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Biomedical subjects

Justin S Feinstein

Publications and source records attributed to Justin S Feinstein.

11 recordsLinked to original sources

Lorazepam dose-dependently decreases risk-taking related activation in limbic areas.

RATIONALE: Several studies have examined the role of different neurotransmitter systems in modulating risk-taking behavior. OBJECTIVE: This investigation was aimed to determine whether the benzodiazepine lorazepam dose-dependently alters risk-taking behavior and underlying neural substrates. MATERIALS AND METHODS: Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18-39 years (mean 27.6 +/- 1.4 years) with 12-18 years of education (mean 15.6 +/- 0.3 years) underwent functional magnetic resonance imaging while performing a risk-taking decision-making task. RESULTS: Our results show that lorazepam did not affect risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in (a) the amygdala and medial prefrontal cortex during the response selection phase, and in (b) the bilateral insular cortex and amygdala during the outcome (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in insular cortex activation was associated with less risky responses. CONCLUSIONS: Taken together, our findings support the idea that GABAergic modulation in limbic and paralimbic structures is important during both the response selection and outcome phase of risk-taking decision-making.

Administration, Oral↗

Young adult stimulant users' increased striatal activation during uncertainty is related to impulsivity.

BACKGROUND: Young adults who use stimulants (e.g., cocaine, amphetamines) are at particular risk of transitioning to dependence. Previously, we demonstrated increased risk-taking in young adults who had used stimulants (Leland, D.S., Paulus, M.P., 2005. Increased risk-taking decision-making but not altered response to punishment in stimulant-using young adults. Drug. Alcohol Depend. 78, 83-90). Since outcome uncertainty is a critical element of risk, we investigated whether such individuals have different neural responses to uncertainty than their stimulant-naive peers. METHOD: Eleven young adults (age 18-25) who had used stimulants were compared with 11 age- and education-matched stimulant-naive controls using functional magnetic resonance imaging and a card prediction task with relatively certain/uncertain outcome conditions. RESULTS: The caudate, an area involved in processing salient events, was among those regions more active in users than controls in response to uncertainty. Personality measures revealed that users were more impulsive than controls, and that neural response to uncertainty in a number of areas, including the thalamus/caudate, was positively correlated with impulsivity. CONCLUSIONS: These results are consistent with the idea that young adults who have used stimulants find uncertainty particularly salient, due in part to preexisting differences in impulsivity, and may be subject to more "action pressure" when making decisions under uncertainty. This neural and personality profile may constitute a marker for increased risk of stimulant use.

Adult↗

Affective ambiguity for a group recruits ventromedial prefrontal cortex.

Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.

Adolescent↗

Left inferior prefrontal cortex activation during a semantic decision-making task predicts the degree of semantic organization.

Semantic organization, an aspect of semantic processing, requires a pre-existing network of semantic knowledge that relies on a widely distributed neural network. The inferior prefrontal cortex (IPFC) has been identified as a vital structure for processing competing semantic information when making a decision about the meaning of a stimulus. However, the precise role of the IPFC in maintaining or creating a consistent semantic organizational structure is unclear. In this study, a semantic triadic decision-making task (Tallent, K.A., Weinberger, D.R., and Goldberg, T.E. 2001. Associating semantic space abnormalities with formal thought disorder in schizophrenia: use of triadic comparisons. J. Clin. Exp. Neuropsychol. 285-296) was used during functional magnetic resonance imaging to test the hypothesis that the degree of activation in the IPFC correlates with the consistency of semantic organization in healthy subjects. In this sample, subjects who had greater activation in the IPFC also demonstrated smaller stress coefficients in a two-dimensional "semantic space", indicating a greater organization of words along semantic dimensions. This finding is consistent with the role of the IPFC in establishing self-generated semantic relationships between stimuli.

Adult↗

Superior temporal gyrus and insula provide response and outcome-dependent information during assessment and action selection in a decision-making situation.

Decision-making is a complex process that comprises the assessment of a situation, the selection of an action, and the evaluation of an outcome. Distinct neural systems may contribute differentially during various stages within a decision-making situation. This study investigated whether neural activation during assessment or action selection is critically dependent on previous outcomes or actions. Twelve healthy, right-handed subjects (6 females) played a Rock Paper Scissors (RPS) computer game during functional magnetic resonance imaging. Bilateral insula and medial prefrontal cortex (including the anterior cingulate) were specifically engaged during the assessment and action selection stages of decision-making, whereas bilateral superior frontal gyrus and right inferior parietal lobule activated more during the outcome. Two regions of activation within the bilateral superior temporal gyrus activated only when the previous outcome was a win. Moreover, right insula and superior temporal gyrus were active more when the subject switched responses relative to staying with the same choice made on the previous trial. These findings support the hypothesis that distinct neural systems underlie different stages of the decision-making process. Furthermore, the superior temporal gyrus may play an important role in integrating previous actions and successful outcomes into one's decision-making strategy.

Adult↗

Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing.

BACKGROUND: Functional neuroimaging may elucidate the pathophysiologic features of anxiety disorders and the site of action of anxiolytic drugs. A large body of evidence suggests that the amygdala and associated limbic structures play a critical role in the expression of anxiety and may be treatment targets for anxiolytic drugs. OBJECTIVE: To determine whether lorazepam dose-dependently attenuates blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) activation in the amygdala and associated limbic structures during an emotion face assessment task. PARTICIPANTS AND DESIGN: Fifteen healthy volunteers participated in a double-blind, placebo-controlled, randomized dose-response study. Subjects underwent imaging 3 times (at least a week apart) and were given either a single-dose placebo or 0.25 mg or 1.0 mg of lorazepam 1 hour prior to an MRI session. During fMRI, subjects completed an emotion face assessment task, which has been shown to elicit amygdala activation. MAIN OUTCOME MEASURES: The BOLD-fMRI activation in amygdala, insula, and medial prefrontal cortex during the emotion face assessment task. RESULTS: Lorazepam significantly attenuated the BOLD-fMRI signal in a dose-dependent manner in bilateral amygdala and insula but not in the medial prefrontal cortex. Lorazepam did not affect the BOLD-fMRI signal in the primary visual cortex. CONCLUSIONS: The current finding provides the first neuroimaging evidence of a dose-dependent change induced by an established therapeutic agent in brain regions known to be critical for the mediation of anxiety. This investigation may help to support the use of BOLD-fMRI with pharmacological probes to investigate the neural circuits underlying anxiety and the use of fMRI as a tool in the development of new anxiolytic agents.

Adolescent↗

Anterior cingulate activation in high trait anxious subjects is related to altered error processing during decision making.

BACKGROUND: Individuals with high trait anxiety (HTA) can be studied to examine the effect of elevated levels of anxiety on the processing of stimuli and the selection of actions. The anterior cingulate cortex has been implicated in the detection and processing of errors. This investigation examined the hypothesis that HTA subjects are more sensitive to errors than nonanxious comparison subjects during a simple decision-making task and show increased activation in the anterior cingulate, particularly at low error rates. METHODS: Thirteen HTA subjects were compared with 13 normal trait anxiety (NTA: 40th-60th percentile) subjects during functional magnetic resonance imaging while performing a two-choice prediction task at three different error rates. RESULTS: Both HTA and NTA subjects performed similarly during a simple two-choice prediction task; however, during the low-error-rate condition, activation in the anterior cingulate and medial prefrontal cortex was significantly higher in HTA subjects and was correlated with trait but not state anxiety. CONCLUSIONS: These results support the idea that HTA subjects devote more processing resources to decision making than do NTA subjects during times in which there is little chance of incorrect responding (i.e., the low-error-rate condition). The extent to which this altered activation within the anterior cingulate contributes to anxiety-proneness remains to be determined.

Adolescent↗

From sensory processes to conscious perception.

In recent years, cognitive neuroscientists have began to explore the process of how sensory information gains access to awareness. To further probe this process, event-related functional magnetic resonance imaging (fMRI) was used while testing subjects with a paradigm known as the "attentional blink." In this paradigm, visually presented information sporadically fails to reach awareness. It was found that the magnitude and time course of activation within the anterior cingulate (BA 32), medial prefrontal cortex (BA 9), and frontopolar cortex (BA 10) predicted whether or not information was consciously perceived during the critical period for the attentional blink. These results are discussed in light of a neural framework for conscious processing.

Adolescent↗

Trend detection via temporal difference model predicts inferior prefrontal cortex activation during acquisition of advantageous action selection.

The process of accurately predicting which actions are associated with advantageous versus disadvantageous outcomes is an important function of daily life. An integral part of this process is being able to detect when the association between an action and an outcome changes. This investigation examined the hypothesis that the inferior prefrontal cortex is critical for the detection of trends and that a trend process derived from the temporal difference model accomplishes this detection. Nineteen normal right-handed volunteers completed 120 4-s trials of a Rock Paper Scissors (RPS) task during functional magnetic resonance imaging. Subjects acquired the selection of advantageous actions during the RPS task. Activations in the medial frontal gyrus (BA 10), left ventrolateral frontal gyrus (BA 11/47), and left pallidum were significantly higher during trials in which subjects acquired the advantageous action. The time course of individually derived trend detection functions was found to be time-locked to the hemodynamic changes in the inferior frontal gyrus. These findings are consistent with the hypothesis that the inferior prefrontal cortex computes a trend from previously experienced action-outcome sequences based on a value function derived from the temporal difference model.

Association Learning↗

Increased activation in the right insula during risk-taking decision making is related to harm avoidance and neuroticism.

Decision making and risk taking are interrelated processes that are important for daily functioning. The somatic marker hypothesis has provided a conceptual basis for processes involved in risk-taking decision making and has been used to link discrete neural substrates to risk-related behaviors. This investigation examined the hypothesis that the degree of risk-taking is related to the degree of activation in the insular cortex. Seventeen healthy, right-handed subjects performed a risk-taking decision-making task during functional magnetic resonance imaging (fMRI) using a fast event-related design. This investigation yielded three main findings. First, right insula (BA 13) activation was significantly stronger when subjects selected a "risky" response versus selecting a "safe" response. Second, the degree of insula activation was related to the probability of selecting a "safe" response following a punished response. Third, the degree of insula activation was related to the subjects' degree of harm avoidance and neuroticism as measured by the TCI and NEO personality questionnaires, respectively. These results are consistent with the hypothesis that insula activation serves as a critical neural substrate to instantiate aversive somatic markers that guide risk-taking decision-making behavior.

Adult↗

Habituation of attentional networks during emotion processing.

Dysfunctional emotion processing is a key aspect of many neuropsychiatric disorders. This dysfunction may be due to an abnormal magnitude of neural substrate activation during emotion processing or due to an altered time course of the neural substrate response. To better understand the temporal characteristics of the neural substrate activation underlying implicit emotion processing, nine healthy female controls were repeatedly exposed to pictures of affective faces while performing a gender identification task in an fMRI. As the salience of the stimuli decreased with repeated exposure, brain areas implicated in a right hemispheric spatial attention network (including the posterior parietal cortex (BA 40) and the frontal eye fields (BA 6)) habituated while brain areas lateralized to the left hemisphere (including the angular gyrus (BA 39), posterior superior temporal gyrus (BA 39) and insula (BA 13)) sensitized. These results provide strong evidence that the time course of activation is a critical component when assessing the function of neural substrates underlying emotion processing (specifically whether habituation is altered) in neuro-psychiatric patients.

Adult↗