Modeling the impact of COPD on the brain.

Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable-COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p < or = 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities.

Functional MRI activation in children with and without dyslexia during pseudoword aural repeat and visual decode: before and after treatment.

Children without dyslexia (n=10) received nonphonological treatment, and those with dyslexia received phonological (n=11) or nonphonological (n=9) treatment. Before and after treatment they performed aural repeat, visual decode, and aural match pseudoword tasks during functional MRI scanning that separated stimulus input from response production. Group map analysis indicated that children with dyslexia overactivated compared with good readers during the aural-repeat/aural-match contrast in bilateral frontal (Brodmann's area [BA] 3, 4, 5, 6, 9), left parietal (BA 2, 3), left temporal (BA 38), and right temporal (BA 20, 21, 37) regions (stimulus input) and underactivated in right frontal (BA 24, 32) and right insula (BA 48) regions (response production); they underactivated in BA 19/V5 during the visual-decode/aural-match contrast (response production). Individual brain analysis for children with dyslexia revealed that during the aural-repeat/aural-match contrast (stimulus input), phonological treatment decreased and normalized activation in left supramarginal gyrus and postcentral gyrus. Nonphonological treatment increased and normalized activation during the visual-decode/aural-match contrast (response production) in BA19/V5 and changed activation in the same direction as good readers during aural-repeat/aural-match contrast (stimulus input) in left postcentral gyrus. The significance of the findings for competing theories of dyslexia is discussed.

Analysis of responses to kava kava in the feline pulmonary vascular bed.

This study was designed to test the hypothesis that kava kava induces a depressor response in the pulmonary vascular bed of the cat and to identify the pathways involved in the mediation or modulation of these effects. In separate experiments, the effects of L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an ATP-sensitive K+ channel blocker, meclofenamate, a nonselective cyclooxygenase inhibitor, nicardipine, a calcium channel blocker, bicuculline, a gamma-aminobutyric acid (GABA)A receptor antagonist, and saclofen, a GABAB antagonist, were investigated on pulmonary arterial responses to kava kava (kava), pinacidil, an ATP-sensitive K+ channel activator, bradykinin, an inducer of nitric oxide synthase, 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF-97541), a GABAB receptor agonist, and muscimol, a GABAA receptor agonist. Lobar arterial perfusion pressure and systemic pressure were continuously monitored, electronically averaged, and recorded. Under elevated tone conditions in the isolated left lower lobe of the feline vascular bed, kava induced a dose-dependent vasodepressor response that was not significantly altered after administration of L-NIO, glibenclamide, meclofenamate, or saclofen. Responses to kava were significantly reduced after administration of either nicardipine or bicuculline. When the calcium channel blocker nicardipine was administered in addition to the GABA blocker bicuculline, there was near complete attenuation of the kava-induced vasodepressor responses. The results of this investigation suggest that kava has potent vasodepressor activity in the feline lung bed and that this response is mediated or modulated by both a calcium channel- and GABA receptor-sensitive pathway.

Replicable functional magnetic resonance imaging evidence of correlated brain signals between physically and sensory isolated subjects.

OBJECTIVES: Previous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) experiments have suggested that correlated neural signals may be detected in the brains of individuals who are physically and sensorily isolated from each other. Functional MRI and EEG methods were used in the present study in an attempt to replicate these findings. DESIGN/SETTINGS: Subjects were electrically and magnetically shielded because of the characteristic surroundings of the scanner room. During the experiment, the nonstimulated subject was placed in the scanner with sensory isolating goggles covering the subject's eyes. The stimulated subject was placed 30 feet away and sat in front of a video monitor that presented an alternating schedule of six stimulus-on/stimulus-off conditions. The stimulus- on condition consisted of a flickering checkerboard pattern whereas the stimulus-off condition consisted of a static checkerboard. Stimulus-on/-off conditions were presented in the sequence on/off/on/off/on/off. The duration of these intervals was randomly assigned but consistently provided a total of 150 seconds of flicker and 150 seconds of static. Sessions were repeated twice to assess possible replication of the phenomenon. OUTCOME MEASURES: Changes in fMRI brain activation (relating to blood oxygenation) and EEG signals were measured in the nonstimulated subjects. Changes occurring during stimulus-on conditions were statistically compared to changes occurring during the stimulus-off conditions. RESULTS: Statistically significant changes in fMRI brain activation and EEG signals were observed when comparing the stimulus-on condition to the stimulus-off condition in nonstimulated subjects (p < 0.001, corrected for multiple comparisons). For fMRI, these changes were observed in visual brain areas 18 and 19 (Brodmann areas). One of the subjects replicated the results. CONCLUSIONS: These data replicate previous findings suggesting that correlated neural signals may be detected by fMRI and EEG in the brains of subjects who are physically and sensorily isolated from each other.

Evidence for correlations between distant intentionality and brain function in recipients: a functional magnetic resonance imaging analysis.

This study, using functional magnetic resonance imaging (fMRI) technology, demonstrated that distant intentionality (DI), defined as sending thoughts at a distance, is correlated with an activation of certain brain functions in the recipients. Eleven healers who espoused some form for connecting or healing at a distance were recruited from the island of Hawaii. Each healer selected a person with whom they felt a special connection as a recipient for DI. The recipient was placed in the MRI scanner and isolated from all forms of sensory contact from the healer. The healers sent forms of DI that related to their own healing practices at random 2-minute intervals that were unknown to the recipient. Significant differences between experimental (send) and control (no send) procedures were found (p = 0.000127). Areas activated during the experimental procedures included the anterior and middle cingulate area, precuneus, and frontal area. It was concluded that instructions to a healer to make an intentional connection with a sensory isolated person can be correlated to changes in brain function of that individual.

Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI.

This study investigated the neural correlates of virtual reality analgesia. Virtual reality significantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was measured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality significantly reduced pain-related brain activity in all five regions of interest; the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction.

Electroencephalographic evidence of correlated event-related signals between the brains of spatially and sensory isolated human subjects.

OBJECTIVE: To determine whether correlated event-related potentials (ERPs) can be detected between the brains of spatially and sensory isolated human subjects. DESIGN AND SETTING: Simultaneous digitized electroencephalograms (EEGs) were recorded from the occipital area in pairs of human subjects placed in sound attenuated rooms separated by 10 meters. One person relaxed in one of the rooms while the other received visual stimulation while in the other room. Prior to each experiment, members of the pair were randomly designated as sender and receiver. Sessions were subsequently repeated with subjects reversing their roles. Previous to each session, the sender was instructed "to attempt sending an image/thought." The receiver was instructed "to remain open to receive any image/thought from his/her partner." Alternating stimulus-on/stimulus-off conditions were presented throughout the session to the sender, while a stimulus-off condition was presented to the receiver. SUBJECTS: Thirty-seven (37) female, and 23 male subjects (n = 60; 30 pairs) participated in the study. Subjects knew each other well and claimed to have previous experience of being emotionally/psychologically connected to one another. OUTCOME MEASURES: A Runs test was applied to compare EEG "hits" in the receiver's EEG during the sender' stimulus-on condition versus sender's stimulus-off conditions. Test results at p < 0.01 were considered evidence of correlated brain signals. Pairs in whom at least one member had significant results were invited back for replication. RESULTS: Of the 60 subjects tested, 5 (4 women/1 man) showed significantly higher brain activation (p < 0.01) during their sending partner's stimulus-on condition as compared to stimulus-off condition. Using the Stouffer z meta-analytic method all receiver EEG results across all 60 subjects were combined by transforming the individual session p values into z scores. Data analyses showed overall significant results for EEG data recorded during the flickering condition (z =-3.28, p = 0.0005) as well as nonsignificant results for data recorded during the static condition (z = 0.35, p = 0.64). Four pairs participated in a replication experiment during which one pair replicated the effect. CONCLUSIONS: These results indicate that in some pairs of human subjects a signal may be detected in the brain of a distant member of the pair when the brain of the other member is visually stimulated. These data support the findings of similar studies performed in seven laboratories reported in the peer-reviewed literature since 1963. Research in this area should now proceed with investigation of its physical and biologic mechanism, its generalizability to varying populations and relationships, and its clinical application.

Analysis of responses to St. John's Wort in the feline pulmonary vascular bed.

OBJECTIVE: To test the hypothesis that St. John's wort induces a depressor response in the feline pulmonary vascular bed and identify the pathways involved in the mediation or modulation of these effects. DESIGN: Prospective vehicle controlled study. SETTING: University research laboratory. SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: In separate experiments, the effects of L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an ATP-sensitive K+ channel blocker, meclofenamate, a non-selective cyclo-oxygenase (COX) inhibitor, nicardipine, a calcium channel blocker, bicuculline, a GABAA receptor antagonist, and saclofen, a GABAB antagonist, were investigated on pulmonary arterial responses of St. John's wort (SJW), pinacidil, an ATP-sensitive K+ channel activator, bradykinin, an inducer of nitric oxide synthase, 3-aminopropyl (methyl) phosphinic acid, hydrochloride (SKF-97541), a GABAB receptor agonist and muscimol, a GABAA receptor agonist. MEASUREMENTS AND MAIN RESULTS: Lobar arterial perfusion pressure and systemic pressure were continuously monitored, electronically averaged and permanently recorded. Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, SJW induced a dose-dependent vasodepressor response that was not significantly altered after administration of L-NIO, glibenclamide, meclofenamate or saclofen. Responses to SJW were significantly reduced after administration of either nicardipine or bicuculline. When the calcium channel blocker nicardipine was administered in addition to the GABA blocker bicuculline, there was near complete attenuation of the SJW-induced vasodepressor responses. CONCLUSIONS: The results of the present study suggest that SJW has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response is mediated or modulated by both a calcium channel and GABA receptor sensitive pathway.

Pulmonary vascular responses to ma huang extract.

OBJECTIVE: To test the hypothesis that ma huang induces a pressor response in the pulmonary vascular bed of the cat by activating alpha(1)-adrenergic receptors DESIGN: Prospective vehicle-controlled study. SETTING: Research laboratory at Texas Tech University School of Medicine, Lubbock, TX. SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: The effects of phentolamine, a nonselective alpha receptor blocker, and prazosin, an alpha(1) selective antagonist, were investigated on pulmonary arterial responses to ma huang, phenylepherine, norepinephrine, and U-46619, a thromboxane A(2) mimic. MEASUREMENTS AND MAIN RESULTS: Lobar arterial perfusion pressure was continuously monitored, electronically averaged, and recorded with constant flow in the isolated left lower lobe vascular bed of the cat. Phentolamine and prazosin significantly reduced vasoconstrictor pulmonary perfusion pressure increases induced by ma huang. CONCLUSIONS: Ma huang has significant vasopressor activity in the pulmonary vascular bed of the cat mediated predominantly by alpha(1)-adrenergic receptor activation.

Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial.

CONTEXT: There is a growing literature on the biological and clinical effects of pulsed electromagnetic fields. Some studies suggest that electromagnetic therapies may be useful in the treatment of chronic illnesses. This study is a follow-up to a placebo controlled pilot study in which multiple sclerosis (MS) patients exposed to weak, extremely low frequency pulsed electromagnetic fields showed significant improvements on a composite symptom measure. OBJECTIVE: To evaluate the effects of a pulsed electromagnetic therapy on MS related fatigue, spasticity, bladder control, and overall quality of life. DESIGN: A multi-site, double-blind, placebo controlled, crossover trial. Each subject received 4 weeks of the active and placebo treatments separated by a 2-week washout period. SETTING: The University of Washington Medical Center in Seattle Wash, the Neurology Center of Fairfax in Fairfax, Va, and the headquarters of the Multiple Sclerosis Association of America in Cherry Hill, NJ. SUBJECTS: 117 patients with clinically definite MS. INTERVENTION: Daily exposure to a small, portable pulsing electromagnetic field generator. MAIN OUTCOME: The MS Quality of Life Inventory (MSQLI) was used to assess changes in fatigue, bladder control, spasticity, and a quality of life composite. RESULTS: Paired t-tests were used to assess treatment differences in the 117 subjects (81% of the initial sample) who completed both treatment sessions. Improvements in fatigue and overall quality of life were significantly greater on the active device. There were no treatment effects for bladder control and a disability composite, and mixed results for spasticity. CONCLUSIONS: Evidence from this randomized, double-bind, placebo controlled trial is consistent with results from smaller studies suggesting that exposure to pulsing, weak electromagnetic fields can alleviate symptoms of MS. The clinical effects were small, however, and need to be replicated. Additional research is also needed to examine the possibility that ambulatory patients and patients taking interferons for their MS may be most responsive to this kind of treatment.

Analysis of responses to valerian root extract in the feline pulmonary vascular bed.

OBJECTIVES: This study was undertaken to investigate pulmonary vascular response to valerian (Valeriana officinalis) in the feline pulmonary vasculature under constant flow conditions. DESIGN: In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium (K+) channel blocker, meclofenamate, a nonselective cyclooxygenase (COX) inhibitor, bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) antagonist, were investigated on pulmonary arterial responses to various agonists in the feline pulmonary vascular bed. These agonists included valerian, muscimol, a GABA(A) agonist, SKF-97541 a GABA(B) agonist, acetylcholine (ACh), and bradykinin, both inducers of nitric oxide synthase, arachidonic acid, a COX substrate, and pinacidil, an ATP-sensitive K+ channel activator, during increased tone conditions induced by the thromboxane A2 mimic, U46619. SETTINGS/LOCATION: Laboratory investigation. SUBJECTS: Mongrel cats of either gender. INTERVENTIONS: Injections of the abovementioned agonists and antagonists were given. OUTCOME MEASURES: Baseline pulmonary tone, responses to the agonists, and responses to the agonists after injections of antagonists were all measured via a pulmonary catheter transducer and recorded. RESULTS: Valerian root extract is a potent smooth muscle dilator in the feline pulmonary vascular bed. The vasodilatory effects of valerian root extract were unchanged after the administration of L-NIO, glibenclamide, and meclofenamate. These effects were ablated, however, by both saclofen and bicuculline. The ability of saclofen and bicuculline to modulate the dilatory effects of valerian root extract was not statistically different. CONCLUSIONS: The vasodilatory effects of valerian root extract are mediated by a nonselective GABA mechanism.