Lack of Ventral Striatal Response to Positive Stimuli in Depressed Versus Normal Subjects

Department of Psychiatry, Cornell University, Итак, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 11/2006; 163(10):1784-90. DOI: 10.1176/appi.ajp.163.10.1784
Source: PubMed


Most of the functional neuroimaging studies of depression have focused primarily on the resting state or responses to negatively valenced stimuli. However, depression consists not only of an accentuation of negative affective processing but of an inability to experience pleasure or positive motivation. The authors tested the hypothesis that depressed subjects would show less activation than healthy comparison subjects, in response to positive stimuli, in ventral striatal regions associated with processing of reward and positive stimuli.
Positive, negative, and neutral words were presented to 10 unmedicated depressed patients and 12 healthy comparison subjects in the context of a 3T functional magnetic resonance imaging (MRI) paradigm. Image processing and analysis were performed using statistical parametric mapping with a mixed-effects model. Significant differences in neural responses were assessed, examining group, condition, and interaction effects of interest within the context of a general linear model.
Relative to comparison subjects, depressed patients demonstrated significantly less bilateral ventral striatal activation to positive stimuli, correlating with decreased interest/pleasure in and performance of activities. They also displayed decreased activation to positive stimuli in a dorsomedial frontal region associated with processing of self-related stimuli. Responses of depressed subjects to negative stimuli were consistent with the growing literature on frontolimbic dysfunction in depression.
This finding 1) supports a pathophysiological model of depression that includes reward/motivational pathway dysfunction, 2) suggests a contributing neural substrate of the inability to experience pleasure or engage in rewarding activities, 3) provides greater specification of abnormalities of basal ganglia function in depression, and 4) may help guide treatment approaches.

Download full-text


Available from: Hong Pan, Aug 07, 2014
1 Follower
106 Reads
  • Source
    • "ence and arousal on 9 - point scales identical to that of the Affective Norms for English Words ( Bradley and Lang , 1999 ) . Two memory metrics were calculated from this questionnaire : 1 ) Recognition performance for each word type was calculated by adjusting hit rate ( p ) with false alarm rate ( fp ) using the formula ( p - fp ) / ( 1 - fp ) ( Epstein et al . , 2006 ) ; and 2 ) Memory bias was calculated by subtracting recognition performance for neutral words from that for negative words and for positive words . One participant from the control group did not complete more than 80% of the valence ratings and two participants did not complete more than 80% of the arousal ratings ; therefore , their "
    [Show abstract] [Hide abstract]
    ABSTRACT: This work investigated the impact of heavy marijuana use during adolescence on emotional functioning, as well as the brain functional mediators of this effect. Participants (n = 40) were recruited from the Michigan Longitudinal Study (MLS). Data on marijuana use were collected prospectively beginning in childhood as part of the MLS. Participants were classified as heavy marijuana users (n = 20) or controls with minimal marijuana use. Two facets of emotional functioning—negative emotionality and resiliency (a self-regulatory mechanism)—were assessed as part of the MLS at three time points: mean age 13.4; mean age 19.6; and mean age 23.1. Functional neuroimaging data during an emotion-arousal word task were collected at mean age 20.2. Negative emotionality decreased and resiliency increased across the three time points in controls but not heavy marijuana users. Compared with controls, heavy marijuana users had less activation to negative words in temporal, prefrontal, and occipital cortices, insula, and amygdala. Activation of dorsolateral prefrontal cortex to negative words mediated an association between marijuana group and later negative emotionality. Activation of the cuneus/lingual gyrus mediated an association between marijuana group and later resiliency. Results support growing evidence that heavy marijuana use during adolescence affects later emotional outcomes.
    Developmental Cognitive Neuroscience 09/2015; DOI:10.1016/j.dcn.2015.09.003 · 3.83 Impact Factor
  • Source
    • "Given the above, we argue that reduced hedonic capacity can also be measured as an enduring trait in nonclinical samples. However, most previous studies have focused exclusively on clinical populations (Epstein et al., 2006; Tremblay et al., 2005). Of the small number of studies focusing on healthy individuals, most investigated the problem with tasks involving monetary rewards (Knutson et al., 2003, 2000). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Anticipatory and consummatory dissociation of hedonic experience may manifest as trait anhedonia in healthy and clinical populations. It is still unclear whether the underlying neural mechanisms of the monetary-based and affect-based incentive delay paradigms are distinct from each other. The present study aimed to examine the similarities and differences between the Affect Incentive Delay (AID) and the Monetary Incentive Delay (MID) imaging paradigms in relation to brain activations. We administered the AID and the MID imaging tasks to 28 adolescent participants. A cue signaling the type of forthcoming feedback (reward or punishment) was displayed to the participants, followed by a target-hit task with corresponding reward or punishment. The striatal and limbic regions were activated during the anticipatory phase of MID, while there was no brain activation during the anticipatory phase of AID. In the consummatory phase, the MID task activated the medial frontal cortex, while the AID task activated the frontal and dorsal limbic regions. We further found that the anhedonic group exhibited significant hypoactivation than the nonanhedonic group at the left pulvinar, the left claustrum and the left insula to positive cues in the anticipatory phase of the AID task. The results suggest that the AID and the MID tasks have unique activation patterns. Our findings also suggest that the AID task may be more sensitive in detecting anhedonia in people with trait anhedonia. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Neuropsychology 08/2015; DOI:10.1037/neu0000233 · 3.27 Impact Factor
  • Source
    • "Our laboratory has previously implemented instructed-fear/safety paradigms to probe frontolimbic and subcortical emotional processing in healthy subjects (Butler et al., 2005, 2007b) and anxiety disorders (Tuescher et al., 2011). Emotional word fMRI paradigms have also been designed by our group to investigate emotionallinguistic processing in healthy subjects (Isenberg et al., 1999; Protopopescu et al., 2005a) and neuropsychiatric populations (Protopopescu et al., 2005b; Epstein et al., 2006, 2011; Silbersweig et al., 2007). The dimensional symptom-specific approach used in this study has been used previously by our laboratory to characterize brain-symptom relationships in other neuropsychiatric disorders (Protopopescu et al., 2005b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social "real world" and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 06/2015; 233(3). DOI:10.1016/j.pscychresns.2015.06.002 · 2.42 Impact Factor
Show more