the N170 is dependent upon a network of such brain areas working serially and in parallel, it is possible that these volumetric decreases conspire to produce the observed attenuations in N170. However, the one extant fMRI study of face processing in first episode schizophrenia (Anilkumar et al 2008) showed no reduction of fusiform, occipital, temporal or frontal face-related hemodynamic responses. In electrophysiological studies of N170 in first episode individuals, Yang et al (2017) showed no reduction in N170 to emotional faces in first-episode/early course (<3 years illness) individuals compared to healthy individuals, and Valkonen-Korhonen et al (2005) showed a larger N145 (which presumably was the N170 based on its morphology) in unmedicated acutely psychotic first hospitalized individuals. Using MEG, Rivolta et al (2014) showed no sensor level reduction of M170 to Mooney faces, but did show widespread increased source activity in the distributed face network. Unlike these previous negative findings for reductions in first episode individuals, our first hospitalized schizophrenia individuals showed marked N170 reductions to faces and cars.

To summarize, both long-term schizophrenia and first hospitalization schizophrenia spectrum individuals showed N170 deficits to complex objects, but were able to modulate N170 to faces compared to cars. Such a general object processing deficit is consistent with findings of distributed visual processing deficits including sequential visual ERPs and dorsal and ventral visual streams, prefrontal, and hippocampal fMRI activity in schizophrenia (Sehatpour et al 2010), demonstrations of impaired fMRI activation in higher cortical areas (V2, V3, V4) in schizophrenia (Silverstein et al 2009), and reduced fMRI coupling of lateral occipital cortex with higher-order parietal and prefrontal regions during difficult visual processing in schizophrenia (Harvey et al 2011). In the long term patients, these results are partially consistent with previous reports, but it is not known why some reports find selective impairments to faces. In first hospitalized individuals, we likewise showed N170 deficits to all objects with intact face-modulation. This is the first report to show such reductions in first hospitalization individuals. Our individuals were medication managed, whereas the one extant study reporting increased N170 (Valkonen-Korhonen et al 2005) and the one report of increased MEG-based source activity (Rivolta et al 2014) were conducted on acutely psychotic medication naïve individuals. Hence, florid psychosis effects on processing and medication effects on neural excitability during processing need to be further examined.

Correlations between clinical measures and face N170 did not support associations between negative symptoms, including social avoidance and poor rapport, and impaired face processing in either sample. Future research using instruments designed to better capture social functioning is needed to explore the association between negative symptoms and face-related processing.

This study revealed complex object processing deficits in both chronically-ill and first hospitalization schizophrenia samples, with intact face-modulation of N170 in both samples. These data suggest a general visual cortical processing impairment in schizophrenia even early in disease course. It remains to be determined whether such impairments are related to social and occupational dysfunction, whether N170 visual processing is impaired in the pre-psychosis (prodromal) stage, and whether targeted interventions for social and emotional processing could ameliorate the development of such deficits in early course schizophrenia or during the prodromal stage.

Highlights.

  • N170 elicited by visual stimuli was reduced to faces and cars in schizophrenia

  • These N170 deficits were also present at the first episode of psychosis in the schizophrenia-spectrum

  • These results suggest visual processing of complex objects is impaired even early in disease

Acknowledgements:

This work was supported in part by NIH R01 MH40799 (RWM). Data collection and partial analyses were conducted while JWK, SKL, and DFS were members of the Cognitive Neuroscience Laboratory, McLean Hospital, Harvard Medical School, and TO was a member of the Brain Imaging Laboratory, Brockton VA. Final analyses and MS preparation were performed by DFS as faculty at University of Pittsburgh School of Medicine.

Footnotes

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Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Competing Interests: The authors have no competing interests to declare and no conflicts of interest.

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