What does visual snow look like? Quantification by matching a simulation.

The primary symptom of visual snow syndrome (VSS) is the unremitting perception of small, flickering dots covering the visual field. VSS is a serious but poorly understood condition that can interfere with daily tasks. Several studies have provided qualitative data about the appearance of visual snow, but methods to quantify the symptom are lacking. Here, we developed a task in which participants with VSS adjusted parameters of simulated visual snow on a computer monitor until the simulation matched their internal visual snow. On each trial, participants (n = 31 with VSS) modified the size, density, update speed, and contrast of the simulation. Participants' settings were highly reliable across trials (intraclass correlation coefficients > 0.89), and they reported that the task was effective at stimulating their visual snow. On average, visual snow was very small (less than 2 arcmin in diameter), updated quickly (mean temporal frequency = 18.2 Hz), had low density (mean snow elements vs. background = 2.87%), and had low contrast (average root mean square contrast = 2.56%). Our task provided a quantitative assessment of visual snow percepts, which may help individuals with VSS communicate their experience to others, facilitate assessment of treatment efficacy, and further our understanding of the trajectory of symptoms, as well as the neural origins of VSS.

Faster bi-stable visual switching in psychosis.

Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception has been observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in the visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in the visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels, specifically disorganization, across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.

Adapting to Visual Noise Alleviates Visual Snow.

Purpose: Visual snow syndrome-characterized by flickering specks throughout the visual field and accompanied by other symptoms-can disrupt daily life and affects roughly 2% of the population. However, its neural bases remain mysterious, and treatments are lacking. Here, we report the first intervention that can temporarily eliminate the visual snow symptom, allowing many observers to see the world without snow for the first time since symptom onset. Prolonged viewing of a visual stimulus strongly reduces the responsiveness of the visual pathways to subsequent stimuli, and we tested whether such adaptation could affect visual snow. Methods: Participants with visual snow (total n = 27) viewed high-contrast dynamic noise patterns, resembling television static, and then judged the strength of the symptom. Results: Visual snow was temporarily reduced in strength to the point that it was invisible at longer adaptation durations for most observers. The effect followed typical trends of adaptation for physical stimuli in normally sighted observers: Effect duration increased monotonically with duration of exposure to the adapter and was specific to dynamic noise. Conclusions: These results establish that spontaneous neural activity in the visual system is causally related to the visual snow percept. Because they perceive this activity, people with visual snow may provide a unique window into the generation and suppression of noise in the visual system. Adaptation allows reliable experimental control over visual snow, and so is a strong candidate for diagnostic testing and a promising tool for further understanding its neural origins, which could in turn aid the development of treatments.

The psychosis human connectome project: Design and rationale for studies of visual neurophysiology.

Visual perception is abnormal in psychotic disorders such as schizophrenia. In addition to hallucinations, laboratory tests show differences in fundamental visual processes including contrast sensitivity, center-surround interactions, and perceptual organization. A number of hypotheses have been proposed to explain visual dysfunction in psychotic disorders, including an imbalance between excitation and inhibition. However, the precise neural basis of abnormal visual perception in people with psychotic psychopathology (PwPP) remains unknown. Here, we describe the behavioral and 7 tesla MRI methods we used to interrogate visual neurophysiology in PwPP as part of the Psychosis Human Connectome Project (HCP). In addition to PwPP (n = 66) and healthy controls (n = 43), we also recruited first-degree biological relatives (n = 44) in order to examine the role of genetic liability for psychosis in visual perception. Our visual tasks were designed to assess fundamental visual processes in PwPP, whereas MR spectroscopy enabled us to examine neurochemistry, including excitatory and inhibitory markers. We show that it is feasible to collect high-quality data across multiple psychophysical, functional MRI, and MR spectroscopy experiments with a sizable number of participants at a single research site. These data, in addition to those from our previously described 3 tesla experiments, will be made publicly available in order to facilitate further investigations by other research groups. By combining visual neuroscience techniques and HCP brain imaging methods, our experiments offer new opportunities to investigate the neural basis of abnormal visual perception in PwPP.

Faster bi-stable visual switching in psychosis.

Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception is observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.

Weakened untuned gain control is associated with schizophrenia while atypical orientation-tuned suppression depends on visual acuity.

Perceptual distortions are core features of psychosis. Weakened contrast surround suppression has been proposed as a neural mechanism underlying atypical perceptual experiences. Although previous work has measured suppression by asking participants to report the perceived contrast of a low-contrast target surrounded by a high-contrast surround, it is possible to modulate perceived contrast solely by manipulating the orientation of a matched-contrast center and surround. Removing the bottom-up segmentation cue of contrast difference and isolating orientation-dependent suppression may clarify the neural processes responsible for atypical surround suppression in psychosis. We examined surround suppression across a spectrum of psychotic psychopathology including people with schizophrenia (PSZ; N = 31) and people with bipolar disorder (PBD; N = 29), first-degree biological relatives of these patient groups (PBDrel, PSZrel; N = 28, N = 21, respectively), and healthy controls (N = 29). PSZ exhibited reduced surround suppression across orientations; although group differences were minimal at the condition that produced the strongest suppression. PBD and PSZrel exhibited intermediate suppression, whereas PBDrel performed most similarly to controls. Intriguingly, group differences in orientation-dependent surround suppression magnitude were moderated by visual acuity. A simulation in which visual acuity and/or focal attention interact with untuned gain control reproduces the observed pattern of results, including the lack of group differences when orientation of center and surround are the same. Our findings further elucidate perceptual mechanisms of impaired center-surround processing in psychosis and provide insights into the effects of visual acuity on orientation-dependent suppression in PSZ.

The psychosis human connectome project: An overview.

Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology.

Assessing methods for geometric distortion compensation in 7 T gradient echo functional MRI data.

Echo planar imaging (EPI) is widely used in functional and diffusion-weighted MRI, but suffers from significant geometric distortions in the phase encoding direction caused by inhomogeneities in the static magnetic field (B0 ). This is a particular challenge for EPI at very high field (≥7 T), as distortion increases with higher field strength. A number of techniques for distortion correction exist, including those based on B0 field mapping and acquiring EPI scans with opposite phase encoding directions. However, few quantitative comparisons of distortion compensation methods have been performed using human EPI data, especially at very high field. Here, we compared distortion compensation using B0 field maps and opposite phase encoding scans in two different software packages (FSL and AFNI) applied to 7 T gradient echo (GE) EPI data from 31 human participants. We assessed distortion compensation quality by quantifying alignment to anatomical reference scans using Dice coefficients and mutual information. Performance between FSL and AFNI was equivalent. In our whole-brain analyses, we found superior distortion compensation using GE scans with opposite phase encoding directions, versus B0 field maps or spin echo (SE) opposite phase encoding scans. However, SE performed better when analyses were limited to ventromedial prefrontal cortex, a region with substantial dropout. Matching the type of opposite phase encoding scans to the EPI data being corrected (e.g., SE-to-SE) also yielded better distortion correction. While the ideal distortion compensation approach likely varies depending on methodological differences across experiments, this study provides a framework for quantitative comparison of different distortion compensation methods.

Reduced influence of perceptual context in schizophrenia: behavioral and neurophysiological evidence.

BACKGROUND: Accurate perception of visual contours is essential for seeing and differentiating objects in the environment. Both the ability to detect visual contours and the influence of perceptual context created by surrounding stimuli are diminished in people with schizophrenia (SCZ). The central aim of the present study was to better understand the biological underpinnings of impaired contour integration and weakened effects of perceptual context. Additionally, we sought to determine whether visual perceptual abnormalities reflect genetic factors in SCZ and are present in other severe mental disorders. METHODS: We examined behavioral data and event-related potentials (ERPs) collected during the perception of simple linear contours embedded in similar background stimuli in 27 patients with SCZ, 23 patients with bipolar disorder (BP), 23 first-degree relatives of SCZ, and 37 controls. RESULTS: SCZ exhibited impaired visual contour detection while BP exhibited intermediate performance. The orientation of neighboring stimuli (i.e. flankers) relative to the contour modulated perception across all groups, but SCZ exhibited weakened suppression by the perceptual context created by flankers. Late visual (occipital P2) and cognitive (centroparietal P3) neural responses showed group differences and flanker orientation effects, unlike earlier ERPs (occipital P1 and N1). Moreover, behavioral effects of flanker context on contour perception were correlated with modulation in P2 & P3 amplitudes. CONCLUSION: In addition to replicating and extending findings of abnormal contour integration and visual context modulation in SCZ, we provide novel evidence that the abnormal use of perceptual context is associated with higher-order sensory and cognitive processes.

Deficits in Auditory and Visual Sensory Discrimination Reflect a Genetic Liability for Psychosis and Predict Disruptions in Global Cognitive Functioning.

Sensory discrimination thresholds (i.e., the briefest stimulus that can be accurately perceived) can be measured using tablet-based auditory and visual sweep paradigms. These basic sensory functions have been found to be diminished in patients with psychosis. However, the extent to which worse sensory discrimination characterizes genetic liability for psychosis, and whether it is related to clinical symptomatology and community functioning remains unknown. In the current study we compared patients with psychosis (PSY; N=76), their first-degree biological relatives (REL; N=44), and groups of healthy controls (CON; N=13 auditory and visual/N=275 auditory/N=267 visual) on measures of auditory and visual sensory discrimination, and examined relationships with a battery of symptom, cognitive, and functioning measures. Sound sweep thresholds differed among the PSY, REL, and CON groups, driven by higher thresholds in the PSY compared to CON group, with the REL group showing intermediate thresholds. Visual thresholds also differed among the three groups, driven by higher thresholds in the REL versus CON group, and no significant differences between the REL and PSY groups. Across groups and among patients, higher thresholds (poorer discrimination) for both sound and visual sweeps strongly correlated with lower global cognitive scores. We conclude that low-level auditory and visual sensory discrimination deficits in psychosis may reflect genetic liability for psychotic illness. Critically, these deficits relate to global cognitive disruptions that are a hallmark of psychotic illnesses such as schizophrenia.

Late fMRI Response Components Are Altered in Autism Spectrum Disorder.

Disrupted cortical neural inhibition has been hypothesized to be a primary contributor to the pathophysiology of autism spectrum disorder (ASD). This hypothesis predicts that ASD will be associated with an increase in neural responses. We tested this prediction by comparing fMRI response magnitudes to simultaneous visual, auditory, and motor stimulation in ASD and neurotypical (NT) individuals. No increases in the initial transient response in any brain region were observed in ASD, suggesting that there is no increase in overall cortical neural excitability. Most notably, there were widespread fMRI magnitude increases in the ASD response following stimulation offset, approximately 6-8 s after the termination of sensory and motor stimulation. In some regions, the higher fMRI offset response in ASD could be attributed to a lack of an "undershoot"-an often observed feature of fMRI responses believed to reflect inhibitory processing. Offset response magnitude was associated with reaction times (RT) in the NT group and may explain an overall reduced RT in the ASD group. Overall, our results suggest that increases in neural responsiveness are present in ASD but are confined to specific components of the neural response, are particularly strong following stimulation offset, and are linked to differences in RT.

Weaker neural suppression in autism.

Abnormal sensory processing has been observed in autism, including superior visual motion discrimination, but the neural basis for these sensory changes remains unknown. Leveraging well-characterized suppressive neural circuits in the visual system, we used behavioral and fMRI tasks to demonstrate a significant reduction in neural suppression in young adults with autism spectrum disorder (ASD) compared to neurotypical controls. MR spectroscopy measurements revealed no group differences in neurotransmitter signals. We show how a computational model that incorporates divisive normalization, as well as narrower top-down gain (that could result, for example, from a narrower window of attention), can explain our observations and divergent previous findings. Thus, weaker neural suppression is reflected in visual task performance and fMRI measures in ASD, and may be attributable to differences in top-down processing.

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder.

The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. Autism Res 2020, 13: 1111-1129. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: γ-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Response Dissociation in Hierarchical Cortical Circuits: a Unique Feature of Autism Spectrum Disorder.

A prominent hypothesis regarding the pathophysiology of autism is that an increase in the balance between neural excitation and inhibition results in an increase in neural responses. However, previous reports of population-level response magnitude in individuals with autism have been inconsistent. Critically, network interactions have not been considered in previous neuroimaging studies of excitation and inhibition imbalance in autism. In particular, a defining characteristic of cortical organization is its hierarchical and interactive structure; sensory and cognitive systems are comprised of networks where later stages inherit and build upon the processing of earlier input stages, and also influence and shape earlier stages by top-down modulation. Here we used the well established connections of the human visual system to examine response magnitudes in a higher-order motion processing region [middle temporal area (MT+)] and its primary input region (V1). Simple visual stimuli were presented to adult individuals with autism spectrum disorders (ASD; n = 24, mean age 23 years, 8 females) and neurotypical controls (n = 24, mean age 22, 8 females) during fMRI scanning. We discovered a strong dissociation of fMRI response magnitude between region MT+ and V1 in individuals with ASD: individuals with high MT+ responses had attenuated V1 responses. The magnitude of MT+ amplification and of V1 attenuation was associated with autism severity, appeared to result from amplified suppressive feedback from MT+ to V1, and was not present in neurotypical controls. Our results reveal the potential role of altered hierarchical network interactions in the pathophysiology of ASD.SIGNIFICANCE STATEMENT An imbalance between neural excitation and inhibition, resulting in increased neural responses, has been suggested as a pathophysiological pathway to autism, but direct evidence from humans is lacking. In the current study we consider the role of interactions between stages of sensory processing when testing increased neural responses in individuals with autism. We used the well known hierarchical structure of the visual motion pathway to demonstrate dissociation in the fMRI response magnitude between adjacent stages of processing in autism: responses are attenuated in a primary visual area but amplified in a subsequent higher-order area. This response dissociation appears to rely on enhanced suppressive feedback between regions and reveals a previously unknown cortical network alteration in autism.

The time course of different surround suppression mechanisms.

What we see depends on the spatial context in which it appears. Previous work has linked the suppression of perceived contrast by surrounding stimuli to reduced neural responses in early visual cortex. This surround suppression depends on at least two separable neural mechanisms, "low-level" and "higher level," which can be differentiated by their response characteristics. We used electroencephalography to demonstrate for the first time that human occipital neural responses show evidence of these two suppression mechanisms. Eighteen adults (10 women, 8 men) each participated in three experimental sessions, in which they viewed visual stimuli through a mirror stereoscope. The first session was used to identify the C1 component, while the second and third comprised the main experiment. Event-related potentials were measured in response to center gratings either with no surround or with surrounding gratings oriented parallel or orthogonal, and presented in either the same eye (monoptic) or the opposite eye (dichoptic). We found that the earliest component of an event-related potential (C1; ∼60 ms) was suppressed by surrounding stimuli, but that suppression did not depend on surround configuration. This suggests a suppression mechanism that is not tuned for relative orientation acting on the earliest cortical response to the target. A later response component (N1; ∼160 ms) showed stronger suppression for parallel and monoptic surrounds, consistent with our earlier psychophysical results and a second form of suppression that is binocular and orientation tuned. We conclude that these two forms of surround suppression have distinct response time courses in the human visual system, which can be differentiated using electrophysiology.

Glutamatergic facilitation of neural responses in MT enhances motion perception in humans.

There is large individual variability in human neural responses and perceptual abilities. The factors that give rise to these individual differences, however, remain largely unknown. To examine these factors, we measured fMRI responses to moving gratings in the motion-selective region MT, and perceptual duration thresholds for motion direction discrimination. Further, we acquired MR spectroscopy data, which allowed us to quantify an index of neurotransmitter levels in the region of area MT. These three measurements were conducted in separate experimental sessions within the same group of male and female subjects. We show that stronger Glx (glutamate + glutamine) signals in the MT region are associated with both higher fMRI responses and superior psychophysical task performance. Our results suggest that greater baseline levels of glutamate within MT facilitate motion perception by increasing neural responses in this region.

Reduced auditory cortical adaptation in autism spectrum disorder.

Adaptation is a fundamental property of cortical neurons and has been suggested to be altered in individuals with autism spectrum disorder (ASD). We used fMRI to measure adaptation induced by repeated audio-visual stimulation in early sensory cortical areas in individuals with ASD and neurotypical (NT) controls. The initial transient responses were equivalent between groups in both visual and auditory cortices and when stimulation occurred with fixed-interval and randomized-interval timing. However, in auditory but not visual cortex, the post-transient sustained response was greater in individuals with ASD than NT controls in the fixed-interval timing condition, reflecting reduced adaptation. Further, individual differences in the sustained response in auditory cortex correlated with ASD symptom severity. These findings are consistent with hypotheses that ASD is associated with increased neural responsiveness but that responsiveness differences only manifest after repeated stimulation, are specific to the temporal pattern of stimulation, and are confined to specific cortical regions.

Sex Differences in Visual Motion Processing.

The importance of sex as a biological variable has recently been emphasized by major funding organizations [1] and within the neuroscience community [2]. Critical sex-based neural differences are indicated by, for example, conditions such as autism spectrum disorder (ASD) that have a strong sex bias with a higher prevalence among males [51, 3]. Motivated by this broader context, we report a marked sex difference in a visual motion perception task among neurotypical adults. Motion duration thresholds [4, 5]-the minimum duration needed to accurately perceive motion direction-were considerably shorter for males than females. We replicated this result across three laboratories and 263 total participants. This type of enhanced performance has previously been observed only in special populations including ASD, depression, and senescence [6-8]. The observed sex difference cannot be explained by general differences in speed of visual processing, overall visual discrimination abilities, or potential motor-related differences. We also show that while individual differences in motion duration thresholds are associated with differences in fMRI responsiveness of human MT+, surprisingly, MT+ response magnitudes did not differ between males and females. Thus, we reason that sex differences in motion perception are not captured by an MT+ fMRI measure that predicts within-sex individual differences in perception. Overall, these results show how sex differences can manifest unexpectedly, highlighting the importance of sex as a factor in the design and analysis of perceptual and cognitive studies.

Suppression and facilitation of human neural responses.

Efficient neural processing depends on regulating responses through suppression and facilitation of neural activity. Utilizing a well-known visual motion paradigm that evokes behavioral suppression and facilitation, and combining five different methodologies (behavioral psychophysics, computational modeling, functional MRI, pharmacology, and magnetic resonance spectroscopy), we provide evidence that challenges commonly held assumptions about the neural processes underlying suppression and facilitation. We show that: (1) both suppression and facilitation can emerge from a single, computational principle - divisive normalization; there is no need to invoke separate neural mechanisms, (2) neural suppression and facilitation in the motion-selective area MT mirror perception, but strong suppression also occurs in earlier visual areas, and (3) suppression is not primarily driven by GABA-mediated inhibition. Thus, while commonly used spatial suppression paradigms may provide insight into neural response magnitudes in visual areas, they should not be used to infer neural inhibition.

The neurobiology of self face recognition among depressed adolescents.

OBJECTIVE: Depression is linked to alterations in both emotion and self-processing. The current study used functional magnetic resonance imaging (fMRI) to assess neural activation in healthy and depressed youth to a novel task that combined emotion processing with self-face recognition. METHODS: An fMRI study involving 81 adolescents (50.6% females; Mage=14.61, SD=1.65) comprised of depressed (DEP, n=43), and healthy controls (HC, n=38). Participants completed a clinical interview and self-report measures during an initial assessment. In the scanner, adolescents completed a face recognition task, viewing emotional (happy, sad, neutral) images of their own face (self) or the face of another youth (other). RESULTS: DEP youth showed higher activity in the cuneus (F=26.29) and post and precentral gyri (F=20.76), across all conditions compared to HC. Sad faces elicited higher posterior cingulate cortex, precuneus (F=10.36) and inferior parietal cortex activity (F=11.0), and self faces elicited higher precuneus, fusiform (F=16.39), insula and putamen (F=16.82) activity in all youth. DEP showed higher middle temporal activity to neutral faces but lower activity to sad faces compared to HC, who showed the opposite pattern (F=12.86). DEP also showed hypoactive mid-temporal limbic activity relative to controls when identifying their self happy face vs. neutral face, yet showed hyperactivity when identifying the other happy face vs. neutral face, and HC showed the opposite pattern (F=10.94). CONCLUSIONS: The neurophysiology of self-face recognition is altered in adolescent depression. Specifically, depression was associated with decreased activity in neural areas that support emotional and associative processing for positive self-faces and increased processing for neutral self-faces. These results suggest that depression in adolescents is associated with hypoactive emotional processing and encoding of positive self-related visual information. This abnormal neural activity at the intersection of reward and self-processing among depressed youth might have long lasting impact in self-formation and future adult self-representations, given that adolescence is a sensitive period for self-development.