The N170 and face perception in psychiatric and neurological disorders: A systematic review.

Clinical Neurophysiology xxx (2014) xxx–xxx

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Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph

The N170 and face perception in psychiatric and neurological disorders: A systematic review Daniel Feuerriegel a,⇑, Owen Churches b, Jessica Hofmann a, Hannah A.D. Keage a a b

Cognitive Neuroscience Laboratory, University of South Australia, Adelaide, Australia Brain and Cognition Laboratory, Flinders University, Adelaide, Australia

a r t i c l e

i n f o

Article history: Accepted 10 September 2014 Available online xxxx Keywords: N170 VPP M170 Systematic review Event-related potentials Face perception

h i g h l i g h t s Smaller N170 and Vertex Positive Potential (VPP) amplitudes following faces in Schizophrenia;

findings were inconsistent for other disorders. N170/M170/VPP amplitude and latency correlated with facial recognition ability rather than disorder-

specific symptoms. Support for the N170 as a biomarker of facial recognition deficits that are broadly characteristic of

psychiatric/neurological disorders.

a b s t r a c t Objective: To systematically evaluate evidence for configural and affective face processing abnormalities as measured by the N170 and Vertex Positive Potential (VPP) event-related potential components, and analogous M170 magnetoencephalography (MEG) component, in neurological and psychiatric disorders. Methods: 1251 unique articles were identified using PsychINFO and PubMed databases. Sixty-seven studies were selected for review, which employed various tasks to measure the N170, M170 or VPP; the 13 neurological/psychiatric conditions were Attention-Deficit Hyperactivity Disorder (ADHD), Alcohol Dependence, Alzheimer’s Disease, Autism Spectrum Disorders (ASDs), Bipolar Disorder, Bulimia Nervosa, Fibromyalgia, Huntington’s Disease, Major Depressive Disorder, Parkinson’s Disease, Prosopagnosia, Schizophrenia and Social Phobia. Results: Smaller N170 and VPP amplitudes to faces compared to healthy controls were consistently reported in Schizophrenia but not in ASDs. In Schizophrenia N170 and VPP measures were not correlated with clinical symptoms. Findings from other disorders were highly inconsistent; however, reported group differences were almost always smaller amplitudes or slower latencies to emotional faces in disordered groups regardless of diagnosis. Conclusions: Results suggest that N170/VPP abnormalities index non-specific facial affect processing dysfunction in these neurological and psychiatric conditions, reflecting social impairments being broadly characteristic of these groups. Significance: The N170 and analogous components hold promise as diagnostic and treatment monitoring biomarkers for social dysfunction. Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction

⇑ Corresponding author at: Cognitive Neuroscience Laboratory, School of Psychology, Social Work and Social Policy, University of South Australia, St Bernards Road, Adelaide, Australia. E-mail address: [email protected] (D. Feuerriegel).

Faces are our most commonly encountered social stimuli and convey information vital for social communication (Ellis and Young, 1998). Abnormalities in facial identity and expression recognition are well documented in psychiatric and neurological disorders including Autism Spectrum Disorders (ASDs), (Langdell,

http://dx.doi.org/10.1016/j.clinph.2014.09.015 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Feuerriegel D et al. The N170 and face perception in psychiatric and neurological disorders: A systematic review. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.09.015

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D. Feuerriegel et al. / Clinical Neurophysiology xxx (2014) xxx–xxx

1978; Boucher and Lewis, 1992) Bipolar Disorder, (Getz et al., 2003) Depression (Gur et al., 1992) and Schizophrenia (Walker et al., 1984; Feinberg et al., 1986) and have been identified in a wider range of disorders such as Attention-Deficit Hyperactivity Disorder (ADHD), (Corbett and Glidden, 2000) Bulimia Nervosa (Harrison et al., 2010) and Parkinson’s Disease (Jacobs et al., 1995). Identifying impairments in processing of information from faces can provide insight into the nature of social communication difficulties experienced in these disorders. The millisecond-level temporal resolution of electroencephalography (EEG) and magnetoencephalography (MEG) is well suited to investigating the time course of visual face processing in the brain. Waveforms indexing different stages of sensory and cognitive processing termed event-related potentials (ERPs) in EEG and event-related fields (ERFs) in MEG can be created by averaging over multiple stimulus presentations (Luck, 2005). A commonly investigated visual ERP component in face perception research is the N170 (Bentin et al., 1996). The N170 is defined as a negative peak occurring approximately 170 ms from stimulus onset, with longer latencies reported in young children (Taylor et al., 1999, 2001). The N170 is generally reported as larger (more negative) in response to faces than to other objects (Bentin et al., 1996; Rossion et al., 2000; Itier and Taylor, 2004). The N170 is generally right-lateralized to faces and bilateral to objects (Rossion et al., 2003) corresponding with higher responses to faces compared to other stimuli in the right fusiform gyrus (Kanwisher et al., 1997). Other evidence suggests that the N170 is larger to objects of visual expertise, with faces being an object in which most people are experts (Gauthier et al., 1999; Rossion et al., 2002). This component is also typically larger in amplitude to inverted faces (i.e. the face inversion effect), but stimulus inversion effects are generally not found for non-face objects (Itier et al., 2006). The N170 is measured at lateral parieto-occipital sites (Rossion and Jacques, 2008) but can be measured from frontocentral sites as a positive peak called the Vertex Positive Potential (VPP) (Botzel and Grusser, 1989; Jeffreys, 1989) which is thought to represent the same neural processes as the N170 (Joyce and Rossion, 2005). In MEG these processes are measured as a component termed the M170 (Liu et al., 2000). The N170 is theorized to represent multiple sources of neural activity (Rossion and Jacques, 2008; Rossion and Caharel, 2011; Sadeh et al., 2010) but predominately represents the integration of face or object features into a meaningful percept, (Jacques and Rossion, 2009) including the spatial configuration of features (i.e. configural processing) (Eimer, 1998, 2000b) and discrimination of individual face identities (Jacques et al., 2007). Modulations of N170 amplitude by facial expression have been reported in the literature (Batty and Taylor, 2003; Caharel et al., 2005; Eimer and Holmes, 2007) suggesting that activity during this time period can index facial expression discrimination, however recent evidence suggests differences in N170 amplitudes by facial expression instead represent an overlapping early posterior component that affects N170 measurements (Rellecke et al., 2012, 2013). There has been extensive clinical research on the N170 and related components (i.e. M170 and VPP) in disordered populations compared to healthy controls. Such studies typically investigate a single clinical sample and ERP differences are interpreted as characteristic of that diagnosis. However, there has been no systematic evaluation of N170/M170/VPP research within disorders or across different disordered populations. As social dysfunction is either diagnostic or characteristic of most psychiatric and neurological disorders, a review across disorders is necessary to determine whether N170 abnormalities are specific to a certain disorder or whether they index facial recognition impairments common across diagnoses (Luck et al., 2011). In addition, systematically reviewing

studies within a disorder can provide an unbiased account of published literature and identify clinical characteristics and experimental design factors that contribute to abnormal N170/M170/ VPP measures between and within disordered groups. Identifying the conditions under which disorder-specific abnormalities occur could inform the development of diagnostic and treatment monitoring tests using these ERP components as biomarkers. This review aimed to systematically evaluate existing research on the N170, M170 and VPP in psychiatric and neurological disorders as compared to healthy controls. These data will enable us to determine whether abnormal neural activity indexed by the N170/ M170/VPP accompanies face recognition deficits, and whether abnormalities are specific to a disordered group. A further aim is to explore discrepancies between results and make suggestions to guide future clinical face processing research. 2. Methods 2.1. Search strategy and selection criteria Article selection was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Moher et al., 2009). A flowchart of this selection process is displayed in Fig. 1. PubMed and PsychINFO databases were searched on February 3, 2014. The search terms used were: (face OR facial OR faces) AND (ERP OR ERF OR ‘‘event related⁄’’ OR ‘‘event-related⁄’’ OR ‘‘evoked potential⁄’’ OR ‘‘evoked-potential⁄’’ OR ‘‘evoked response⁄’’ OR ‘‘evoked-response⁄’’) AND (VPP OR ‘‘vertex-positive’’ OR ‘‘vertex positive’’ OR ‘‘N170’’ OR ‘‘N-170’’ OR ‘‘N1’’ OR ‘‘N-1’’ OR negative OR negativity OR ‘‘M170’’ OR ‘‘M-170’’ OR ‘‘M1’’ OR ‘‘M-1’’). Searches were limited to English language publications from the year 1989 (the year that the earliest discovered ERP component of interest was named) (Botzel and Grusser, 1989; Jeffreys, 1989). Duplicates were removed. A total of 1251 unique articles were identified. Articles were retained if they measured the N170, M170 or VPP ERP/ERF components, measured ERP/ERFs to visual presentations of singular real or schematic face stimuli, provided comparison data with a healthy control group and defined participant groups based on psychiatric or neurological diagnoses. Only peer-reviewed original research articles were included. Studies based on subclinical diagnoses or diagnoses of someone other than participants (e.g. family members of someone with Schizophrenia) were excluded. Case study methodologies without group-level statistics were excluded. Articles were included if they employed ERP component measures of peak amplitude, mean amplitude or peak latency. ERP analyses using other measures exclusively (for example Topographic Analyses of Variance) were excluded. Studies that measured the N170 (not as the VPP) from frontal or central sites were excluded as the N170 is most appropriately measured at lateral parieto-occipital sites (Rossion and Jacques, 2008). Titles and abstracts were read by two of the authors. A total of 84 articles were selected to be read full-text. Of these, 67 articles were selected for review. The following data were extracted from all selected papers: sample size, age and gender distribution of participants, reference electrode, prestimulus fixation cross presence/ absence, ERP component measured, stimuli used, experimental task and N170/M170/VPP amplitude and latency measurements (to upright faces unless specified; specific facial expressions are denoted if they were associated with N170/M170 effects), and reported correlations between ERP measures and measures of symptoms, social cognition and task performance. Non-face object stimuli categories are generally used to test for preferential N170/ M170 responses to faces.



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Fig. 1. PRISMA flow diagram of the article screening and selection process. Article selection was conducted in accordance with PRISMA guidelines for reporting systematic reviews (Moher et al., 2009).

3. Results A total of 67 articles met inclusion criteria and were selected for review, which are summarized in Table 1. Of these, 63 measured the N170, 1 measured the M170 and 6 measured the VPP. Included studies compared one or more clinical groups against a control group. Disorders are categorized according to criteria of the DSM5 (American Psychiatric Association, 2013) and ICD-10 (World Health Organization, 1993) and their previous editions. Disorders included Attention-Deficit Hyperactivity Disorder (ADHD), Alcohol Dependence, Alzheimer’s Disease, Autism Spectrum Disorders (ASDs), Bipolar Disorder, Bulimia Nervosa, Fibromyalgia, Huntington’s Disease, Major Depressive Disorder, Parkinson’s Disease, Prosopagnosia, Schizophrenia and Social Phobia (13 disorder groups in total). The N170 and M170 components were measured from parietal and parieto-occipital regions corresponding to electrode locations P7/8, PO7/8, and PO9/10 of the extended international 10–20 system. The VPP was typically measured from sites FCz and Cz. ERP components were quantified using measures of peak amplitude (the most positive or negative point within the time range of the ERP component of interest), peak latency (the time from stimulus onset to the most positive or negative point within the defined

time window of interest) and mean amplitude (the average of activity within a predefined time window centered around the peak activity of an ERP component). Results are reviewed by disorder relative to the number of studies included per disorder. Results of between-group N170/M170/ VPP amplitude and latency comparisons for each disorder are displayed in Table 1. Results of individual studies are displayed in Table 2. 3.1. Autism Spectrum Disorders (ASDs) (23 studies) Between-group differences in N170 and VPP amplitudes or latencies to faces were not consistently reported in children or adults with ASDs in the 23 included studies. One investigation reported larger N170 amplitudes in ASDs (Gunji et al., 2009), while 2 studies found smaller amplitudes (Churches et al., 2012b; Webb et al., 2012). In O’Connor et al. (2005) smaller N170 amplitudes compared to controls were found in adults but not children with ASDs. The remaining eighteen studies did not find amplitude differences for the N170 (McPartland et al., 2004, 2011; Grice et al., 2005; Senju et al., 2005; Webb et al., 2006, 2010; O’Connor et al., 2007; Magnée et al., 2008, 2011; Wong et al., 2008; Akechi et al., 2010, 2014; Churches et al., 2010, 2012a; Batty et al.,


4


Table 1 Between-groups results by disorder. Numbers in each column refer to the number of studies reporting that result. All results refer to N170, M170 or VPP responses to upright faces relative to controls (unless specified). Total numbers of included studies for each disorder are in parentheses. Disorder

Amplitude Clinical < Controls

Autism Spectrum Disorders (23) Schizophrenia (20) Bipolar Disorder (5) Major Depressive Disorder (4) Alcohol Dependence (4) Alzheimer’s Disease (3) Attention-Deficit Hyperactivity Disorder (3) Social Phobia (3) Parkinson’s Disease (2) Prosopagnosia (2) Bulimia Nervosa (1) Fibromyalgia (1) Huntington’s Disease (1)

4 16 3 1 1 2 1

Peak latency Clinical > Controls

1 1

No group differences 19 4 2 3 3 1 1

Clinical < Controls

Clinical > Controls

No group differences

1

6 3 2

17 7 1 3 2 1 2

2 2 2

1 1

2 1

1 2 1 1

1

2011; Hileman et al., 2011; Tye et al., 2013; Cygan et al., 2014) or VPP (Akechi et al., 2010). Slower N170 peak latencies compared to controls were reported in six studies (McPartland et al., 2004, 2011; O’Connor et al., 2005, 2007; Batty et al., 2011; Hileman et al., 2011). However, 17 studies did not report peak latency differences for the N170 or VPP (Grice et al., 2005; O’Connor et al., 2005; Senju et al., 2005; Webb et al., 2006, 2010, 2012; Magnée et al., 2008; Wong et al., 2008; Gunji et al., 2009; Akechi et al., 2010, 2014; Churches et al., 2010; Magnée et al., 2011; Tye et al., 2013; Cygan et al., 2014). Several within-group measures compared responses to stimuli and task manipulations. Churches et al. (2010) reported an attention-related N170 amplitude enhancement for task-relevant faces in controls, whereas this was not found in Asperger’s Syndrome. McPartland et al. (2004) and Webb et al. (2012) found typical face inversion-related N170 amplitude enhancement in adults with ASDs, whereas McPartland et al. (2011) reported smaller amplitudes to inverted compared to upright faces in children with ASDs. McPartland et al. (2004) reported increased latencies to inverted compared to upright faces in controls, but not in participants with ASDs. Akechi et al. (2010) presented angry and fearful faces with direct and averted gaze and reported that N170s in controls were larger with direct gaze for anger and averted gaze for fearful faces, however this was not found in ASDs. No group differences by gaze were reported when using neutral faces (Tye et al., 2013). Larger N170s were found during a face-likeness judgment task than a roundness judgment task in controls only (Akechi et al., 2014). Group differences were also found in response to non-face objects. In Churches et al. (2012a) smaller amplitudes to non face-like objects were reported in Asperger’s Syndrome, however group differences were not found to face-like objects. In O’Connor et al. (2007) controls displayed faster peak latencies to faces than non-face objects but latency differences were not found in participants with Asperger’s Syndrome. Webb et al. (2006) measured the prN170: an ERP component theorized to be the precursor of the N170 in very young children. Children with ASDs showed smaller prN170s to non-face objects. PrN170 peak latencies in control children were faster to faces than non-face objects whereas the opposite was found in children with ASDs. Scores on the Social Communication Questionnaire (Berument et al., 1999) were not correlated with N170 amplitude (Hileman et al., 2011) or latency (Akechi et al., 2014) but lower scores were associated with reduced N170 lateralization (Tye et al., 2013). N170 amplitudes were not correlated with scores on the Autism Diagnostic Observation Schedule (Lord et al., 1989; Hileman

et al., 2011). Better facial recognition performance was associated with faster N170 peak latencies in one study (McPartland et al., 2011) and slower peak latencies in another, (McPartland et al., 2004) while one investigation found no relationship (Webb et al., 2012). Differences in peak latency between upright and inverted faces correlated with higher social functioning scores (Webb et al., 2012).

3.2. Schizophrenia (20 studies) Smaller N170 and VPP amplitudes, but not slower latencies, were consistently reported in Schizophrenia. In thirteen studies N170 or VPP amplitudes were smaller in Schizophrenia (Herrmann et al., 2004; Johnston et al., 2005; Onitsuka et al., 2006, 2009; Caharel et al., 2007; Turetsky et al., 2007; Lynn and Salisbury, 2008; Onitsuka et al., 2009; Lee et al., 2010; Ibáñez et al., 2012a,b; Kirihara et al., 2012; Tsunoda et al., 2012; Jetha et al., 2013). One study found smaller amplitudes at trend level (Wynn et al., 2013) and one other found smaller N170 amplitudes during a facial expression task but not a gender task (Bediou et al., 2007). Campanella et al. (2006) administered the Positive and Negative Symptoms Scale (PANSS) (Kay et al., 1987) to participants with Schizophrenia. Participants with high PANSS scores exhibited smaller N170 amplitudes to faces compared to controls and low PANSS score participants, which did not differ. The remaining four investigations reported no N170 or VPP amplitude differences (Lee et al., 2007; Wynn et al., 2008; Ramos-Loyo et al., 2009; Komlosi et al., 2013). N170 peak latencies were delayed to faces in Schizophrenia in three studies, (Caharel et al., 2007; Lee et al., 2010; Wynn et al., 2013) however seven studies did not find N170 or VPP latency differences (Johnston et al., 2005; Campanella et al., 2006; Lee et al., 2007; Turetsky et al., 2007; Wynn et al., 2008; Obayashi et al., 2009; Tsunoda et al., 2012). Within-subjects stimuli manipulations also revealed group differences in Schizophrenia. N170 amplitude differences by facial expression were found in controls but not in participants with Schizophrenia in four studies (Campanella et al., 2006; Lynn and Salisbury, 2008; Ibáñez et al., 2012a,b; Kirihara et al., 2012). However, the same amplitude modulations by facial expression were found for both groups in two other investigations (Lee et al., 2007, 2010). Others reported no amplitude differences by facial expression in either group for the N170 (Bediou et al., 2007) or VPP (Johnston et al., 2005).


Author

Year

Participant demographics

Autism Spectrum Disorders (ASDs) Akechi et al. 2014 ASD: n = 15 (14 males, mean age 15.0 ± 1.9). Controls: n = 14 (12 males, mean age 15.0 ± 2.1) Akechi et al. 2010 ASD: n = 14 (10 males, mean age 13.7 ± 2.3). Controls: n = 14 (8 males, mean age 12.3 ± 2.1) Batty et al. 2011 ASD: n = 15 (13 males, mean age 10.6 ± 3.3). Controls: n = 15 chronological age matched (mean age 10.5 ± 3.2), n = 15 verbal age matched (mean age = 7.7 ± 3.8) Churches et al. 2012a ASD: n = 10 (all male, mean age 30.6 ± 6.2). Controls: n = 13 (all male, mean age 29.5 ± 4.8) Churches et al. 2012b ASD: n = 11 (all male, mean age 31.8 ± 6.9). Controls: n = 11 (all male, mean age 30.1 ± 4.9) Churches et al. 2010 ASD: n = 15 (all male, mean age 31.4 ± 6.7). Controls: n = 15 (all male, mean age 29.3 ± 4.6) Cygan et al. 2014 ASD: n = 23 (mean age 20.4 ± 2.8). Controls: n = 23 (mean age 20.8 ± 2.7) Grice et al. 2005 ASD: n = 10 (9 males, mean age 5.1). Controls: n = 10 (9 males, mean age 5.3) Gunji et al. 2009 ASD: n = 8 (7 males, mean age 10.8 ± 2.9). Controls: n = 9 (4 males, mean age 11.3 ± 2.3) Hileman et al.

2011

ASD: n = 27 (23 males, mean age 13.3 ± 2.8). Controls: n = 22 (17 males, mean age 14.4 ± 2)

Stimuli

Task

Fixation cross

ERP component

Reference electrode

N170/M170/VPP results Amplitude

Latency

Reported correlations

Face-like objects, non face-like objects

Face-likeness and roundness judgement tasks

Yes

N170

Nose

=

=

Angry and fearful faces of direct and averted gaze

Emotion discrimination task

Yes

N170, VPP

Linked earlobes

=

Angry, disgusted, happy, sad, surprised, fearful and neutral faces, cars, butterflies, planes Faces, face-like objects, non face-like objects

Non-face object detection task

No

N170

Average

N170: Interaction of gaze and facial expression in controls but not ASD. VPP: No group differences =

Oddball task

No

N170

Nose

ASD < controls to nonfacelike objects

=

Unfamiliar faces

Identity discrimination task

No

N170

Nose

ASD < controls

=

Neutral faces, chairs

Stimulus repetition detection task

No

N170

Nose

Larger N170s to attended faces in controls but not ASD

=

Own, closeother’s famous and unknown faces and words Faces of direct and averted gaze

Stimulus detection task

Yes

N170

Linked earlobes

=

=

No task

No

N170

Average

=

=

Self, familiar and unfamiliar faces, scrambled faces, non-face objects Upright and inverted faces (angry, fearful, happy, neutral), vehicles

Non-face object detection task

No

N170

Average

ASD > controls

=

Gender and orientation discrimination tasks

No

N170

Average

=

Controls < ASD

N170 latencies not correlated with SCQ scores

Chronological agematched controls < ASD. Verbal age-matched controls = ASD


In ASDs N170 amplitudes not correlated with SCQ, ADOS or Theory of Mind scores. In controls larger N170 amplitudes correlated with higher SCQ and ADOS scores (continued on next page)

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Table 2 Results of individual studies by disorder. Disorders are organized by the number of included studies (most studies to least studies).

6

Author

Year

Magnée et al.

2011

Magnée et al.

2008

McPartland et al.

2011

McPartland et al.

2004

O’Connor et al.

2007

O’Connor et al. (Children)

2005

O’Connor et al. (Adults)

2005

Senju et al.

2005

Tye et al.

2013

Webb et al.

2012


Stimuli

ASD: n = 23 (all male, mean age 22.7 ± 3.8). Controls: n = 24 (all male, mean age 22.7 ± 1.9) ASD: n = 12 (all male, mean age 21.5 ± 4). Controls: n = 13 (all male, mean age 23.0 ± 2.9) ASD: n = 32 (mean age 11.2 ± 3.4). Controls: n = 17 (mean age 12.6 ± 2.4)

Happy and fearful faces

ASD: n = 9 (8 males, mean age 21.2 ± 8.3). Controls: n = 14 (13 males, mean age 24.6 ± 6.3) ASD: n = 15 (all male, mean age 23.5 ± 5.2). Controls: n = 15 (all male, mean age 23.8 ± 4.4)

ASD: n = 15 (all male, mean age 11.6 ± 1.9). Controls: n = 15 (all male, mean age 11.2 ± 1.8) ASD: n = 15 (13 males, mean age 24.6 ± 8.8). Controls: n = 15 (13 males, mean age 24.8 ± 8.7) ASD: n = 11 (all male, mean age 12.1). Controls: n = 15 (13 males, mean age 12.1)

ASD: n = 19 (all male, mean age 11.7 ± 1.7). Controls: n = 26 (all male, mean age 10.6 ± 1.8) ASD: n = 32 (30 males, mean age 23.1 ± 6.9). Controls: n = 32 (29 males, mean age 23.7 ± 6.7)

Task

Fixation cross

ERP component

Reference electrode


Latency


Oddball task

Yes

N170

Average

=

=

Happy and fearful faces

Gender discrimination task

No

N170

Average

=

=

Upright and inverted faces and houses

Stimulus repetition detection task

Yes

N170

Average

ASD < Controls

Controls < ASD

Upright and inverted faces and furniture, butterflies

Butterfly detection task

No

N170

Average

=

Controls < ASD for faces but not furniture

Neutral and sad faces, face parts (eyes, mouth), non-face objects (vehicles, furniture) Angry, happy, neutral, sad and scared faces


Yes

N170

Average

=

Controls < ASD to face parts but not to faces or non-face objects

Emotion identification task

Yes

N170

Average

=

=

Angry, happy, neutral, sad and scared faces

Emotion identification task

Yes

N170

Average

ASD < controls

Controls < ASD

Laterally averted female faces with direct, averted and downward gazes Upright and inverted faces of direct and averted gaze

Gaze discrimination task

Yes

N170

Linked earlobes

=

=

Object detection task (during fixation)

No

N170

Average

=

=

SCQ scores correlated with reduced N170 lateralisation

Upright and inverted faces and houses, scrambled faces

Scrambled face detection task

Yes

N170

Average

ASD < controls

=

N170 latencies not correlated with facial recognition performance. Upright/inverted face N170 latency difference correlated with higher social functioning scores

Faster N170 latencies correlated with face recognition performance. In ASDs larger N170 amplitudes to inverted faces correlated with face recognition performance In ASDs face recognition memory correlated with slower N170 peak latencies in left hemisphere



Table 2 (continued)

2010

Webb et al.

2006

Wong et al.

2008

Schizophrenia Bediou et al.

2007

Caharel et al.

2007

Campanella et al.

2006

Herrmann et al.

2004

Ibáñez et al.

2012b

Jetha et al.

2013

Johnston et al.

2005

ASD: n = 29 (27 males, mean age 22.4 ± 6.1). Controls: n = 28 (26 males, mean age 24 ± 7) ASD: n = 45 (mean age 3.7 ± 0.4). Controls: n = 18 (mean age 3.7 ± 0.6) ASD: n = 10 (all male, mean age 8.5 ± 1.5). Controls: n = 12 (all male, mean age 8.5 ± 1.4)

Familiar and unfamiliar faces, houses

House detection task

Yes

N170

Average

=

=

Familiar and unfamiliar faces and nonface objects Angry, happy, fearful, neutral and sad faces

No task

No

prN170

Average

Controls: faces = non-face objects. ASD: faces > nonface objects

Controls: faces < nonface objects. ASD: nonface objects < faces

Gender and emotion discrimination tasks

Yes

N170

Average

=

=

Schizophrenia: n = 10 (6 males, mean age 27.8 ± 8.4). Controls: n = 10 (4 males, mean age 27.5 ± 4.6) Schizophrenia: n = 18 (8 males, mean age 37.7 ± 8.3). Controls: n = 18 (9 males, mean age 36.3 ± 9.8)

Disgusted, fearful, happy, neutral and surprised faces


Yes

N170

Nose

Schizophrenia < controls in emotion task but not gender task

Self, familiar and unfamiliar faces (disgusted, neutral and smiling) Fearful, happy, neutral and sad faces

Familiarity judgement task

Yes

N170

Average

Schizophrenia < controls

Controls < Schizophrenia

N170 measures not correlated with disease duration, age of onset, medication or task performance

Oddball task

No

N170

Average

High PANSS < Low PANSS = controls for neutral faces. Fearful > happy and sad faces in controls but not in Schizophrenia

=

Smaller N170 amplitudes correlated with PANSS positive symptoms

Faces, buildings

Stimuli category discrimination task

No

N170

Average

Schizophrenia < controls to faces but not buildings

Angry and happy faces

Valence judgement task

Yes

N170

Average

Angry, fearful, happy and neutral faces

No task

Yes

N170

Average

Schizophrenia < controls for happy faces only. Happy > angry faces for controls but not Schizophrenia group Schizophrenia < controls

Angry, disgusted, fearful, happy, neutral, sad and surprised faces


Yes

VPP

Nose


Schizophrenia: n = 14 (9 males): 7 low PANSS scores (mean age 49 ± 12), 7 high PANSS scores (mean age 47 ± 12). Controls: n = 7 (mean age 48) Schizophrenia: n = 24 (19 males, mean age 32.2 ± 10). Controls: n = 28 (12 males, mean age 33.8 ± 13) Schizophrenia: n = 13 (9 males), mean age 38.6 ± 12). Controls: n = 13 (9 males, mean age 39.5 ± 14.6) Schizophrenia: n = 40 (28 males, mean age 42.2 ± 6.4). Controls: n = 39 (27 males, mean age 39.3 ± 7.8)

Schizophrenia: n = 12 (10 males, mean age 34 ± 8.3). Controls: n = 15 (9 males, mean age 29.5 ± 7.3)

N170 amplitudes not correlated with PANSS scores or medication

=


Shyness positively correlated with larger N170 amplitudes for angry and fearful faces in Schizophrenia. Shyness correlated with smaller N170 amplitudes to angry and happy faces in controls Larger VPP amplitudes correlated with better task performance. VPP amplitudes positively correlated with BOLD activation in right fusiform gyrus, right amygdala and left superior temporal sulcus (continued on next page) 7


Webb et al.

8

Author

Year


Stimuli

Schizophrenia: n = 24 (13 males, mean age 34.2 ± 10.3). Controls: n = 24 (13 males, mean age 33.2 ± 9.8) Schizophrenia: n = 15 (all male, mean age 34.5 ± 6.8). Controls: n = 15 (all male, mean age 31.9 ± 9.7)

Fearful and neutral faces, phaserandomised faces Angry, disgusted, fearful, happy neutral, sad and surprised faces, cars, butterflies Fearful, happy and neutral faces

Komlósi et al.

2013

Kirihara et al.

2012

Lee et al.

2010

Schizophrenia: n = 38 (16 males, mean age 30.2 ± 10.3). Controls: n = 38 (18 males, mean age 34.2 ± 11.9)

Lee et al.

2007

Lynn and Salisbury

2008

Schizophrenia: n = 11 (7 males, mean age 37.5 ± 8.5). Controls: n = 10 (4 males, mean age 26.9 ± 6.8) Schizophrenia: n = 24 (15 males, mean age 35.5 ± 9.4). Controls: n = 8 (5 males, mean age 41 ± 7.9)

Obayashi et al.

2009

Schizophrenia: n = 16 (all male, mean age 32.9 ± 10). Controls: n = 23 (all male, mean age 30.1 ± 4.5)

Onitsuka et al.

2009

Onitsuka et al.

2006

Ramos-Loyo et al.

2009

Schizophrenia: n = 17 (all male, mean age 42.4 ± 10.8). Controls: n = 13 (all male, mean age 43.3 ± 11.2) Schizophrenia: n = 20 (all male, age range 20–55). Controls: n = 16 (all male, age range 20–55) Schizophrenia: n = 10 (all male, mean age 30.2 ± 7.3). Controls: n = 10 (all male, age range 18–45)

Task

Fixation cross

ERP component

Reference electrode

N170/M170/VPP results

Facial expression judgement task

Yes

N170

Average

=

N170 amplitude not correlated with PANSS scores, duration of illness, task performance or medication


Yes

N170

Average

Schizophrenia < controls. Emotional > neutral faces in controls but not in Schizophrenia

Larger N170 amplitudes at right hemisphere electrodes correlated with higher extraversion

Emotional face detection task

Yes

N170

Average



Fearful, happy and neutral faces

Emotional face detection task

Yes

N170

Vertex

=

=

Angry, disgusted, fearful, happy, neutral and sad faces, cars, butterflies Unfiltered and high or low spatial frequency filtered faces (fearful, happy and neutral expressions), houses, shoes Neutral faces

Neutral face and butterfly detection tasks

Yes

N170

Average

Schizophrenia < controls Differences by facial expression in controls but not Schizophrenia

Shoe detection task

Yes

N170

Nose

Schizophrenia < controls for faces but not houses. Differences by spatial frequency in controls but not Schizophrenia

Gender discrimination task

Yes

N170

Average


N170 amplitudes not correlated with positive, negative or general PANSS scores

Neutral faces, hands, cars and butterflies


Yes

N170

Average

Schizophrenia < controls for faces and hands but not cars

Smaller N170s correlated with less gray matter volume in bilateral fusiform gyrus in Schizophrenia

Angry, disgusted, fearful, happy, neutral, sad and surprised faces

Emotional face and identity detection tasks

No

N170, VPP

Linked earlobes

=

Amplitude

Reported correlations Latency

=

N170 amplitudes and latencies not correlated with medication, illness duration, number of hospitalisations, onset age, PANSS positive of negative scores or task performance Higher PANSS scores correlated with longer N170 latencies for happy and neutral faces. N170 amplitude not correlated with PANSS scores N170 amplitudes not correlated with task performance or medication

Smaller N170 amplitudes correlated with lower general functioning. N170 amplitude not correlated with positive or negative symptoms



Table 2 (continued)

Smaller N170 amplitudes correlated with more social dysfunction in Schizophrenia. N170 amplitudes not correlated with positive or negative symptoms Smaller N170 amplitudes to sad faces correlated with delusional symptoms. N170 amplitudes not correlated with other positive or negative symptoms or depression

2012


Upright and inverted faces, cars, butterflies


Yes

N170

Nose

Schizophrenia < controls to faces but not cars. Inverted faces > upright faces in controls only

Turetsky et al.

2007


Happy, neutral and sad faces


No

N170

Average


Wynn et al.

2013

Gender, emotion and object height discrimination tasks Gender, emotion and object height discrimination tasks

N170

Nose

Schizophrenia < controls at trend level (p = 0.08)


2008

Afraid, angry, ashamed, happy, sad and surprised faces, buildings Afraid, angry, ashamed, happy, sad and surprised faces, buildings

No

Wynn et al.

Schizophrenia: n = 30 (20 males, mean age 45.3 ± 9.4). Controls: n = 30 (19 males, mean age 40.6 ± 10.4) Schizophrenia: n = 26 (21 males, mean age 43.9 ± 10.2). Controls: n = 27 (24 males, mean age 39.7 ± 9.6)

Yes

N170

Nose

=

=

Bipolar Disorder (BD) Degabriele and Lagopoulos

2012

Happy and sad faces

Emotion-based go/nogo task

Yes

VPP

Average

=

Controls < BD

VPP measures not correlated with depression or anxiety

Degabriele et al.

2011

Happy and sad faces

Emotion-based go/nogo task

Yes

N170

Average

BD < controls

=

N170 measures not correlated with reaction times

Ibáñez et al.

2012a

BD: n = 18 (mean age 39.9 ± 11). Controls: n = 18 (mean age 39.9 ± 13.3) BD: n = 18 (mean age 39.9 ± 11). Controls: n = 18 (mean age 39.9 ± 13.3) BD: n = 13 (8 males, mean age 40.1 ± 2.5). Controls: n = 13 (8 males, mean age 39.3 ± 2.5)

Happy and angry faces, words


Yes

N170

Average

BD < controls. Happy faces > angry faces in controls but not BD

Sokhadze et al.

2011

Contempt, disgusted, happy, neutral and sad faces

Gender detection task

No

N170

Average

BD < controls for happy and contempt faces. BD only: happy and disgust faces < neutral faces

BD < controls for disgust, neutral and sad target faces

Wynn et al.

2013

BD: n = 9 (3 males, mean age 41.8 ± 15.9). Controls: n = 9 (4 males, mean age 31.4 ± 11.1) BD: n = 57 (32 males, mean age 44.9 ± 10.4). Controls: n = 30 (19 males, mean age 40.6 ± 10.1)

Afraid, angry, ashamed, happy, sad and surprised faces, buildings

Gender, emotion and object height discrimination tasks

Yes

N170

Nose

=

Controls < BD

Depression: n = 24 (10 males, mean age 26.6 ± 4.2). Controls: n = 24 (8 males, mean age 25.5 ± 3.4)

Happy, neutral and sad faces

Facial expression intensity rating task

Yes

N170

Average

Depression < controls

=

Major Depressive Disorder Dai and Feng 2012

N170 stimulus type amplitude differences (faces – words) correlated with Theory of Mind scores in BD. N170 amplitude valence differences (positive – negative) correlated with Theory of Mind scores


N170 not correlated with depression or task performance

(continued on next page)

9


=

Tsunoda et al.

10

Author

Year


Stimuli

Depression: n = 19 (9 males, mean age 39 ± 16.6). Controls: n = 25 (7 males, mean age 40.8 ± 13.2) Depression: n = 53 (24 males, mean age 40.7 ± 11.8). Controls: n = 43 (20 males, mean age 36.5 ± 9.8) Depression: n = 12 (7 males, mean age 41.7 ± 8.4). Controls: n = 12 (7 males, mean age 41.8 ± 9.1)

Angry, fearful and neutral faces

Task

Fixation cross

ERP component

Reference electrode

N170/M170/VPP results

No task

Yes

VPP

Linked Mastoids

=

Happy, neutral, sad and surprised faces

Surprised face detection task

No

N170, VPP

Linked Mastoids

=

=

Faces morphed along gender and emotion (neutral to angry/happy/ sad)


Yes

N170

Average

=

=

No correlations between N170 measures and medication, state/trait anxiety or depression. Faster N170 latencies correlated with increased performance on the emotion task and faster mean RTs. Increased N170 amplitudes correlated with longer RTs N170 measures not correlated with medication, state/trait anxiety or depression. Faster N170 latencies correlated with increased performance on the emotion task and faster mean RTs. Increased N170 amplitudes correlated with longer RTs N170 not correlated with depression, anxiety or facial emotion discrimination performance

Amplitude

Reported correlations Latency

Foti et al.

2010

Jaworska et al.

2012

Maurage et al.

2008a

Alcohol Dependence Maurage et al.

2008a

Alcohol Dependence: n = 12 (7 males, mean age 41.8 ± 6.7). Controls: n = 12 (7 males, mean age 41.8 ± 9.1)

Faces morphed along gender and emotion (neutral to angry/happy/ sad)


Yes

N170

Average

=

Controls < Alcohol Dependence only during an emotion task

Maurage et al.

2008b

Neutral, happy and angry faces

Emotion judgement task

No

N170

Average

=

=

Maurage et al.

2008c

Faces morphed between anger and disgust

Oddball task

Yes

N170

Average

=

=

Maurage et al.

2007

Alcohol Dependence: n = 15 (10 males, mean age 46.7 ± 12). Controls: n = 15 (10 males, mean age 42.1 ± 14.2) Alcohol Dependence: n = 15 (7 males, mean age 49.1 ± 8). Controls: n = 15 (8 female, mean age 48.1 ± 7.2) Alcohol Dependence: n = 10 (9 males, mean age 46.9 ± 11.4). Controls: n = 10 (9 males, mean age 43.9 ± 9.5)

Neutral, happy, sad and fearful faces

Oddball task

No

N170

Average

Alcohol Dependence < Controls

Controls < Alcohol Dependence

Alzheimer’s Disease Cheng and Pai

2010

AD/MCI: n = 20 (12 males, mean age 71.1 ± 8.2). Controls: n = 17 (9 males, mean age 69.5 ± 9.6)

Famous, personally familiar and unfamiliar faces and scenes

Familiarity judgement task

Yes

N170

Linked Mastoids

AD/MCI < controls

=

N170 not correlated with depression or medication



Table 2 (continued)

Famous and unfamiliar faces (happy and neutral expressions) Angry and neutral faces

Familiarity and facial expression judgement tasks Emotion discrimination task

No

N170

Nose

AD/MCI < controls

Yes

N170

Average

=

ADHD: n = 10 (9 males, mean age 33.1 ± 3.6). Controls: n = 10 (9 males, mean age 33.0 ± 3.8) ADHD: n = 18 (all male, mean age 10.5 ± 1.9). Controls: n = 26 (all male, mean age 10.6 ± 1.8) ADHD: n = 51 (mean age 13.8 ± 2.3). Controls: n = 51 (mean age 13.1 ± 2.4)

Happy and angry faces


No

N170

Average

ADHD < controls for happy but not angry faces

Upright and inverted faces of direct and averted gaze

Object detection task (during fixation)

Yes

N170

Average

=

=

Fearful, angry, sad, disgusted, happy and neutral faces

No task

Yes

N170

Linked Mastoids

ADHD > controls

=

Whole sample: mean age 23.2 ± 3.4. Social Phobia: n = 18 (8 males). Controls: n = 16 (7 males) Whole sample: mean age 23 ± 3.6. Social Phobia: n = 15 (7 males). Controls: n = 15 (7 males)

Angry, happy and neutral faces


No

N170

Average

Social Phobia > controls to angry faces in an emotion task

=

1 neutral schematic face and morphs between neutral and angry, happy and sad schematic faces Red and blue schematic faces (angry, happy and neutral expressions)

Emotion classification task

No

N170

Average

=

Emotional Stroop task

No

N170

Average

=

Angry, disgusted, fearful, happy, neutral and sad faces

Emotion recognition task, passive viewing

Yes

N170

Average

=

2012

Schefter et al.

2013

ADHD Ibáñez et al.

2011

Tye et al.

2013

Williams et al.

2008

Social Phobia Kolassa and Miltner

2006

Kolassa et al.

2009

Kolassa et al.

2007

Total sample: mean age 23.2 ± 3.5. Social phobia: n = 17 (8 males). Controls: n = 16 (7 males)

Parkinson’s Disease Wieser et al.

2012

Parkinson’s Disease: n = 18 (13 males, mean age 62.9 ± 9.9). Controls: n = 13 (9 males, mean age 63.2 ± 8.7)

aMCI > controls

Faster N170 latencies correlated with faster RTs

N170 amplitude valence discrimination (happy–angry) correlated with Theory of Mind scores SCQ scores correlated with reduced N170 lateralisation. N170 measures not correlated with inattention or hyperactivity-impulsivity Larger N170s at right hemisphere correlated with higher emotional liability (for N170s to angry faces) and oppositional behaviour (for N170s to fearful faces) Social phobia and anxiety scores correlated with larger right N170s to angry faces in social phobia (but not controls)


(continued on next page)

11


AD/MCI: n = 12 (all female, mean age 81.8 ± 9.2). Controls: n = 15 (4 males, mean age 83.5 ± 8.1) AD/MCI: n = 15 (4 males, mean age 67.1 ± 6.2). Controls: n = 17 (7 males, mean age 68 ± 5.2)

Saavedra et al.

12

Author

Yoshimura et al.

Year

2005


Stimuli

Parkinson’s Disease: n = 9 (7 males, mean age 69.5 ± 8.9). Controls: n = 10 (all male, mean age 61.3 ± 6.9)

Fearful, neutral and surprised faces

Prosopagnosia (Congenital/Developmental) Rivolta et al. 2012 Prosopagnosia: n = 6 (3 males, mean age 42.7 ± 13.8). Controls: n = 11 (6 males, mean age 37.3 ± 11.2). Towler et al. 2012 Prosopagnosia: n = 16 (4 males, mean age 40 ± 12.2). Controls: n = 16 (9 males, mean age 40)

Bulimia Nervosa Kühnpast et al.

Fibromyalgia González-Roldan et al.

Task

Fixation cross

ERP component

Reference electrode


Latency


Oddball task

No

N170

Right earlobe

=

=

Familiar and unfamiliar faces and scenes

Target detection task

Yes

M170

N/A

=

Upright and inverted fearful and neutral faces, upright houses

One-back task

No

N170

Linked earlobes

For younger adult controls inverted faces > upright faces but not in Prosopagnosia

Inverted faces > upright faces in controls but not Prosopagnosia

2012

Bulimia Nervosa: n = 13 (all female, mean age 24.6 ± 7.1). Controls: n = 13 (all female, mean age 25.4 ± 3.2)

Angry, fearful, happy and neutral faces

No task

Yes

N170

Linked Mastoids

Bulimia Nervosa < controls for angry faces only

=

2013

Fibromyalgia: n = 20 (mean age 53.4 ± 8.1). Controls: n = 20 (mean age 52.7 ± 9.9)

Anger, happiness, neutral and pain faces

Recognition task

Yes

N170

Average

=

=

HD: n = 11 (8 males, mean age 55.6 ± 7.1). Controls: n = 11 (8 males, mean age 56.8 ± 9.8)

Angry, disgust, happy and neutral faces, scrambled faces

Emotion identification and intensity rating tasks

Yes

N170

Average

HD < Controls. Face > Scrambled face in controls but not in HD

Huntington’s Disease (HD) Croft et al. 2014

N170 face/non-face and upright/inverted face amplitude differences positively correlated with facial recognition ability No correlation between face inversion effect and face recognition ability. Larger N170 amplitude face inversion effect correlated with better target detection of upright stimuli and larger performance deficits for inverted faces in prosopagnosics Larger N170 amplitudes correlated with higher performance in an emotion categorization task

N170 amplitudes not correlated with disease symptoms



Table 2 (continued)


Smaller N170 amplitudes were found to non-face objects (buildings and cars) compared to controls in two reports (Herrmann et al., 2004; Lynn and Salisbury, 2008) but not in three others (Onitsuka et al., 2006; Obayashi et al., 2009; Tsunoda et al., 2012). N170 amplitudes were larger in response to faces compared to cars in controls but not in Schizophrenia (Onitsuka et al., 2006; Tsunoda et al., 2012). Obayashi et al. (2009) altered the spatial frequency information in presented faces and reported N170 amplitude modulations by spatial frequency information in controls only. Peak latency differences were not found for faces of any spatial frequency band. Tsunoda et al. (2012) presented upright and inverted faces and reported face inversion effects in controls but not in Schizophrenia. Onitsuka et al. (2009) employed a neural adaptation paradigm and reported reduced N170s to repeated faces in the right hemisphere in controls, but in the left hemisphere in Schizophrenia. In Schizophrenia larger N170 amplitudes were correlated with better social functioning, (Obayashi et al., 2009; Tsunoda et al., 2012) higher scores on extraversion (Kirihara et al., 2012) and lower scores on shyness (Jetha et al., 2013). Two studies found correlations between N170 measures and positive and negative symptoms (Campanella et al., 2006; Lee et al., 2007) and one found an association between N170 amplitude and delusional symptoms, (Turetsky et al., 2007) however seven others did not find any correlations between N170 measures and positive of negative symptoms (Herrmann et al., 2004; Caharel et al., 2007; Obayashi et al., 2009; Onitsuka et al., 2009; Lee et al., 2010; Tsunoda et al., 2012; Komlosi et al., 2013). N170 measures were not associated with medication (Herrmann et al., 2004; Lynn and Salisbury, 2008; Lee et al., 2010; Komlosi et al., 2013) or depression (Turetsky et al., 2007). Smaller VPP amplitudes were correlated with less BOLD activation in the right fusiform gyrus (Johnston et al., 2005). Smaller N170 amplitudes correlated with less gray matter volume in bilateral fusiform gyri in Schizophrenia (Obayashi et al., 2009). 3.3. Bipolar Disorder (5 studies) Two studies found smaller N170 or VPP amplitudes in Bipolar Disorder (Degabriele et al., 2011; Ibáñez et al., 2012a,b). Two others reported no amplitude differences (Degabriele and Lagopoulos, 2012; Wynn et al., 2013) and one reported smaller amplitudes in Bipolar Disorder to happy and contemptuous faces but not to sad, disgusted or neutral faces (Sokhadze et al., 2011). Slower N170 and VPP peak latencies in Bipolar Disorder were reported in two studies (Degabriele and Lagopoulos, 2012; Wynn et al., 2013). One found no differences (Degabriele et al., 2011) and one reported faster latencies in Bipolar Disorder to target faces of neutral, sad and disgust facial expressions (Sokhadze et al., 2011). Ibáñez et al. (2012a,b) reported modulations of N170 amplitude by facial expression in controls (happy faces > angry faces) but not in Bipolar Disorder. VPP amplitudes were not correlated with depression or anxiety scores (Degabriele and Lagopoulos, 2012). Larger differences in N170 amplitudes between positive and negative facial expressions correlated with higher scores on Theory of Mind tests (Ibáñez et al., 2012a,b).

13

N170 amplitudes did not correlate with medication dosage (Maurage et al., 2008a) or symptoms of depression (Maurage et al., 2008a; Dai and Feng, 2012) or anxiety (Maurage et al., 2008a). 3.5. Alcohol Dependence (4 studies) Smaller N170 amplitudes in alcohol dependent participants were reported in one investigation (Maurage et al., 2007). The other three did not report group amplitude differences (Maurage et al., 2008a,b,c). Alcohol dependent participants had slower N170 peak latencies to faces in two reports, (Maurage et al., 2007, 2008a) with no latency differences in two others (Maurage et al., 2008b,c). In Maurage et al. (2008a) slower N170 peak latencies were reported in Alcohol Dependence during a facial expression discrimination task but not during a gender discrimination task. Peak latencies differed by facial expression (happy < sad = fearful) in Alcohol Dependence but not in controls (Maurage et al., 2007). N170 measures were not correlated with depression scores, (Maurage et al., 2007, 2008a,c) state or trait anxiety (Maurage et al., 2008a,c) or medication (Maurage et al., 2007, 2008a). Earlier N170 latencies and smaller amplitudes correlated with improved facial emotion discrimination performance (Maurage et al., 2008a). 3.6. Alzheimer’s Disease (3 studies) Smaller N170 amplitudes in participants with Alzheimer’s Disease were reported in two of three studies (Cheng and Pai, 2010; Saavedra et al., 2012). Schefter et al. (2013) did not find N170 amplitude differences between controls and participants with Amnestic Mild Cognitive Impairment (aMCI; prodromal Alzheimer’s Disease), although smaller N170s were found to angry faces compared to neutral faces in the aMCI group only. No latency differences were found for Alzheimer’s Disease (Cheng and Pai, 2010) although slower peak latencies were reported in participants with aMCI (Schefter et al., 2013). Earlier N170 latencies were correlated with faster reaction times in an emotion discrimination task (Schefter et al., 2013). 3.7. Attention-Deficit Hyperactivity Disorder (ADHD) (3 studies) N170 amplitudes to faces were larger in children and adolescents with ADHD in one study (Williams et al., 2008) but not in another (Tye et al., 2013). Adults with ADHD exhibited smaller N170 amplitudes than controls to happy but not angry faces (Ibáñez et al., 2011). No peak latency differences were found between ADHD and control groups (Williams et al., 2008; Tye et al., 2013). Tye et al. (2013) reported larger N170s to inverted faces with averted compared to direct gaze in controls but not in ADHD. Larger N170 differences between facial expressions correlated with higher scores on Theory of Mind tests (Ibáñez et al., 2011). N170 amplitudes were not correlated with inattention and hyperactivity (Tye et al., 2013) but were associated with emotional liability and oppositional behavior (Williams et al., 2008). 3.8. Social Phobia (3 studies)

3.4. Major Depressive Disorder (4 studies) One of the four included studies found smaller N170 amplitudes in Major Depressive Disorder (Dai and Feng, 2012). Three investigations did not find amplitude or latency differences for the N170 or VPP (Maurage et al., 2008a; Foti et al., 2010; Jaworska et al., 2012).

Participants with Social Phobia exhibited larger N170 amplitudes than controls over right hemisphere electrodes to angry faces during a facial expression task, which correlated with higher scores of social phobia and anxiety (Kolassa and Miltner, 2006). Group differences were not observed during a gender task. However, group amplitude differences were not found in the other two


14


studies (Kolassa et al., 2007, 2009). No N170 peak latency differences were reported (Kolassa and Miltner, 2006). 3.9. Parkinson’s Disease (2 studies) No N170 amplitude differences were reported in Parkinson’s Disease (Yoshimura et al., 2005; Wieser et al., 2012). 3.10. Prosopagnosia (2 studies) N170 amplitude differences were not found to upright face or house stimuli (Towler et al., 2012). However, participants with Prosopagnosia did not show increased N170 amplitudes or latencies to inverted faces (i.e. the N170 face inversion effect) as reported in younger (but not older) controls. An investigation of the M170 found no amplitude differences to faces or scenes (Rivolta et al., 2012). Larger N170 differences between upright and inverted faces were correlated with holistic and facial feature discrimination performance (Rivolta et al., 2012) and target detection of upright face stimuli (Towler et al., 2012). 3.11. Bulimia Nervosa (1 study) Kühnpast et al. (2012) reported smaller N170 amplitudes in participants with Bulimia Nervosa to angry faces but not to happy, fearful or neutral faces. Group differences were not found for N170 peak latency. Larger N170 amplitudes correlated with higher performance in an emotion categorization task (Kühnpast et al., 2012). 3.12. Fibromyalgia (1 study) No differences in N170 amplitude or latency were reported in Fibromyalgia (Gonzalez-Roldan et al., 2013). 3.13. Huntington’s Disease (1 study) Croft et al. (2014) reported smaller N170 amplitudes in Huntington’s Disease. Controls displayed larger amplitudes to faces compared to scrambled faces, whereas no differences were found in Huntington’s Disease. N170 measures were not correlated with disease symptoms in Huntington’s Disease (Croft et al., 2014).

13 psychiatric or neurological disorders including ADHD, Alcohol Dependence, Alzheimer’s Disease, ASDs, Bipolar Disorder, Bulimia Nervosa, Fibromyalgia, Huntington’s Disease, Major Depressive Disorder, Parkinson’s Disease, Prosopagnosia, Schizophrenia and Social Phobia. In Schizophrenia there was consistent evidence of smaller amplitudes for the N170 and VPP to both emotional and nonemotional faces in a variety of tasks. In contrast, studies of ASDs did not find N170 abnormalities to upright faces. No N170 differences were found to faces in Fibromyalgia, Major Depressive Disorder, Parkinson’s Disease, Prosopagnosia and Social Phobia based on the small number of included reports. Investigations of ADHD, Alcohol Dependence, Alzheimer’s Disease and Mild Cognitive Decline, Bipolar Disorder, Bulimia Nervosa and Huntington’s Disease reported smaller N170 amplitudes and slower peak latencies to faces in patient groups, however the small number of included studies does not warrant strong conclusions. With the exception of Schizophrenia and ASDs all reports of smaller amplitudes or slower latencies were found when using emotional face stimuli, indicating impairment in facial affect processing rather than configural face processing. ERP measures rarely correlated with disorder-specific clinical symptoms, supporting the idea that N170 abnormalities index social functioning impairments that are characteristic of many disorders rather than clinical symptoms specific to a disorder. Findings of smaller N170 amplitudes and slower latencies to emotional stimuli limits the ability to dissociate evidence of configural face processing impairments from facial emotion-specific impairment. Fifty of the 67 included studies presented emotional face stimuli without manipulating configural information of faces, making it difficult to assess the specificity of N170 abnormalities to facial affect or configural processing. Additionally, recent evidence suggests that N170 differences by facial expression do not index the activity of the N170 generators but instead represent an overlapping early posterior negativity (EPN) that confounds N170 measures (Rellecke et al., 2012, 2013). As only two included studies measured this EPN in conjunction with the N170 (Gunji et al., 2009; Wieser et al., 2012) we cannot determine whether facial expression-based modulations of the N170 more accurately reflect differences in the EPN. To better connect behavioral clinical research to specific configural or emotion-specific neural processing future research should include independent manipulations of both configural and emotional information in faces.

3.14. Multiple disorder groups (3 studies)

4.1. Schizophrenia

Three studies compared the N170 in multiple disorder groups in addition to control group comparisons. Maurage et al. (2008a) included participants with Alcohol Dependence and Major Depressive Disorder. Wynn et al. (2013) compared participants with Schizophrenia and Bipolar Disorder. Neither study reported N170 amplitude or latency differences between disorder groups. Tye et al. (2013) compared groups with ASDs, ADHD, ASDs/ADHD comorbid and controls. When splitting groups based on ADHD diagnosis presence/absence, participants with ADHD did not show N170 modulations of gaze in inverted faces, whereas those without ADHD displayed larger N170s to averted gaze in inverted faces. When splitting groups based on ASD diagnosis presence/absence, those with an ASD diagnosis displayed larger N170 amplitudes over left hemisphere electrodes, whereas amplitudes were larger in the right hemisphere in those without ASDs.

Investigations of Schizophrenia provided consistent evidence of smaller N170 and VPP amplitudes in patients compared to controls across a variety of tasks. Reported abnormalities included those specific to facial expressions, for example a lack of N170 amplitude modulation to different emotional faces (Campanella et al., 2006; Lynn and Salisbury, 2008; Ibáñez et al., 2012a,b; Kirihara et al., 2012) showing insensitivity to facial affect as indexed by the N170. In addition, abnormalities were reported to emotionally neutral faces (Herrmann et al., 2004; Onitsuka et al., 2006, 2009; Tsunoda et al., 2012) demonstrating differences in processing the structure of faces. This is supported by findings of N170 insensitivity to face inversion in Schizophrenia (Tsunoda et al., 2012) and behavioral findings of impairments in configural processing of faces (Shin et al., 2008). Insensitivity to facial configuration may represent atrophy of face-specific brain areas, as supported by correlations of smaller N170 and VPP amplitudes with decreased BOLD activity and gray matter volume in the right Fusiform Gyrus (Johnston et al., 2005; Onitsuka et al., 2006). Alternatively, findings of abnormalities in earlier visual processing indexed by the P1 component (Campanella et al., 2006; Bediou et al., 2007; Caharel

4. Discussion This review was systematic and included 67 peer-reviewed articles assessing the N170/M170/VPP in comparison with controls in



et al., 2007; Lee et al., 2010) suggest that N170 abnormalities may reflect a more generalized visual information processing deficit. Despite strong evidence for smaller N170 amplitudes in Schizophrenia associations between N170 measures and positive or negative symptoms were not found in seven of the nine studies that tested for them (Herrmann et al., 2004; Caharel et al., 2007; Obayashi et al., 2009; Onitsuka et al., 2009; Lee et al., 2010; Tsunoda et al., 2012; Komlosi et al., 2013). This indicates that N170 measures index face processing impairment in Schizophrenia independently of positive or negative symptoms.

4.2. Autism Spectrum Disorders N170 between-groups comparisons to upright faces in ASDs did not find N170 abnormalities in these disorders. There were also no consistent differences in findings between children and adults with ASDs. In addition, the seven of eight studies that included stimuli with different facial expressions found no differences in participants with ASDs, (O’Connor et al., 2007; Magnée et al., 2008, 2011; Wong et al., 2008; Akechi et al., 2010; Batty et al., 2011; Hileman et al., 2011) suggesting that there is no impairment in processing emotional faces at the N170. However, these conclusions stand in opposition to behavioral evidence of abnormal face processing strategies in individuals with ASDs (Jemel et al., 2006). Rather, the majority of N170 abnormalities reported in ASDs were to stimuli or task manipulations, providing support for N170 differences in ASDs that are specific to certain types of facial information. Findings such as reduced effects of face inversion on N170 amplitude (McPartland et al., 2011) and latency, (McPartland et al., 2004) lack of modulations by task and feature-based attention (Churches et al., 2010; Akechi et al., 2014) and abnormal interactions of gaze and emotion processing (Akechi et al., 2010) warrant further investigation to determine how N170 abnormalities in ASDs are dependent on the facial information utilized in different social cognition tasks. Individuals with ASDs have also been found to fixate on different parts of the face compared to healthy controls (Pelphrey et al., 2002) which can result in differences in evoked N170 amplitudes and latencies (de Lissa et al., 2014). These differences in fixation appear to be attenuated when presenting a prestimulus fixation cross. Seventy-seven percent of studies that did not use a fixation cross reported amplitude or latency differences in ASDs, compared to 28% of studies using a fixation cross. Concurrent ERP and eye tracking measures are needed to determine whether N170 abnormalities are due in part to abnormal patterns of fixation. Notably, fixation crosses were used in investigations of all other disorders except Social Phobia. This issue would be relevant to other disorders that display abnormalities in visuospatial attention to faces, especially given some placements of fixation crosses can result in abnormal responses in healthy controls (Klin, 2008). The choice of reference electrode may have also contributed to the lack of reported group differences in ASDs. Differing the reference electrode location (e.g. nose, average, linked mastoids, linked earlobes) affects the size and topography of the N170 and VPP (Joyce and Rossion, 2005). Most studies used an average reference, however three studies of ASDs that did not find group differences referenced to mastoids or linked ears, which would not be maximally sensitive to the N170 (Akechi et al., 2010; Senju et al., 2005; Cygan et al., 2014) and may have contributed to the lack of group differences reported in this disorder. Notably, reference electrodes that would not be maximally sensitive to the N170 or VPP were also used in studies of other disorders (Cheng and Pai, 2010; Kühnpast et al., 2012; Yoshimura et al., 2005; Ramos-Loyo et al., 2009; Towler et al., 2012).

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4.3. Other disorders The limited number of studies of ADHD, Alcohol Dependence, Alzheimer’s Disease and Mild Cognitive Decline, Bipolar Disorder, Bulimia Nervosa and Huntington’s Disease warrant caution in determining the existence of N170 abnormalities, however in these clinical groups there were findings of smaller amplitudes or slower latencies of the N170/M170/VPP. In these disorders there were also reports of no differences between groups. Discrepancies across studies within a disorder likely reflect the high between-subject variability of ERPs to faces and objects, (Luck, 2005) and related, varying facial recognition performance found within disorders (for example Hedley et al., 2011). Within these disorders all reports of smaller amplitudes or slower latencies were found following emotional face stimuli (O’Connor et al., 2005; Maurage et al., 2007, 2008a; Degabriele et al., 2011; Ibáñez et al., 2011; Sokhadze et al., 2011; Dai and Feng, 2012; Degabriele and Lagopoulos, 2012; Ibáñez et al., 2012a,b, Kühnpast et al., 2012; Schefter et al., 2013; Wynn et al., 2013; Croft et al., 2014). In addition, although results were largely inconsistent across studies, N170 measures more commonly correlated with task performance (McPartland et al., 2004, 2011; Johnston et al., 2005; Maurage et al., 2008a; Gunji et al., 2009; Rivolta et al., 2012; Towler et al., 2012) or social functioning measures (Obayashi et al., 2009; Ibáñez et al., 2011; Ibáñez et al., 2012a,b; Tsunoda et al., 2012; Tye et al., 2013) than disorder symptoms (Campanella et al., 2006; Kolassa and Miltner, 2006; Williams et al., 2008; Webb et al., 2012) indicating that the N170 indexes impairments in the extraction of facial emotion information that is common across disorders rather than disorder-specific mechanisms in these clinical populations. Future studies may wish to investigate clusters of symptoms common across disorders in relation to N170 measures, including in subclinical and healthy populations. 4.4. Clinical implications Findings show that the N170 holds promise as a diagnostic aid in Schizophrenia. Smaller N170 and VPP amplitudes in Schizophrenia indicate promise of these ERP components as biomarkers of configural or facial emotion-specific processing dysfunction. Development of these biomarkers will require more evidence differentiating facial emotion processing from configural processing abnormalities. Development of the N170 as a biomarker in other disorders will also benefit from a systematic investigation of the N170 under different face processing demands in the same participants, for example to inverted faces and during discrimination tasks of facial affect. The sensitivity of the N170 and analogous components to behavioral face processing strategies (Schyns et al., 2007; Monroe et al., 2013) and feature-based attention (Barcelo et al., 2000; Eimer, 2000a) highlights potential as a biomarker for the assessment of behavioral or pharmacological treatment of social dysfunction (for example Williams et al., 2008) if abnormalities specific to different types of facial information can be identified within or across disorders. 4.5. Limitations and future directions Aspects of experimental design were identified that may exaggerate or obscure differences between disorder and control groups. Some included studies used analog high-pass filters of 1 Hz during recording, which can substantially distort ERP waveforms and peak latency measurements (Luck, 2005). Offline digital filters may be preferable in these cases, as filtered and unfiltered waveforms


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can be compared to assess ERP distortions caused by different filter types and parameters. Overall clinical sample sizes were small (average n = 18.7) which may have limited power to detect group effects. Large sample sizes are important due to the high between-subject variability of ERP measures (Luck, 2005) and variation in facial recognition ability within disorders (e.g. Hedley et al., 2011) and inherent variability in symptomatology within clinical groups. In the studies reviewed here, there was a trend of studies with larger samples finding slower latencies in Schizophrenia, suggesting that small sample sizes may have contributed to the lack of latency differences in this disorder. In addition, numerous participant samples reported use of psychoactive medications (e.g. methylphenidate, antipsychotics, antidepressants, anxiolytics) with heterogeneity within samples. The effects of medication on cognitive faculties such as sustained attention should be considered when designing tasks for clinical participants. Tasks with self-paced responses (Caharel et al., 2007; Saavedra et al., 2012; Wynn et al., 2013) may be more suitable for participants with generalized cognitive deficits and young children. This review interpreted the significance of study findings based on p-values rather than effect sizes, which provide a better estimate of effect. Effect sizes could not be derived from most included studies as they did not provide sufficient statistical information for effect size calculation (such as group means and standard deviations). Recent developments in N170 face perception research can be applied to study clinical groups. Robust statistics can increase statistical power and avoid errors in descriptive and inferential statistics (Wilcox, 2012). Heterogeneity in experimental effects within clinical and control groups could be assessed using single-trial analyses (e.g. Rousselet et al., 2011). In addition, repetitionsuppression (Grill-Spector et al., 2006) may be used to test for sensitivity in clinical groups to specific types of facial information, such as identity (e.g. Onitsuka et al., 2009).

5. Conclusions This review provides strong evidence for both configural and facial affect-related visual processing abnormalities in Schizophrenia as indexed by the N170 and VPP ERP components. These abnormalities appear to index facial identity and emotion recognition deficits and possibly generalized information processing deficits, independently of disorder symptoms. In other disorders N170/M170/VPP measures were associated with facial recognition ability rather than disorder-specific symptoms, indicating that the N170 and related components hold promise as a biomarker of facial emotion recognition dysfunction, which is characteristic of many diagnoses, rather than disorder-specific impairment. A clearer dissociation of N170/M170/VPP abnormalities specific to facial emotion as opposed to facial configuration processing will be aid development of these ERP components as biomarkers of social dysfunction in neurological and psychiatric disorders. Acknowledgements H.A.D.K. was supported by an Australian National Health and Medical Research Council Training Award (568890). We thank Dr Mark Kohler for his support within the UniSA Cognitive Neuroscience Laboratory. Conflict of interest: None of the authors have potential conflicts of interest to be disclosed.

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Neuroimaging distinction between neurological and psychiatric disorders.

Hepatitis C virus infection, and neurological and psychiatric disorders - A review.

Guided Internet-based vs. face-to-face cognitive behavior therapy for psychiatric and somatic disorders: a systematic review and meta-analysis.

Neurological and psychiatric disorders as a neuroglial failure.

Modulating GluN2B for the Treatment of Neurological and Psychiatric Disorders.

Editorial: neurological and psychiatric disorders in endocrine diseases.

Deep Brain Stimulation in Neurological and Psychiatric Disorders.

Literature, neurology, and neuroscience: neurological and psychiatric disorders. Preface.

Paternal age and psychiatric disorders: A review.

Prokineticin Receptor Modulators May Potentially Treat Psychiatric and Neurological Disorders.

CK2-An Emerging Target for Neurological and Psychiatric Disorders.

Psoriasis and Associated Psychiatric Disorders: A Systematic Review on Etiopathogenesis and Clinical Correlation.

"Soft" neurological signs and later psychiatric disorder-a review.

[Neurological and psychiatric disorders following acute arsine poisoning (author's transl)].

A decade from discovery to therapy: Lingo-1, the dark horse in neurological and psychiatric disorders.

The "psychomicrobiotic": Targeting microbiota in major psychiatric disorders: A systematic review.

Integrating children with psychiatric disorders in the classroom: a systematic review.

Ghrelin in psychiatric disorders - A review.

Alexithymia and Suicide Risk in Psychiatric Disorders: A Mini-Review.

A systematic review of self-reported swallowing assessments in progressive neurological disorders.

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis.

Association between variants of zinc finger genes and psychiatric disorders: systematic review and meta-analysis.