Digital Media and Developing Brains: Concerns and Opportunities.

Purpose of Review: The incorporation of digital technologies and their use in youth's everyday lives has been increasing rapidly over the past several decades with possible impacts on youth development and mental health. This narrative review aimed to consider how the use of digital technologies may be influencing brain development underlying adaptive and maladaptive screen-related behaviors. Recent Findings: To explore and provide direction for further scientific inquiry, an international group of experts considered what is known, important gaps in knowledge, and how a research agenda might be pursued regarding relationships between screen media activity and neurodevelopment from infancy through childhood and adolescence. While an understanding of brain-behavior relationships involving screen media activity has been emerging, significant gaps exist that have important implications for the health of developing youth. Summary: Specific considerations regarding brain-behavior relationships involving screen media activity exist for infancy, toddlerhood, and early childhood; middle childhood; and adolescence. Transdiagnostic frameworks may provide a foundation for guiding future research efforts. Translating knowledge gained into better interventions and policy to promote healthy development is important in a rapidly changing digital technology environment.

Family history of substance use disorder and parental impulsivity are differentially associated with neural responses during risky decision-making.

Background: Risky decision-making is associated with the development of substance use behaviors during adolescence. Although prior work has investigated risky decision-making in adolescents at familial high risk for developing substance use disorders (SUDs), little research has controlled for the presence of co-morbid externalizing disorders (EDs). Additionally, few studies have investigated the role of parental impulsivity in offspring neurobiology associated with risky decision-making. Methods: One-hundred twenty-five children (28 healthy controls, 47 psychiatric controls with EDs without a familial history of SUD, and 50 high-risk children with co-morbid EDs with a familial history of SUD) participated in the Balloon Analog Risk Task while undergoing functional magnetic resonance imaging. Impulsivity for parents and children was measured using the UPPS-P Impulsive Behavior Scale. Results: We found that individuals in the psychiatric control group showed greater activation, as chances of balloon explosion increased, while making choices, relative to the healthy control and high-risk groups in the rostral anterior cingulate cortex (rACC) and lateral orbitofrontal cortex (lOFC). We also found a positive association between greater activation and parental impulsivity in these regions. However, within rACC, this relationship was moderated by group, such that there was a positive relationship between activation and parental impulsivity in the HC group, but an inverse relationship in the HR group. Conclusions: These findings suggest that there are key differences in the neurobiology underlying risky decision-making in individuals with EDs with and without a familial history of SUD. The current findings build on existing models of neurobiological factors influencing addiction risk by integrating parental factors. This work paves the way for more precise risk models in which to test preventive interventions.

Androstadienone sensitivity is associated with attention to emotions, social interactions, and sexual behavior in older U.S. adults.

Δ 4,16-androstadien-3-one (androstadienone) is a putative human pheromone often linked to sexual attraction in young adults, although specific associations with sexual behavior are not yet established. Androstadienone also serves a broader social-emotional function beyond the sexual domain, specifically tuning the brain to efficiently process emotional information. Whether these effects persist throughout the lifespan into post-reproductive life is unknown. In a laboratory study of older adults, those with greater androstadienone odor sensitivity paid greater attention to subliminal emotional information, specifically, angry faces (p = 0.05), with a similar relationship to happy faces. In contrast, the physical odor n-butanol (a control) did not affect emotional attention (p = 0.49). We then extended this laboratory research and determined whether sensitivity to androstadienone affects the everyday lives of older adults by measuring their social and sexual behavior. In this second study, we surveyed in a nationally representative sample of US older adults living in their homes (National Social Life and Aging Project, 62-90 years; n = 2,086), along with their sensitivity to androstadienone, general olfactory function, health and demographics. Greater sensitivity to androstadienone was associated with richer social lives: having more friends, increased communication with close friends and family, and more participation in organized social events and volunteer activities (all p's ≤ 0.05, generalized linear models, adjusted for age and gender). It was also associated with more recent sexual activity, more frequent sexual thoughts, and viewing sex as an important part of life (all p's ≤ 0.05). General olfactory function did not explain these associations, supporting a specialized function for this pheromone during everyday life, and expanding its role to social life as well as sexual behavior, likely mediated by enhanced attention to emotional information.

Assessment of Boys' Responses to Interpersonal Conflict in Virtual Reality.

Background: Continuous advances in virtual reality (VR) technology have increased its potential for clinical use in the research, assessment, and treatment of mental health difficulties. One potential target for VR use is childhood behavior problems, which are often associated with social-cognitive deficits that can be difficult to measure or modify. Materials and Methods: We enrolled 36 boys between the ages of 8-13 to assess the usability of a VR device and its feasibility as a psychiatric tool for youth. Each participant experienced three virtual school cafeteria scenes that varied in antisocial content and the intentions of a virtual counterpart (VC) (control, ambiguous, or hostile). Following each scene, participants completed questions about ease and comfort in using the headset as well as an assessment of hostile attribution bias (HAB). HAB is the tendency to attribute hostile motivations to others' behaviors, which contributes to antisocial thoughts and behaviors. Following this VR use, participants completed a standard text assessment of HAB. Results: In general, participants reported the VR headset to be enjoyable and easy to use, and scenes worked as intended, with VCs in the hostile scene rated the meanest. In addition, boys with more conduct problems reported that virtual characters were meaner to them, despite no difference in text vignette measures of HAB. Conclusion: This study provides preliminary evidence supporting the further development of VR programs to assess and treat childhood behavior problems.

Repetitive Transcranial Magnetic Stimulation as a Therapeutic and Probe in Schizophrenia: Examining the Role of Neuroimaging and Future Directions.

Schizophrenia is a complex condition associated with perceptual disturbances, decreased motivation and affect, and disrupted cognition. Individuals living with schizophrenia may experience myriad poor outcomes, including impairment in independent living and function as well as decreased life expectancy. Though existing treatments may offer benefit, many individuals still experience treatment resistant and disabling symptoms. In light of the negative outcomes associated with schizophrenia and the limitations in currently available treatments, there is a significant need for novel therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate the activity of discrete cortical regions, allowing direct manipulation of local brain activation and indirect manipulation of the target's associated neural networks. rTMS has been studied in schizophrenia for the treatment of auditory hallucinations, negative symptoms, and cognitive deficits, with mixed results. The field's inability to arrive at a consensus on the use rTMS in schizophrenia has stemmed from a variety of issues, perhaps most notably the significant heterogeneity amongst existing trials. In addition, it is likely that factors specific to schizophrenia, rather than the rTMS itself, have presented barriers to the interpretation of existing results. However, advances in approaches to rTMS as a biologic probe and therapeutic, many of which include the integration of neuroimaging with rTMS, offer hope that this technology may still play a role in improving the understanding and treatment of schizophrenia.

Functional connectivity in frontostriatal networks differentiate offspring of parents with substance use disorders from other high-risk youth.

BACKGROUND: Family history (FH) of substance use disorders (SUDs) is known to elevate SUD risk in offspring. However, the influence of FH SUDs has been confounded by the effect of externalizing psychopathologies in the addiction risk neuroimaging literature. Thus, the current study aimed to assess the association between parental SUDs and offspring functional connectivity in samples matched for psychopathology and demographics. METHODS: Ninety 11-12-year-old participants with externalizing disorders were included in the study (48 FH+, 42 FH-). We conducted independent component analyses (ICA) and seed-based analyses (orbitofrontal cortex; OFC, nucleus accumbens (NAcc), dorsolateral prefrontal cortex) with resting state data. RESULTS: FH+ adolescents showed stronger functional connectivity between the right lateral OFC seed and anterior cingulate cortex compared to FH- adolescents (p < 0.05, corrected). Compared to FH-, FH+ adolescents showed stronger negative functional connectivity between the left lateral OFC seed and right postcentral gyrus and between the left NAcc seed and right middle occipital gyrus (p < 0.05, corrected). Poorer emotion regulation was associated with more negative connectivity between right occipital/left NAcc among FH+ adolescents based on the seed-based analysis. FH- adolescents had stronger negative functional connectivity between ventral attention/salience networks and dorsal attention/visuospatial networks in the ICA. CONCLUSIONS: Both analytic methods found group differences in functional connectivity between brain regions associated with executive functioning and regions associated with sensory input (e.g., postcentral gyrus, occipital regions). We speculate that families densely loaded for SUD may confer risk by altered neurocircuitry that is associated with emotion regulation and valuation of external stimuli beyond what would be explained by externalizing psychopathology alone.

Effects of fingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, on white matter microstructure, cognition and symptoms in schizophrenia.

Several lines of evidence have implicated white matter (WM) deficits in schizophrenia, including microstructural alterations from diffusion tensor (DTI) brain imaging studies. It has been proposed that dysregulated inflammatory processes, including heightened activity of circulating lymphocytes, may contribute to WM pathology in this illness. Fingolimod is a sphingosine-1-phosphate (S1P) receptor agonist that is approved for the treatment of relapsing multiple sclerosis (MS). Fingolimod robustly decreases the number of circulating lymphocytes through sequestration of these cells in lymph tissue. In addition, this agent improved WM microstructure as shown by increases in DTI fractional anisotropy (FA). In this pilot study, we assessed the effects of fingolimod on WM microstructure, cognition and symptoms in an eight-week, double-blind trial. Forty subjects with schizophrenia or schizoaffective disorder were randomized 1:1 to fingolimod (0.5 mg/day) and placebo. Fingolimod caused significant reductions in circulating lymphocytes (p < .001). In addition, there was a statistically non-significant association (p = .089) between DTI-FA change in the WM skeleton and fingolimod. There were significant relationships between the degree of lymphocyte reductions and increases in FA in the corpus collosum (p = .004) and right superior longitudinal fasciculus ( p = .02), and a non-significant correlation with the WM skeleton. There were no significant fingolimod versus placebo interactions on cognitive or symptom measures. There were no serious adverse events related to fingolimod treatment. Future studies with larger samples and treatment durations are needed to further establish fingolimod's potential therapeutic effects in schizophrenia.

Atypical Cortical Activation During Risky Decision Making in Disruptive Behavior Disordered Youths With Histories of Suicidal Ideation.

BACKGROUND: Suicidality is a leading cause of death among adolescents. In addition to other psychiatric conditions, youths with attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) are at heightened risk for suicide. Decision-making deficits are a hallmark symptom of ADHD and DBDs and are also implicated in suicidal behavior. We examined behavioral and neural differences in decision making among youths with ADHD and DBDs with (SI+) and without (SI-) histories of suicidal ideation. METHODS: The Balloon Analog Risk Task, a risky decision-making task, was completed by 57 youths with ADHD and DBDs (38% SI+) during functional magnetic resonance imaging. Mean stop wager (mean wager at which youths bank money) was the primary measure of risk taking. We conducted whole-brain and region-of-interest analyses in the anterior cingulate cortex and orbitofrontal cortex (OFC) during choice (win vs. inflate) and outcome (inflate vs. explode) contrasts using parametric modulators accounting for probability of balloon explosion. RESULTS: There were no differences between SI+ and SI- youths in Balloon Analog Risk Task performance. SI+ youths showed decreasing activation in the right medial frontal gyrus when choosing inflate as explosion probability increased compared with SI- youths. During explosions, SI- youths showed increasing activation in the left OFC as explosions became more likely. SI+ showed increasing left medial OFC activity in response to inflations as explosion probability increased. CONCLUSIONS: SI+ youths may show heightened sensitivity to immediate reward and decreased sensitivity to potential loss as evidenced by medial frontal gyrus activity. OFC findings suggest that SI+ youths may be drawn to reward even when there is high probability of loss.

Functional network connectivity in early-stage schizophrenia.

Schizophrenia is a disorder of altered neural connections resulting in impaired information integration. Whole brain assessment of within- and between-network connections may determine how information processing is disrupted in schizophrenia. Patients with early-stage schizophrenia (n = 56) and a matched control sample (n = 32) underwent resting-state fMRI scans. Gray matter regions were organized into nine distinct functional networks. Functional connectivity was calculated between 278 gray matter regions for each subject. Network connectivity properties were defined by the mean and variance of correlations of all regions. Whole-brain network measures of global efficiency (reflecting overall interconnectedness) and locations of hubs (key regions for communication) were also determined. The control sample had greater connectivity between the following network pairs: somatomotor-limbic, somatomotor-default mode, dorsal attention-default mode, ventral attention-limbic, and ventral attention-default mode. The patient sample had greater variance in interactions between ventral attention network and other functional networks. Illness duration was associated with overall increases in the variability of network connections. The control group had higher global efficiency and more hubs in the cerebellum network, while patient group hubs were more common in visual, frontoparietal, or subcortical networks. Thus, reduced functional connectivity in patients was largely present between distinct networks, rather than within-networks. The implications of these findings for the pathophysiology of schizophrenia are discussed.

Relationship of negative urgency to cingulo-insular and cortico-striatal resting state functional connectivity in tobacco use.

Negative urgency, defined as a tendency to act rashly under extreme negative emotion, is strongly associated with tobacco use. Despite the robust evidence linking negative urgency and tobacco use and accumulating evidence suggesting that localized, segregated brain regions such as the nucleus accumbens (NAcc), insula, and amygdala are related to negative urgency, resting state functional connectivity (rsFC) of negative urgency in tobacco use has not yet been examined. This study included 34 daily tobacco users and 62 non-users matched on age, gender, race/ethnicity, and lifetime psychiatric diagnosis from a publicly available neuroimaging dataset collected by the Nathan Kline Institute-Rockland Project. Using the bilateral NAcc, insula, and amygdala as seed regions, seed-based rsFC analyses were conducted on the whole brain. In the whole sample, negative urgency was positively correlated with rsFC between the left insula and right dorsal anterior cingulate cortex (dACC). Compared to non-users, tobacco users had a stronger rsFC strength between the right amygdala and right middle temporal gyrus. In tobacco users, negative urgency was negatively associated with rsFC between the left NAcc and right dACC and between the left NAcc and right dorsolateral prefrontal cortex; these relationships were positive in non-users. Identifying functional connectivity implicated in negative urgency and tobacco use is the crucial first step to design and test pharmacological and physiological interventions to reduce negative urgency related tobacco use.

Relationship of auditory electrophysiological responses to magnetic resonance spectroscopy metabolites in Early Phase Psychosis.

Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.

Pubertal influences on neural activation during risky decision-making in youth with ADHD and disruptive behavior disorders.

OBJECTIVE: Risk-taking during adolescence is a leading cause of mortality; Neuroscience research examining pubertal effects on decision-making is needed to better inform interventions, particularly among youth with attention-deficit/hyperactivity (ADHD) and disruptive behavior disorders (DBD), who are particularly prone to risky decision-making. We examined effects of pubertal development on risky decision-making and neural activation during decision-making among youth with ADHD/DBDs. METHOD: Forty-six 11-12-year-olds (29.4% girls; 54.9% white; Tanner M(SD) = 2.08(1.32)) who met DSM-5 criteria for ADHD/DBD completed the Balloon Analog Risk Task (BART) during fMRI scanning. We examined effects of Tanner stage, sex, and age on risky decision-making (mean wager at which individuals stopped balloon inflation) and neural activation in the middle frontal gyrus and the ventral striatum during the choice and outcome phases of decision-making. RESULTS: Those in earlier pubertal stages made riskier decisions during the BART compared to those in later Tanner stages (ß=-0.62, p = .02). Later pubertal stage was associated with greater activation in the left middle frontal gyrus (ß=0.61, p = .03) during the choice phase and in the right ventral striatum in response to rewards (ß=0.59, p = .03). CONCLUSION: Youth with ADHD/DBD in later stages of puberty, regardless of age, show greater ventral striatal activation in response to rewards.

Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders.

BACKGROUND: Currently approved medications for schizophrenia are relatively ineffective for negative symptoms and cognitive impairment. N-Acetyl Cysteine (NAC) is a neuroprotective agent that improved general symptoms, cognitive impairment and negative symptoms in some but not all studies, but failed to improve positive symptoms in patients with schizophrenia. Progressive brain mass loss (PBML) has been consistently observed in early phase schizophrenia. NAC mitigates the deleterious effects oxidative stress, inflammation and glutamatergic excitotoxicity and these three pathological processes are hypothesized to contribute to PBML. METHODS: In this study, we assessed the effects NAC (3600mg/day) in a 52-week, double-blind, placebo controlled trial on symptoms, and cognition in early phase schizophrenia spectrum disorders (N=60). In the context of the clinical trial, we explored the effects of NAC on brain morphology. RESULTS: NAC significantly improved (time×group) PANSS total (F=14.7, p<0.001), negative (F=5.1, p=0.024) and disorganized thought (F=13.7, p<0.001) symptom scores. NAC failed to improve PANSS positive symptoms and BACS cognitive scores. In preliminary analyses, baseline right (r=-0.48, p=0.041) and left (r=-0.45, p=0.018) total cortical thickness, and thickness in other cortical regions, were associated with NAC related improvement in PANSS total scores, but NAC, as compared to placebo, did not significantly impact brain morphology over the study treatment period. CONCLUSIONS: These results replicate some but not all previous findings of NAC efficacy. Preliminary results suggest that NAC's symptom effects may be related to structural integrity, but NAC failed to demonstrate treatment effects on longitudinal measures of brain morphology. ClinicalTrials.gov Identifier: NCT01339858.

Characterization of white matter abnormalities in early-stage schizophrenia.

AIM: White matter abnormalities have been reported in schizophrenia and may indicate altered cortical network integrity and structural connectivity, which have been hypothesized as key pathophysiological components of this illness. In this study, we aimed to further characterize the nature and progression of white matter alterations during the early stages of the disorder. METHODS: We employed diffusion tensor imaging (DTI) approaches to investigate fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) in 40 patients with schizophrenia and related psychotic disorders (aged 18-30 years) who were within 5 years of illness, along with an age-, sex- and race-matched sample of 21 healthy controls. Relationships with illness duration, lifetime antipsychotic medication exposure and symptom levels were examined. RESULTS: Patients had lower FA and higher RD than controls in numerous white matter tracts, including the corpus callosum (CC) and the superior longitudinal fasciculus. Illness duration was associated with lower FA and higher RD, most prominently in the CC. No group differences or relationships to illness duration were detected with AD, and no relationships between any DTI measurements and lifetime antipsychotic medication use were found. CONCLUSIONS: This investigation provides evidence of widespread disruptions to structural connectivity in the early stages of schizophrenia. The relationship to illness duration, coupled with an absence of relationships to AD or antipsychotic drug exposure, provides evidence of a progressive disease process, although prospective assessments with repeated DTI measurements are needed to fully characterize the trajectory of white matter abnormalities in this illness.

Global white matter microstructural abnormalities associated with addiction liability score in drug naïve youth.

Abnormalities in brain white matter (WM) structure have been reported in youths having a family history of substance use disorders (SUDs). It was hypothesized that these abnormalities constitute features of the liability for SUDs transmitted across generations. The association between severity of intergenerational risk for SUD, measured by the Transmissible Liability Index (TLI), and white matter microstructure was examined. Diffusion tensor imaging (DTI) measured WM microstructure in forty-four drug-naïve 10-14 year-olds (N = 19 with parental SUD). Metrics of WM microstructure (i.e., fractional anisotropy, radial diffusivity, mean diffusivity and axial diffusivity) were quantified across the whole brain and in four tracts of interest: anterior corona radiata, superior and inferior longitudinal fasciculi and superior fronto-occipital fasciculi. The TLI was completed by the youths, their parents and, when available, their teachers. The relationship between WM structure and TLI score across the entire group was evaluated using linear multiple regression and between group comparisons were also examined. Fractional anisotropy and radial diffusivity in multiple tracts across the brain were significantly associated with TLI scores. Confirming and extending prior research, the findings indicate that global atypicality in WM tracts was linearly related to liability for eventual SUD development in drug naïve youths.

Screen Violence and Youth Behavior.

Violence in screen entertainment media (ie, television, film, video games, and the Internet), defined as depictions of characters (or players) trying to physically harm other characters (or players), is ubiquitous. The Workgroup on Media Violence and Violent Video Games reviewed numerous meta-analyses and other relevant research from the past 60 years, with an emphasis on violent video game research. Consistent with every major science organization review, the Workgroup found compelling evidence of short-term harmful effects, as well as evidence of long-term harmful effects. The vast majority of laboratory-based experimental studies have revealed that violent media exposure causes increased aggressive thoughts, angry feelings, physiologic arousal, hostile appraisals, aggressive behavior, and desensitization to violence and decreases prosocial behavior (eg, helping others) and empathy. Still, to more fully understand the potential for long-term harm from media violence exposure, the field is greatly in need of additional large-sample, high-quality, longitudinal studies that include validated measures of media violence exposure and measures of other known violence risk factors. Also, although several high-quality media violence intervention studies have been conducted, larger-scale studies with more comprehensive and longer-term assessments are needed to fully understand long-term effects and to inform the development of tools that will help to reduce problems associated with aggression and violence. The evidence that violent screen media constitutes a causal risk factor for increased aggression is compelling. Modern social-cognitive theories of social behavior provide useful frameworks for understanding how and why these effects occur.

Association of medial prefrontal resting state functional connectivity and metacognitive capacity in early phase psychosis.

Metacognition refers to a range of cognitive processes that allow one to form complex ideas of self and others and to use this information to navigate psychosocial challenges. Several studies in both early-phase and prolonged schizophrenia have demonstrated not only that significant deficits in metacognitive ability are present, but importantly that they are associated with significant functional impairment and decreased quality of life. In spite of the importance of metacognitive impairment in schizophrenia, relatively little is known about the biological substrates that may contribute to this dysfunction. In this study, we examined the relationship between resting state functional connectivity of the medial prefrontal cortex (mPFC), a structure shown in prior voxel-based morphometry studies to be associated with metacognition, with metacognitive function in an early-phase psychosis cohort (n=18). Analyses revealed a positive association of resting state functional connectivity between the mPFC and precuneus and posterior cingulate structures and metacognitive ability. These results provide evidence of disrupted resting state connectivity in structures relevant to metacognitive dysfunction in early-phase psychosis, which may have implications for pathophysiological models of complex cognitive deficits in this illness.

A human chemosignal modulates frontolimbic activity and connectivity in response to emotional stimuli.

Evidence suggests the putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a natural component of human sweat, increases attention to emotional information when passively inhaled, even in minute amounts. However, the neural mechanisms underlying androstadienone's impact on the perception of emotional stimuli have not been clarified. To characterize how the compound modifies neural circuitry while attending to emotional information, 22 subjects (11 women) underwent two fMRI scanning sessions, one with an androstadienone solution and one with a carrier control solution alone on their upper lip. During each session, participants viewed blocks of emotionally positive, negative, or neutral images. The BOLD response to emotional images (relative to neutral images) was greater during exposure to androstadienone in right orbitofrontal and lateral prefrontal cortex, particularly during positive image blocks. Androstadienone did not impact the response to social images, compared to nonsocial images, and results were not related to participant sex or olfactory sensitivity. To examine how androstadienone influences effective connectivity of this network, a dynamic causal model was employed with primary visual cortex (V1), amygdala, prefrontal cortex, and orbitofrontal cortex on each side. These models indicated that emotional images increased the drive from V1 to the amygdala during the control session. With androstadienone present, this drive to amygdala was decreased specifically for positive images, which drove downstream increases in orbitofrontal and prefrontal activity. This evidence suggests that androstadienone may act as a chemical signal to increase attention to positively valenced information via modifications to amygdala connectivity.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis.

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n = 35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness.