Reward signals, attempted suicide, and impulsivity in late-life depression

Abstract

IMPORTANCE—Suicide can be viewed as an escape from unendurable punishment at the cost of any future rewards. Could faulty estimation of these outcomes predispose to suicidal behavior? In behavioral studies, many of those who have attempted suicide misestimate expected rewards on gambling and probabilistic learning tasks.OBJECTIVES—To describe the neural circuit abnormalities that underlie disadvantageous choices in people at risk for suicide and to relate these abnormalities to impulsivity, which is one of the components of vulnerability to suicide.DESIGN—Case-control functional magnetic resonance imaging study of reward learning using are inforcement learning model.SETTING—University hospital and outpatient clinic.PATIENTS—Fifty-three participants 60 years or older, including 15 depressed patients who had attempted suicide, 18 depressed patients who had never attempted suicide (depressed control subjects), and 20 psychiatrically healthy controls.MAIN OUTCOMES AND MEASURES—Components of the cortical blood oxygenation level–dependent response tracking expected and unpredicted rewards.RESULTS—Depressed elderly participants displayed 2 distinct disruptions of control over reward-guided behavior. First, impulsivity and a history of suicide attempts (particularly poorly planned ones) were associated with a weakened expected reward signal in the paralimbic cortex,which in turn predicted the behavioral insensitivity to contingency change. Second, depression was associated with disrupted corticostriatothalamic encoding of unpredicted rewards, which in turn predicted the behavioral over sensitivity to punishment. These results were robust to the effects of possible brain damage from suicide attempts, depressive severity, co-occurring substance use and anxiety disorders, antidepressant and anticholinergic exposure, lifetime exposure to electroconvulsive therapy, vascular illness, and incipient dementia.CONCLUSIONS AND RELEVANCE—Altered paralimbic reward signals and impulsivity and/or carelessness may facilitate unplanned suicidal acts. This pattern, also seen in gambling and cocaine use, may reflect a primary deficit in the paralimbic cortex or in its mesolimbic input. The over reactivity to punishment in depression may be caused in part by a disruption of appetitive learning in the corticostriatothalamic circuits.

Figure 1. Modulation by Expected Reward

A, Within-group analyses. In controls, high expected reward (shown in blue) positively modulated the blood oxygenation level–dependent signal in the ventromedial prefrontal cortex (vmPFC; Brodmann areas [BAs] 10, 32, and 24), the posterior insula (area 1), and other paralimbic structures (the midcingulate cortex [BA 24] and precuneus [BAs 7 and 31; area 2]). A large cortical network responded to high ambiguity/low value (shown in red). This network included the lateral prefrontal areas of the ventrolateral PFC (vlPFC; lateral BA 10 and BAs 13, 44, and 45; operculoinsular cortex [area 3]) and the dorsolateral PFC (dlPFC; BA 9 and lateral BA 8) that we expected to be activated a priori and the lateral parietal cortex (lat parietal; BAs 7 and 40) and dorsomedial PFC (dmPFC; medial BA 8; shown in red). Although the maps were qualitatively similar in nonsuicidal depressed participants, suicide attempters did not display paralimbic responses to high expected reward. Area 4 indicates associative striatum and thalamus. P < .005, uncorrected for illustration. B, A history of suicide attempts was related to a weaker response to expected reward in the pericallosal vmPFC (pregenual cingulate [BA 32, 24, and 25] on the posterior periphery of the reward-modulated vmPFC region of interest). P < .05, corrected, controlling for depression group status. The x and z values indicate Montreal Neurological Institute coordinates.

Figure 2. Impulsivity and Paralimbic Expected Reward Signals in Depressed Participants

A, Paralimbic functional network masks were independently derived in controls. B, Depressed participants (nonsuicidal and suicide attempters) with weaker paralimbic responses to expected reward were more likely to ignore negative feedback after a reversal, making multiple perseverative errors. C, Weak paralimbic responses were related to bets against the odds on the Cambridge Gamble Task (CGT). D, Weak paralimbic responses were related to poor attempt planning in suicide attempters. E, Weak paralimbic responses were related to higher scores on the Impulsive/Careless Style subscale of the Social Problem-Solving Inventory. F, Weak paralimbic responses were related to higher scores on the Nonplanning subscale of the Barratt Impulsiveness Scale.

Figure 3. Time Course of Reward Signals in Healthy Controls

We compared the paralimbic (blue) vs neocortical task (red) networks in healthy controls (n = 20). The onset of the time window corresponds to reward delivery on the preceding trial. Paralimbic responses to high expected value peaked earlier than responses to the low expected value in the lateralized frontoparietal network, operculoinsular cortex, ventrolateral prefrontal cortex (vlPFC), and dorsolateral prefrontal cortex (dlPFC), ostensibly aligned with the next stimulus presentation. This alignment suggests that paralimbic structures responded to the reward from the preceding trial. Indeed, the timing of paralimbic response is unlikely to coincide with actual choice because the peak to response would have to be less than 4 seconds. ANOVA indicates analysis of variance; vmPFC, ventromedial prefrontal cortex.

Figure 4. Modulation by Positive Prediction Error

A, Within-group analysis in controls (n = 20). Unexpected rewards (positive prediction error) modulated the same networks as ambiguity, plus the midcingulate cortex, striatum, and thalamus. Area 1 indicates the putamen; area 2, inferior parietal lobule; area 3, operculoinsular cortex; area 4, thalamus; and dmPFC, dorsomedial prefrontal cortex. P < .05, corrected. B, As a group, depressed participants (nonsuicidal and suicide attempters) displayed weaker modulation by positive prediction error in the right thalamus, the bilateral superior temporal gyrus (Brodmann area [BA] 22 and 39), the bilateral operculoinsular cortex (BA 13, 45, and 46), the bilateral postcentral gyrus (BA 40), and the bilateral supplementary motor area/cingulate. P < .05, corrected, controlling for a history of suicide attempts.