Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents

BACKGROUND: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance abuse disorders. Studies in non-human primates have identified brain regions, including the dorsal / ventral striatum and orbital-frontal cortex (OFC), in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level dependant (BOLD) responses in these regions during functional magnetic resonance imaging (FMRI) paradigms. However no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents. METHODS: We used event-related FMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in non-psychiatric children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth. RESULTS: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum, lateral and medial OFC; specifically, these regions showed larger responses to positive than to negative feedback. CONCLUSIONS: These results provide further evidence for the value of event-related FMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth

Gender specific neural correlates of emotion and cognition

Evidence suggests that regions within the anterior cingulate cortex (ACC) are sensitive both to emotional and cognitive task demands. This experiment asked whether emotional and cognitive demands are processed separately by ventral and dorsal regions within the ACC, respectively. Results revealed significant individual variability between changes in anxiety and response times with practice during performance of a verb generation task. Correlational analyses of the functional magnetic resonance imaging (fMRI) data were inconclusive. However, exploratory analyses suggest that while the ventral and dorsal subdivisions of the medial prefrontal cortex, which encompasses the ACC, make specialized contributions to the processing of emotion and cognition, respectively, the two subdivisions also appear to interact. These analyses also suggest that there could be a difference in how women and men balance the competing demands of emotion and cognition that might be related to differences in self-concept and neural activity in the default mode network

Temporal precedence of emotion over attention modulations in the lateral amygdala: Intracranial ERP evidence from a patient with temporal lobe epilepsy

Previous fMRI studies have reported mixed evidence for the influence of selective attention on amygdala responses to emotional stimuli, with some studies showing "automatic" emotional effects to threat-related stimuli without attention (or even without awareness), but other studies showing a gating of amygdala activity by selective attention with no response to unattended stimuli. We recorded intracranial local field potentials from the intact left lateral amygdala in a human patient prior to surgery for epilepsy and tested, with a millisecond time resolution, for neural responses to fearful faces appearing at either task-relevant or task-irrelevant locations. Our results revealed an early emotional effect in the amygdala arising prior to, and independently of, attentional modulation. However, at a later latency, we found a significant modulation of the differential emotional response when attention was directed toward or away from fearful faces. These results suggest separate influences of emotion and attention on amygdala activation and may help reconcile previous discrepancies concerning the relative responsiveness of the human amygdala to emotional and attentional factors

Time Scales of Auditory Habituation in the Amygdala and Cerebral Cortex

Habituation is a fundamental form of learning manifested by a decrement of neuronal responses to repeated sensory stimulation. In addition, habituation is also known to occur on the behavioral level, manifested by reduced emotional reactions to repeatedly presented affective stimuli. It is, however, not clear which brain areas show a decline in activity during repeated sensory stimulation on the same time scale as reduced valence and arousal experience and whether these areas can be delineated from other brain areas with habituation effects on faster or slower time scales. These questions were addressed using functional magnetic resonance imaging acquired during repeated stimulation with piano melodies. The magnitude of functional responses in the laterobasal amygdala and in related cortical areas and that of valence and arousal ratings, given after each music presentation, declined in parallel over the experiment. In contrast to this long-term habituation (43 min), short-term decreases occurring within seconds were found in the primary auditory cortex. Sustained responses that remained throughout the whole investigated time period were detected in the ventrolateral prefrontal cortex extending to the dorsal part of the anterior insular cortex. These findings identify an amygdalocortical network that forms the potential basis of affective habituation in human

BOLD Correlates of Trial-by-Trial Reaction Time Variability in Gray and White Matter: A Multi-Study fMRI Analysis

Reaction time (RT) is one of the most widely used measures of performance in experimental psychology, yet relatively few fMRI studies have included trial-by-trial differences in RT as a predictor variable in their analyses. Using a multi-study approach, we investigated whether there are brain regions that show a general relationship between trial-by-trial RT variability and activation across a range of cognitive tasks.The relation between trial-by-trial differences in RT and brain activation was modeled in five different fMRI datasets spanning a range of experimental tasks and stimulus modalities. Three main findings were identified. First, in a widely distributed set of gray and white matter regions, activation was delayed on trials with long RTs relative to short RTs, suggesting delayed initiation of underlying physiological processes. Second, in lateral and medial frontal regions, activation showed a "time-on-task" effect, increasing linearly as a function of RT. Finally, RT variability reliably modulated the BOLD signal not only in gray matter but also in diffuse regions of white matter.The results highlight the importance of modeling trial-by-trial RT in fMRI analyses and raise the possibility that RT variability may provide a powerful probe for investigating the previously elusive white matter BOLD signal

Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivit

Effects of Aversive Stimuli on Prospective Memory. An Event-Related fMRI Study

Prospective memory (PM) describes the ability to execute a previously planned action at the appropriate point in time. Although behavioral studies clearly showed that prospective memory performance is affected by the emotional significance attributed to the intended action, no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance. The general aim of the present study was to explore brain regions involved in prospective memory processes when PM cues are associated with emotional stimuli. In particular, based on the hypothesised critical role of the prefrontal cortex in prospective memory in the presence of emotionally salient stimuli, we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus. To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions. Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area (BA 10) and in the left caudate nucleus. Moreover a temporal shift between the response of the caudate nucleus that preceded that of aPFC was observed. These findings suggest that the caudate nucleus might provide an early analysis of the affective properties of the stimuli, whereas the anterior lateral prefrontal cortex (BA10) would be involved in a slower and more deliberative analysis to guide goal-directed behaviour

Sustained and Transient Reward Effect on Cognitive Control in Schizophrenia: The Relevance of Negative Symptoms

Schizophrenia (SCZ) is characterized by severe cognitive impairments and amotivation, generally referred to as negative symptoms, including anhedonia and/or avolition. Amotivation tends to exist in prodromal patients and persist over the illness course regardless of successful antipsychotic medications, which are known to reduce positive symptoms, including hallucination and delusions (e.g., (Horan, Blanchard, Clark, & Green, 2008; Tarbox et al., 2013). Importantly, amotivation is a promising predictor for later social functioning in SCZ, even after accounting for patients\u27 cognitive impairments (e.g., (Evensen et al., 2012; Faerden et al., 2010). Despite this crucial impact on functioning outcome in SCZ, to date, no study has systematically investigated neural mechanism underlying amotivation in SCZ. To date, it has been well documented that many of cognitive impairments in SCZ may reflect a core deficit of non-emotional context processing, supported by the dorsolateral prefrontal cortex (DLPFC), and defined by the ability to maintain non-emotional context information necessary to regulate upcoming behavioral response towards goal-directed behavior (e.g., (Cohen, Barch, Carter, & Servan-Schreiber, 1999). Recent evidence from both animal and healthy human neuroimaging work suggests that the DLPFC plays a crucial role in representing and integrating reward-related context information. However, it has been unexplored whether individuals with SCZ can represent and integrate reward-related contextual information to modulate cognitive control function implicated in the DLPFC. Thirty-six individuals with SCZ and twenty-seven healthy controls (HC) underwent behavioral and fMRI data collection at 3Tsela while performing a modified response conflict processing task under two contexts, that is, no-reward baseline and reward contexts. Participants first performed baseline conditions without any knowledge regarding the future potential for incentives (Baseline-Context; BCXT). Each trial started with a baseline cue, XX that was pre-instructed to participants as being irrelevant to the task. After each cue, XX, either a house or building picture (with overlaid words that are either congruent or incongruent) was presented to each participant one at a time. The job of the task was to categorize each picture as either a house or a building by pressing a certain button while ignoring the overlaid word. Following the baseline condition, participants performed additional reward blocks on which they were told that they could win money on some trials by performing fast (faster than their median correct reaction times (RT) in the baseline and accurately). Each trial was then preceded either by a $20 cue (Reward-Cue; RC), indicating that a fast and correct response would be rewarded or by a XX cue (Reward-Context; RCXT), indicating zero money would be possible on the trial. After the target stimulus, participants received immediate feedback regarding the reward points they earned on the trials, as well as their cumulative earning in points. As such, this response conflict task paradigm enabled examination of: (1) reward context effects by comparing performance and brain activity when the cue, XX was presented in the baseline context versus in the reward context (BCXT vs. RCXT trials cued by the same cue, XX ) and (2) reward cue effects by comparing performance during RC (cued by$20 ) versus RCXT (cued by XX ) within reward blocks. Importantly, by employing a mixed state-item fMRI design, I investigated both sustained (block-based) context-dependent and transient (trial-by-trial) reward-related cue activity at both behavioral and neural levels

ORIGINAL ARTICLES Can’t Shake that Feeling: Event-Related fMRI Assessment of Sustained Amygdala Activity in Response to Emotional Information in Depressed Individuals

individuals engage in prolonged elaborative processing of emotional information. A computational neural network model of emotional information processing suggests this process involves sustained amygdala activity in response to processing negative features of information. This study examined whether brain activity in response to emotional stimuli was sustained in depressed individuals, even following subsequent distracting stimuli. Methods: Seven depressed and 10 never-depressed individuals were studied using event-related functional magnetic resonance imaging during alternating 15-sec emotional processing (valence identification) and nonemotional processing (Sternberg memory) trials. Amygdala regions were traced on high-resolution structural scans and coregistered to the functional data. The time course of activity in these areas during emotional and nonemotional processing trials was examined. Results: During emotional processing trials, never-depressed individuals displayed amygdalar responses to all stimuli, which decayed within 10 sec. In contrast, depressed individuals displayed sustained amygdala responses to negative words that lasted throughout the following nonemotional processing trials (25 sec later). The difference in sustained amygdala activity to negative and positive words was moderately related to self-reported rumination. Conclusions: Results suggest that depression is associated with sustained activity in brain areas responsible for coding emotional features. Biol Psychiatry 2002;51