Childhood anhedonia symptoms and stressful life events predict the development of reward-related brain activity across adolescence.

The reward positivity (RewP) is an event-related potential that indexes reinforcement learning and reward system activation. The RewP has been shown to increase across adolescence; however, most studies have examined the RewP across two assessments, and no studies have examined within-person changes across adolescence into young adulthood. Moreover, the RewP has been identified as a neurobiological risk factor for adolescent-onset depression, but it is unclear whether childhood psychosocial risk factors might predict RewP development across adolescence. In a sample of 317 8- to 14-year-old girls (Mage = 12.4, SD = 1.8), the present study examined self-report measures of depression symptoms and stressful life events at baseline and the ΔRewP during the doors guessing task across three timepoints. Growth modeling indicated that, across all participants, the ΔRewP did not demonstrate linear change across adolescence. However, baseline anhedonia symptoms predicted within-person changes in the ΔRewP, such that individuals with low anhedonia symptoms demonstrated a linear increase in the ΔRewP, but individuals with high anhedonia symptoms had no change in the ΔRewP across adolescence. Similar patterns were observed for stressful life events. The present study suggests that childhood risk factors impact the development of reward-related brain activity, which might subsequently increase risk for psychopathology.

Error-related brain activity in pediatric major depressive disorder: An ERP and time-frequency investigation.

BACKGROUND: The error-related negativity (ERN) reflects individual differences in error monitoring. However, findings on the ERN in adult and adolescent depression have been inconsistent. Analyzing electroencephalographic (EEG) data in both the time- and time-frequency domain can be useful to better quantify neural response to errors. The present study aimed at examining electrocortical measures of error monitoring in early adolescents with and without depression. METHOD: EEG activity was collected during an arrowhead version of the flanker task in 29 (25 females) early adolescents with depression and 34 without MDD (29 females). RESULTS: The depression group showed reduced ERN amplitude, reduced error-related theta power and increased error-related beta power compared to the control group. When all variables that related to MDD diagnosis were considered simultaneously, both theta and beta power, but not the ERN, were independently related to an increased likelihood of being diagnosed with depression. CONCLUSIONS: By examining both time-domain and separate time-frequency measures, the present study provided novel evidence on error monitoring alterations in youth depression, suggesting that depression during adolescence may be characterized by reduced error monitoring (i.e., reduced ERN and error-related theta) and post-error inhibition (i.e., greater error-related beta power). These results support that time-frequency measures might be better suited for examining error-related neural activity in MDD relative to time-domain measures.

Affective modulation of the startle response among children at high and low risk for anxiety disorders.

BACKGROUND: Identifying early markers of risk for anxiety disorders in children may aid in understanding underlying mechanisms and informing prevention efforts. Affective modulation of the startle response indexes sensitivity to pleasant and unpleasant environmental contexts and has been shown to relate to anxiety, yet the extent to which abnormalities in affect-modulated startle reflect vulnerability for anxiety disorders in children has yet to be examined. The current study assessed the effects of parental psychopathology on affective modulation of startle in offspring. METHOD: Nine-year-old children (n = 144) with no history of anxiety or depressive disorders completed a passive picture viewing task in which eye-blink startle responses were measured during the presentation of pleasant, neutral, and unpleasant images. RESULTS: Maternal anxiety was associated with distinct patterns of affective modulation of startle in offspring, such that children with maternal histories of anxiety showed potentiation of the startle response while viewing unpleasant images, but not attenuation during pleasant images, whereas children with no maternal history of anxiety exhibited attenuation of the startle response during pleasant images, but did not exhibit unpleasant potentiation - even when controlling for child symptoms of anxiety and depression. No effects of maternal depression or paternal psychopathology were observed. CONCLUSIONS: These findings suggest that both enhanced startle responses in unpleasant conditions and failure to inhibit startle responses in pleasant conditions may reflect early emerging vulnerabilities that contribute to the later development of anxiety disorders.

Familial risk for distress and fear disorders and emotional reactivity in adolescence: an event-related potential investigation.

BACKGROUND: The late positive potential (LPP) is an event-related potential component that is sensitive to the motivational salience of stimuli. Children with a parental history of depression, an indicator of risk, have been found to exhibit an attenuated LPP to emotional stimuli. Research on depressive and anxiety disorders has organized these conditions into two empirical classes: distress and fear disorders. The present study examined whether parental history of distress and fear disorders was associated with the LPP to emotional stimuli in a large sample of adolescent girls. METHOD: The sample of 550 girls (ages 13.5-15.5 years) with no lifetime history of depression completed an emotional picture-viewing task and the LPP was measured in response to neutral, pleasant and unpleasant pictures. Parental lifetime history of psychopathology was determined via a semi-structured diagnostic interview with a biological parent, and confirmatory factor analysis was used to model distress and fear dimensions. RESULTS: Parental distress risk was associated with an attenuated LPP to all stimuli. In contrast, parental fear risk was associated with an enhanced LPP to unpleasant pictures but was unrelated to the LPP to neutral and pleasant pictures. Furthermore, these results were independent of the adolescent girls' current depression and anxiety symptoms and pubertal status. CONCLUSIONS: The present study demonstrates that familial risk for distress and fear disorders may have unique profiles in terms of electrocortical measures of emotional information processing. This study is also one of the first to investigate emotional/motivational processes underlying the distress and fear disorder dimensions.

Impaired emotion regulation in schizophrenia: evidence from event-related potentials.

BACKGROUND: Although several aspects of emotion seem to be intact in schizophrenia, there is emerging evidence that patients show an impaired ability to adaptively regulate their emotions. This event-related potential (ERP) study examined whether schizophrenia is associated with impaired neural responses to appraisal frames, that is when negative stimuli are presented in a less negative context. METHOD: Thirty-one schizophrenia out-patients and 27 healthy controls completed a validated picture-viewing task with three conditions: (1) neutral pictures preceded by neutral descriptions ('Neutral'), (2) unpleasant pictures preceded by negative descriptions ('Preappraised negative'), and (3) unpleasant pictures preceded by more neutral descriptions ('Preappraised neutral'). Analyses focused on the late positive potential (LPP), an index of facilitated attention to emotional stimuli that is reduced following cognitive emotion regulation strategies, during four time windows from 300 to 2000 ms post-picture onset. RESULTS: Replicating prior studies, controls showed smaller LPP in Preappraised neutral and Neutral versus Preappraised negative conditions throughout the 300-2000-ms time period. By contrast, patients showed (a) larger LPP in Preappraised neutral and Preappraised negative versus Neutral conditions in the initial period (300-600 ms) and (b) an atypical pattern of larger LPP to Preappraised neutral versus Preappraised negative and Neutral conditions in the 600-1500-ms epochs. CONCLUSIONS: Modulation of neural responses by a cognitive emotion regulation strategy seems to be impaired in schizophrenia during the first 2 s after exposure to unpleasant stimuli.

Additive effects of the dopamine D2 receptor and dopamine transporter genes on the error-related negativity in young children.

The error-related negativity (ERN) is a negative deflection in the event-related potential that occurs approximately 50 ms following the commission of an error at fronto-central electrode sites. Previous models suggest dopamine plays a role in the generation of the ERN. We recorded event-related potentials (ERPs) while 279 children aged 5-7 years completed a simple Go/No-Go task; the ERN was examined in relation to the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes. Results suggest an additive effect of the DRD2 and DAT1 genotype on ERN magnitude such that children with at least one DRD2 A1 allele and children with at least one DAT1 9 allele have an increased (i.e. more negative) ERN. These results provide further support for the involvement of dopamine in the generation of the ERN.

Impaired neural response to internal but not external feedback in schizophrenia.

BACKGROUND: Accurate monitoring and integration of both internal and external feedback is crucial for guiding current and future behavior. These aspects of performance monitoring are commonly indexed by two event-related potential (ERP) components: error-related negativity (ERN) and feedback negativity (FN). The ERN indexes internal response monitoring and is sensitive to the commission of erroneous versus correct responses, and the FN indexes external feedback monitoring of positive versus negative outcomes. Although individuals with schizophrenia consistently demonstrate a diminished ERN, the integrity of the FN has received minimal consideration. METHOD: The current research sought to clarify the scope of feedback processing impairments in schizophrenia in two studies: study 1 examined the ERN elicited in a flanker task in 16 out-patients and 14 healthy controls; study 2 examined the FN on a simple monetary gambling task in expanded samples of 35 out-patients and 33 healthy controls. RESULTS: Study 1 replicated prior reports of an impaired ERN in schizophrenia. By contrast, patients and controls demonstrated comparable FN differentiation between reward and non-reward feedback in study 2. CONCLUSIONS: The differential pattern across tasks suggests that basic sensitivity to external feedback indicating reward versus non-reward is intact in schizophrenia, at least under the relatively simple task conditions used in this study. Further efforts to specify intact and impaired reward-processing subcomponents in schizophrenia may help to shed light on the diminished motivation and goal-seeking behavior that are commonly seen in this disorder.

Dorsolateral prefrontal cortex stimulation modulates electrocortical measures of visual attention: evidence from direct bilateral epidural cortical stimulation in treatment-resistant mood disorder.

Electrocortical activity is increasingly being used to study emotion regulation and the impact of cognitive control on neural response to visual stimuli. In the current study, we used direct epidural cortical stimulation (EpCS) to examine regional specificity of PFC stimulation on the parietally-maximal late positive potential (LPP), an event-related potential (ERP) biomarker of visual attention to salient stimuli. Five patients with treatment-resistant mood disorders were stereotactically implanted with stimulating paddles over frontopolar (FP) and dorsolateral (DL) prefrontal cortex bilaterally. On their first day of activation, patients underwent sham-controlled EpCS coupled with 64-channel electroencephalograph (EEG) recordings and passive viewing of aversive and neutral images. In addition to sham, patients had either FP or DL prefrontal cortex stimulated at 2 or 4 V while they viewed neutral and aversive pictures. As expected during the sham condition, LPP was larger for aversive compared to neutral stimuli (F(1,4)=232.07, P<.001). Stimulation of DL compared to FP prefrontal cortex resulted in a reduction of the LPP (F(1,4)=8.15, P=.048). These data provide additional and unique support to the role of the DL prefrontal cortex in regulating measures of neural activity that have been linked to emotional arousal and attention. Future studies with EpCS can help directly map out various prefrontal functions in treatment-resistant mood disorder.

Genetic variation in brain-derived neurotrophic factor and human fear conditioning.

Brain-derived neurotrophic factor (BDNF) has been implicated in hippocampal-dependent learning processes, and carriers of the Met allele of the Val66Met BDNF genotype are characterized by reduced hippocampal structure and function. Recent nonhuman animal work suggests that BDNF is also crucial for amygdala-dependent associative learning. The present study sought to examine fear conditioning as a function of the BDNF polymorphism. Fifty-seven participants were genotyped for the BDNF polymorphism and took part in a differential-conditioning paradigm. Participants were shocked following a particular conditioned stimulus (CS+) and were also presented with stimuli that ranged in perceptual similarity to the CS+ (20, 40 or 60% smaller or larger than the CS+). The eye blink component of the startle response was measured to quantify fear conditioning; post-task shock likelihood ratings for each stimulus were also obtained. All participants reported that shock likelihood varied with perceptual similarity to the CS+ and showed potentiated startle in response to CS +/- 20% stimuli. However, only the Val/Val group had potentiated startle responses to the CS+. Met allele carrying individuals were characterized by deficient fear conditioning--evidenced by an attenuated startle response to CS+ stimuli. Variation in the BDNF genotype appears related to abnormal fear conditioning, consistent with nonhuman animal work on the importance of BDNF in amygdala-dependent associative learning. The relation between genetic variation in BDNF and amygdala-dependent associative learning deficits is discussed in terms of potential mechanisms of risk for psychopathology.