V. Andrew Stenger

Can’t shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals

BACKGROUND Previous research suggests that depressed 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 non-emotional processing (Sternberg memory) trials. Amygdala regions were traced on high-resolution structural scans and co-registered to the functional data. The time course of activity in these areas during emotional and non-emotional 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 non-emotional 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.

Anterior Cingulate Cortex, Conflict Monitoring, and Levels of Processing

It has been hypothesized that the anterior cingulate cortex (ACC) contributes to cognition by detecting conflicts that might occur during information processing, to signal the need to engage top-down attentional processes. The present study was designed to investigate which levels of processing are being monitored by the ACC for the presence of conflict. Event-related fMRI was used to measure the response of the ACC during an interference task in which distracting information could be congruent, conflicting at the level of stimulus identification, or conflicting at the response level. Although both types of conflict caused reaction time interference, the fMRI data showed that the ACC is responsive only to response conflict, even when controlling for reaction times. These results suggest a highly specific contribution of the ACC to executive functions, through the detection of conflicts occurring at later or response-related levels of processing.

Overactive Action Monitoring in Obsessive-Compulsive Disorder Evidence From Functional Magnetic Resonance Imaging

The anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been found to be hyperactive at rest, during symptom provocation, and after commission of errors in cognitive tasks. This hyperactivity might reflect an abnormality in conflict detection, a hypothesized basic mechanism for the action-monitoring function of the ACC. This hypothesis was tested using functional magnetic resonance imaging, by scanning 11 OCD patients and 13 matched control subjects while they performed a version of the continuous-performance task with four trial types that induced graded levels of response conflict. Although a behavioral index of conflict (i.e., accuracy) was similar for patients and control subjects, the ACC activation was increased in patients during high-conflict trials. The error-related activity in the same brain region was also higher in patients, consistent with previous electrophysiological findings. Both conflict- and error-related activity showed trends for positive correlations with severity of OCD symptoms, but not with anxiety. These findings suggest that as part of an overactive action-monitoring system, the ACC is more directly involved in the pathophysiology of OCD than previously thought.

Spatial Domain Method for the Design of RF Pulses in Multicoil Parallel Excitation

Parallel excitation has been introduced as a means of accelerating multidimensional, spatially‐selective excitation using multiple transmit coils, each driven by a unique RF pulse. Previous approaches to RF pulse design in parallel excitation were either formulated in the frequency domain or restricted to echo‐planar trajectories, or both. This paper presents an approach that is formulated as a quadratic optimization problem in the spatial domain and allows the use of arbitrary k‐space trajectories. Compared to frequency domain approaches, the new design method has some important advantages. It allows for the specification of a region of interest (ROI), which improves excitation accuracy at high speedup factors. It allows for magnetic field inhomogeneity compensation during excitation. Regularization may be used to control integrated and peak pulse power. The effects of Bloch equation nonlinearity on the large‐tip‐angle excitation error of RF pulses designed with the method are investigated, and the utility of Tikhonov regularization in mitigating this error is demonstrated. Magn Reson Med, 2006.

Cerebral activation during hypnotically induced and imagined pain

The continuing absence of an identifiable physical cause for disorders such as chronic low back pain, atypical facial pain, or fibromyalgia, is a source of ongoing controversy and frustration among pain physicians and researchers. Aberrant cerebral activity is widely believed to be involved in such disorders, but formal demonstration of the brain independently generating painful experiences is lacking. Here we identify brain areas directly involved in the generation of pain using hypnotic suggestion to create an experience of pain in the absence of any noxious stimulus. In contrast with imagined pain, functional magnetic resonance imaging (fMRI) revealed significant changes during this hypnotically induced (HI) pain experience within the thalamus and anterior cingulate (ACC), insula, prefrontal, and parietal cortices. These findings compare well with the activation patterns during pain from nociceptive sources and provide the first direct experimental evidence in humans linking specific neural activity with the immediate generation of a pain experience.

Opiate Addicts Lack Error-Dependent Activation of Rostral Anterior Cingulate

BACKGROUND Healthy individuals performing response suppression tasks activate anterior cingulate cortex with occurrence of false alarm error responses to nontargets. Fundamental questions include whether this error-related activation provides a signal contributing to behavioral control and, given generally poorer performance on such tasks by addicts, whether this signal is disrupted in addiction. METHODS We used rapid, event-related functional magnetic resonance imaging to study 13 individuals with opiate dependence and 26 healthy control individuals performing a Go/NoGo task. RESULTS Compared with controls, opiate addicts exhibited an attenuated anterior cingulate cortex error signal and significantly poorer task performance. In controls, the individual level of event-related anterior cingulate cortex activation accompanying false alarm error positively predicted task performance, particularly sensitivity in discriminating targets from nontargets. CONCLUSIONS The attenuation of this error signal in anterior cingulate cortex may play a role in loss of control in addiction and other forms of impulsive behavior.

Dissociation in human prefrontal cortex of affective influences on working memory-related activity

Although neural activity associated with emotion is becoming better understood, the influence of affective parameters on brain activity reflecting cognitive functioning in humans remains poorly characterized. We examined affective influences on working memory (WM) and tested the hypotheses that (i) dorsolateral prefrontal cortex (DLPFC) activity reflecting WM is influenced by the emotion-evoking qualities of task-relevant stimuli, but only when brought “on-line” by task demands, and (ii) DLPFC and orbitofrontal cortex (OFC) activities are inversely related as a function of emotional valence. Participants performed two tasks while event-related functional MRI measured brain activity; one task required active maintenance of stimulus representations in WM, and the other task required target detection responses with no demand for WM. Stimuli were standardized emotional (pleasant and unpleasant) and neutral pictures. Emotional stimuli differentially influenced DPFC and OFC activity during WM; DLPFC was influenced by emotional valence, enhanced by pleasant and reduced by unpleasant, compared to neutral stimuli, only when task conditions required WM. OFC was valence-sensitive during both tasks, greater to arousing than neutral stimuli when WM demand was low and in inverse relationship to DLPFC with high WM demand. Further, DLPFC and OFC activities are inversely related with respect to emotional valence during the WM task. The results are consistent with the hypothesis that the intrinsic valence of task-relevant stimuli maintained in WM modulates DLPFC activity but only when the DLPFC is required for task demands. Findings suggest a conceptualization of DLPFC and its involvement in WM that takes into account a role for affective parameters.

Neural mechanisms of planning: A computational analysis using event-related fMRI

To investigate the neural mechanisms of planning, we used a novel adaptation of the Tower of Hanoi (TOH) task and event-related functional MRI. Participants were trained in applying a specific strategy to an isomorph of the five-disk TOH task. After training, participants solved novel problems during event-related functional MRI. A computational cognitive model of the task was used to generate a reference time series representing the expected blood oxygen level-dependent response in brain areas involved in the manipulation and planning of goals. This time series was used as one term within a general linear modeling framework to identify brain areas in which the time course of activity varied as a function of goal-processing events. Two distinct time courses of activation were identified, one in which activation varied parametrically with goal-processing operations, and the other in which activation became pronounced only during goal-processing intensive trials. Regions showing the parametric relationship comprised a frontoparietal system and include right dorsolateral prefrontal cortex [Brodmanns area (BA 9)], bilateral parietal (BA 40/7), and bilateral premotor (BA 6) areas. Regions preferentially engaged only during goal-intensive processing include left inferior frontal gyrus (BA 44). The implications of these results for the current model, as well as for our understanding of the neural mechanisms of planning and functional specialization of the prefrontal cortex, are discussed.

Errors without conflict: Implications for performance monitoring theories of anterior cingulate cortex

Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would differentiate between correct and incorrect feedback stimuli in a time estimation task. The design controlled for response conflict and frequency and expectancy effects. Although participants in the current study adjusted their performance following error feedback, we did not observe error feedback-evoked ACC activity. In contrast, we did observe ACC activity while the same subjects performed the Stroop task, in which an area of the ACC activated during both conflict and error trials. These findings are inconsistent with previous dipole models of the error feedback negativity, and suggest the ACC may not be involved in the generation of this ERP component. These results question involvement of the ACC in the detection of errors per se when controlling for conflict.

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 nonhuman primates have identified brain regions, including the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level-dependent (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 psychiatrically healthy 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 and lateral and medial orbital-frontal cortex; 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.