Biomedical subjects

K Luan Phan

Publications and source records attributed to K Luan Phan.

At least 19 recordsLinked to original sources

PubMed2007

Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression.

BACKGROUND: Converging evidence from animal and human lesion studies implicates the amygdala and orbitofrontal cortex (OFC) in emotional regulation and aggressive behavior. However, it remains unknown if functional deficits exist in these specific brain regions in clinical populations in which the cardinal symptom is impulsive aggression. We have previously shown that subjects diagnosed with intermittent explosive disorder (IED), a psychiatric disorder characterized by reactive aggressive behavior, perform poorly on facial emotion recognition tasks. In this study we employed a social-emotional probe of amygdala-OFC function in individuals with impulsive aggression. METHODS: Ten unmedicated subjects with IED and 10 healthy, matched comparison subjects (HC) underwent functional magnetic resonance imaging while viewing blocks of emotionally salient faces. We compared amygdala and OFC reactivity to faces between IED and HC subjects, and examined the relationship between the extent of activation in these regions and extent of prior history of aggressive behavior. RESULTS: Relative to controls, individuals with IED exhibited exaggerated amygdala reactivity and diminished OFC activation to faces expressing anger. Extent of amygdala and OFC activation to angry faces were differentially related to prior aggressive behavior across subjects. Unlike controls, aggressive subjects failed to demonstrate amygdala-OFC coupling during responses to angry faces. CONCLUSIONS: These findings provide evidence of amygdala-OFC dysfunction in response to an ecologically-valid social threat signal (processing angry faces) in individuals with a history of impulsive aggressive behavior, and further substantiate a link between a dysfunctional cortico-limbic network and aggression.

Adult↗

PubMed2006

Acute serotonin and dopamine depletion improves attentional control: findings from the stroop task.

Schizophrenia is associated with impairments of attentional control on classic experimental paradigms such as the Stroop task. However, at a basic level the neurochemical mechanisms that may be responsible for such impairments are poorly understood. In this study, we sought to investigate the influence of brain monoamine function on Stroop task performance in healthy participants using the established methods of acute dietary serotonin, dopamine, and combined monoamine depletion. The study was a double-blind placebo controlled design in which 12 healthy male participants completed the Stroop task under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/phenylalanine/tryptophan depletion (combined monoamine depletion). Decreased Stroop interference indicating improved attentional control was observed after both tryptophan depletion and tyrosine/phenylalanine depletion, while there was no significant change in interference after combined monoamine depletion. Findings suggest that reduced tonic dopamine or serotonin activity within specific neural circuits (such as the striatum, anterior cingulate, or prefrontal cortex) may play a critical role in attentional control, possibly by improving gating of information via reducing noise in monoaminergic systems. These findings enhance our understanding of the neurochemical basis of attentional control and the possible cause of attentional control deficits in schizophrenia.

Adult↗

PubMed2006

Amygdala reactivity to emotional faces at high and low intensity in generalized social phobia: a 4-Tesla functional MRI study.

Using functional magnetic resonance imaging, we measured amygdala reactivity to faces varying on emotional intensity in subjects with generalized social phobia (GSP) and matched healthy controls, and observed greater bilateral activation to high (vs. low) intensity expressions in the phobic group, suggesting that more arousing social-emotional cues contribute to limbic hyperactivity in GSP.

Adult↗

PubMed2006

Altered central micro-opioid receptor binding after psychological trauma.

BACKGROUND: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing. METHODS: Here we examined the micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n = 14) and without combat exposure (n = 15). Differences in micro-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions. RESULTS: Relative to healthy controls, both trauma-exposed groups had lower micro-opioid receptor BP2 in extended amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior cingulate cortex compared with both control groups. Micro-opioid receptor BP2 in combat-exposed subjects without PTSD was lower in the amygdala but higher in the orbitofrontal cortex compared with both PTSD patients and healthy controls. CONCLUSIONS: These findings differentiate the general response of the micro-opioid system to trauma from more specific changes associated with PTSD.

Adaptation, Physiological↗

PubMed2006

Pindolol does not augment central serotonin function increases to citalopram in humans: an auditory evoked potential investigation.

Animal studies have demonstrated that the co-administration of pindolol and selective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic functioning to a greater degree than SSRIs alone. However, clinical trials of pindolol augmentation in patients with major depressive disorder have reported contradictory findings, and the central effects of this treatment regime on serotonin functioning in humans are unknown. The current double-blind placebo controlled repeated measures investigation used the loudness dependence auditory evoked potential (LDAEP) to assess central serotonin functioning in healthy participants across three acute treatment conditions: placebo, citalopram (20 mg), and pindolol (10 mg)+citalopram (20 mg). The current paper focuses on the effects of pindolol augmentation of citalopram as compared to the administration of citalopram alone. Enhancement of serotonin function with citalopram in comparison to placebo decreased the slope of the LDAEP (i.e. weaker LDAEP). However, there were no significant differences between the changes in the LDAEP induced by co-administration of pindolol and citalopram compared to citalopram. The present results indicate that, in healthy controls, pindolol augmentation of SSRIs does not potentiate central serotonin function to a greater degree than the administration of an SSRI alone. The findings may provide further support for why pindolol may not be an effective therapeutic strategy to augment serotonin function and antidepressant response.

Adult↗

PubMed2006

Dopamine receptor stimulation does not modulate the loudness dependence of the auditory evoked potential in humans.

RATIONALE: The Loudness Dependence of the Auditory Evoked Potential (LDAEP) has been suggested as a reliable measure of central serotonin function in humans; however, its specificity for the serotonin system remains a topic of debate, with possible modulation of this purported serotonin marker by other neurotransmitters, including dopamine. OBJECTIVES: We examined the effect of dopaminergic modulation on the LDAEP using the D1/D2/D3 dopamine receptor agonist pergolide and the D2/D3 agonist bromocriptine. METHODS: The study was a double-blind, placebo-controlled repeated-measures design in which healthy participants were tested under three acute treatment conditions: placebo, bromocriptine (2.5 mg), and pergolide (0.1 mg). Changes in the amplitude of the N1/P2 at intensities (60, 70, 80, 90, and 100 dB) were examined at C Z. RESULTS: Acute stimulation of D1/D2/D3 receptors with pergolide and D2/D3 receptors with bromocriptine in comparison with placebo had no effect on the LDAEP. CONCLUSION: These findings indicate that acute stimulation of dopamine D1, D2, and D3 receptors does not modulate the LDAEP in humans. Although the findings suggest that the LDAEP may not be modulated by acute changes in dopamine neurotransmission, further studies are needed to fully characterize its dopaminergic sensitivity.

Acoustic Stimulation↗

PubMed2006

Neural correlates of social and nonsocial emotions: An fMRI study.

Common theories of emotion emphasize valence and arousal dimensions or alternatively, specific emotions, and the search for the underlying neurocircuitry is underway. However, it is likely that other important dimensions for emotional neurocircuitry exist, and one of them is sociality. A social dimension may code whether emotions are addressing an individual's biological/visceral need versus more remote social goals involving semantic meaning or intentionality. Thus, for practical purposes, social emotions may be distinguished from nonsocial emotions based in part on the presence of human forms. In the current fMRI study, we aimed to compare regional coding of the sociality dimension of emotion (nonsocial versus social) versus the valence dimension of emotion (positive versus negative). Using a novel fMRI paradigm, film and picture stimuli were combined to induce and maintain four emotions varying along social and valence dimensions. Nonsocial emotions of positively valenced appetite and negatively valenced disgust and social emotions of positively valenced joy/amusement and negatively valenced sadness were studied. All conditions activated the thalamus. Appetite and disgust activated posterior insula and visual cortex, whereas joy/amusement and sadness activated extended amygdala, superior temporal gyrus, hippocampus, and posterior cingulate. Activations within the anterior cingulate, nucleus accumbens, orbitofrontal cortex, and amygdala were modulated by both social and valence dimensions. Overall, these findings highlight that sociality has a key role in processing emotional valence, which may have implications for patient populations with social and emotional deficits.

Adult↗

PubMed2006

Corticolimbic blood flow during nontraumatic emotional processing in posttraumatic stress disorder.

CONTEXT: Recent brain imaging studies implicate dysfunction of limbic and paralimbic circuitry, including the amygdala and medial prefrontal cortex (MPFC), in the pathogenesis of posttraumatic stress disorder (PTSD) during traumatic recollection and imagery. However, the relationship between activity in these regions and general emotional processing unrelated to traumatic experience has not been fully examined. OBJECTIVE: To investigate activity in the limbic and paralimbic brain regions in PTSD in response to a challenge with emotionally salient generic visual images. DESIGN: Cross-sectional, case-control study. SETTING: Academic medical center. PARTICIPANTS: Sixteen Vietnam veterans with combat-related PTSD (PTSD group), 15 combat-exposed Vietnam veterans without PTSD (combat control group), and 15 age- and sex-matched healthy controls (normal control group). MAIN OUTCOME MEASURES: We used positron emission tomography to study regional cerebral blood flow while participants viewed complex visual pictures with negatively valenced/aversive, nonaversive ("neutral"), and blank pictures. Psychophysiologic and emotional self-report data were also recorded. RESULTS: All 3 groups activated the dorsal MPFC to general salient content. Controls without PTSD activated the left amygdala in response to aversive stimuli. Normal controls activated the ventral MPFC and combat-exposed non-PTSD and PTSD participants exhibited either no response or deactivation in these regions, respectively, during negative emotional experience. CONCLUSIONS: Consistent with current functional neuroanatomic models, patients with PTSD exhibited altered neural responses in the amygdala and ventral MPFC during the processing of emotionally salient but trauma-unrelated stimuli, potentially reflecting disorder-specific changes. Activation of the amygdala and lack of ventral MPFC deactivation to negatively valenced images in combat controls may reflect compensatory changes after trauma exposure that are not associated with PTSD.

Adult↗

PubMed2006

Direct evidence that acutely enhancing serotonin with the selective serotonin reuptake inhibitor citalopram modulates the loudness dependence of the auditory evoked potential (LDAEP) marker of central serotonin function.

The loudness dependence of the auditory evoked potential (LDAEP) has been suggested as a reliable measure of central serotonin function in humans. The most convincing evidence for a direct relationship between serotonergic function and LDAEP to date has come from animal studies, while evidence in humans has been circumstantial and inconsistent. In the current study, we examine the direct effect of serotonergic modulation with the selective serotonin reuptake inhibitor (SSRI) citalopram on the LDAEP. The study was a double-blind placebo controlled design in which healthy participants were tested under two acute treatment conditions: placebo and citalopram (20 mg). Enhancement of serotonin function with citalopram in comparison to placebo decreased the slope of the LDAEP (i.e. weaker LDAEP). The findings provide direct evidence in humans, of a relationship between central serotonin function and the LDAEP, supporting findings previously observed in animals and clinical populations. Together the results provide further support for the validity of the LDAEP as a non-invasive in vivo measure of central serotonin function in humans.

Acoustic Stimulation↗

PubMed2005

Beyond threat: amygdala reactivity across multiple expressions of facial affect.

The amygdala has been consistently isolated as a key neural substrate for processing facial displays of affect. Recent evidence from human lesion and functional neuroimaging studies have begun to challenge the notion that the amygdala is reserved for signals of threat (fear/anger). We performed a 4 T fMRI study in which 20 subjects viewed a contemporary set of photographs displaying 6 different facial expressions (fearful, disgusted, angry, sad, neutral, happy) while performing a task with minimal cognitive demand. Across subjects, the left amygdala was activated by each face condition separately, and its response was not selective for any particular emotion category. These results challenge the notion that the amygdala has a specialized role in processing certain emotions and suggest that the amygdala may have a more general-purpose function in processing salient information from faces.

Adult↗

PubMed2005

Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia.

BACKGROUND: Previous functional brain imaging studies of social anxiety have implicated amygdala hyperactivity in response to social threat, though its relationship to quantitative measures of clinical symptomatology remains unknown. The primary aim of this study was to examine the association between response to emotionally harsh faces in the amygdala, a region implicated in social and threat-related processing, and severity of social anxiety symptoms in patients with generalized social phobia (GSP). METHODS: Ten subjects with GSP naive to psychotropic medications and without psychiatric comorbidity and ten healthy comparison subjects matched on age, gender, ethnicity, and education completed the Liebowitz Social Anxiety Scale and underwent high-field (4Tesla) functional magnetic resonance imaging while viewing blocks of emotionally salient faces. RESULTS: Relative to happy faces, activation of the amygdala in response to harsh (angry, disgusted, fearful) faces was greater in GSP patients than in controls, and the extent of amygdala activation was positively correlated with severity of social anxiety symptoms, but not general state or trait anxiety levels. CONCLUSIONS: Our findings suggest that amygdala activation to interpersonal threat can be specifically linked to the severity of social anxiety symptoms of individual GSP patients, and thus, may serve as a useful functional marker of disease severity.

Adult↗

PubMed2005

Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery.

BACKGROUND: Functional neuroimaging experiments targeting personal recall of emotional events may help elucidate neural substrates underlying posttraumatic stress disorder (PTSD). Studies suggest that limbic and paralimbic function might be altered in PTSD, as compared with trauma-exposed control subjects; however, little is known about functional changes resulting from traumatic experience itself. The present study examined both PTSD-specific and trauma-specific regional cerebral blood flow (rCBF) patterns during script-driven imagery. METHODS: Sixteen combat veterans with PTSD (PP); 15 combat veterans without PTSD (CC); and 14 healthy, aged-matched noncombat control subjects (NC) underwent [15O] H20 positron emission tomography (PET) scanning during script-driven imagery of emotionally evocative and neutral autobiographic events. RESULTS: Differential patterns of activation were detected in amygdala and medial frontal cortex. Past trauma experience was associated with decreased amygdala activity (i.e., less activity than healthy control subjects); however, combat control subjects deactivated this region (i.e., greater activity to neutral scripts). All subjects deactivated medial frontal cortex; PTSD patients had greater rostral anterior cingulate (rACC) deactivation compared with control groups, who deactivated ventromedial prefrontal cortex (vmPFC). CONCLUSIONS: Trauma-specific patterns may represent potential compensatory changes to traumatic reminders, while patterns observed only in the PTSD group may reflect neural substrates specific to PTSD pathophysiology.

Amygdala↗

PubMed2005

Anterior cingulate neurochemistry in social anxiety disorder: 1H-MRS at 4 Tesla.

Recent studies suggest exaggerated responses in the limbic system of patients with generalized social anxiety disorder in response to threat/anxiety-related social situations and aversive conditioning, processes mediated by the glutamatergic system. This single-voxel, high-field 1H-magnetic resonance spectroscopy study examined concentrations of glutamate, and other metabolites, in the anterior cingulate cortex and occipital cortex (control region) of 10 medication-naive patients with generalized social anxiety and 10 matched healthy comparison subjects. Glutamate (relative to creatine) levels were significantly higher in patients than controls in the anterior cingulate, but not occipital, cortex. Anterior cingulate glutamate/creatine levels were also correlated with intensity of social anxiety symptoms. These findings provide new evidence of glutamate's involvement in the neural mechanism underlying social phobia.

Anxiety Disorders↗

PubMed2005

Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study.

BACKGROUND: Successful control of affect partly depends on the capacity to modulate negative emotional responses through the use of cognitive strategies. Although the capacity to regulate emotions is critical to mental well-being, its neural substrates remain unclear. METHODS: We used functional magnetic resonance imaging to ascertain brain regions involved in the voluntary regulation of emotion and whether dynamic changes in negative emotional experience can modulate their activation. Fourteen healthy subjects were scanned while they either maintained the negative affect evoked by highly arousing and aversive pictures (e.g., experience naturally) or suppressed their affect using cognitive reappraisal. In addition to a condition-based analysis, online subjective ratings of intensity of negative affect were used as covariates of brain activity. RESULTS: Inhibition of negative affect was associated with activation of dorsal anterior cingulate, dorsal medial prefrontal, and lateral prefrontal cortices, and attenuation of brain activity within limbic regions (e.g., nucleus accumbens/extended amygdala). Furthermore, activity within dorsal anterior cingulate was inversely related to intensity of negative affect, whereas activation of the amygdala was positively covaried with increasing negative affect. CONCLUSIONS: These findings highlight a functional dissociation of corticolimbic brain responses, involving enhanced activation of prefrontal cortex and attenuation of limbic areas, during volitional suppression of negative emotion.

Adult↗

PubMed2005

Neuroimaging and personality disorders.

Within the past several years, neuroimaging research on personality disorders has begun to develop. Personality disorders can be thought of as trait-like dysfunctional patterns in cognitive, affective, impulse control, and interpersonal domains. These domains of dysfunction have been linked to specific neural circuits. Developments in brain imaging techniques have allowed researchers to examine the neural integrity of these circuits in personality-disordered individuals. This article reviews the neuroimaging literature on borderline personality disorder, antisocial personality disorder (including psychopathy) and schizotypal personality disorder. Functional and structural studies provide support for dysfunction in fronto-limbic circuits in borderline and antisocial personality disorder, whereas temporal lobe and basal striatal-thalamic compromise is evident in schizotypal personality disorder.

Antisocial Personality Disorder↗

PubMed2005

Neural correlates of telling lies: a functional magnetic resonance imaging study at 4 Tesla.

RATIONALE AND OBJECTIVE: Intentional deception (ie, lying) is a complex cognitive act, with important legal, moral, political, and economic implications. Prior studies have identified activation of discrete anterior frontal regions, such as the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), dorsal medial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC) during deception. To extend these findings, we used novel real-time functional magnetic resonance imaging (fMRI) technology to simulate a polygraph experience in order to evoke performance anxiety about generating lies, and sought to ascertain the neural correlates of deception. MATERIALS AND METHODS: In this investigational fMRI study done with a 4-T scanner, we examined the neural correlates of lying in 14 healthy adult volunteers while they performed a modified card version of the Guilty Knowledge Test (GKT), with the understanding that their brain activity was being monitored in real time by the investigators conducting the study. The volunteers were instructed to attempt to generate Lies that would not evoke changes in their brain activity, and were told that their performance and brain responses were being closely monitored. RESULTS: Subjects reported performance anxiety during the task. Deceptive responses were specifically associated with activation of the VLPFC, DLPFC, DMPFC, and superior temporal sulcus. DISCUSSION: These findings suggest the involvement of discrete regions of the frontal cortex during lying, and that the neural substrates responsible for cognitive control of behavior may also be engaged during deception.

Adult↗

PubMed2005

Muscarinic and nicotinic receptor modulation of object and spatial n-back working memory in humans.

Working memory impairments in the n-back task in schizophrenia have been linked to sustained deficiency in mesocortical dopamine function. More recently, abnormalities in the cholinergic system have also been documented in schizophrenia, with cortical reductions in both nicotinic and muscarinic receptors. While the cholinergic hypothesis of memory is well established, the role of cholinergic receptors in modulating n-back working memory is not known. We investigated the effects of selective and simultaneous muscarinic and nicotinic antagonism on spatial and object n-back working memory performance. The study was a double-blind, placebo-controlled repeated-measures design in which 12 healthy subjects were tested under four acute treatment conditions; placebo (P), mecamylamine (M), scopolamine (S) and mecamylamine+scopolamine (MS). Muscarinic antagonism with scopolamine significantly impaired both object and spatial n-back working memory, whereas nicotinic antagonism with mecamylamine had little effect. Simultaneous antagonism of both muscarinic and nicotinic receptors produced greater impairments in both object and spatial n-back working memory performance than muscarinic or nicotinic antagonism alone. These results suggest that: (1) both muscarinic and nicotinic receptors may functionally interact to synergistically modulate n-back working memory, and (2) that n-back working memory impairments in schizophrenia may in part be due to reductions in both muscarinic and nicotinic receptors.

Adult↗

PubMed2005

The role of glutamate in anxiety and related disorders.

Anxiety, stress, and trauma-related disorders are a major public health concern in the United States. Drugs that target the gamma-aminobutyric acid or serotonergic system, such as benzodiazepines and selective serotonin reuptake inhibitors, respectively, are the most widely prescribed treatments for these disorders. However, the role of glutamate in anxiety disorders is becoming more recognized with the belief that drugs that modulate glutamatergic function through either ionotropic or metabotropic glutamate receptors have the potential to improve the current treatment of these severe and disabling illnesses. Animal models of fear and anxiety have provided a method to study the role of glutamate in anxiety. This research has demonstrated that drugs that alter glutamate transmission have potential anxiolytic action for many different paradigms including fear-potentiated startle, punished responding, and the elevated plus maze. Human clinical drug trials have demonstrated the efficacy of glutamatergic drugs for the treatment of obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, and social phobia. Recent data from magnetic resonance imaging studies provide an additional link between the glutamate system and anxiety. Collectively, the data suggest that future studies on the mechanism of and clinical efficacy of glutamatergic agents in anxiety disorders are appropriately warranted.

Animals↗