Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes ...correlate with blood oxygenation level—dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26±0.06 μmol/g (∼30%) and 0.28±0.03 μmol/g (∼3%), respectively, while aspartate and glucose decreased by 0.20±0.04 μmol/g (∼5%) and 0.19±0.03 μmol/g (∼16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms.
High-impact temporomandibular disorder (TMD) pain may involve brain mechanisms related to maladaptive central pain modulation. We investigated brain responses to stimulation of trigeminal sites not ...typically associated with TMD pain by applying noxious dentoalveolar pressure to high- and low-impact TMD pain cases and pain-free controls during functional magnetic resonance imaging (fMRI). Fifty female participants were recruited and assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and Graded Chronic Pain Scale: controls (n = 17), low-impact (n = 17) and high-impact TMD (n = 16). Multimodal whole-brain MRI was acquired following the Human Connectome Project Lifespan protocol, including stimulus-evoked fMRI scans during which painful dentoalveolar pressure was applied to the buccal gingiva of participants. Group analyses were performed using non-parametric permutation tests for parcellated cortical and subcortical neuroimaging data. There were no significant between-group differences for brain activations/deactivations evoked by the noxious dentoalveolar pressure. For individual group mean activations/deactivations, a gradient in the number of parcels surviving thresholding was found according to the TMD pain grade, with the highest number seen in the high-impact group. Among the brain regions activated in chronic TMD pain groups were those previously implicated in sensory-discriminative and motivational-affective pain processing. These results suggest that dentoalveolar pressure pain evokes abnormal brain responses to sensory processing of noxious stimuli in high-impact TMD pain participants, which supports the presence of maladaptive brain plasticity in chronic TMD pain.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain ...during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. OBJECTIVE: To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. MAIN OUTCOMES AND MEASURES: Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level–dependent signal of each voxel in the whole brain with that of the amygdala. RESULTS: Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = −.523, P = .01), dysphoria (R = −.455, P = .05), and lassitude (R = −.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls. CONCLUSIONS AND RELEVANCE: Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.
Cigarette smoking increases the risk of coronary heart disease, but whether smoking increases atrial fibrillation (AF) is uncertain.
The purpose of this study was to determine the association of ...cigarette smoking with incident AF in a population-based cohort of blacks and whites.
We determined the risk of incident AF through December 2002 in relation to baseline (1987-1989) smoking status and cigarette-years of smoking in over 15,000 participants of the prospective Atherosclerosis Risk in Communities (ARIC) study.
Over a mean follow-up of 13.1 years, 876 incident AF events were identified. Compared to never smokers, the multivariable-adjusted hazard ratios (HRs) for AF were 1.32 (95% confidence interval CI 1.10-1.57) in former smokers, 2.05 (95% CI 1.71-2.47) in current smokers, and 1.58 (95% CI 1.35-1.85) in ever smokers. In the highest tertile of accumulated smoking amount (>675 cigarette-years), the incidence of AF was 2.10 times greater (95% CI 1.74-2.53) than in those who never smoked. Associations were similar by gender, race, type of event (AF and atrial flutter), and when only AF events identified by study exam ECGs were included. Finally, individuals who quit smoking exhibited a trend indicating a slightly lower risk of developing AF (HR 0.88, 95% CI 0.65-1.17) compared to those who continued to smoke.
Smoking was associated with the incidence of AF, with more than a two-fold increased risk of AF attributed to current smoking. In addition, a trend toward a lower incidence of AF appeared among smokers who quit compared to continued smokers.
In mammalian species with prolonged maternal investment in which high-ranking males gain disproportionate numbers of mating opportunities, males that quickly ascend the hierarchy may benefit from ...eliminating the dependent offspring of their competitors. In savanna baboons, high-ranking females are the most profitable targets of infanticide or feticide, because their offspring have higher survival rates and their daughters reach sexual maturity at a younger age. However, such patterns may be obscured by environmental stressors that are known to exacerbate fetal losses, especially in lower-ranking females. Using 30 years of data on wild olive baboons (Papio anubis) in Gombe National Park, Tanzania, we found evidence that rapidly-rising immigrant males induced miscarriages in high-ranking females outside of drought conditions. However, miscarriage rates were largely reversed during prolonged periods of low rainfall, suggesting that low-ranking females are particularly vulnerable to low food availability and social instability. Infanticide did not emerge as a recurrent male strategy in this population, likely because of the protective behavior of resident males towards vulnerable juveniles.
Objective
To investigate whether early neurochemical abnormalities are detectable by high‐field magnetic resonance spectroscopy (MRS) in individuals with spinocerebellar ataxias (SCAs) 1, 2, 3, and ...6, including patients without manifestation of ataxia.
Methods
A cohort of 100 subjects (N = 18–21 in each SCA group, including premanifest mutation carriers; mean score on the Scale for the Assessment and Rating of Ataxia SARA <10 for all genotypes, and 22 matched controls) was scanned at 7 Tesla to obtain neurochemical profiles of the cerebellum and brainstem. A novel multivariate approach (distance‐weighted discrimination) was used to combine regional profiles into an “MRS score.”
Results
MRS scores robustly distinguished individuals with SCA from controls, with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6). Premanifest mutation carriers with estimated disease onset within 10 years had MRS scores in the range of early‐manifest SCA subjects. Levels of neuronal and glial markers significantly correlated with SARA and an Activities of Daily Living score in subjects with SCA. Regional neurochemical alterations were different between SCAs at comparable disease severity, with SCA2 displaying the most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6.
Interpretation
Neurochemical abnormalities are detectable in individuals before manifest disease, which may allow premanifest enrollment in future SCA trials. Correlations with ataxia and quality‐of‐life scores show that neurochemical levels can serve as clinically meaningful endpoints in trials. Ranking of SCA types by degree of neurochemical abnormalities indicates that the neurochemistry may reflect synaptic function or density. Ann Neurol 2018;83:816–829
A major hurdle in the development of effective treatments for amyotrophic lateral sclerosis (ALS) has been the lack of robust biomarkers for use as clinical trial endpoints. Neurochemical profiles ...obtained in vivo by high field proton magnetic resonance spectroscopy (
1
H-MRS) can potentially provide biomarkers of cerebral pathology in ALS. However, previous
1
H-MRS studies in ALS have produced conflicting findings regarding alterations in the levels of neurochemical markers such as glutamate (Glu) and
myo
-inositol (mIns). Furthermore, very few studies have investigated the neurochemical abnormalities associated with ALS early in its course. In this study, we measured neurochemical profiles using single-voxel
1
H-MRS at 7 T (T) and glutathione (GSH) levels using edited MRS at 3 T in 19 subjects with ALS who had relatively high functional status ALS Functional Rating Scale-Revised (ALSFRS-R) mean ± SD = 39.8 ± 5.6 and 17 healthy controls. We observed significantly lower total
N
-acetylaspartate over mIns (tNAA/mIns) ratio in the motor cortex and pons of subjects with ALS versus healthy controls. No group differences were detected in GSH at 3 and 7 T. In subjects with ALS, the levels of tNAA, mIns, and Glu in the motor cortex were dependent on the extent of disease represented by El Escorial diagnostic subcategories. Specifically, combined probable/definite ALS had lower tNAA than possible ALS and controls (both
p
= 0.03), higher mIns than controls (
p
< 0.01), and lower Glu than possible ALS (
p
< 0.01). The effect of disease stage on MRS-measured metabolite levels may account for dissimilar findings among previous
1
H-MRS studies in ALS.
OBJECTIVE:To determine the prevalence of epilepsy/seizure (epi/sz) comorbid with other neurologic disorders in elderly nursing home residents and to examine demographic and regional variability and ...associations with clinical characteristics.
METHODS:We studied 5 cross-sectional cohorts of all residents in any Medicare/Medicaid–certified nursing home in the United States on July 15 of each year from 2003 to 2007. Epi/sz was identified by ICD-9 codes (345.xx or 780.39) or check box (Minimum Data Set). Epi/sz prevalence was stable across all years, so only 2007 data were examined further. Logistic regression with generalized estimating equations was used to model cross-sectional prevalence of epi/sz as a function of demographics and neurologic comorbidities of interest, with adjustment for clinical characteristics, including cognitive status, comorbidity burden, medication burden, and activities of daily living.
RESULTS:Point prevalence of epi/sz in 2007 was 7.7% (n = 91,372 of N = 1,186,579) differing by geographical region, race/ethnicity, age group, and sex. Neurologic conditions having the highest association with epi/sz were brain tumor (epi/sz prevalence 23.4%–35.2%), head injury (17.9%), hemiplegia (17.7%), and stroke (13.7%). Epi/sz comorbid with stroke or dementia had a strong decreasing association with age (65–74 years had ≈3.8-times higher odds of epi/sz than 85+ years). Activities of daily living, comorbidity burden, and cognition scores were worse in persons with than without epi/sz.
CONCLUSIONS:The prevalence of epi/sz in the elderly nursing home population is >7-fold higher compared to community-dwelling elderly and is 7 to 30 times higher among those with certain comorbid neurologic conditions. Demographics and clinical characteristics had weaker associations with epi/sz prevalence.
Abstract Introduction Stress has been found to be a significant risk factor for cigarette smoking. Stress affects males and females differently, as does the use of smoking for stress reduction. Few ...studies have examined gender differences with the interrelation of perceived stress and smoking behaviors and nicotine related symptomatology. Our study investigates this association, as well as the influence of sociodemographic variables. Methods This is a retrospective analysis of 62 smokers (41 males, 21 females) enrolled in a smoking cessation study. At the screening visit sociodemographic information, smoking behaviors and survey measures were completed. These included the Perceived Stress Scale (PSS), Minnesota Nicotine Withdrawal Scale (MNWS), and others. Analyses were conducted using multiple linear regression models. Results PSS score was found to have a negative association with number of cigarettes smoked in males (slope − 0.29 ± 0.08; p = 0.0009) and females (slope − 0.20 ± 0.18; p = 0.26) with no difference in effect between genders (p = 0.64). Linear regression of MNWS on PSS revealed a positive association for both males (slope 0.41 ± 0.068; p < 0.0001) and females (slope 0.73 ± 0.14; p < 0.0001). There was a significant difference in effect between genders (p = 0.04). Conclusions A strong positive association was observed between perceived stress and nicotine withdrawal symptomatology in smokers of both sexes, with a larger effect seen in women. These findings emphasize the importance of stress reduction in smokers, which may lead to fewer withdrawal symptoms and more effective smoking cessation.
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