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1.
Neuroimage ; 182: 441-455, 2018 11 15.
Article in English | MEDLINE | ID: mdl-29242104

ABSTRACT

Chronic musculoskeletal pain is a condition that influences central nervous system structure. In this study, we combined novel structural neuroimaging techniques, using well-validated software packages including FSL, Mrtrix3, and DSI Studio, to characterize brain grey (GM) and white matter (WM) differences in chronic musculoskeletal pain participants (n = 74), compared to age-matched pain-free controls (n = 31). In participants with chronic pain, we identified significantly higher volume in subcortical GM structures using voxel-based morphometry (FSLVBM). These differences were most prominent in the caudate, amygdala, and the hippocampus. At the same time, volume was lower in the dorsolateral prefrontal cortex, as well as the primary motor and sensory regions in patients with chronic pain. To delineate WM microstructural differences of neuronal (e.g., activity-dependent myelin remodeling) and non-neuronal (e.g., neuroinflammation) origins, we utilized Mrtrix3 software pipelines to investigate WM fiber complexity, density, and cross-section. Whole-brain analyses revealed lower WM fiber complexity within the corpus callosum and the anterior limb of the left internal capsule. Whole brain and region of interest analyses revealed fiber complexity differences within the salience and the sensorimotor networks. In contrast, we detected non-neuronal white matter density differences within the dorsal attention network: density was lower in the inferior fronto-occipital fasciculus and the splenium of the corpus callosum in chronic musculoskeletal pain. Consistent with the involvement of the dorsal attention network, WM tractography analysis, conducted with DSI Studio and Network Based Statistics, revealed higher connectivity from the superior parietal lobule to the hippocampus in patients with chronic pain. No differences were detected in measures of fiber cross-section, suggesting the absence of neuronal degeneration in chronic pain. The combination of multiple neuroimaging techniques in this study offers a unique window into the structural differences within the chronic pain brain and provides the first evidence of microstructural variations in fiber complexity and density.


Subject(s)
Cerebral Cortex/diagnostic imaging , Chronic Pain/diagnostic imaging , Corpus Callosum/diagnostic imaging , Diffusion Tensor Imaging/methods , Gray Matter/diagnostic imaging , Internal Capsule/diagnostic imaging , Musculoskeletal Pain/diagnostic imaging , Nerve Net/diagnostic imaging , White Matter/diagnostic imaging , Adult , Anisotropy , Humans
2.
PLoS One ; 12(6): e0178360, 2017.
Article in English | MEDLINE | ID: mdl-28604837

ABSTRACT

The goal of this study was to investigate patterns of axonal injury in the first week after mild traumatic brain injury (mTBI). We performed a prospective cohort study of 20 patients presenting to the emergency department with mTBI, using 3.0T diffusion tensor MRI immediately after injury and again at 1 week post-injury. Corresponding data were acquired from 16 controls over a similar time interval. Fractional anisotropy (FA) and other diffusion measures were calculated from 11 a priori selected axon tracts at each time-point, and the change across time in each region was quantified for each subject. Clinical outcomes were determined by standardized neurocognitive assessment. We found that mTBI subjects were significantly more likely to have changes in FA in those 11 regions of interest across the one week time period, compared to control subjects whose FA measurements were stable across time. Longitudinal imaging was more sensitive to these subtle changes in white matter integrity than cross-sectional assessments at either of two time points, alone. Analyzing the sources of variance in our control population, we show that this increased sensitivity is likely due to the smaller within-subject variability obtained by longitudinal analysis with each subject as their own control. This is in contrast to the larger between-subject variability obtained by cross-sectional analysis of each individual subject to normalized data from a control group. We also demonstrated that inclusion of all a priori ROIs in an analytic model as opposed to measuring individual ROIs improves detection of white matter changes by overcoming issues of injury heterogeneity. Finally, we employed genetic programming (a bio-inspired computational method for model estimation) to demonstrate that longitudinal changes in FA have utility in predicting the symptomatology of patients with mTBI. We conclude concussive brain injury caused acute, measurable changes in the FA of white matter tracts consistent with evolving axonal injury and/or edema, which may contribute to post-concussive symptoms.


Subject(s)
Brain Concussion/diagnosis , Diffusion Magnetic Resonance Imaging , Adolescent , Adult , Brain Injuries, Traumatic/diagnosis , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
3.
Menopause ; 24(2): 163-170, 2017 02.
Article in English | MEDLINE | ID: mdl-27676634

ABSTRACT

OBJECTIVE: The current study examined the effects of pharmacologic dopaminergic manipulations on working memory-related brain activation in postmenopausal women to further understand the neurochemistry underlying cognition after menopause. METHODS: Eighteen healthy postmenopausal women, mean age 55.21 years, completed three study days with dopaminergic drug challenges during which they performed a functional magnetic resonance imaging visual verbal N-back test of working memory. Acute stimulation with 1.25 mg oral D2 agonist bromocriptine, acute blockade with 1.5 mg oral haloperidol, and matching placebo were administered randomly and blindly on three study days. RESULTS: We found that dopaminergic stimulation increased activation primarily in the posterior regions of the working memory network compared with dopaminergic blockade using a whole brain cluster-level corrected analysis. The dopaminergic medications did not affect working memory performance. CONCLUSIONS: Patterns of increased blood-oxygen-level dependent signal activation after dopaminergic stimulation were found in this study in posterior brain regions with no effect on working memory performance. Further studies should examine specific dopaminergic contributions to brain functioning in healthy postmenopausal women to determine the effects of the increased brain activation on cognition and behavior.


Subject(s)
Bromocriptine/pharmacology , Dopamine Antagonists/pharmacology , Haloperidol/pharmacology , Memory, Short-Term/drug effects , Postmenopause/psychology , Brain/diagnostic imaging , Brain/drug effects , Brain/physiology , Cognition/drug effects , Female , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Middle Aged , Postmenopause/drug effects
4.
PLoS One ; 10(5): e0126110, 2015.
Article in English | MEDLINE | ID: mdl-25962067

ABSTRACT

Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to controls. Increases in activation were greater in those mTBI subjects without cognitive recovery. As workload increased in mTBI subjects, activation increased in cortical regions in the right hemisphere. In summary, we found neuroimaging evidence for working memory deficits during the first week following mild traumatic brain injury. Subjects with persistent cognitive symptoms after mTBI had increased requirement for posterior cingulate activation to complete memory tasks at 1 week following a brain injury. These results provide insight into functional activation patterns during initial recovery from mTBI and expose the regional activation networks that may be involved in working memory deficits.


Subject(s)
Brain Injuries/pathology , Magnetic Resonance Imaging/methods , Adolescent , Adult , Female , Functional Neuroimaging/methods , Humans , Male , Middle Aged , Prospective Studies , Young Adult
5.
J Pain ; 15(11): 1110-1119, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25135468

ABSTRACT

UNLABELLED: There is emerging evidence that chronic musculoskeletal pain is associated with anatomic and functional abnormalities in gray matter. However, little research has investigated the relationship between chronic musculoskeletal pain and white matter. In this study, we used whole-brain tract-based spatial statistics and region-of-interest analyses of diffusion tensor imaging data to demonstrate that patients with chronic musculoskeletal pain exhibit several abnormal metrics of white matter integrity compared with healthy controls. Chronic musculoskeletal pain was associated with lower fractional anisotropy in the splenium of the corpus callosum and the left cingulum adjacent to the hippocampus. Patients also had higher radial diffusivity in the splenium, right anterior and posterior limbs of the internal capsule, external capsule, superior longitudinal fasciculus, and cerebral peduncle. Patterns of axial diffusivity (AD) varied: patients exhibited lower AD in the left cingulum adjacent to the hippocampus and higher AD in the anterior limbs of the internal capsule and in the right cerebral peduncle. Several correlations between diffusion metrics and clinical variables were also significant at a P < .01 level: fractional anisotropy in the left uncinate fasciculus correlated positively with total pain experience and typical levels of pain severity. AD in the left anterior limb of the internal capsule and left uncinate fasciculus was correlated with total pain experience and typical pain level. Positive correlations were also found between AD in the right uncinate and both total pain experience and pain catastrophizing. These results demonstrate that white matter abnormalities play a role in chronic musculoskeletal pain as a cause, a predisposing factor, a consequence, or a compensatory adaptation. PERSPECTIVE: Patients with chronic musculoskeletal pain exhibit altered metrics of diffusion in the brain's white matter compared with healthy volunteers, and some of these differences are directly related to symptom severity.


Subject(s)
Chronic Pain/pathology , Musculoskeletal Pain/pathology , White Matter/pathology , Adult , Diffusion Magnetic Resonance Imaging , Female , Humans , Image Interpretation, Computer-Assisted , Male , Middle Aged
6.
Alcohol Alcohol ; 49(1): 60-5, 2014.
Article in English | MEDLINE | ID: mdl-23847021

ABSTRACT

AIMS: The goal of this study was to better understand the predictive relationship in both directions between negative (anger, sadness) and positive (happiness) moods and alcohol consumption using daily process data among heavy drinkers. METHODS: Longitudinal daily reports of moods, alcohol use and other covariates such as level of stress were assessed over 180 days using interactive voice response telephone technology. Participants were heavy drinkers (majority meeting criteria for alcohol dependence at baseline) recruited through their primary care provider. The sample included 246 (166 men, 80 women) mostly Caucasian adults. Longitudinal statistical models were used to explore the varying associations between number of alcoholic drinks and mood scores the next day and vice versa with gender as a moderator. RESULTS: Increased alcohol use significantly predicted decreased happiness the next day (P < 0.005), more strongly for females than males. Increased anger predicted higher average alcohol use the next day for males only (P < 0.005). CONCLUSION: This daily process study challenges the notion that alcohol use enhances positive mood for both males and females. Our findings also suggest a strong association between anger and alcohol use that is specific to males. Thus, discussions about the effects of drinking on one's feeling of happiness may be beneficial for males and females as well as anger interventions may be especially beneficial for heavy-drinking males.


Subject(s)
Affect/physiology , Alcohol Drinking/psychology , Alcohol Drinking/trends , Sex Characteristics , Telephone/trends , Adult , Aged , Aged, 80 and over , Emotions/physiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Speech Recognition Software/statistics & numerical data , Speech Recognition Software/trends , Telephone/statistics & numerical data , Time Factors , Young Adult
7.
Neuroimage Clin ; 5: 365-76, 2014.
Article in English | MEDLINE | ID: mdl-26958466

ABSTRACT

Chronic pain is a complex physiological and psychological phenomenon. Implicit learning mechanisms contribute to the development of chronic pain and to persistent changes in the central nervous system. We hypothesized that these central abnormalities can be remedied with Cognitive Behavioral Therapy (CBT). Specifically, since regions of the anterior Default Mode Network (DMN) are centrally involved in emotional regulation via connections with limbic regions, such as the amygdala, remediation of maladaptive behavioral and cognitive patterns as a result of CBT for chronic pain would manifest itself as a change in the intrinsic functional connectivity (iFC) between these prefrontal and limbic regions. Resting-state functional neuroimaging was performed in patients with chronic pain before and after 11-week CBT (n = 19), as well as a matched (ages 19-59, both sexes) active control group of patients who received educational materials (n = 19). Participants were randomized prior to the intervention. To investigate the differential impact of treatment on intrinsic functional connectivity (iFC), we compared pre-post differences in iFC between groups. In addition, we performed exploratory whole brain analyses of changes in fractional amplitude of low frequency fluctuations (fALFF). The course of CBT led to significant improvements in clinical measures of pain and self-efficacy for coping with chronic pain. Significant group differences in pre-post changes in both iFC and fALFF were correlated with clinical outcomes. Compared to control patients, iFC between the anterior DMN and the amygdala/periaqueductal gray decreased following CBT, whereas iFC between the basal ganglia network and the right secondary somatosensory cortex increased following CBT. CBT patients also had increased post-therapy fALFF in the bilateral posterior cingulate and the cerebellum. By delineating neuroplasticity associated with CBT-related improvements, these results add to mounting evidence that CBT is a valuable treatment option for chronic pain.


Subject(s)
Chronic Pain/psychology , Chronic Pain/therapy , Cognitive Behavioral Therapy/methods , Nerve Net/physiopathology , Adaptation, Psychological , Adolescent , Adult , Brain/pathology , Chronic Pain/pathology , Emotions , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Pain Management/methods , Pain Measurement , Principal Component Analysis , Young Adult
8.
J Pain ; 14(12): 1573-84, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24135432

ABSTRACT

UNLABELLED: Several studies have reported reduced cerebral gray matter (GM) volume or density in chronic pain conditions, but there is limited research on the plasticity of the human cortex in response to psychological interventions. We investigated GM changes after cognitive-behavioral therapy (CBT) in patients with chronic pain. We used voxel-based morphometry to compare anatomic magnetic resonance imaging scans of 13 patients with mixed chronic pain types before and after an 11-week CBT treatment and to 13 healthy control participants. CBT led to significant improvements in clinical measures. Patients did not differ from healthy controls in GM anywhere in the brain. After treatment, patients had increased GM in the bilateral dorsolateral prefrontal, posterior parietal, subgenual anterior cingulate/orbitofrontal, and sensorimotor cortices, as well as hippocampus, and reduced GM in supplementary motor area. In most of these areas showing GM increases, GM became significantly higher than in controls. Decreased pain catastrophizing was associated with increased GM in the left dorsolateral prefrontal and ventrolateral prefrontal cortices, right posterior parietal cortex, somatosensory cortex, and pregenual anterior cingulate cortex. Although future studies with additional control groups will be needed to determine the specific roles of CBT on GM and brain function, we propose that increased GM in the prefrontal and posterior parietal cortices reflects greater top-down control over pain and cognitive reappraisal of pain, and that changes in somatosensory cortices reflect alterations in the perception of noxious signals. PERSPECTIVE: An 11-week CBT intervention for coping with chronic pain resulted in increased GM volume in prefrontal and somatosensory brain regions, as well as increased dorsolateral prefrontal volume associated with reduced pain catastrophizing. These results add to mounting evidence that CBT can be a valuable treatment option for chronic pain.


Subject(s)
Chronic Pain/psychology , Chronic Pain/therapy , Cognitive Behavioral Therapy/methods , Pain Measurement/psychology , Prefrontal Cortex/growth & development , Adaptation, Psychological/physiology , Adult , Aged , Chronic Pain/diagnosis , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Middle Aged , Organ Size , Pain Measurement/methods , Young Adult
9.
Physiol Meas ; 34(10): N97-105, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24065623

ABSTRACT

Anticipatory postural adjustments (APAs) stabilize potential disturbances to posture caused by movement. Impaired APAs are common with disease and injury. Brain functions associated with generating APAs remain uncertain due to a lack of paired tasks that require similar limb motion from similar postural orientations, but differ in eliciting an APA while also being compatible with brain imaging techniques (e.g., functional magnetic resonance imaging; fMRI). This study developed fMRI-compatible tasks differentiated by the presence or absence of APAs during leg movement. Eighteen healthy subjects performed two leg movement tasks, supported leg raise (SLR) and unsupported leg raise (ULR), to elicit isolated limb motion (no APA) versus multi-segmental coordination patterns (including APA), respectively. Ground reaction forces under the feet and electromyographic activation amplitudes were assessed to determine the coordination strategy elicited for each task. Results demonstrated that the ULR task elicited a multi-segmental coordination that was either minimized or absent in the SLR task, indicating that it would serve as an adequate control task for fMRI protocols. A pilot study with a single subject performing each task in an MRI scanner demonstrated minimal head movement in both tasks and brain activation patterns consistent with an isolated limb movement for the SLR task versus multi-segmental postural coordination for the ULR task.


Subject(s)
Neurophysiology/methods , Posture/physiology , Adult , Brain/physiology , Humans , Leg/physiology , Magnetic Resonance Imaging , Male , Movement/physiology , Pilot Projects
10.
Neurobiol Aging ; 34(4): 1145-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23036586

ABSTRACT

Individuals who report subjective cognitive complaints but perform normally on neuropsychological tests might be at increased risk for pathological cognitive aging. The current study examined the effects of the presence of subjective cognitive complaints on functional brain activity during a working memory task in a sample of middle-aged postmenopausal women. Twenty-three postmenopausal women aged 50-60 completed a cognitive complaint battery of questionnaires. Using 20% of items endorsed as the threshold, 12 women were categorized as cognitive complainers (CC) and 11 were noncomplainers (NC). All subjects then took part in a functional magnetic resonance imaging scanning session during which they completed a visual-verbal N-back test of working memory. Results showed no difference in working memory performance between CC and NC groups. However, the CC group showed greater activation relative to the NC group in a broad network involved in working memory including the middle frontal gyrus (Brodmann area [BA] 9 and 10), the precuneus (BA 7), and the cingulate gyrus (BA 24 and 32). The CC group recruited additional regions of the working memory network compared with the NC group as the working memory load and difficulty of the task increased. This study showed brain activation differences during working memory performance in a middle-aged group of postmenopausal women with subjective cognitive complaints but without objective cognitive deficit. These findings suggest that subjective cognitive complaints in postmenopausal women might be associated with increased cortical activity during effort-demanding cognitive tasks.


Subject(s)
Cerebral Cortex/physiopathology , Cognition Disorders/physiopathology , Cognition , Memory, Short-Term , Nerve Net/physiopathology , Postmenopause , Brain Mapping , Female , Humans , Male , Middle Aged
11.
Am J Geriatr Psychiatry ; 20(9): 734-43, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22832417

ABSTRACT

OBJECTIVE: The current study examined whether age after menopause impacted the effect of estradiol (E2) on mood after a psychosocial stress manipulation. BACKGROUND: Previous studies have shown that E2 improves mood in women around the menopause transition but does not improve mood for older postmenopausal women. We have previously shown that E2 treatment in nondepressed women resulted in increased negative mood after psychosocial stress. DESIGN: Participants were 22 postmenopausal women placed on either oral placebo or 17ß-estradiol (1 mg/day for 1 month, then 2 mg/day for 2 months). METHOD: At the end of the 3-month treatment phase, the participants performed the Trier Social Stress Test followed by mood ratings. To examine the effects of age on the estrogen-stress interaction, we performed a median split on age and created four groups of participants: younger-placebo (mean age: 55.5 years), younger-E2 (mean age: 55.5 years), older-placebo (mean age: 73.0 years), and older-E2 (mean age: 76.8 years). RESULTS: : The results showed that both older and younger E2-treated participants exhibited a significant and similar increase in negative mood after psychosocial stress compared with placebo-treated women. CONCLUSIONS: These results suggest that E2 may play a significant role in modulating emotional reactivity to stressful events and that this effect persists in older women. Furthermore, responsivity to E2 effects on emotional processing appears to be intact even years after menopause in contrast with other cognitive and behavioral effects of E2, which may be limited to the early postmenopausal years.


Subject(s)
Affect/drug effects , Estradiol/pharmacology , Postmenopause/drug effects , Stress, Psychological/psychology , Age Factors , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Psychiatric Status Rating Scales , Psychological Tests
12.
Psychol Serv ; 9(2): 174-84, 2012 May.
Article in English | MEDLINE | ID: mdl-22662731

ABSTRACT

Relapse after alcoholism treatment is high. Alcohol Therapeutic Interactive Voice Response (ATIVR) is an automated telephone program for posttreatment self-monitoring, skills practice, and feedback. This pilot study examined feasibility of ATIVR. Participants (n = 21; 57% male) had access to ATIVR for 90 days following outpatient group cognitive-behavioral therapy (CBT) to make daily reports of mood, confidence in sobriety, urges to use substances, and actual use. Reports of relapse or risk were followed with additional questions. Participants received personalized therapist feedback based on responses, and could access recorded CBT skill reviews. Pre-post assessments included: alcohol consumption (Timeline Follow-Back), self-efficacy (Situational Confidence Questionnaire), and perceived coping ability (Effectiveness of Coping Behaviors Inventory). Participants called on 59% of scheduled days and continued making calls for an average of 84 days. Following ATIVR, participants gave feedback that ATIVR was easy to use and increased self-awareness. Participants particularly liked the therapist feedback component. Abstinence rate increased significantly during ATIVR (p = .03), and both self-efficacy and coping significantly improved from pre-CBT to post-ATIVR (p < .01). Results indicate ATIVR is feasible and acceptable. Its efficacy should be evaluated in a randomized controlled trial.


Subject(s)
Alcoholism/therapy , Cognitive Behavioral Therapy , Telephone , Adaptation, Psychological , Adult , Alcoholism/psychology , Awareness , Feasibility Studies , Feedback , Female , Humans , Male , Middle Aged , Pilot Projects , Secondary Prevention , Self Care , Self Concept , Speech Recognition Software , Telemedicine/methods , Treatment Outcome
13.
Transl Behav Med ; 2(1): 93-101, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22448205

ABSTRACT

Chronic pain is a medical condition that severely decreases the quality of life for those who struggle to cope with it. Interactive voice response (IVR) technology has the ability to track symptoms and disease progression, to investigate the relationships between symptom patterns and clinical outcomes, to assess the efficacy of ongoing treatments, and to directly serve as an adjunct to therapeutic treatment for chronic pain. While many approaches exist toward the management of chronic pain, all have their pitfalls and none work universally. Cognitive behavioral therapy (CBT) is one approach that has been shown to be fairly effective, and therapeutic interactive voice response technology provides a convenient and easy-to-use means of extending the therapeutic gains of CBT long after patients have discontinued clinical visitations. This review summarizes the advantages and disadvantages of IVR technology, provides evidence for the efficacy of the method in monitoring and managing chronic pain, and addresses potential future directions that the technology may take as a therapeutic intervention in its own right.

14.
Neuroimage ; 60(2): 1394-403, 2012 Apr 02.
Article in English | MEDLINE | ID: mdl-22266175

ABSTRACT

Estradiol has been shown to affect cholinergic modulation of cognition in human and nonhuman animal models. This study examined the brain-based interaction of estradiol treatment and anticholinergic challenge in postmenopausal women during the performance of a working memory task and functional MRI. Twenty-four postmenopausal women were randomly and blindly placed on 1mg oral 17-ß estradiol or matching placebo pills for three months after which they participated in three anticholinergic challenge sessions. During the challenge sessions, subjects were administered the antimuscarinic drug scopolamine, the antinicotinic drug mecamylamine, or placebo. After drug administration, subjects completed an fMRI session during which time they performed a visual verbal N-back test of working memory. Results showed that scopolamine increased activation in the left medial frontal gyrus (BA 10) and mecamylamine increased activation in the left inferior frontal gyrus (BA 46). Estradiol treatment compared to placebo treatment significantly reduced the activation in this left medial frontal region during scopolamine challenge. Estradiol treatment also increased activation in the precuneus (BA 31) during mecamylamine challenge. These data are the first to show that estradiol modulated antimuscarinic- and anitnicotinic-induced brain activity and suggest that estradiol affected cholinergic system regulation of cognition-related brain activation in humans.


Subject(s)
Brain/drug effects , Brain/physiology , Cholinergic Fibers/drug effects , Cholinergic Fibers/physiology , Estradiol/pharmacology , Estrogens/pharmacology , Memory, Short-Term/drug effects , Memory, Short-Term/physiology , Aged , Double-Blind Method , Female , Humans , Middle Aged , Postmenopause
15.
Compr Psychiatry ; 52(6): 731-6, 2011.
Article in English | MEDLINE | ID: mdl-21349510

ABSTRACT

This article examines temporal relationships between negative emotions and pain in a cohort of 33 patients with chronic musculoskeletal pain enrolled in a telephone-based relapse prevention program (Therapeutic Interactive Voice Response [TIVR]), after 11 weeks of group cognitive behavioral therapy (CBT). Patients were asked to make daily reports to the TIVR system for 4 months after CBT. Patients' daily reports were analyzed with path analysis to examine temporal relationships between 3 emotion variables (anger, sadness, and stress) and 2 pain variables (pain and pain control). As expected, same-day correlations were significant between emotion variables and both pain and pain control. The lagged associations revealed unidirectional relationships between pain and next-day emotions: increased pain predicted higher reports of sadness the following day (P < .05). Conversely, increased pain control predicted decreased sadness and anger the following day (P < .05). Unlike some previous studies, this study did not reveal that an increase of negative emotions predicted increased next-day pain. We speculate that CBT treatment followed by the relapse prevention program teaches patients how to modulate negative emotions such that they no longer have a negative impact on next-day pain perception. The clinical implications of our findings are discussed.


Subject(s)
Chronic Pain/psychology , Emotions , Anger , Chronic Pain/complications , Chronic Pain/physiopathology , Chronic Pain/prevention & control , Cognitive Behavioral Therapy , Depression/etiology , Depression/psychology , Emotions/physiology , Female , Humans , Male , Middle Aged , Secondary Prevention , Stress, Psychological/etiology , Stress, Psychological/psychology , Surveys and Questionnaires , Telephone
16.
Horm Behav ; 58(5): 929-35, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20849856

ABSTRACT

Prior research shows that menopause is associated with changes in cognition in some older women. However, how estrogen loss and subsequent estrogen treatment affects cognition and particularly the underlying brain processes responsible for any cognitive changes is less well understood. We examined the ability of estradiol to modulate the manipulation of information in working memory and related brain activation in postmenopausal women. Twenty healthy postmenopausal women (mean age (SD)=59.13 (5.5)) were randomly assigned to three months of 1mg oral 17-ß estradiol or placebo. At baseline and three months later each woman completed a visual verbal N-back sequential letter test of working memory during functional magnetic resonance imaging (fMRI). The fMRI data showed that women who were treated with estradiol for three months had increased frontal activation during the more difficult working memory load conditions compared to women treated with placebo. Performance on the verbal working memory task showed no difference between estradiol and placebo treated subjects. These data are consistent with prior work showing increases in frontal activation on memory tasks after estrogen treatment. However, this is the first study to show that estrogen-induced increases in brain activity were tied to cognitive load during a verbal working memory task. These data suggest that estradiol treatment effects on cognition may be in part produced through modulation of frontal lobe functioning under difficult task conditions.


Subject(s)
Estradiol/therapeutic use , Frontal Lobe/drug effects , Memory/drug effects , Postmenopause/drug effects , Administration, Oral , Aged , Estradiol/administration & dosage , Estrogen Replacement Therapy/psychology , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiology , Humans , Magnetic Resonance Imaging , Memory/physiology , Middle Aged , Placebos , Postmenopause/physiology , Postmenopause/psychology , Radiography , Task Performance and Analysis , Up-Regulation/drug effects
17.
J Pain ; 11(12): 1410-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20620119

ABSTRACT

UNLABELLED: This paper examines whether a telephone-based, automated maintenance enhancement program can help to reduce opioid and nonsteroidal anti-inflamatory drugs (NSAID) analgesic use in patients with chronic pain. Following 11 weeks of group cognitive-behavioral therapy (CBT), 51 subjects with chronic musculoskeletal pain were randomized to 1 of 2 study groups. Twenty-six subjects participated in 4 months of a Therapeutic Interactive Voice Response (TIVR) program in addition to standard follow-up care, while a control group of 25 subjects received standard follow-up care only. TIVR is an automated, telephone-based tool developed for the maintenance and enhancement of CBT skills. Opioid analgesic use decreased in the experimental group in both follow-ups: 4 and 8 months postCBT. In addition, at 8-month follow-up, 21% of the TIVR subjects had discontinued the use of opioid analgesics, 23% had discontinued NSAIDS, and 10% had discontinued antidepressant medications. In contrast, the control group showed increases in opioid and NSAIDS use. Analysis of covariance (ANCOVA) revealed significant between-group differences in opioid analgesic use at 8-month follow up (P = .004). We have previously demonstrated the efficacy of TIVR to decrease pain and improve coping; this analysis demonstrates that the use of TIVR may also result in concurrent reductions in opioid analgesic and NSAID medications use. PERSPECTIVE: This article demonstrates that the Therapeutic Interactive Voice Response maintenance enhancement program can help to reduce opioid analgesic use in patients with chronic pain. This automated maintenance enhancement program could potentially assist patients not only to decrease pain and improve coping, but also to diminish the likelihood of opioid dependence.


Subject(s)
Analgesics, Opioid/therapeutic use , Cognitive Behavioral Therapy/methods , Pain Management , Telemedicine/methods , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Computers , Female , Humans , Male , Middle Aged , Telephone
18.
Pain ; 134(3): 335-345, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18178011

ABSTRACT

We developed Therapeutic Interactive Voice Response (TIVR) as an automated, telephone-based tool for maintenance enhancement following group cognitive-behavioral therapy (CBT) for chronic pain. TIVR has four components: a daily self-monitoring questionnaire, a didactic review of coping skills, pre-recorded behavioral rehearsals of coping skills, and monthly personalized feedback messages from the CBT therapist based on a review of the patient's daily reports. The first three components are pre-recorded and all four can be accessed remotely by patients via touch-tone telephone on demand. Following 11 weeks of group CBT, 51 subjects with chronic musculoskeletal pain were randomized to one of two study groups. Twenty-six subjects participated in 4 months of TIVR, while a control group of 25 subjects received standard care only. The TIVR group showed maximum improvement over baseline at the 8-month follow-up for seven of the eight outcome measures; improvement was found to be significant for all outcomes (p

Subject(s)
Cognitive Behavioral Therapy/methods , Pain Management , Secondary Prevention , Self Care/methods , Telemedicine/methods , Therapy, Computer-Assisted/methods , Chronic Disease , Humans , Middle Aged , Self-Assessment
19.
J Pain ; 3(6): 429-38, 2002 Dec.
Article in English | MEDLINE | ID: mdl-14622728

ABSTRACT

The objective of this study was to test whether Interactive Voice Response (IVR) can be used to enhance the therapeutic outcome of patients receiving group cognitive behavioral therapy (CBT) for chronic pain. Ten subjects with chronic pain syndromes participated in 10 weeks of group CBT followed by 4 months of Therapeutic Interactive Voice Response (TIVR). Our specially designed TIVR is based on a computerized telephone system in which callers are asked questions and respond by using the telephone keypad. It was created to reinforce pain coping skills and to provide messages for relaxation, sleep induction, and emotional support that can be accessed by patients on demand. Within-subject analysis showed that maximum positive change for nearly all outcome measures was observed at the post-TIVR point. For some measures, improvement compared to baseline was significant after TIVR despite the fact it had not been significant after CBT. Measures showing this pattern included SF-36 Mental Health Composite Score (P < .0004), McGill Pain Questionnaire pain (P < .01), Coping Strategies Questionnaire Catastrophizing (P < .0006), Treatment Outcomes in Pain Survey Total Pain Experience (P < .03), and Perceived Family/Social Disability (P < .02). Our preliminary results suggest that TIVR can be used to improve coping skills adherence and to prevent relapse into pain behavior.

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