Publications (10)79.9 Total impact
-
Article: Nucleus Accumbens, Thalamus and Insula Connectivity During Incentive Anticipation in Typical Adults and Adolescents.
[show abstract] [hide abstract]
ABSTRACT: Reward neurocircuitry links motivation with complex behavioral responses. Studies of incentive processing have repeatedly demonstrated activation of nucleus accumbens (NAc), thalamus, and anterior insula, three key components of reward neurocircuitry. The contribution of the thalamus to this circuitry in humans has been relatively ignored, a gap that needs to be filled, given the central role of this structure in processing and filtering information. This study aimed to understand how these three regions function as a network during gain or loss anticipation in adults and youth. Towards this goal, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to examine effective connectivity among these three nodes in healthy adults and adolescents who performed the monetary incentive delay (MID) task. Seven connectivity models, based on anatomic connections, were tested. They were estimated for incentive anticipation and underwent Bayesian Model Selection (BMS) to determine the best-fit model for each adult and adolescent group. Connection strengths were extracted from the best-fit model and examined for significance in each group. These variables were then entered into a linear mixed model to test between-group effects on effective connectivity in reward neurocircuitry. The best-fit model for both groups included all possible anatomic connections. Three main findings emerged: (1) Across the task, thalamus and insula significantly influenced NAc; (2) A broader set of significant connections was found for the loss-cue condition than the gain-cue condition in both groups; (3) Finally, between-group comparisons of connectivity strength failed to detect statistical differences, suggesting that adults and adolescents use this incentive-processing network in a similar manner. This study demonstrates the way in which the thalamus and insula influence the NAc during incentive processing in humans. Specifically, this is the first study to demonstrate in humans the key role of thalamus projections onto the NAc in support of reward processing. Our results suggest that anticipation of gain/loss involves an 'alerting' signal (thalamus) that converges with interoceptive information (insula) to shape action selection programs in the ventral striatum.NeuroImage 10/2012; · 5.89 Impact Factor -
Article: Neural correlates of sleepiness induced by catecholamine depletion.
[show abstract] [hide abstract]
ABSTRACT: Although extensive indirect evidence exists to suggest that the central dopaminergic system plays a significant role in the modulation of arousal, the functional effect of the dopaminergic influence on the regulation of the sleep-wake cycle remains unclear. Thirteen healthy volunteers and 15 unmedicated subjects with a history of major depressive disorder underwent catecholamine depletion (CD) using oral alpha-methyl-para-tyrosine in a randomized, placebo-controlled, double-blind, crossover study. The main outcome measures in both sessions were sleepiness (Stanford-Sleepiness-Scale), cerebral glucose metabolism (positron emission tomography), and serum prolactin concentration. CD consistently induced clinically relevant sleepiness in both groups. The CD-induced prolactin increase significantly correlated with CD-induced sleepiness but not with CD-induced mood and anxiety symptoms. CD-induced sleepiness correlated with CD-induced increases in metabolism in the medial and orbital frontal cortex, bilateral superior temporal cortex, left insula, cingulate motor area and in the vicinity of the periaqueductal gray. This study suggests that the association between dopamine depletion and sleepiness is independent of the brain reward system and the risk for depression. The visceromotor system, the cingulate motor area, the periaqueductal gray and the caudal hypothalamus may mediate the impact of the dopaminergic system on regulation of wakefulness and sleep.Psychiatry Research 08/2011; 194(1):73-8. · 2.52 Impact Factor -
Article: Neural response to catecholamine depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects.
[show abstract] [hide abstract]
ABSTRACT: The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between catecholaminergic function and depression has involved the mood response to experimental catecholamine depletion (CD). To determine whether catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD. Randomized, double-blind, placebo-controlled, crossover, single-site experimental trial. Psychiatric outpatient clinic. Fifteen unmedicated subjects with MDD in full remission (hereinafter referred to as RMDD subjects) and 13 healthy controls. Induction of CD by oral administration of alpha-methylparatyrosine. Sham depletion used identical capsules containing hydrous lactose. Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of CD and sham depletion. Behavioral assessments included the Montgomery-Asberg Depression Rating Scale and the Snaith-Hamilton Pleasure Scale (anhedonia). Depressive and anhedonic symptoms increased during CD to a greater extent in RMDD subjects than in controls. In both groups, CD increased metabolism in the anteroventral striatum and decreased metabolism in the orbital gyri. In a limbic-cortical-striatal-pallidal-thalamic network previously implicated in MDD, composed of the ventromedial frontal polar cortex, midcingulate and subgenual anterior cingulate cortex, temporopolar cortex, ventral striatum, and thalamus, metabolism increased in RMDD subjects but decreased or remained unchanged in controls. Metabolic changes induced by CD in the left ventromedial frontal polar cortex correlated positively with depressive symptoms, whereas changes in the anteroventral striatum were correlated with anhedonic symptoms. This study provides direct evidence for catecholaminergic dysfunction as a trait abnormality in MDD. It demonstrates that depressive and anhedonic symptoms as a result of decreased catecholaminergic neurotransmission are related to elevated activity within the limbic-cortical-striatal-pallidal-thalamic circuitry.Archives of general psychiatry 06/2008; 65(5):521-31. · 12.26 Impact Factor -
Article: A developmental examination of amygdala response to facial expressions.
[show abstract] [hide abstract]
ABSTRACT: Several lines of evidence implicate the amygdala in face-emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala's response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9-17 years old) and 30 adults (21-40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala-hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions.Journal of Cognitive Neuroscience 04/2008; 20(9):1565-82. · 5.18 Impact Factor -
Article: Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression.
[show abstract] [hide abstract]
ABSTRACT: Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions. Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, anxiety, or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials while attention was unconstrained (passive viewing) and constrained (rate nose width on face, rate subjective fear while viewing face). When attention was unconstrained, high-risk subjects showed greater amygdala and nucleus accumbens activation to fearful faces and lower nucleus accumbens activation to happy faces (small volume corrected for the amygdala and nucleus accumbens). No group differences emerged in amygdala or nucleus accumbens activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than in the low-risk group. Amygdala and nucleus accumbens responses to affective stimuli may reflect vulnerability for major depression. Constraining attention may normalize emotion-related neural function possibly by engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for major depression.American Journal of Psychiatry 02/2008; 165(1):90-8. · 12.54 Impact Factor -
Article: Cerebral blood flow in immediate and sustained anxiety.
[show abstract] [hide abstract]
ABSTRACT: The goal of this study was to compare cerebral blood flow (CBF) changes associated with phasic cued fear versus those associated with sustained contextual anxiety. Positron emission tomography images of CBF were acquired using [O-15]H2O in 17 healthy human subjects as they anticipated unpleasant electric shocks that were administered predictably (signaled by a visual cue) or unpredictably (threatened by the context). Presentation of the cue in either threat condition was associated with increased CBF in the left amygdala. A cue that specifically predicted the shock was associated with CBF increases in the ventral prefrontal cortex (PFC), hypothalamus, anterior cingulate cortex, left insula, and bilateral putamen. The sustained threat context increased CBF in the right hippocampus, mid-cingulate gyrus, subgenual PFC, midbrain periaqueductal gray, thalamus, bilateral ventral striatum, and parieto-occipital cortex. This study showed distinct neuronal networks involved in cued fear and contextual anxiety underlying the importance of this distinction for studies on the pathophysiology of anxiety disorders.Journal of Neuroscience 07/2007; 27(23):6313-9. · 7.11 Impact Factor -
Article: Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.
[show abstract] [hide abstract]
ABSTRACT: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. Case-control study. Government clinical research institute. Fifteen adolescents with generalized anxiety disorder and 20 controls. Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.Archives of General Psychiatry 02/2007; 64(1):97-106. · 12.02 Impact Factor -
Article: Hierarchical and asymmetric temporal sensitivity in human auditory cortices.
[show abstract] [hide abstract]
ABSTRACT: Lateralization of function in auditory cortex has remained a persistent puzzle. Previous studies using signals with differing spectrotemporal characteristics support a model in which the left hemisphere is more sensitive to temporal and the right more sensitive to spectral stimulus attributes. Here we use single-trial sparse-acquisition fMRI and a stimulus with parametrically varying segmental structure affecting primarily temporal properties. We show that both left and right auditory cortices are remarkably sensitive to temporal structure. Crucially, beyond bilateral sensitivity to timing information, we uncover two functionally significant interactions. First, local spectrotemporal signal structure is differentially processed in the superior temporal gyrus. Second, lateralized responses emerge in the higher-order superior temporal sulcus, where more slowly modulated signals preferentially drive the right hemisphere. The data support a model in which sounds are analyzed on two distinct timescales, 25-50 ms and 200-300 ms.Nature Neuroscience 04/2005; 8(3):389-95. · 15.53 Impact Factor -
Article: fMRI study comparing names versus pictures of objects.
[show abstract] [hide abstract]
ABSTRACT: We performed an fMRI one-back recognition study aimed at distinguishing the semantic versus perceptual aspects of how objects and their written forms are processed. There were three types of visually presented items: pictures (schematic drawings of objects); words identifying these objects; and a mixed condition in which pictures were interleaved with words. A semantic decision about object identity was required when pictures were interleaved with words. This condition, contrasted with the other two, invoked a larger signal in multiple areas, including frontal cortex, bilateral occipitotemporal cortex, and the right middle temporal gyrus. We propose that the left occipitotemporal and right temporal activations are indicative of the neural substrate mediating picture-word conversions, whereas the frontal activations reflect the coordinating functions of the central executive.Human Brain Mapping 08/2002; 16(3):168-75. · 5.88 Impact Factor -
Article: Effect of attention on central auditory processing: an fMRI study.
[show abstract] [hide abstract]
ABSTRACT: Functional magnetic resonance imaging was used to investigate preattentive and attentional processing of auditory stimuli in 18 right-handed normal volunteers. Responses to trains of 1000-Hz pure tones and infrequent (15%) deviant 1300-Hz tones were characterized while subjects ignored all tones; listened for deviants in the left ear; or listened for deviants in the right ear. Preattentive detection of deviants, associated with the mismatch negativity in electrophysiology, was associated with bilateral temporal lobe activation, with a rightward predominance. Processing of deviant stimuli while attending to either ear produced a more robust and widespread activation of these temporal regions, again with a rightward predominance. Thus, preattentive tone processing appears to be linked to asymmetric activation of a core set of temporal regions in which activity is significantly amplified by selective attention. Extratemporal regions activated by attending to targets in either ear included the anterior cingulate cortex, supramarginal gyrus, and dorsolateral prefrontal cortex.International Journal of Neuroscience 06/2002; 112(5):587-606. · 0.97 Impact Factor
Top co-authors
Top Journals
Institutions
-
2012
-
University Center Rochester
- Department of Neurobiology and Anatomy
Rochester, MN, USA
-
-
2008
-
National Institutes of Health
Bethesda, MD, USA -
University of Michigan
- Department of Psychology
Ann Arbor, MI, USA
-
