Lisa Kilpatrick | University of California, Los Angeles (original) (raw)

Papers by Lisa Kilpatrick

Behavioral Neuroscience, 2003

The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfa... more The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfactory stimulus and footshock was investigated with a reversible lesion technique of post-training intra-BLA infusions of tetrodotoxin. Rats receiving tetrodotoxin infusions following paired odor-shock presentations spent more time near the odor, and reacted differently on contact with the odor when tested 24 hr after training, than did rats receiving paired presentations and saline infusions, but they did not differ from rats receiving unpaired presentations and saline infusions. The results indicate that the BLA plays a similar role in influencing consolidation of olfactory-based memory as it does for memory based on other modalities. Thus, these findings strengthen the view that the BLA plays a general role in modulation of memory storage for emotionally arousing events.

Neuroimage, 2006

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala... more Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders. D

Neuroimage, 2003

Considerable evidence from both animal and human subject research supports the hypothesis that th... more Considerable evidence from both animal and human subject research supports the hypothesis that the amygdala, when activated by emotional arousal, modulates memory storage processes in other brain regions. By this hypothesis, changes in the functional interactions of the amygdala with other brain regions during emotional conditions should underlie, at least in part, enhanced memory for emotional material. Here we examined the influence of the human amygdala on other brain regions under emotional and nonemotional learning conditions using structural equation modeling (SEqM). Eleven male subjects received two PET scans for regional cerebral glucose metabolism-one scan while viewing a series of emotionally provocative (negative) film clips and a second scan while viewing a series of more emotionally neutral film clips. Enhanced activity in the right amygdala was related to enhanced memory for the emotional films. To identify potential candidate voxels for SEqM, the functional connectivity of the maximally activated voxel within the right amygdala was investigated using partial least squares. A subset of regions identified by this analysis showing differences functional connectivity with the amygdala between the emotional versus neutral film conditions were then submitted to SEqM, which revealed significantly increased amygdala influences on the ipsilateral parahippocampal gyrus and ventrolateral prefrontal cortex during the emotional relative to the neutral film viewing condition. These findings support the view that increased influences from the amygdala, presumably reflecting its memorymodulation function, occur during emotionally arousing learning situations.

Neurobiology of Learning and Memory, 2001

We tested the possibility suggested by previous imaging studies that amygdala participation in th... more We tested the possibility suggested by previous imaging studies that amygdala participation in the storage of emotionally influenced memory is differentially lateralized in men and women. Male and female subjects received two PET scans for regional cerebral glucose-one while viewing a series of emotionally provocative (negative) films, and a second while viewing a series of matched, but emotionally more neutral, films. Consistent with suggestions from several previously published studies, enhanced activity of the right, but not the left, amygdala in men was related to enhanced memory for the emotional films. Conversely, enhanced activity of the left, but not the right, amygdala in women was related to enhanced memory for the emotional films. These results demonstrate a clear gender-related lateralization of amygdala involvement in emotionally influenced memory, and indicate that theories of the neurobiology of emotionally influenced memory must begin to account for the influence of gender. ᭧ 2001 Academic Press Converging evidence from both animal and human subject investigations strongly indicates that the amygdala is critical for enhanced explicit memory associated with emotional arousal. The evidence suggests that the amygdala interacts with endogenous stress hormones released during and after emotionally charged events to modulate memory storage occurring in other brain regions

Behavioral Neuroscience, 2003

The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfa... more The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfactory stimulus and footshock was investigated with a reversible lesion technique of post-training intra-BLA infusions of tetrodotoxin. Rats receiving tetrodotoxin infusions following paired odor-shock presentations spent more time near the odor, and reacted differently on contact with the odor when tested 24 hr after training, than did rats receiving paired presentations and saline infusions, but they did not differ from rats receiving unpaired presentations and saline infusions. The results indicate that the BLA plays a similar role in influencing consolidation of olfactory-based memory as it does for memory based on other modalities. Thus, these findings strengthen the view that the BLA plays a general role in modulation of memory storage for emotionally arousing events.

Gastroenterology, 2010

neurons; P<0.05). In contrast, UK14,304 had no effect on the amplitude of evoked inhibitory (GABA... more neurons; P<0.05). In contrast, UK14,304 had no effect on the amplitude of evoked inhibitory (GABAergic) postsynaptic currents (IPSCs) in any of 5 neurons tested (4.5±2.0% inhibition; P>0.05). Exposure to the adenylate cyclase stimulating agent, forskolin (10μM), for 5 minutes "uncovered" the ability of UK14,304 to inhibit GABAergic IPSCs in 3 of 3 neurons tested (8±1.4% inhibition in control vs 24±6.8% inhibition following forskolin; P<0.05). The present data suggest that α2 adrenoceptors are present on the membrane of gastric-projecting DMV neurons, where their activation presumably inhibits vagal efferent outflow to the stomach. In addition, α2 adrenoceptors are present on the nerve terminals of excitatory and inhibitory nerve terminals impinging upon gastric-projecting DMV neurons. As with our previous studies investigating Gi/o coupled receptors within the brainstem, α2 adrenoceptor activation modulates inhibitory synaptic transmission only after elevation of cAMP levels within the GABAergic terminal. This suggest that the response to α2 adrenoceptor activation within vagally-mediated gastric circuits will be dependent upon the "state of activation" of vagal neurocircuits and may be modified drastically by neurotransmitters or neurohormones positively coupled to adenylate cyclase. Supported by DK 55530

Journal of Neuroscience, 2008

Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chro... more Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls ( p Ͻ 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS.

Gastroenterology, 2010

achalasia. Aim: To determine the frequencies of rs2237025 and rs6554199 polymorphisms of the c-ki... more achalasia. Aim: To determine the frequencies of rs2237025 and rs6554199 polymorphisms of the c-kit gene in a case control-study of achalasia. Method: Eighty eight achalasia patients diagnosed by esophageal manometry and 101 healthy controls were included in the study. Genomic DNA was isolated from the peripheral blood, amplified and the results were analyzed using melting curve analysis. Results: The T allele at the rs6554199 locus was significantly associated with achalasia (p=0.03 OR: 1.55; 95% CI, 1.03-2.34). In a T dominant model, TT+GT genotype was significantly more frequent in achalasia patients (80.7%) than controls (65.3%) (p=0.02; OR: 2.21; %95CI, 1.13-4.32). Within the achalasia group, the presence of the G allele (GG+GT) increases the occurrence of regurgitation (p=0.008; OR: 5.09; 95% CI 1. 56-16.58). The polymorphism at rs2237025 was not associated with achalasia. Conclusion: The T allele at rs6554199 of the c-kit gene is significantly associated with achalasia in this population. The functional consequences of this variant in achalasia remain to be determined. The distribution of rs6554199 polymorphism 996 Achalasia Subtypes: an Assessment of Inter-And Intra-Rater Reproducibility

Neuroimage, 2011

The beneficial effects of mindful awareness and mindfulness meditation training on physical and p... more The beneficial effects of mindful awareness and mindfulness meditation training on physical and psychological health are thought to be mediated in part through changes in underlying brain processes. Functional connectivity MRI (fcMRI) allows identification of functional networks in the brain. It has been used to examine state-dependent activity and is well suited for studying states such as meditation. We applied fcMRI to determine if Mindfulness-Based Stress Reduction (MBSR) training is effective in altering intrinsic connectivity networks (ICNs). Healthy women were randomly assigned to participate in an 8-week Mindfulness-Based Stress Reduction (MBSR) training course or an 8-week waiting period. After 8 weeks, fMRI data (1.5 T) was acquired while subjects rested with eyes closed, with the instruction to pay attention to the sounds of the scanner environment. Group independent component analysis was performed to investigate training-related changes in functional connectivity. Significant MBSR-related differences in functional connectivity were found mainly in auditory/salience and medial visual networks. Relative to findings in the control group, MBSR subjects showed (1) increased functional connectivity within auditory and visual networks, (2) increased functional connectivity between auditory cortex and areas associated with attentional and self-referential processes, (3) stronger anticorrelation between auditory and visual cortex, and (4) stronger anticorrelation between visual cortex and areas associated with attentional and selfreferential processes. These findings suggest that 8 weeks of mindfulness meditation training alters intrinsic functional connectivity in ways that may reflect a more consistent attentional focus, enhanced sensory processing, and reflective awareness of sensory experience.

Pain, 2011

The present study examined whether a moderately aversive abdominal threat would lead to greater e... more The present study examined whether a moderately aversive abdominal threat would lead to greater enhancement in affect-and pain-related defensive responding as indexed by the acoustic startle reflex (ASR) and nociceptive flexion reflex (NFR) in women compared to men. We also predicted sex differences in threat-related autonomic arousal measured by skin conductance responses (SCRs) to acoustic startle and noxious sural nerve stimulation. Unpredictable threat was manipulated by alternating 30-second safe (''no abdominal stimulation will be given'') and threat (''abdominal stimulation may occur at anytime'') periods. The experiment consisted of 2 blocks, each containing 4 safe and 4 threat periods in which the ASR or NFR was randomly probed 9-21 seconds following period onset. Unpredictable abdominal threat potentiated both ASR and NFR responses compared to periods signaling safety. SCRs to acoustic startle probes and noxious sural nerve stimulation were also significantly elevated during the threat vs safe periods. No sex differences in ASR or startle-evoked SCRs emerged. However, nociceptive responding was moderated by sex; females showed significant increases in NFR magnitudes across both safe and threat periods compared to males. Females also showed greater threat-potentiated SCRs to sural nerve stimulation than males. Our findings indicate that both affect-and pain-related defense and arousal systems are strongly influenced by threat of an aversive, unpredictable event, a situation associated with anticipatory anxiety. Females, compared to males, showed greater nociceptive responding and pain modulation when exposed to an unpredictable threatening context, whereas affect-driven ASR responses showed no such sex differentiation.

Journal of Urology, 2010

Background and Aims-Altered sensory processing in interstitial cystitis/painful bladder syndrome ... more Background and Aims-Altered sensory processing in interstitial cystitis/painful bladder syndrome (IC/PBS) may result from a deficiency of the central nervous system to adequately filter incoming visceral afferent information. The current study used prepulse inhibition (PPI) as an operational measure of sensorimotor gating to examine early pre-attentive stages of information processing in female IC/PBS and healthy controls (HCs).

Gastroenterology, 2008

Impaired gastric accommodation is one of the key pathophysiological mechanisms in functional dysp... more Impaired gastric accommodation is one of the key pathophysiological mechanisms in functional dyspepsia. Paroxetin, a selective 5-hydroxytryptamine re-uptake inhibitor, has been shown to enhance gastric accommodation in healthy volunteers. The aim of this study was to investigate the effect of paroxetin on postprandial (pp) relaxation and emptying of the stomach in patients diagnosed with FD-PDS using the non-invasive technique of MRI. Material & Methods: 10 patients diagnosed with FD-PDS (6 ♀, MA 36 years) underwent MRI studies before and during treatment with paroxetin 20 mg/d of at least 4 weeks. MRI sequences covering the complete gastric region were performed after a liquid meal. Total, proximal, and distal stomach volumes and meal volumes were determined. Changes in gastric and meal volumes were calculated. Symptoms and quality of life (QoL) were assessed before and during treatment using the Nepean Dyspepsia (ND) questionnaire. Results: The cumulative increase of total gastric volume in the early pp phase (0-15 min) was significantly higher during treatment compared to before treatment . This difference between both groups was due to higher increases in proximal gastric volume during treatment . In contrast, the cumulative change in the distal gastric volume was not significantly different between both groups (table 1). 7 of the 10 patients showed an increase in pp total and proximal gastric volumes during treatment which were lacking in all patients before treatment. No significant differences in the total, proximal, or distal intragastric liquid volume could be shown before and during treatment (table 1). During treatment the ND symptom score was significantly lower than before treatment (before: 91 ±12, during treatment 53 ±8; p<0.01). The ND QoL index improved significantly during treatment (before: 38 ±2, during treatment 29 ±3; p<0.05) Conclusion: Paroxetin improves gastric relaxation of especially the proximal stomach in patients with postprandial distress syndrome and alleviates dyspeptic symptoms. These findings should be confirmed in larger sized randomized trials.

Gastroenterology, 2011

BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT) 3 receptor (5-HT 3 R) antagonists are effective in ... more BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT) 3 receptor (5-HT 3 R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism in HTR3A, c.-42CϾT;(C178T; rs1062613), is associated with altered reactivity of the amygdala during emotional face processing in healthy subjects (controls). We evaluated the influence of this single nucleotide polymorphism on amygdala reactivity to emotional faces and nonemotional stimuli in female patients with IBS and controls. METH-ODS: We measured brain responses during an affectmatching paradigm in 54 women (26 with IBS, 29 controls) using functional magnetic resonance imaging. We examined associations between HTR3A c.-42CϾT genotype (C/C vs T carrier) and responses in amygdala and other regions of brain that expressed high levels of 5-HT 3 R. RESULTS: The C/C genotype was associated with greater anxiety symptoms in patients with IBS and controls and increased activation of the amygdala under emotional and nonemotional conditions. Among patients with IBS, C/C genotype was associated with greater symptom ratings. A subset of IBS patients with the C/C genotype had increased amygdala responses to nonemotional stimuli, compared with other subjects with C/C genotype. CONCLUSIONS: Regardless of diagnosis, the C/C genotype of the c.-42C>T polymorphism in HTR3A, compared with T carrier status, is associated with increased anxiety and amygdala responsiveness during emotional and nonemotional tasks. This polymorphism was associated with severity of IBS symptoms. Although this genotype is not sufficient for diagnosis of IBS, it is associated with severity of symptoms.

Psychosomatic Medicine, 2008

Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (I... more Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (IBS) are both exacerbated by stress. The eye-blink startle response represents a noninvasive measure of central defensive responding. Evidence for central hyperexcitability was studied in IBS patients by examining potentiation of the startle reflex to a nociceptive threat.

Gastroenterology, 2011

younger on average (65.5 ±10.7) than bleeding cases (70.0±11.4; p = 0.056). Conclusions: 1. The r... more younger on average (65.5 ±10.7) than bleeding cases (70.0±11.4; p = 0.056). Conclusions: 1. The rate of gastrointestinal bleeding among patients on dual antiplatelet therapy after PCI with PPI co-therapy is 1.8 cases per 100 patient-years. 2. Most bleeding events occur during the first year of follow-up and are located in the lower GI tract. 3. Risk factors predictive of a bleeding event are co-therapy with warfarin, age and a peptic ulcer history.

Journal of Urology, 2009

Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (I... more Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (IBS) are both exacerbated by stress. The eye-blink startle response represents a noninvasive measure of central defensive responding. Evidence for central hyperexcitability was studied in IBS patients by examining potentiation of the startle reflex to a nociceptive threat.

Behavioral Neuroscience, 2003

The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfa... more The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfactory stimulus and footshock was investigated with a reversible lesion technique of post-training intra-BLA infusions of tetrodotoxin. Rats receiving tetrodotoxin infusions following paired odor-shock presentations spent more time near the odor, and reacted differently on contact with the odor when tested 24 hr after training, than did rats receiving paired presentations and saline infusions, but they did not differ from rats receiving unpaired presentations and saline infusions. The results indicate that the BLA plays a similar role in influencing consolidation of olfactory-based memory as it does for memory based on other modalities. Thus, these findings strengthen the view that the BLA plays a general role in modulation of memory storage for emotionally arousing events.

Neuroimage, 2006

Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala... more Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders. D

Neuroimage, 2003

Considerable evidence from both animal and human subject research supports the hypothesis that th... more Considerable evidence from both animal and human subject research supports the hypothesis that the amygdala, when activated by emotional arousal, modulates memory storage processes in other brain regions. By this hypothesis, changes in the functional interactions of the amygdala with other brain regions during emotional conditions should underlie, at least in part, enhanced memory for emotional material. Here we examined the influence of the human amygdala on other brain regions under emotional and nonemotional learning conditions using structural equation modeling (SEqM). Eleven male subjects received two PET scans for regional cerebral glucose metabolism-one scan while viewing a series of emotionally provocative (negative) film clips and a second scan while viewing a series of more emotionally neutral film clips. Enhanced activity in the right amygdala was related to enhanced memory for the emotional films. To identify potential candidate voxels for SEqM, the functional connectivity of the maximally activated voxel within the right amygdala was investigated using partial least squares. A subset of regions identified by this analysis showing differences functional connectivity with the amygdala between the emotional versus neutral film conditions were then submitted to SEqM, which revealed significantly increased amygdala influences on the ipsilateral parahippocampal gyrus and ventrolateral prefrontal cortex during the emotional relative to the neutral film viewing condition. These findings support the view that increased influences from the amygdala, presumably reflecting its memorymodulation function, occur during emotionally arousing learning situations.

Neurobiology of Learning and Memory, 2001

We tested the possibility suggested by previous imaging studies that amygdala participation in th... more We tested the possibility suggested by previous imaging studies that amygdala participation in the storage of emotionally influenced memory is differentially lateralized in men and women. Male and female subjects received two PET scans for regional cerebral glucose-one while viewing a series of emotionally provocative (negative) films, and a second while viewing a series of matched, but emotionally more neutral, films. Consistent with suggestions from several previously published studies, enhanced activity of the right, but not the left, amygdala in men was related to enhanced memory for the emotional films. Conversely, enhanced activity of the left, but not the right, amygdala in women was related to enhanced memory for the emotional films. These results demonstrate a clear gender-related lateralization of amygdala involvement in emotionally influenced memory, and indicate that theories of the neurobiology of emotionally influenced memory must begin to account for the influence of gender. ᭧ 2001 Academic Press Converging evidence from both animal and human subject investigations strongly indicates that the amygdala is critical for enhanced explicit memory associated with emotional arousal. The evidence suggests that the amygdala interacts with endogenous stress hormones released during and after emotionally charged events to modulate memory storage occurring in other brain regions

Behavioral Neuroscience, 2003

The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfa... more The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfactory stimulus and footshock was investigated with a reversible lesion technique of post-training intra-BLA infusions of tetrodotoxin. Rats receiving tetrodotoxin infusions following paired odor-shock presentations spent more time near the odor, and reacted differently on contact with the odor when tested 24 hr after training, than did rats receiving paired presentations and saline infusions, but they did not differ from rats receiving unpaired presentations and saline infusions. The results indicate that the BLA plays a similar role in influencing consolidation of olfactory-based memory as it does for memory based on other modalities. Thus, these findings strengthen the view that the BLA plays a general role in modulation of memory storage for emotionally arousing events.

Gastroenterology, 2010

neurons; P<0.05). In contrast, UK14,304 had no effect on the amplitude of evoked inhibitory (GABA... more neurons; P<0.05). In contrast, UK14,304 had no effect on the amplitude of evoked inhibitory (GABAergic) postsynaptic currents (IPSCs) in any of 5 neurons tested (4.5±2.0% inhibition; P>0.05). Exposure to the adenylate cyclase stimulating agent, forskolin (10μM), for 5 minutes "uncovered" the ability of UK14,304 to inhibit GABAergic IPSCs in 3 of 3 neurons tested (8±1.4% inhibition in control vs 24±6.8% inhibition following forskolin; P<0.05). The present data suggest that α2 adrenoceptors are present on the membrane of gastric-projecting DMV neurons, where their activation presumably inhibits vagal efferent outflow to the stomach. In addition, α2 adrenoceptors are present on the nerve terminals of excitatory and inhibitory nerve terminals impinging upon gastric-projecting DMV neurons. As with our previous studies investigating Gi/o coupled receptors within the brainstem, α2 adrenoceptor activation modulates inhibitory synaptic transmission only after elevation of cAMP levels within the GABAergic terminal. This suggest that the response to α2 adrenoceptor activation within vagally-mediated gastric circuits will be dependent upon the "state of activation" of vagal neurocircuits and may be modified drastically by neurotransmitters or neurohormones positively coupled to adenylate cyclase. Supported by DK 55530

Journal of Neuroscience, 2008

Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chro... more Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls ( p Ͻ 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS.

Gastroenterology, 2010

achalasia. Aim: To determine the frequencies of rs2237025 and rs6554199 polymorphisms of the c-ki... more achalasia. Aim: To determine the frequencies of rs2237025 and rs6554199 polymorphisms of the c-kit gene in a case control-study of achalasia. Method: Eighty eight achalasia patients diagnosed by esophageal manometry and 101 healthy controls were included in the study. Genomic DNA was isolated from the peripheral blood, amplified and the results were analyzed using melting curve analysis. Results: The T allele at the rs6554199 locus was significantly associated with achalasia (p=0.03 OR: 1.55; 95% CI, 1.03-2.34). In a T dominant model, TT+GT genotype was significantly more frequent in achalasia patients (80.7%) than controls (65.3%) (p=0.02; OR: 2.21; %95CI, 1.13-4.32). Within the achalasia group, the presence of the G allele (GG+GT) increases the occurrence of regurgitation (p=0.008; OR: 5.09; 95% CI 1. 56-16.58). The polymorphism at rs2237025 was not associated with achalasia. Conclusion: The T allele at rs6554199 of the c-kit gene is significantly associated with achalasia in this population. The functional consequences of this variant in achalasia remain to be determined. The distribution of rs6554199 polymorphism 996 Achalasia Subtypes: an Assessment of Inter-And Intra-Rater Reproducibility

Neuroimage, 2011

The beneficial effects of mindful awareness and mindfulness meditation training on physical and p... more The beneficial effects of mindful awareness and mindfulness meditation training on physical and psychological health are thought to be mediated in part through changes in underlying brain processes. Functional connectivity MRI (fcMRI) allows identification of functional networks in the brain. It has been used to examine state-dependent activity and is well suited for studying states such as meditation. We applied fcMRI to determine if Mindfulness-Based Stress Reduction (MBSR) training is effective in altering intrinsic connectivity networks (ICNs). Healthy women were randomly assigned to participate in an 8-week Mindfulness-Based Stress Reduction (MBSR) training course or an 8-week waiting period. After 8 weeks, fMRI data (1.5 T) was acquired while subjects rested with eyes closed, with the instruction to pay attention to the sounds of the scanner environment. Group independent component analysis was performed to investigate training-related changes in functional connectivity. Significant MBSR-related differences in functional connectivity were found mainly in auditory/salience and medial visual networks. Relative to findings in the control group, MBSR subjects showed (1) increased functional connectivity within auditory and visual networks, (2) increased functional connectivity between auditory cortex and areas associated with attentional and self-referential processes, (3) stronger anticorrelation between auditory and visual cortex, and (4) stronger anticorrelation between visual cortex and areas associated with attentional and selfreferential processes. These findings suggest that 8 weeks of mindfulness meditation training alters intrinsic functional connectivity in ways that may reflect a more consistent attentional focus, enhanced sensory processing, and reflective awareness of sensory experience.

Pain, 2011

The present study examined whether a moderately aversive abdominal threat would lead to greater e... more The present study examined whether a moderately aversive abdominal threat would lead to greater enhancement in affect-and pain-related defensive responding as indexed by the acoustic startle reflex (ASR) and nociceptive flexion reflex (NFR) in women compared to men. We also predicted sex differences in threat-related autonomic arousal measured by skin conductance responses (SCRs) to acoustic startle and noxious sural nerve stimulation. Unpredictable threat was manipulated by alternating 30-second safe (''no abdominal stimulation will be given'') and threat (''abdominal stimulation may occur at anytime'') periods. The experiment consisted of 2 blocks, each containing 4 safe and 4 threat periods in which the ASR or NFR was randomly probed 9-21 seconds following period onset. Unpredictable abdominal threat potentiated both ASR and NFR responses compared to periods signaling safety. SCRs to acoustic startle probes and noxious sural nerve stimulation were also significantly elevated during the threat vs safe periods. No sex differences in ASR or startle-evoked SCRs emerged. However, nociceptive responding was moderated by sex; females showed significant increases in NFR magnitudes across both safe and threat periods compared to males. Females also showed greater threat-potentiated SCRs to sural nerve stimulation than males. Our findings indicate that both affect-and pain-related defense and arousal systems are strongly influenced by threat of an aversive, unpredictable event, a situation associated with anticipatory anxiety. Females, compared to males, showed greater nociceptive responding and pain modulation when exposed to an unpredictable threatening context, whereas affect-driven ASR responses showed no such sex differentiation.

Journal of Urology, 2010

Background and Aims-Altered sensory processing in interstitial cystitis/painful bladder syndrome ... more Background and Aims-Altered sensory processing in interstitial cystitis/painful bladder syndrome (IC/PBS) may result from a deficiency of the central nervous system to adequately filter incoming visceral afferent information. The current study used prepulse inhibition (PPI) as an operational measure of sensorimotor gating to examine early pre-attentive stages of information processing in female IC/PBS and healthy controls (HCs).

Gastroenterology, 2008

Impaired gastric accommodation is one of the key pathophysiological mechanisms in functional dysp... more Impaired gastric accommodation is one of the key pathophysiological mechanisms in functional dyspepsia. Paroxetin, a selective 5-hydroxytryptamine re-uptake inhibitor, has been shown to enhance gastric accommodation in healthy volunteers. The aim of this study was to investigate the effect of paroxetin on postprandial (pp) relaxation and emptying of the stomach in patients diagnosed with FD-PDS using the non-invasive technique of MRI. Material & Methods: 10 patients diagnosed with FD-PDS (6 ♀, MA 36 years) underwent MRI studies before and during treatment with paroxetin 20 mg/d of at least 4 weeks. MRI sequences covering the complete gastric region were performed after a liquid meal. Total, proximal, and distal stomach volumes and meal volumes were determined. Changes in gastric and meal volumes were calculated. Symptoms and quality of life (QoL) were assessed before and during treatment using the Nepean Dyspepsia (ND) questionnaire. Results: The cumulative increase of total gastric volume in the early pp phase (0-15 min) was significantly higher during treatment compared to before treatment . This difference between both groups was due to higher increases in proximal gastric volume during treatment . In contrast, the cumulative change in the distal gastric volume was not significantly different between both groups (table 1). 7 of the 10 patients showed an increase in pp total and proximal gastric volumes during treatment which were lacking in all patients before treatment. No significant differences in the total, proximal, or distal intragastric liquid volume could be shown before and during treatment (table 1). During treatment the ND symptom score was significantly lower than before treatment (before: 91 ±12, during treatment 53 ±8; p<0.01). The ND QoL index improved significantly during treatment (before: 38 ±2, during treatment 29 ±3; p<0.05) Conclusion: Paroxetin improves gastric relaxation of especially the proximal stomach in patients with postprandial distress syndrome and alleviates dyspeptic symptoms. These findings should be confirmed in larger sized randomized trials.

Gastroenterology, 2011

BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT) 3 receptor (5-HT 3 R) antagonists are effective in ... more BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT) 3 receptor (5-HT 3 R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism in HTR3A, c.-42CϾT;(C178T; rs1062613), is associated with altered reactivity of the amygdala during emotional face processing in healthy subjects (controls). We evaluated the influence of this single nucleotide polymorphism on amygdala reactivity to emotional faces and nonemotional stimuli in female patients with IBS and controls. METH-ODS: We measured brain responses during an affectmatching paradigm in 54 women (26 with IBS, 29 controls) using functional magnetic resonance imaging. We examined associations between HTR3A c.-42CϾT genotype (C/C vs T carrier) and responses in amygdala and other regions of brain that expressed high levels of 5-HT 3 R. RESULTS: The C/C genotype was associated with greater anxiety symptoms in patients with IBS and controls and increased activation of the amygdala under emotional and nonemotional conditions. Among patients with IBS, C/C genotype was associated with greater symptom ratings. A subset of IBS patients with the C/C genotype had increased amygdala responses to nonemotional stimuli, compared with other subjects with C/C genotype. CONCLUSIONS: Regardless of diagnosis, the C/C genotype of the c.-42C>T polymorphism in HTR3A, compared with T carrier status, is associated with increased anxiety and amygdala responsiveness during emotional and nonemotional tasks. This polymorphism was associated with severity of IBS symptoms. Although this genotype is not sufficient for diagnosis of IBS, it is associated with severity of symptoms.

Psychosomatic Medicine, 2008

Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (I... more Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (IBS) are both exacerbated by stress. The eye-blink startle response represents a noninvasive measure of central defensive responding. Evidence for central hyperexcitability was studied in IBS patients by examining potentiation of the startle reflex to a nociceptive threat.

Gastroenterology, 2011

younger on average (65.5 ±10.7) than bleeding cases (70.0±11.4; p = 0.056). Conclusions: 1. The r... more younger on average (65.5 ±10.7) than bleeding cases (70.0±11.4; p = 0.056). Conclusions: 1. The rate of gastrointestinal bleeding among patients on dual antiplatelet therapy after PCI with PPI co-therapy is 1.8 cases per 100 patient-years. 2. Most bleeding events occur during the first year of follow-up and are located in the lower GI tract. 3. Risk factors predictive of a bleeding event are co-therapy with warfarin, age and a peptic ulcer history.

Journal of Urology, 2009

Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (I... more Background and Aims-Visceral hypersensitivity and symptom severity in Irritable Bowel Syndrome (IBS) are both exacerbated by stress. The eye-blink startle response represents a noninvasive measure of central defensive responding. Evidence for central hyperexcitability was studied in IBS patients by examining potentiation of the startle reflex to a nociceptive threat.