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To gain insight into the neurophysiological mechanisms involved in Zen meditation, we evaluated the effects of focused attention (FA) on breathing movements in the lower abdomen (Tanden) in novices. We investigated hemodynamic changes in the prefrontal cortex (PFC), an attention-related brain region, using 24-channel near-infrared spectroscopy during a 20-minute session of FA on Tanden breathing in 15 healthy volunteers. We found that the level of oxygenated hemoglobin in the anterior PFC was significantly increased during FA on Tanden breathing, accompanied by a reduction in feelings of negative mood compared to before the meditation session. Electroencephalography (EEG) revealed increased alpha band activity and decreased theta band activity during and after FA on Tanden breathing. EEG changes were correlated with a significant increase in whole blood serotonin (5-HT) levels. These results suggest that activation of the anterior PFC and 5-HT system may be responsible for the improvement of negative mood and EEG signal changes observed during FA on Tanden breathing.
Cyclic AMP (cAMP) is a second messenger involved in many processes including mnemonic processing and anxiety. Memory deficits and anxiety are noted in the phenotype of fragile X (FX), the most common heritable cause of mental retardation and autism. Here we review reported observations of altered cAMP cascade function in FX and autism. Cyclic AMP is a potentially useful biochemical marker to distinguish autism comorbid with FX from autism per se and the cAMP cascade may be a viable therapeutic target for both FX and autism.
This article presents an overview of ways to think about the brain and emotion and consider the role of evolution and expression in shaping the neural circuitry of affective processing. Issues pertaining to whether there are separate unique neural modules hard-wired for emotion processing or whether affective processing uses more generalized circuitry are considered. Relations between affect and cognition--specifically, memory--are examined from the perspective of overlapping neural systems. The role of individual differences in neural function in affective style are discussed, and the concepts of affective chronometry, or the time course of emotional responding and emotion regulation, are introduced. Finally, the extent to which certain emotional traits can be viewed as trainable skills is considered, and the relevance of work on neural plasticity to the skill framework is addressed. Data from a variety of sources using different types of measures is brought to bear on these questions, including neuroimaging and psychophysiological measures, studies of individuals of different ages ranging from early childhood to old age, studies of nonhuman primates, and observations of patients with localized brain damage. Emotions are viewed as varying in both type and dimension. Honoring brain circuitry in parsing the domain of affects will result in distinctions and differentiations that are not currently incorporated in traditional classification schemes.
This study aimed at studying the effect of yogic package (YP) with some selected pranayama, cleansing practices and meditation on pain intensity, inflammation, stiffness, pulse rate (PR), blood pressure (BP), lymphocyte count (LC), C-reactive protein (CRP) and serum uric acid (UA) level among subjects of rheumatoid arthritis (RA). Randomized control group design was employed to generate pre and post data on participants and controls. Repealed Measure ANOVAs with Bonferroni adjustment were applied to check significant overall difference among pre and post means of participants and controls by using PASW (SPSS Inc. 18th Version). Observed result favored statistically significant positive effect of YP on selected RA parameters and symptoms under study at P<0.05, 0.01 and 0.001 respectively that showed remarkable improvement in RA severity after 40-day practice of YP. It concluded that YP is a significant means to reduce intensity of RA.
Regional modulation of the level of cortical neurotransmitters in the brain would serve as a new functional brain mapping technique to interrogate the neurochemical actions of the brain. We investigated the utility of the application of low-intensity, pulsed sonication of focused ultrasound (FUS) to the brain to modulate the extracellular level of dopamine (DA) and serotonin (5-HT). FUS was delivered to the thalamic areas of rats, and extracellular DA and 5-HT were sampled from the frontal lobe using the microdialysis technique. The concentration changes of the sampled DA and 5-HT were measured through high-performance liquid chromatography. We observed a significant increase of the extracellular concentrations of DA and 5-HT in the FUS-treated group as compared with those in the unsonicated group. Our results provide the first direct evidence that FUS sonication alters the level of extracellular concentration of these monoamine neurotransmitters and has a potential modulatory effect on their local release, uptake, or degradation. Our findings suggest that the pulsed application of FUS offers new perspectives for a possible noninvasive modulation of neurotransmitters and may have diagnostic as well as therapeutic implications for DA/5-HT-mediated neurological and psychiatric disorders. © 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 232–240, 2011
BACKGROUND: Functional magnetic resonance imaging (fMRI) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial. Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex (ACC). Here, we sought to determine whether pretreatment amygdala and rostral ACC (rACC) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder (GAD). METHODS: Fifteen subjects (12 female subjects) with GAD participated in an open-label venlafaxine treatment trial. Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration. In addition, the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects (12 female subjects) who did not have GAD and did not receive venlafaxine treatment. RESULTS: The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala. These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group. CONCLUSIONS: These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD.
BACKGROUND: Functional magnetic resonance imaging (fMRI) techniques were used to identify the neural circuitry underlying emotional processing in control and depressed subjects. Depressed subjects were studied before and after treatment with venlafaxine. This new technique provides a method to noninvasively image regional brain function with unprecedented spatial and temporal resolution. METHOD: Echo-planar imaging was used to acquire whole brain images while subjects viewed positively and negatively valenced visual stimuli. Two control subjects and two depressed subjects who met DSM-IV criteria for major depression were scanned at baseline and 2 weeks later. Depressed subjects were treated with venlafaxine after the baseline scan. RESULTS: Preliminary results from this ongoing study revealed three interesting trends in the data. Both depressed patients demonstrated considerable symptomatic improvement at the time of the second scan. Across control and depressed subjects, the negative compared with the positive pictures elicited greater global activation. In both groups, activation induced by the negative pictures decreased from the baseline scan to the 2-week scan. This decrease in activation was also present in the control subjects when they were exposed to the positive pictures. In contrast, when the depressed subjects were presented with the positive pictures they showed no activation at baseline, whereas after 2 weeks of treatment an area of activation emerged in right secondary visual cortex. CONCLUSION: While preliminary, these results demonstrate the power of using fMRI to study emotional processes in normal and depressed subjects and to examine mechanisms of action of antidepressant drugs.
Our outside world changes continuously, for example, when driving through traffic. An important question is how our brain deals with this constant barrage of rapidly changing sensory input and flexibly selects only newly goal-relevant information for further capacity-limited processing in working memory. The challenge our brain faces is experimentally captured by the attentional blink (AB): an impairment in detecting the second of two target stimuli presented in close temporal proximity among distracters. Many theories have been proposed to explain this deficit in processing goal-relevant information, with some attributing the AB to capacity limitations related to encoding of the first target and others assigning a critical role to on-line selection mechanisms that control access to working memory. The current study examined the role of striatal dopamine in the AB, given its known role in regulating the contents of working memory. Specifically, participants performed an AB task and their basal level of dopamine D2-like receptor binding was measured using PET and [F-18]fallypride. As predicted, individual differences analyses showed that greater D2-like receptor binding in the striatum was associated with a larger AB, implicating striatal dopamine and mechanisms that control access to working memory in the AB. Specifically, we propose that striatal dopamine may determine the AB by regulating the threshold for working memory updating, providing a testable physiological basis for this deficit in gating rapidly changing visual information. A challenge for current models of the AB lies in connecting more directly to these neurobiological data.
The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. Positron emission tomography scans using [(11)C]DASB [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relationship between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology.
The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology. METHODS: Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass. RESULTS: There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males. CONCLUSIONS: Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.
A variant allele in the promoter region of the serotonin transporter gene, SLC6A4, the s allele, is associated with increased vulnerability to develop anxiety-related traits and depression. Furthermore, functional magnetic resonance imaging (fMRI) studies reveal that s carriers have increased amygdala reactivity in response to aversive stimuli, which is thought to be an intermediate phenotype mediating the influences of the s allele on emotionality. We used high-resolution microPET [18F]fluoro-2-deoxy-D-glucose (FDG) scanning to assess regional brain metabolic activity in rhesus monkeys to further explore s allele-related intermediate phenotypes. Rhesus monkeys provide an excellent model to understand mechanisms underlying human anxiety, and FDG microPET allows for the assessment of brain activity associated with naturalistic environments outside the scanner. During FDG uptake, monkeys were exposed to different ethologically relevant stressful situations (relocation and threat) as well as to the less stressful familiar environment of their home cage. The s carriers displayed increased orbitofrontal cortex activity in response to both relocation and threat. However, during relocation they displayed increased amygdala reactivity and in response to threat they displayed increased reactivity of the bed nucleus of the stria terminalis. No increase in the activity of any of these regions occurred when the animals were administered FDG in their home cages. These findings demonstrate context-dependent intermediate phenotypes in s carriers that provide a framework for understanding the mechanisms underlying the vulnerabilities of s-allele carriers exposed to different types of stressors.
Rats were implanted bilaterally with cannulae into the dorsal hippocampus and trained in a Pavlovian fear-conditioning paradigm. Four groups of rats were infused intra-cranially with 1-(5'-isoquinolinesulfonyl)-2-methylpiperazine (H7-dihydrochloride), a potent inhibitor of both protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), at different time intervals in order to examine their involvement in the acquisition and consolidation of contextual fear memory. We demonstrate a significant consolidation deficit of long-term contextual fear-conditioning memory that is maximal when PKA and PKC are inhibited at 90 min post-training. These results suggest the existence of a critical time window, during which these enzymes must be activated for the consolidation of long-term memories.
We have developed a low dose Mindfulness-Based Intervention (MBI-ld) that reduces the time committed to meetings and formal mindfulness practice, while conducting the sessions during the workday. This reduced the barriers commonly mentioned for non-participation in mindfulness programs. In a controlled randomized trial we studied university faculty and staff (n=186) who were found to have an elevated CRP level,>3.0 mg/ml, and who either had, or were at risk for cardiovascular disease. This study was designed to evaluate if MBI-ld could produce a greater decrease in CRP, IL-6 and cortisol than an active control group receiving a lifestyle education program when measured at the end of the 2 month interventions. We found that MBI-ld significantly enhanced mindfulness by 2-months and it was maintained for up to a year when compared to the education control. No significant changes were noted between interventions in cortisol, IL-6 levels or self-reported measures of perceived stress, depression and sleep quality at 2-months. Although not statistically significant (p=.08), the CRP level at 2-months was one mg/ml lower in the MBI-ld group than in the education control group, a change which may have clinical significance (Ridker et al., 2000; Wassel et al., 2010). A larger MBI-ld effect on CRP (as compared to control) occurred among participants who had a baseline BMI <30 (-2.67 mg/ml) than for those with BMI >30 (-0.18 mg/ml). We conclude that MBI-ld should be more fully investigated as a low-cost self-directed complementary strategy for decreasing inflammation, and it seems most promising for non-obese subjects.