Coupling between spontaneous pupillary fluctuations and brain activity relates to inattentiveness.

Autonomic activity in neurological and psychiatric disorders is often dysregulated, particularly in the context of attentional behaviors. This suggests that interplay between the autonomic nervous system and aspects of the central nervous system subserving attention may be disrupted in these conditions. Better understanding these interactions and their relationship with individual variation in attentional behaviors could facilitate development of mechanistic biomarkers. We identified brain regions defined by trait-sensitive central-autonomic coupling as a first step in this process. As spontaneous neural activity measured during the resting state is sensitive to phenotypic variability, unconfounded by task performance, we examined whether spontaneous fluctuations in brain activity and an autonomic measure, pupil diameter, were coupled during the resting state, and whether that coupling predicted individual differences in attentional behavior. By employing concurrent pupillometry and fMRI during the resting state, we observed positive coupling in regions comprising cingulo-opercular, default mode, and fronto-parietal networks, as well as negative coupling with visual and sensorimotor regions. Individuals less prone to distractibility in everyday behavior demonstrated stronger positive coupling in cingulo-opercular regions often associated with sympathetic activity. Overall, our results suggest that individuals less prone to distractibility have tighter intrinsic coordination between specific brain areas and autonomic systems, which may enable adaptive autonomic shifts in response to salient environmental cues. These results suggest that incorporating autonomic indices in resting-state studies should be useful in the search for biomarkers for neurological and psychiatric disorders.

Paralimbic and lateral prefrontal encoding of reward value during intertemporal choice in attempted suicide.

BACKGROUND: Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters' inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior. METHOD: A total of 48 participants aged 46-90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls. RESULTS: More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses. CONCLUSIONS: Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.

Corticostriatothalamic reward prediction error signals and executive control in late-life depression.

BACKGROUND: Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions. METHOD: Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning). RESULTS: Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure. CONCLUSIONS: Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.

Sleep deprivation amplifies striatal activation to monetary reward.

BACKGROUND: Sleep loss produces abnormal increases in reward seeking but the mechanisms underlying this phenomenon are poorly understood. The present study examined the influence of one night of sleep deprivation on neural responses to a monetary reward task in a sample of late adolescents/young adults. METHOD: Using a within-subjects crossover design, 27 healthy, right-handed late adolescents/young adults (16 females, 11 males; mean age 23.1 years) underwent functional magnetic resonance imaging (fMRI) following a night of sleep deprivation and following a night of normal sleep. Participants' recent sleep history was monitored using actigraphy for 1 week prior to each sleep condition. RESULTS: Following sleep deprivation, participants exhibited increased activity in the ventral striatum (VS) and reduced deactivation in the medial prefrontal cortex (mPFC) during the winning of monetary reward, relative to the same task following normal sleep conditions. Shorter total sleep time over the five nights before the sleep-deprived testing condition was associated with reduced deactivation in the mPFC during reward. CONCLUSIONS: These findings support the hypothesis that sleep loss produces aberrant functioning in reward neural circuitry, increasing the salience of positively reinforcing stimuli. Aberrant reward functioning related to insufficient sleep may contribute to the development and maintenance of reward dysfunction-related disorders, such as compulsive gambling, eating, substance abuse and mood disorders.

The temptation of suicide: striatal gray matter, discounting of delayed rewards, and suicide attempts in late-life depression.

BACKGROUND: Converging evidence implicates basal ganglia alterations in impulsivity and suicidal behavior. For example, D2/D3 agonists and subthalamic nucleus stimulation in Parkinson's disease (PD) trigger impulse control disorders and possibly suicidal behavior. Furthermore, suicidal behavior has been associated with structural basal ganglia abnormalities. Finally, low-lethality, unplanned suicide attempts are associated with increased discounting of delayed rewards, a behavior dependent upon the striatum. Thus, we tested whether, in late-life depression, changes in the basal ganglia were associated with suicide attempts and with increased delay discounting. METHOD: Fifty-two persons aged ≥ 60 years underwent extensive clinical and cognitive characterization: 33 with major depression [13 suicide attempters (SA), 20 non-suicidal depressed elderly] and 19 non-depressed controls. Participants had high-resolution T1-weighted magnetization prepared rapid acquisition gradient-echo (MPRAGE) magnetic resonance imaging (MRI) scans. Basal ganglia gray matter voxel counts were estimated using atlas-based segmentation, with a highly deformable automated algorithm. Discounting of delayed rewards was assessed using the Monetary Choice Questionnaire (MCQ) and delay aversion with the Cambridge Gamble Task (CGT). RESULTS: SA had lower putamen but not caudate or pallidum gray matter voxel counts, compared to the control groups. This difference persisted after accounting for substance use disorders and possible brain injury from suicide attempts. SA with lower putamen gray matter voxel counts displayed higher delay discounting but not delay aversion. Secondary analyses revealed that SA had lower voxel counts in associative and ventral but not sensorimotor striatum. CONCLUSIONS: Our findings, although limited by small sample size and the case-control design, suggest that striatal lesions could contribute to suicidal behavior by increasing impulsivity.

Pupillary and reaction time measures of sustained processing of negative information in depression.

BACKGROUND: Disruptions of emotional information processing (i.e., attention to, memory for, and interpretation of emotional information) have been implicated in the onset and maintenance of depression. The research presented here investigated cognitive and psychophysiological features of a particularly promising correlate of depression: sustained processing of negative information 4--5 sec after an emotional stimulus. METHODS: Pupil dilation data and reaction times were collected from 24 unmedicated depressed and 25 nondepressed adults in response to emotional processing tasks (lexical decision and valence identification) that employed idiosyncratically generated personally relevant and normed stimuli. Pupil dilation was used to index sustained cognitive processing devoted to stimuli. RESULTS: Consistent with predictions, depressed individuals were especially slow to name the emotionality of positive information, and displayed greater sustained processing (pupil dilation) than nondepressed individuals when their attention was directed toward emotional aspects of information. Contrary to predictions, depressed participants did not dilate more to negative than positive stimuli, compared to nondepressed participants. CONCLUSIONS: These data suggest depressed individuals may not initially attend to emotional aspects of information but may continue to process them seconds after they have reacted to the information.

Brain activation and pupil response during covert performance of the Stroop Color Word task.

Patterns of brain activation associated with covert performance of the Stroop Color-Word task were studied in young, healthy, adult volunteers using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Comparisons of the incongruous Stroop condition were made with both color naming and word reading baselines. Areas of the left and right anterior cingulate, the right precuneus, and the left pars opercularis displayed larger BOLD signal responses during the incongruous Stroop condition than during baseline conditions. Activation of BOLD signals in these areas was highly repeatable. In a second experiment, pupil diameter was used to assess cognitive load in 7 individuals studied during overt and covert performance of both Stroop and color naming conditions. Cognitive load was similar in overt and covert response conditions. Results from the BOLD study indicate that brain regions participating in selective visual attention and in the selection of motor programs involved in speech were activated more by the Stroop task than by the baseline tasks. The neural substrate involved in the resolution of the perceptual and motor conflicts elicited by the Stroop Color-Word task does not appear to be a single brain region. Rather, a network of brain regions is implicated, with separate regions within this system supporting distinct functions.

Sex differences in visual recognition memory: support for a sex-related difference in attention in adults and children.

The selectivity hypothesis of Meyers-Levy (1989) proposes that cognitive sex differences reflect underlying differences in information processing between males and females. Males are considered to be more likely to organize information in a self-related manner, whereas females are more likely to adopt a comprehensive approach to information processing. We tested this hypothesis in children (10-15 years) and adults using recognition memory tasks. Tests were devised which employed male-oriented objects, female oriented objects, or random objects. In both the child and adult samples, females performed significantly better than males on tests using random and female-oriented objects. Males performed at the level of females only when tested for recognition of male-oriented objects. These results demonstrate that this sex difference is present prior to puberty and support the concept of sex differences in information processing.