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1.  A factor analysis of different temperament domains in a border region in rural Southern California 
Journal of affective disorders  2010;126(0):46-48.
Temperament has been described as an oligogenic model that confers attributes to individuals in their daily functioning. Understanding of these temperaments can help understanding psychiatric status and therapeutic needs of a patient population. As the Latino population grows providers need to become more familiar with their psychiatric status.
To describe how the characteristics of different temperament domains in a community vs a private practice clinic of patients being treated for a mood disorder.
Retrospective record review was conducted in 117 patients with mood disorders who received the Temperament Scale (TEMPS). Forty nine were from a community clinic (CM) and 68 from a private practice (PP).
The following temperament domains were found. In PP: depressed 17/69 (25%); cyclothymic 18/69 (26%); hyperthymic 16/69 (23%); anxious 14/68 (20%); irritable 4/69 (5%). Among CM: depressed 10/49 (20%); cyclothymic 14/49 (28%); hyperthymic 8/49 (16%); anxious 15/49 (30%); irritable 2/49 (5%). Using factor analysis to determine the significant domains among clinics, cyclothima (0.82) and irritability (0.81) were the most relevant, regardless of psychosocial background and language differences.
Cross-sectional retrospective study without longitudinal follow up.
This study elucidates how temperament domains could be considered a valuable tool in evaluating patients in mood disorders clinic. The tool elucidates valuable characteristics that could be applied for guidance in diagnosis and treatment without being biased by different socio-cultural background or language differences. The factor analysis helps elucidate the pertinence of TEMPS scores that may not be the focus of clinical intervention although they contribute significantly to the structure of an individual's temperament, specifically emotional labiality (i.e., cyclothima and irritability).
PMCID: PMC3782388  PMID: 20392499
Temperament; Rural; Cyclothymia
Recent evidence raises the possibility that symptoms of anorexia nervosa (AN) could be related to impaired interoception. Pain is an interoceptive process with well-characterized neuroanatomical pathways that may overlap to a large degree with neural systems that may be dysregulated in AN individuals, such as the insula.
Functional Magnetic Resonance Imaging (fMRI) was used to assess neural substrates of pain anticipation and processing in ten healthy control women (CW) and 12 individuals recovered from AN (REC AN) in order to avoid the confounding effects of malnutrition. Painful heat stimuli were applied while different colors signaled the intensity of the upcoming stimuli.
REC AN compared to CW showed greater activation within right anterior insula (rAI), dorsolateral prefrontal cortex (dlPFC) and cingulate during pain anticipation, and greater activation within dlPFC and decreased activation within posterior insula during painful stimulation. Greater anticipatory rAI activation correlated positively with alexithymic feelings in REC AN subjects.
REC AN showed a mismatch between anticipation and objective responses, suggesting altered integration and, possibly, disconnection between reported and actual interoceptive state. Alexithymia assessment provided additional evidence of an altered ability to accurately perceive bodily signals in women recovered from anorexia nervosa.
PMCID: PMC3507323  PMID: 22836447
Anorexia; insula; pain; anticipation; homeostasis; fmri; interoception; alexithymia; eating disorders; dorsolateral prefrontal
4.  High versus Low Level of Response to Alcohol: Evidence of Differential Reactivity to Emotional Stimuli 
Biological psychiatry  2012;72(10):848-855.
The low level of response (LR) or sensitivity to alcohol is genetically influenced and predicts heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies using cognitive tasks suggest that subjects with a low LR process cognitive information differently after placebo and alcohol than those with a high LR, but no studies have evaluated if similar LR group differences are seen during an emotional processing task.
fMRI data were gathered from 116 non-alcoholic subjects (60 women) following oral placebo or ~0.7 ml/kg of ethanol while performing a modified emotional faces processing task. These included 58 low- and high-LR pairs matched on demography and aspects of substance use.
Blood alcohol levels and task performance were similar across LR groups, but low LR subjects consumed ~ 0.8 drinks more per occasion. Thirteen brain regions (mostly the middle and inferior frontal gyri, cingulate, and insula) showed significant LR group or LR by placebo/alcohol condition interactions for emotional (mostly happy) faces relative to non-face trials. Low LR subjects generally showed decreasing BOLD response contrasts across placebo to alcohol, while high LR showed increasing contrasts from placebo to alcohol, even after controlling for drinking quantities and alcohol-related changes in cerebral blood flow.
Thus, LR group fMRI differences are as prominent during an emotional face task as during cognitive paradigms. Low LR individuals processed both types of information in a manner that might contribute to an impaired ability to recognize modest levels of alcohol intoxication in a range of life situations.
PMCID: PMC3433640  PMID: 22608014
fMRI; alcohol sensitivity; emotional stimuli; fear; Hariri; alcoholism
5.  Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol 
A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk for alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption.
30 matched high- and low-LR pairs (N=60 healthy young adults) were recruited from the University of California, San Diego and administered a structured diagnostic interview and laboratory alcohol challenge followed by two fMRI sessions under placebo and alcohol conditions, in randomized order. Task performance and BOLD response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task was examined across 120 fMRI sessions.
Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p<.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity.
Alcohol had differential effects on brain activation for low and high LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR, and identify brain regions that may be associated with the low LR response.
PMCID: PMC3774836  PMID: 20477775
Level of response; fMRI; visual working memory; cerebral blood flow
6.  fMRI Differences between Subjects with Low and High Responses to Alcohol during a Stop Signal Task 
A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed.
Forty-nine drinking but not yet alcoholic matched pairs of 18-25-year-old subjects (N = 98; 53% female) with low and high LRs as established in separate alcohol challenges were evaluated in two event-related functional magnetic resonance imaging (fMRI) sessions (placebo and ~ 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session.
Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level dependent (BOLD) signal during error and inhibitory processing, despite similar LR-group performance on the task. In most clusters with significant (corrected p<.05, clusters >1344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared to placebo.
This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks for a future life threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk for future heavy drinking and alcohol dependence.
PMCID: PMC3253183  PMID: 22003983
alcohol; reaction; risk; fMRI
7.  Alcohol Attenuates Activation in the Bilateral Anterior Insula during an Emotional Processing Task: A Pilot Study † 
Aims: Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. Methods: Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. Results: Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 μl; corrected P < 0.05). Conclusion: Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.
PMCID: PMC3201697  PMID: 21665869
8.  Adolescent subgenual anterior cingulate activity is related to harm avoidance 
Neuroreport  2009;20(1):19-23.
Recent adult studies suggest that the subgenual anterior cingulate cortex (sgACC) is involved in fundamental mental operations such as affective processing and inhibitory control. However, little is known about inhibition-associated sgACC function in adolescents, and there are no published data regarding whether personality characteristics are related to inhibition-associated sgACC brain activity in adolescents. This study examined the relationship between personality and inhibition-associated sgACC response in healthy adolescents. Seventeen adolescents of 13–17 years of age underwent functional magnetic resonance imaging while performing a parametric stop-signal task. Greater harm avoidance levels were significantly associated with increased inhibition-related sgACC activity. These results establish, for the first time, a link between personality and differential sgACC activation in adolescents.
PMCID: PMC2852645  PMID: 19034055
adolescents; emotion; functional MRI; harm avoidance; personality; subgenual anterior cingulate; temperament and character inventory
9.  The Parametric, Psychological, Neuropsychological, and Neuroanatomical Properties of Self and World Evaluation 
PLoS ONE  2012;7(2):e31509.
As an individual moves from adolescence to adulthood, they need to form a new sense of self as their environment changes from a limited to a more expansive structure. During this critical stage in development the last dramatic steps of neural development occur and numerous psychiatric conditions begin to manifest. Currently, there is no measure that aids in the quantification of how the individual is adapting to, and conceptualizing their role in, these new structures. To fill this gap we created the Self and World Evaluation Expressions Test(SWEET).
Sixty-five young adults (20.6 years-old), 36 with a history of drug use, completed the SWEET. A factor analysis was performed on the SWEET and the resultant factors were correlated with psychological, neuropsychological, and neuroanatomical battery that included both T1-wieghted and diffusion tensor magnetic resonance imaging scans.
We derived four factors: Self, Social-Emotional, Financial-Intellectual, and Spirituality. While showing limited relationships to psychological and neuropsychological measures, both white matter integrity and gray matter density showed significant relationships with SWEET factors.
These findings suggest that while individual responses may not be indicative of psychological or cognitive processes they may relate to changes in brain structure. Several of these structures, such as the negative correlation of the affective impact of world with the dorsal anterior corpus callosum white matter integrity have been observed in psychiatric conditions (e.g., obsessive-compulsive disorder). Further longitudinal research using the SWEET may help understand the impact of dramatic shifts in self/world conceptualization and potentially link these shifts to underlying changes in brain structure.
PMCID: PMC3278451  PMID: 22348093
10.  Altered amygdala activation during face processing in Iraqi and Afghanistani war veterans 
Exposure to combat can have a significant impact across a wide array of domains, and may manifest as post-traumatic stress disorder (PTSD), a debilitating mental illness that is associated with neural and affective sequelae. This study tested the hypothesis that combat-exposed individuals with and without PTSD, relative to healthy control subjects with no history of PTSD or combat exposure, would show amygdala hyperactivity during performance of a well-validated face processing task. We further hypothesized that differences in the prefrontal cortex would best differentiate the combat-exposed groups with and without PTSD.
Twelve men with PTSD related to combat in Operations Enduring Freedom and/or Iraqi Freedom, 12 male combat-exposed control patients with a history of Operations Enduring Freedom and/or Iraqi Freedom combat exposure but no history of PTSD, and 12 healthy control male patients with no history of combat exposure or PTSD completed a face-matching task during functional magnetic resonance imaging.
The PTSD group showed greater amygdala activation to fearful versus happy faces than both the combat-exposed control and healthy control groups. Both the PTSD and the combat-exposed control groups showed greater amygdala activation to all faces versus shapes relative to the healthy control group. However, the combat-exposed control group relative to the PTSD group showed greater prefrontal/parietal connectivity with the amygdala, while the PTSD group showed greater connectivity with the subgenual cingulate. The strength of connectivity in the PTSD group was inversely related to avoidance scores.
These observations are consistent with the hypothesis that PTSD is associated with a deficiency in top-down modulation of amygdala activation by the prefrontal cortex and shows specific sensitivity to fearful faces.
PMCID: PMC3384263  PMID: 22738183
11.  Escitalopram attenuates posterior cingulate activity during self evaluation in healthy volunteers 
Psychiatry research  2010;182(2):81-87.
Medial cortex is critically involved in self-referential processing. Little is known about how SSRIs affect medial cortical activity during self-assessment. We hypothesized that 3 week oral administration of escitalopram 10mg per day would alter activity related to self-referential processing in medial cortex. Fifteen healthy females performed a self-assessment task during fMRI on two occasions – once after 3 weeks of placebo and once at the end of 3 weeks of escitalopram. Task conditions involved responding “yes” or “no” to whether various positive and negative adjectives described the subject (i.e., “self” evaluation trials) or the subject’s best friend (i.e., “other” evaluation trials), whereas the comparison condition involved responding whether the valence of various adjectives was positive or negative (i.e., “word” evaluation trials). Behaviorally after escitalopram, subjects less frequently endorsed that negative adjectives described themselves. Three main neuroimaging results were observed: (1) increased activation in medial prefrontal cortex and posterior cingulate related to self minus word evaluation trials, (2) increased activation in posterior cingulate related to escitalopram minus placebo for self and word evaluation trials, (3) drug by task interactions in the insula, cerebellum and prefrontal cortex. These results show that SSRIs change medial cortical activity and may alter self-evaluation.
PMCID: PMC2882791  PMID: 20418072
SSRI; medial cortex; fMRI; self; cingulate; emotion processing
Psychosomatic medicine  2010;72(3):316-323.
An intact ability to mount preparatory emotional, cognitive and bodily responses to anticipated environmental change is necessary for adaptive responding. Although abnormal insula activity during aversive anticipation has been observed in Major Depressive Disorder (MDD) individuals, the extent to which shifts in homeostatic state during anticipation affect insular activity in MDD subjects has not been reported. The aim of this study was to use functional Magnetic Resonance Imaging (fMRI) to examine how shifts in homeostatic state affect anticipatory insular activity in MDD.
Cued hot and warm stimuli were delivered while subjects either passively viewed a fixation cross or performed an attentional task during fMRI. The task was designed so that anticipatory brain activation related to the following three types of shifts could be measured: (1) anticipatory shifts in stimulus intensity, (2) anticipatory shifts in cognitive demand, (3) dual anticipatory shifts (i.e., shifts in both stimulus intensity and cognitive demand). Brain activation related to each of these three contrasts was compared between 15 (12F) unmedicated subjects with current MDD and 17 (10F) age- and education-comparable healthy control (HC) subjects.
MDD versus HC subjects showed lower right anterior insula activity related to anticipatory shifts in stimulus intensity, and altered brain activation during anticipatory shifts in cognitive demand and dual anticipatory shifts.
These results indicate that MDD individuals show altered brain responses to shifts in homeostatic state during anticipation, and may suggest that MDD is associated with an impaired ability to effectively prepare for changes in the environment.
PMCID: PMC2884370  PMID: 20100882
Homeostatsis; emotion; interoception; fmri; emotional allodynia; heat; pain
13.  The Relationship between Amygdala Activation and Passive Exposure Time to an Aversive Cue during a Continuous Performance Task 
PLoS ONE  2010;5(11):e15093.
The allocation of attention modulates negative emotional processing in the amygdala. However, the role of passive exposure time to emotional signals in the modulation of amygdala activity during active task performance has not been examined. In two functional Magnetic Resonance Imaging (fMRI) experiments conducted in two different groups of healthy human subjects, we examined activation in the amygdala due to cued anticipation of painful stimuli while subjects performed a simple continuous performance task (CPT) with either a fixed or a parametrically varied trial duration. In the first experiment (N = 16), engagement in the CPT during a task with fixed trial duration produced the expected attenuation of amygdala activation, but close analysis suggested that the attenuation occurred during the period of active engagement in CPT, and that amygdala activity increased proportionately during the remainder of each trial, when subjects were passively exposed to the pain cue. In the second experiment (N = 12), the duration of each trial was parametrically varied, and we found that amygdala activation was linearly related to the time of passive exposure to the anticipatory cue. We suggest that amygdala activation during negative anticipatory processing depends directly on the passive exposure time to the negative cue.
PMCID: PMC2993966  PMID: 21124739
14.  Adolescents With Major Depression Demonstrate Increased Amygdala Activation 
Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have consistently demonstrated a hyperactive amygdala in depressed adults, the few published pediatric studies have reported opposite results in the amygdala. Thus, the main purpose of this study was to further our knowledge of the underlying neural substrates of adolescent depression by examining the bilateral amygdala specifically and the whole brain in depressed adolescents compared to healthy controls.
Twelve unmedicated adolescents diagnosed with current major depressive disorder without a comorbid psychiatric disorder and 12 well-matched controls ages 13 to 17 years performed a facial-emotion matching task during functional magnetic resonance imaging at 3 T.
Region-of-interest analyses demonstrated: (1) significant bilateral amygdala activation in depressed and healthy adolescents, and (2) significantly greater left amygdala activation in depressed adolescents compared to controls. Whole-brain analysis revealed areas of significantly different brain activity in depressed adolescents compared to controls.
These results suggest that (1) depressed adolescents without a comorbid psychiatric disorder exhibit an abnormally hyperactive amygdala compared to healthy controls; (2) models of adult depression might be extended to include depressed adolescents; and (3) neuropsychiatric interventions that have been developed in depressed adults should be further examined in adolescents. J. Am. Acad. Child Adolesc.
PMCID: PMC2935523  PMID: 20215925
functional magnetic resonance imaging; amygdala; neuroimaging; anterior cingulate cortex; major depressive disorder
15.  Initial evidence of a failure to activate right anterior insula during affective set-shifting in PTSD 
Psychosomatic medicine  2009;71(4):373-377.
Interoception is the perception of one's internal physiological, sensory, and emotional status. Extensive evidence supports a link between interoception and subjective experience. An altered ability to monitor or modulate interoception as it relates to subjective experience may provide a mechanistic explanation for the development of some forms of psychiatric illness.
We investigated which neural networks are activated when anticipating a change in affective (and thus interoceptive) state, which we term “affective set-shifting”, in women with posttraumatic stress disorder (PTSD) related to intimate partner violence, and in non-traumatized healthy volunteers.
Although both groups activated the dorsolateral prefrontal cortex during affective set-shifting, the PTSD group showed significantly less activation in the right anterior insula than did the controls.
These findings may suggest that although individuals with PTSD are cognitively aware of the impending shift in interoceptive state, they fail to appropriately activate neural circuitry involved in modulating interoceptive responses.
PMCID: PMC2888032  PMID: 19398499
Interoception; emotional set-shifting; PTSD; insula; anticipation; DLPFC
16.  Depressed adolescents demonstrate greater subgenual anterior cingulate activity 
Neuroreport  2009;20(4):440-444.
Neuroimaging studies implicate the subgenual anterior cingulate cortex (sgACC) as a critical brain region in adult depression. However, unlike adult depression, little is known about the underlying neural substrates of adolescent depression, and there are no published data examining differences in sgACC activation between depressed and healthy adolescents. This study used functional magnetic resonance imaging to examine sgACC activity in twenty-six depressed and normal 13- to 17-year olds during the performance of a stop-signal task. Significantly greater sgACC activation was found in the depressed adolescents relative to controls. These results establish for the first time abnormal functioning of the sgACC in depressed adolescents and have important implications for understanding the underlying neural correlates and potential treatments of adolescent depression.
PMCID: PMC2672880  PMID: 19218875
adolescent; depression; FMRI; subgenual anterior cingulate cortex; prefrontal cortex; major depressive disorder; functional neuroimaging; functional MRI; pediatrics; mood disorder
17.  Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence 
Biological psychiatry  2008;64(8):681-690.
Intimate partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) in women. Victims of IPV are often preoccupied by the anticipation of impending harm. This investigation tested the hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity to the anticipation of aversive stimuli.
Fifteen women with a history of IPV and consequent PTSD (IPV-PTSD) and 15 non-traumatized control (NTC) women performed a task involving cued anticipation to images of positive and negative events during functional magnetic resonance imaging.
Both groups showed increased activation of bilateral anterior insula during anticipation of negative images minus anticipation of positive images. Activation in right anterior/middle insula was significantly greater in the IPV-PTSD relative to the NTC group. Functional connectivity analysis revealed that changes in activation in right middle insula and bilateral anterior insula were more strongly associated with amygdala activation changes in NTC than in IPV-PTSD subjects.
Increased activation in the anterior/middle insula during negative anticipation in women with IPV-related PTSD. These findings in women with IPV could be a consequence of the IPV exposure, reflect pre-existing differences in insular function, or due to the development of PTSD. Thus, future longitudinal studi4s need to examine these possibilities.
PMCID: PMC2634744  PMID: 18639236
18.  Increased Affective Bias Revealed Using Experimental Graded Heat Stimuli in Young Depressed Adults: Evidence of “Emotional Allodynia” 
Psychosomatic medicine  2008;70(3):338-344.
Pain and depression often occur together. Pain is both a sensation and an affective experience. Similarly, depression is associated frequently with somatic symptoms as well as emotional dysphoria. Existing evidence indicates that major depressive disorder (MDD) may be associated with altered pain processing. However, the extent to which alterations in experimentally controlled heat pain sensations are related to increased affective bias in MDD is unknown. This psychophysical study examined the hypothesis that young adults with MDD would show increased affective bias to painful and non-painful experimental heat stimuli, as evidenced by an increased responsiveness to warm and hot temperatures.
Graded non-noxious and noxious heat stimuli were delivered randomly with a thermode applied to the volar surface of the left arm of 15 unmedicated subjects with current MDD and 15 age- and gender-matched healthy comparison subjects. MDD and non-MDD subjects rated the intensity and unpleasantness of all stimuli.
Two main results were observed. Firstly, MDD relative to non-MDD subjects showed decreased heat pain thresholds. Secondly, a significantly increased affective bias (= unpleasantness/intensity) was observed in MDD subjects, particularly over the range of non-noxious heat stimuli. This bias was independent of the change in sensory pain thresholds.
These findings represent corroborative evidence of abnormal affective heat pain processing in young adults with MDD, and suggest that MDD is associated with “emotional allodynia”, a qualitatively altered negative emotional response to normally non-aversive thermal stimuli.
PMCID: PMC2742693  PMID: 18378870
psychophysics; allodynia; MDD; thermode; heat; nociception
19.  Major Depressive Disorder is Associated with Altered Functional Brain Response During Anticipation and Processing of Heat Pain 
Archives of general psychiatry  2008;65(11):1275-1284.
Chronic pain and depression are highly comorbid conditions, yet little is known about the neurobiological basis of pain processing in major depressive disorder (MDD).
To examine the neural substrates underlying anticipation and processing of heat pain in a group of unmedicated young adults with current MDD.
Functional magnetic resonance neuroimaging (fMRI) data were collected during an event-related factorial experimental pain paradigm. Painful and non-painful heat stimuli were applied to the left volar forearm while different color shapes explicitly signaled the intensity of the upcoming stimulus.
University brain imaging center.
15 (12 F) young adults with current MDD and 15 (10F) healthy subjects with no history of MDD were recruited and matched for age and level of education. The Structured Clinical Interview for DSM-IV was administered to all participants by a board-certified psychiatrist.
Main Outcome measure
Between-group differences in blood oxygen level-dependent fMRI signal change to anticipation and processing of painful versus non-painful temperature stimuli.
MDD compared to healthy controls showed: (1) increased activation in right anterior insular region, dorsal anterior cingulate and right amygdala during anticipation of painful relative to non-painful stimuli, (2) increased activation in right amygdala and decreased activation in periaqueductal gray, rostral anterior cingulate and prefrontal cortices during painful stimulation relative to non-painful stimulation, and (3) in MDD subjects greater activation in the right amygdala during anticipation of pain was associated with greater levels of perceived helplessness.
These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in MDD. Future studies should examine the degree to which altered functional brain response during anticipatory processing affects ability to modulate negative affective states in MDD, which is a core characteristic of this disorder.
PMCID: PMC2702160  PMID: 18981339
20.  Intolerance of uncertainty correlates with insula activation during affective ambiguity 
Neuroscience letters  2007;430(2):92-97.
Intolerance of uncertainty (IU), or the increased affective response to situations with uncertain outcomes, is an important component process of anxiety disorders. Increased IU is observed in panic disorder (PD), obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD), and is thought to relate to dysfunctional behaviors and thought patterns in these disorders. Identifying what brain systems are associated with IU would contribute to a comprehensive model of anxiety processing, and increase our understanding of the neurobiology of anxiety disorders. Here, we used a behavioral task, Wall of Faces (WOF), during functional magnetic resonance imaging (fMRI), which probes both affect and ambiguity, to examine the neural circuitry of IU in fourteen (10 females) college age (18.8 yrs) subjects. All subjects completed the Intolerance of Uncertainty Scale (IUS), Anxiety Sensitivity Index (ASI), and a measure of neuroticism (i.e. the NEO-N). IUS scores but neither ASI nor NEO-N scores, correlated positively with activation in bilateral insula during affective ambiguity. Thus, the experience of IU during certain types of emotion processing may relate to the degree to which bilateral insula processes uncertainty. Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty.
PMCID: PMC2692473  PMID: 18079060
21.  Increased Amygdala Activation is Related to Heart Rate During Emotion Processing in Adolescent Subjects 
Neuroscience letters  2007;428(2-3):109-114.
Emotions have been conceptualized as representations of bodily responses to a stimulus that critically involves the autonomic nervous system (ANS). An association between amygdala activation and ANS activity has been shown in adults. However, to date, no studies have demonstrated this association in adolescents. Examining the interaction between the ANS and amygdala in healthy adolescents may provide information about age-related changes in the association between amygdala activation and ANS measures. Therefore, the aim of this study was to examine the relationship between amygdala activation and heart rate in normal adolescents. Eighteen 12- to 17-year old adolescents participated. Heart rate data was collected during functional magnetic resonance imaging while subjects performed a facial expression matching task that reliably activates the amygdala. Adolescents showed significant amygdala activation for all facial expressions relative to the shape-matching, control task. Moreover, the degree of activation in the right amygdala for Fearful faces was significantly correlated with heart rate (Spearman’s rho = 0.55, p = 0.018, two-tailed). This study shows that amygdala activity is related to heart rate in healthy adolescents. Thus, similar to adults, adolescents show a coupling between processing emotional events and adjusting the ANS accordingly. Furthermore, this study confirms previous adolescent studies showing amygdala activation to Fearful, Angry, and Happy faces. Finally, the results of the present study lay the foundation for future research to investigate whether adolescents with mood or anxiety disorders show an altered coupling between processing emotionally salient events and ANS activity.
PMCID: PMC2171034  PMID: 18029095

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