Dynamics between psychological distress and body mass index throughout adult life; evidence from 3 large cohort studies.

BACKGROUND: Associations between body mass index (BMI) and psychological distress (PD) have been reported; however, few longitudinal studies have accounted for likely life-course differences in BMI and PD stability, consistency, and their interplay across time. METHODS: Via random intercepts cross-lagged panel models, we assessed the predictive effects (from BMI to PD or vice-versa) across the last two centuries in the Coronary Artery Risk Development in Young Adults [CARDIA, beginning in 1985-6] study using the Center for Epidemiological Studies-Depression Scale [CES-D], and in the National Child Development Study [NCDS, beginning in 1958] and British Cohort Study [BCS, beginning in 1970] using the Malaise Inventory [MI]), assessed at least 4 times in adult life. FINDINGS: In CARDIA (n = 4724), NCDS58 (n = 7149) and BCS70 (n = 5967), autoregressive effects were stronger for BMI than for PD, meaning that carry-over effects from one occasion to the next were larger for BMI than for PD. Small interindividual correlations between traits of higher BMI and higher PD were identified among females (rfemale<|0·2|) but not males (rmale<|0·03|) in CARDIA and NCDS. Cross-lagged effects were very weak or close to zero (standardized effects η<|0·1|). INTERPRETATION: In the United States, depressive symptoms and BMI were positively correlated at the trait level among females. In the United Kingdom, relationships between PD and BMI were inconsistent between generations, with effect sizes of unlikely clinical importance, indicating negligible dominance of an intraindividual effect of BMI on PD or vice versa.

Cerebrovascular Reactivity during Prolonged Breath-Hold in Experienced Freedivers.

BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity. This multiparametric study investigated CBF, the spatial coefficient of variation as a correlate of arterial transit time and brain metabolism, dynamics during prolonged apnea. MATERIALS AND METHODS: Fifteen male freedivers (age range, 20-64 years; cumulative previous prolonged breath-holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T pseudocontinuous arterial spin-labeling and 31P-/1H-MR spectroscopy before, during, and after a 5-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. Correlation of temporal and regional cerebrovascular reactivity to blood gases and cumulative previous breath-holds of >2 minutes and 30 seconds in a lifetime was assessed. RESULTS: The spatial coefficient of variation of CBF (by arterial spin-labeling) decreased during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%, P = .001). CBF differed between the anterior and the posterior circulation during all phases (eg, during late breath-hold: MCA, 57.3 ± 14.2 versus posterior cerebral artery, 42.7 ± 10.8 mL/100 g/min; P = .001). There was an association between breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, -24.0%), cerebral lactate and adenosine diphosphate remained within physiologic ranges despite early signs of oxidative stress [-6.4% phosphocreatine / (adenosine triphosphate + adenosine diphosphate); P = .02]. CONCLUSIONS: This study revealed that the cerebral energy metabolism of trained freedivers withstands severe hypoxic hypercarbia in prolonged breath-hold due to a complex cerebrovascular hemodynamic response.

Temporal and Spatial Variances in Arterial Spin-Labeling Are Inversely Related to Large-Artery Blood Velocity.

BACKGROUND AND PURPOSE: The relationship between extracranial large-artery characteristics and arterial spin-labeling MR imaging may influence the quality of arterial spin-labeling-CBF images for older adults with and without vascular pathology. We hypothesized that extracranial arterial blood velocity can explain between-person differences in arterial spin-labeling data systematically across clinical populations. MATERIALS AND METHODS: We performed consecutive pseudocontinuous arterial spin-labeling and phase-contrast MR imaging on 82 individuals (20-88 years of age, 50% women), including healthy young adults, healthy older adults, and older adults with cerebral small vessel disease or chronic stroke infarcts. We examined associations between extracranial phase-contrast hemodynamics and intracranial arterial spin-labeling characteristics, which were defined by labeling efficiency, temporal signal-to-noise ratio, and spatial coefficient of variation. RESULTS: Large-artery blood velocity was inversely associated with labeling efficiency (P = .007), temporal SNR (P < .001), and spatial coefficient of variation (P = .05) of arterial spin-labeling, after accounting for age, sex, and group. Correction for labeling efficiency on an individual basis led to additional group differences in GM-CBF compared to correction using a constant labeling efficiency. CONCLUSIONS: Between-subject arterial spin-labeling variance was partially explained by extracranial velocity but not cross-sectional area. Choosing arterial spin-labeling timing parameters with on-line knowledge of blood velocity may improve CBF quantification.

Effects of acute aerobic exercise on neural correlates of attention and inhibition in adolescents with bipolar disorder.

Executive dysfunction is common during and between mood episodes in bipolar disorder (BD), causing social and functional impairment. This study investigated the effect of acute exercise on adolescents with BD and healthy control subjects (HC) to test for positive or negative consequences on neural response during an executive task. Fifty adolescents (mean age 16.54±1.47 years, 56% female, 30 with BD) completed an attention and response inhibition task before and after 20 min of recumbent cycling at ~70% of age-predicted maximum heart rate. 3 T functional magnetic resonance imaging data were analyzed in a whole brain voxel-wise analysis and as regions of interest (ROI), examining Go and NoGo response events. In the whole brain analysis of Go trials, exercise had larger effect in BD vs HC throughout ventral prefrontal cortex, amygdala and hippocampus; the profile of these effects was of greater disengagement after exercise. Pre-exercise ROI analysis confirmed this 'deficit in deactivation' for BDs in rostral ACC and found an activation deficit on NoGo errors in accumbens. Pre-exercise accumbens NoGo error activity correlated with depression symptoms and Go activity with mania symptoms; no correlations were present after exercise. Performance was matched to controls and results survived a series of covariate analyses. This study provides evidence that acute aerobic exercise transiently changes neural response during an executive task among adolescents with BD, and that pre-exercise relationships between symptoms and neural response are absent after exercise. Acute aerobic exercise constitutes a biological probe that may provide insights regarding pathophysiology and treatment of BD.

Regional cerebral arterial transit time hemodynamics correlate with vascular risk factors and cognitive function in men with coronary artery disease.

BACKGROUND AND PURPOSE: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. MATERIALS AND METHODS: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. RESULTS: Principal component analysis identified 2 components of vascular risk: 1) "pressor" (age, systolic blood pressure, and pulse pressure) and 2) "obesity" (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r(2) = 0.21, t = -2.65, P = .01). CONCLUSIONS: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.

Cerebral small vessel disease in aging and Alzheimer's disease: a comparative study using MRI and SPECT.

BACKGROUND: White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). METHODS: Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. RESULTS: WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. CONCLUSION: Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.

Hemodynamic alterations in vertebrobasilar large artery disease assessed by arterial spin-labeling MR imaging.

BACKGROUND AND PURPOSE: VB artery stenosis is associated with a high risk of recurrent ischemic events, and knowledge about the hemodynamic relevance of VB stenosis is important for clinical decision making. In this study, multiple inflow pulsed ASL MR imaging was assessed for its ability to measure CBF and ATT in patients with VB disease. MATERIALS AND METHODS: ASL was performed on a 3T MR imaging scanner in 41 participants. Twenty-one patients had a history of ischemic events in the VB circulation (14 men, 7 women, age 66 ± 11 years). Clinical data and CE-MRA were used to classify VB disease severity. Twenty age-matched adults were controls. Group and within-VB analyses were performed. Mean CBF and ATT values in the ROIs were adjusted by excluding voxels that did not produce a reliable ASL estimate. RESULTS: CBF was reduced (P < .003) in patients compared with controls, which was significant after excluding voxels with a poor fit. Differences in ATT between patients and controls were not significant after voxel correction. There was a strong correlation between CBF and ATT among patients. Finally, ATT was significantly correlated with VB disease severity (P = .026). CONCLUSIONS: Multiple inflow ASL distinguished patients with VB disease from age matched-controls. VB disease rating was associated with prolonged ATT downstream. ASL may have diagnostic potential among patients in whom risk of intervention is high.

Partial volume correction of multiple inversion time arterial spin labeling MRI data.

The accuracy of cerebral blood flow (CBF) estimates from arterial spin labeling (ASL) is affected by the presence of both gray matter (GM) and white matter within any voxel. Recently a partial volume (PV) correction method for ASL has been demonstrated (Asllani et al. Magn Reson Med 2008; 60:1362-1371), where PV estimates were used with a local linear regression to separate the GM and white matter ASL signal. Here a new PV correction method for multi-inversion time ASL is proposed that exploits PV estimates within a spatially regularized kinetic curve model analysis. The proposed method exploits both PV estimates and the different kinetics of the ASL signal arising from GM and white matter. The new correction method is shown, on both simulated and real data, to provide correction of GM CBF comparable to a linear regression approach, whilst preserving greater spatial detail in the CBF image. On real data corrected GM CBF values were found to be largely independent of GM PV, implying that the correction had been successful. Increases of mean GM CBF after correction of 69-80% were observed.

Differential effects of the APOE genotype on brain function across the lifespan.

Increasing age and carrying an APOE ε4 allele are well established risk factors for Alzheimer's disease (AD). The earlier age of onset of AD observed in ε4-carriers may reflect an accelerated aging process. We recently reported that APOE genotype modulates brain function decades before the appearance of any cognitive or clinical symptoms. Here we test the hypothesis that APOE influences brain aging by comparing healthy ε4-carriers and non-carriers, using the same imaging protocol in distinct groups of younger and older healthy volunteers. A cross-sectional factorial design was used to examine the effects of age and APOE genotype, and their interaction, on fMRI activation during an encoding memory task. The younger (N=36; age range 20-35; 18 ε4-carriers) and older (35 middle-age/elderly; age range 50-78 years; 15 ε4-carriers) healthy volunteers taking part in the study were cognitively normal. We found a significant interaction between age and ε4-status in the hippocampi, frontal pole, subcortical nuclei, middle temporal gyri and cerebellum, such that aging was associated with decreased activity in e4-carriers and increased activity in non-carriers. Reduced cerebral blood flow was found in the older ε4-carriers relative to older non-carriers despite preserved grey matter volume. Overactivity of brain function in young ε4-carriers is disproportionately reduced with advancing age even before the onset of measurable memory impairment. The APOE genotype determines age-related changes in brain function that may reflect the increased vulnerability of ε4-carriers to late-life pathology or cognitive decline.

Multiple inflow pulsed arterial spin-labeling reveals delays in the arterial arrival time in minor stroke and transient ischemic attack.

Our purpose was to use multiple inflow pulsed ASL to investigate whether hemodynamic AAT information is sensitive to hemispheric asymmetry in acute ischemia. The cohorts included 15 patients with acute minor stroke or TIA and 15 age-matched controls. Patients were scanned by using a stroke MR imaging protocol at a median time of 74 hours. DWI lesion volumes were small and functional impairment was low; however, perfusion abnormalities were evident. Prolonged AAT values were more likely to reside in the affected hemisphere (significant when compared with controls, P < .048). An advantage of this ASL technique is the ability to use AAT information in addition to CBF to characterize ischemia.

Challenging the brain: Exploring the link between effort and cortical activation.

To better understand the contributions of effort on cortical activation associated with motor tasks, healthy participants with varying capacities for isolating the control of individual finger movements performed tasks consisting of a single concurrent abduction of all digits (Easy) and paired finger abduction with digits 2 and 3 abducted together concurrently with digits 4 and 5 (Hard). Brain activity was inferred from measurement using functional magnetic resonance imaging. Effort was measured physiologically using electrodermal responses (EDR) and subjectively using the Borg scale. On average, the Borg score for the Hard task was significantly higher (p=0.007) than for the Easy task (2.9+/-1.1 vs. 1.4+/-0.7, respectively). Similarly, the average normalized peak-to-peak amplitude of the EDR was significantly higher (p=0.002) for the Hard task than for the Easy task (20.4+/-6.5% vs. 12.1+/-4.9%, respectively). The Hard task produced increases in sensorimotor network activation, including supplementary motor area, premotor, sensorimotor and parietal cortices, cerebellum and thalamus. When the imaging data were subdivided based on Borg score, there was an increase in activation and involvement of additional areas, including extrastriate and prefrontal cortices. Subdividing the data based on EDR amplitude produced greater effects including activation of the premotor and parietal cortices. These results show that the effort required for task performance influences the interpretation of fMRI data. This work establishes understanding and methodology for advancing future studies of the link between effort and motor control, and may be clinically relevant to sensorimotor recovery from neurologic injury.

Assessing linear time-invariance in human primary somatosensory cortex with BOLD fMRI using vibrotactile stimuli.

The assumption of linear time-invariance (LTI) in the human primary somatosensory cortex (SI) is assessed for fMRI signals generated by variable-duration vibrotactile stimuli. Predictions based on time-shifted summation (TSS) of responses to 2 s stimuli overestimate observed BOLD signal amplitudes in response to longer-duration stimuli, in agreement with previous findings in other primary sensory cortices. To interpret these results, we undertook an alternative approach for LTI assessment by characterizing BOLD signals using two biophysical models. The first model assumes that the input stimulus envelope is proportional to neural activity. The second assumes that neural activity exhibits both transient and steady-state components, consistent with extensive electrophysiological data, and fits the experimental data better. Although nonlinearity remains evident for short stimulus durations, the latter model shows that the TSS procedure to assess LTI overestimates the BOLD signal because the temporal characteristics of neural activity have not been considered adequately. Further research to investigate the BOLD response to time-varying neural activity is required.