Generalized cue reactivity in dopamine neurons after opioids.

Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. The leading hypothesis is that dopamine release by addictive drugs represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation compared to non-drug reward alternatives. However, this hypothesis has not been directly tested. Here we developed Pavlovian and operant procedures to measure firing responses, within the same dopamine neurons, to drug versus natural reward cues, which we found to be similarly enhanced compared to cues predicting natural rewards in drug-naïve controls. This enhancement was associated with increased behavioral reactivity to the drug cue, suggesting that dopamine release is still critical to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting new models of dopaminergic function in drug addiction, and provide critical insights into the neurobiology of cue reactivity with potential implications for relapse prevention.

Scaling of smaller pyramidal neuron size and lower energy production in schizophrenia.

BACKGROUND: Dorsolateral prefrontal cortex (DLPFC) dysfunction in schizophrenia appears to reflect alterations in layer 3 pyramidal neurons (L3PNs), including smaller cell bodies and lower expression of mitochondrial energy production genes. However, prior somal size studies used biased strategies for identifying L3PNs, and somal size and levels of energy production markers have not been assessed in individual L3PNs. STUDY DESIGN: We combined fluorescent in situ hybridization (FISH) of vesicular glutamate transporter 1 (VGLUT1) mRNA and immunohistochemical-labeling of NeuN to determine if the cytoplasmic distribution of VGLUT1 mRNA permits the unbiased identification and somal size quantification of L3PNs. Dual-label FISH for VGLUT1 mRNA and cytochrome C oxidase subunit 4I1 (COX4I1) mRNA, a marker of energy production, was used to assess somal size and COX4I1 transcript levels in individual DLPFC L3PNs from schizophrenia (12 males; 2 females) and unaffected comparison (13 males; 1 female) subjects. STUDY RESULTS: Measures of L3PN somal size with NeuN immunohistochemistry or VGLUT1 mRNA provided nearly identical results (ICC = 0.96, p < 0.0001). Mean somal size of VGLUT1-identified L3PNs was 8.7% smaller (p = 0.004) and mean COX4I1 mRNA levels per L3PN were 16.7% lower (p = 0.01) in schizophrenia. These measures were correlated across individual L3PNs in both subject groups (rrm = 0.81-0.86). CONCLUSIONS: This preliminary study presents a novel method for combining unbiased neuronal identification with quantitative assessments of somal size and mRNA levels. We replicated findings of smaller somal size and lower COX4I1 mRNA levels in DLPFC L3PNs in schizophrenia. The normal scaling of COX4I1 mRNA levels with somal size in schizophrenia suggests that lower markers of energy production are secondary to L3PN morphological alterations in the illness.

Efficacy of an Individually Tailored, Internet-Mediated Physical Activity Intervention in Older Adults: A Randomized Controlled Trial.

OBJECTIVE: This study determined the effectiveness of an individually tailored, Internet-mediated physical activity (PA) intervention for increasing walking behavior in inactive older adults. METHOD: This 12-week randomly controlled intervention divided participants ( N = 170) into three groups: control (CON, n = 51), pedometer only (PED, n = 62), and an individually tailored, Internet-mediated pedometer (TI-PED, n = 57) group. The PED group was instructed to increase weekly step count by 10% until 10,000 steps per day was achieved. The TI-PED group was given the same goal and received tailored feedback via an online platform. Changes in average step count pre-to-post were assessed. RESULTS: Total retention rate at postintervention was 75.3%. PED ( p < .001) and TI-PED ( p < .001) increased step count pre-to-post, which was higher than the CON group at 12 weeks (PED, p < .001; TI-PED, p < .001). The TI-PED group had a higher step count at 12 weeks than the PED group ( p < .001). DISCUSSION: Individually tailored, Internet-mediated PA interventions are an effective way to significantly increase PA in older adults.

Isotemporal Substitution of Sedentary Behavior and Physical Activity on Function.

The amount of time spent in sedentary behaviors (SB) progressively increases with age, while reducing time spent in light-intensity physical activity (LPA) and moderate- to vigorous-intensity physical activity (MVPA). These trajectories in PA and SB are linked to accelerated reductions in physical functioning. PURPOSE: This study aimed to examine the association of substituting SB time with LPA and MVPA on physical function in older adults. METHODS: Ninety-one older adults (mean age, 70.7 ± 10.2 yr) wore a hip-mounted accelerometer to measure SB, LPA, and MVPA time. Measures of physical function included a 400-m walk test (400W), the usual gait speed (UGS), the five times sit-to-stand (5xSTS) test, and the short physical performance battery (SPPB). Isotemporal substitution regression modeling was performed to assess the relationship of replacing the amount of time spent in one activity for another. RESULTS: Replacing 30 min·d of SB with LPA was associated with a significant improvement in 400W (P = 0.0497), whereas MVPA resulted in a significant improvement (P < 0.01) in 400W, UGS, 5xSTS, and SPPB. Replacing 60 min·d of SB with 10 min·d of MVPA and 50 min·d of LPA was associated with significant improvements in the 400W, UGS, and 5xSTS (P < 0.05). Meanwhile, as little as 5 min·d of MVPA and 55 min·d of LPA were linked to a 78% increased odds of scoring with good function in the SPPB (P = 0.0247). CONCLUSION: Replacing SB with LPA was linked to a significant improvement in the 400W, but not the other brief functional measures. Mixed doses of LPA and MVPA may add flexibility to interventions targeting reductions of SB in older adults for clinically relevant improvements in physical function.

Individualized Estimation of Physical Activity in Older Adults with Type 2 Diabetes.

PURPOSE: Compare physical activity intensity in older adults with type 2 diabetes mellitus (T2DM) using individualized, relative cutpoints with standard, absolute cutpoints. METHODS: One hundred older adults with T2DM (68.9 ± 5.1 yr, 65% male, 32.7 ± 6.3 kg·m, 7.2% ± 1.1% glycosylated hemoglobin) completed a two-speed walking protocol (varying, walking between 1 and 2.5 mph), followed by a modified Bruce peak exercise test. Participants wore an accelerometer-based physical activity monitor at their waist, and oxygen consumption was measured. Afterward, participants wore the activity monitor for seven consecutive days. Linear equations for each individual were derived from the activity counts and energy expenditure measured during the walking protocol. Relative intensity cutpoints were calculated by using standard classifications of 44% oxygen consumption (V˙O2)peak to determine moderate and 59% V˙O2peak to determine vigorous intensity. Average time spent in intensity categories per day were calculated using relative and absolute (moderate, 2020 counts per minute; vigorous, 5999 counts per minute) cutpoints. t-Tests were run to compare estimated time spent in intensity category by cutpoint. RESULTS: Mean V˙O2peak was 17.9 ± 4.5 mL·kg·min and relative cutpoints were, on average, 1033.5 counts per minute (SD, 741.2 counts per minute) for moderate and 2211.7 counts per minute (SD, 1512.4) for vigorous activity. Using the relative cutpoints, participants accumulated an average of 157.2 min (SD, 73.7 min) of light, 33.3 min (SD, 35.6 min) of moderate, and 15.6 min (SD, 26.7 min) of vigorous activity per day. Use of the absolute cutpoint resulted in significantly different estimations based on intensity category: light, 200.7 min (SD, 74.7 min; P < 0.05); moderate, 7.1 min (SD, 9.2 min; P < 0.05); and vigorous, 0.006 min (SD, 0.04 min; P < 0.05) of activity per day. CONCLUSIONS: These results suggest utilization of absolute cutpoints may underestimate daily relative intensity levels of physical activity in older adults with T2DM. This misclassification may improperly inform dose-response relationships and population-based prevalence of physical activity in these and may extend to other clinically important populations.

A prospective examination of the impact of high levels of exercise training on sedentary behaviour.

The aim of this study is to determine changes in sedentary behaviour in response to extensive aerobic exercise training. Participants included adults who self-selected to run a marathon. Sedentary behaviour, total activity counts and physical activity (PA) intensity were assessed (Actigraph GT3X) for seven consecutive days during seven assessment periods (-3, -2, and -1 month prior to the marathon, within 2 weeks of the marathon, and +1, +2, and +3 months after the marathon). Models were fitted with multiple imputation data using the STATA mi module. Random intercept generalized least squares (GLS) regression models were used to determine change in sedentary behaviour with seven waves of repeated measures. RESULTS: Twenty-three individuals (mean ± Sx: 34.4 ± 2.1y, 23.0 ± 1.9% fat, 15 women, 8 men) completed the study. Marathon finishing times ranged from 185 to 344 minutes (253.2 ± 9.6 minutes). Total counts in the vertical axis were 1,729,414 lower one month after the race, compared with two months prior to the race (peak training). Furthermore, counts per minute decreased by 252.7 counts·minute-1 during that same time period. Daily sedentary behaviour did not change over the seven assessment periods, after accounting for age, gender, per cent body fat, wear time, marathon finishing time, and previous marathon experience. This prospective study supports the notion that PA and sedentary behaviours are distinct, showing that sedentary behaviour was not impacted by high levels of aerobic training.

A positive association between active lifestyle and hemispheric lateralization for motor control and learning in older adults.

Physical activity (PA) is well known to have general health benefits for older adults, but it is unclear whether it can also positively affect brain function involved in motor control and learning. We have previously shown that interlimb transfer of visuomotor adaptation occurs asymmetrically in young adults, while that occurs symmetrically in older adults, which suggests that the lateralized function of each hemisphere during motor tasks is diminished with aging. Here, we investigated the association between the level of PA and hemispheric motor lateralization by comparing the pattern of interlimb transfer following visuomotor adaptation between physically active and inactive older adults. Subjects were divided into two groups based on their PA level (active, inactive). They were further divided into two groups, such that a half of the subjects in each group adapted to a 30° rotation during targeted reaching movements with the left arm first, then with the right arm; and the other half with the right arm first, then with the left arm. Results indicated asymmetrical transfer (from left to right only) in the active subjects, whereas symmetrical transfer (from left to right, and vice versa) was observed in the inactive subjects. These findings suggest that older adults who maintain active lifestyle have a central nervous system that is more intact in terms of its lateralized motor function as compared with those who are inactive.

Accuracy of uploadable pedometers in laboratory, overground, and free-living conditions in young and older adults.

PURPOSE: The purpose of this study was to examine the accuracy of uploadable pedometers to accurately count steps during treadmill (TM) and overground (OG) walking, and during a 24 hour monitoring period (24 hr) under free living conditions in young and older adults. METHODS: One hundred and two participants (n=53 aged 20-49 yrs; n=49 aged 50-80 yrs) completed a TM protocol (53.6, 67.0, 80.4, 93.8, and 107.2 m/min, five minutes for each speed) and an OG walking protocol (self-determined "< normal", "normal", and "> normal" walking speeds) while wearing two waist-mounted uploadable pedometers (Omron HJ-720ITC [OM] and Kenz Lifecorder EX [LC]). Actual steps were manually tallied by a researcher. During the 24 hr period, participants wore a New Lifestyles-1000 (NL) pedometer (standard of care) attached to a belt at waist level over the midline of the left thigh, in addition to the LC on the belt over the midline of the right thigh. The following day, the same procedure was conducted, replacing the LC with the OM. One-sample t-tests were performed to compare measured and manually tallied steps during the TM and OG protocols, and between steps quantified by the NL with that of the OM and LC during the 24 hr period. Mean error step scores (MES, criterion - device) and 95% Limits of Agreement (LoA) were calculated. RESULTS: There were no significant differences between the OM and tallied steps for any of the TM speeds for either the young or older adult groups. The LC significantly underestimated steps for the young adult group during the 53.6 m/min TM speed (MES 31.4 [14.5, 48.3]) and during the OG < normal walking speed (MES 12.0 [0.9, 23.1] (p<0.01 for both age groups). The LC also significantly underestimated steps for the older adult group during the TM speeds of 53.6 m/min (MES 64.5 [45.6, 83.4]), 67.0 m/min (MES 15.1 [6.1, 24.0]), and 80.4 m/min (MES 3.2 [0.6, 5.9]) (p<0.01 for all speeds), in addition to the OG < normal walking speed (MES 14.7 [-13.3, 42.6] (p<0.01). The OM reported significantly lower steps during the 24 hr period for the young adult group by 949.1 steps (t=6.111, p<0.025) and for the older adult group by 612.9 steps (t=2.397, p<0.025). CONCLUSION: Both the OM and LC pedometers were more accurate as TM and OG walking speed increased. The OM significantly underestimated steps during the 24 hr compared with a standard of care evaluation. Overall, both uploadable pedometers appear acceptable to use in young or old age groups to measure walking behavior.

Comparison of the IPAQ-Short Form and accelerometry predictions of physical activity in older adults.

Older adult physical activity (PA) levels obtained from the International Physical Activity Questionnaire-Short Form (IPAQ) and accelerometry (ACC) were compared. Mean difference scores between accumulated or bout ACC PA and the IPAQ were computed. Spearman rank-order correlations were used to assess relations between time spent in PA measured from ACC and self-reported form of the IPAQ, and percentage agreement across measures was used to classify meeting or not meeting PA recommendations. The IPAQ significantly underestimated sitting and overestimated time spent in almost all PA intensities. Group associations across measures revealed significant relations in walking, total PA, and sitting for the whole group (r = .29-.36, p < .05). Significant relationships between bout ACC and IPAQ walking (r = .28-.39, p < .05) were found. There was 40-46% agreement between measures for meeting PA recommendations. The IPAQ appears not to be a good indicator of individual older adult PA behavior but is better suited for larger population-based samples.

Prediction of body fat in older adults by time spent in sedentary behavior.

The purpose of the study was to determine the relationship between sedentary behavior (SB), physical activity (PA), and body fat (total, abdominal) or body size (body-mass index [BMI], waist circumference [WC]) in community-dwelling adults 50 yr old and over. This study included 232 ambulatory adults (50-87 yr, 37.4% ± 9.6% body fat [BF]). Average daily time spent in SB (<100 counts/min) and light (100-759 counts/min), lifestyle-moderate (760-1,951 counts/min), walking-moderate (1,952-5,724 cts/min), and vigorous-intensity (≥ 5,725 counts/min) PA were determined by accelerometer and corrected for wear time. BF was measured with dual-energy X-ray absorptiometry. SB was positively related to measures of BF. Measures of SB, PA, and gender accounted for 55.6% of the variance in total BF, 32.4% of the variance in abdominal fat, and 28.0% of the variance in WC. SB, PA, and age accounted for 27.1% of the variance in BMI. Time spent in SB should be considered when designing obesity interventions for adults 50 yr old and over.

A pilot randomized controlled trial evaluating motivationally matched pedometer feedback to increase physical activity behavior in older adults.

BACKGROUND: Increasing physical activity (PA) levels in older adults represents an important public health challenge. The purpose of this study was to evaluate the feasibility of combining individualized motivational messaging with pedometer walking step targets to increase PA in previously inactive and insufficiently active older adults. METHODS: In this 12-week intervention study older adults were randomized to 1 of 4 study arms: Group 1--control; Group 2--pedometer 10,000 step goal; Group 3--pedometer step goal plus individualized motivational feedback; or Group 4--everything in Group 3 augmented with biweekly telephone feedback. RESULTS: 81 participants were randomized into the study, 61 participants completed the study with an average age of 63.8 ± 6.0 years. Group 1 did not differ in accumulated steps/day following the 12-week intervention compared with participants in Group 2. Participants in Groups 3 and 4 took on average 2159 (P < .001) and 2488 (P < .001) more steps/day, respectively, than those in Group 1 after the 12-week intervention. CONCLUSION: In this 12-week pilot randomized control trial, a pedometer feedback intervention partnered with individually matched motivational messaging was an effective intervention strategy to significantly increase PA behavior in previously inactive and insufficiently active older adults.

A Pilot Randomized Controlled Trial Evaluating Motivationally Matched Pedometer Feedback to Increase Physical Activity Behavior in Older Adults.

BACKGROUND: Increasing physical activity (PA) levels in older adults represents an important public health challenge. The purpose of this study was to evaluate the feasibility of combining individualized motivational messaging with pedometer walking step targets to increase PA in previously inactive and insufficiently active older adults. METHODS: In this 12-week intervention study older adults were randomized to 1 of 4 study arms: Group 1-control; Group 2-pedometer 10,000 step goal; Group 3-pedometer step goal plus individualized motivational feedback; or Group 4-everything in Group 3 augmented with biweekly telephone feedback. RESULTS: 81 participants were randomized into the study, 61 participants completed the study with an average age of 63.8 ± 6.0 years. Group 1 did not differ in accumulated steps/day following the 12-week intervention compared with participants in Group 2. Participants in Groups 3 and 4 took on average 2159 (P < .001) and 2488 (P < .001) more steps/day, respectively, than those in Group 1 after the 12-week intervention. CONCLUSION: In this 12-week pilot randomized control trial, a pedometer feedback intervention partnered with individually matched motivational messaging was an effective intervention strategy to significantly increase PA behavior in previously inactive and insufficiently active older adults.

Estimating absolute and relative physical activity intensity across age via accelerometry in adults.

This study examined the predictive validity of accelerometers (ACC) to estimate physical activity intensity (PAI) across age and differences in intensity predictions when expressed in relative and absolute PAI terms. Ninety adults categorized into 3 age groups (20-29, 40-49, and 60-69 yr) completed a treadmill calibration study with simultaneous ACC (7164 Actigraph) and oxygen-consumption assessment. Results revealed strong linear relations between ACC output and measured PAI (R2 = .62-.89) across age and similar ACC cut-point ranges across age delineating absolute PAI ranges compared with previous findings. Comparing measured metabolic equivalents (METs) with estimated METs derived from previously published regression equations revealed that age did not affect predictive validity of ACC estimates of absolute PAI. Comparing ACC output expressed in relative vs. absolute terms across age revealed substantial differences in PAI ACC count ranges. Further work is warranted to increase the applicability ofACC use relative to PAI differences associated with physiological changes with age.

Validity of Physical Activity Monitors in Assessing Energy Expenditure in Normal, Overweight, and Obese Adults.

A comparison of the validity of downloadable motion sensors, which use either a glass-enclosed magnetic reed proximity switch technology, a piezo-electric sensor accelerometer with a horizontal beam technology, or an internal pendulum based mechanism to determine energy expenditure (EE), across different body sizes does not exist. Therefore, the purpose of this study was to determine the validity of three different downloadable motion sensors to estimate EE during walking activity in normal weight, overweight and obese volunteers. Forty-eight participants completed this study. Each participant had their body height and mass measured and completed a treadmill walking protocol. Body mass index (BMI) was calculated. The treadmill walking protocol included six 5-minute stages starting at 1.5 mph and increasing by 0.5 mph, up to 4.0 mph while grade was constant at 0% for the duration of the test. The Kenz Life-Corder EX (LC), the Omron HJ-700IT (OM) and the Sportbrain iStep X1 (SB) were worn during the treadmill walking protocol. Heart rate, oxygen consumption, carbon dioxide production and EE estimated from the motion sensors were monitored throughout the walking protocol. Results showed the OM overestimated net EE in normal, overweight and obese participants. The LC underestimated gross EE in all groups. The SB overestimated net EE in normal BMI participants, was not significantly different from the criterion measure of net EE in overweight participants and underestimated net EE in obese individuals. This study demonstrates that these devices do not offer the accuracy needed to provide precise feedback on EE for individuals with varying BMI levels.

The impact of body-mass index and steps per day on blood pressure and fasting glucose in older adults.

The purpose of this study was to investigate the combined impact of obesity and physical activity (PA) on the health of older adults. Pedometer-determined steps/d, body-mass index (BMI), resting blood pressure, and fasting glucose (FG) were assessed in 137 older adults (69.0 +/- 8.9 yr). The active group (>4,227 steps/d) had lower systolic blood pressure (SBP; p = .001), diastolic blood pressure (DBP; p = .028), and FG (p < .001) than the inactive group (< or = 4,227 steps/d). The normal-BMI group (18.5-24.9 kg/m2) had lower SBP (p < .001) and DBP (p = .01) than the obese group (> or =30 kg/m2). There were no differences in SBP (p = .963) or DBP (p = 1.0) between active obese and inactive normal-BMI groups. The active obese group, however, had a more favorable FG than the inactive normal-BMI group (chi 2 = 18.9, df = 3, p = .001). Efforts to increase PA of older adults should receive the same priority as reducing obesity to improve BP and FG levels.

Glucose control and walking in a multiethnic sample of older adults.

BACKGROUND: Although walking is the most commonly reported physical activity by older adults, there is a paucity of data determining the relationship between objectively determined walking behavior and glucose dynamics in older adults. OBJECTIVE: This study was designed to investigate the relationship between objectively determined walking behavior and glucose control in a multiethnic sample of older adults. METHODS: Data were collected on 142 older adults (age 72.1 +/- 9.2 years; body mass index (BMI) 29.4 +/- 6.3; 37 males, 105 females). Anthropometric measures, fasting plasma glucose (FG), and glycosylated hemoglobin A(1c) (HbA(1c)) were assessed; race/ethnicity was self-reported. The study participants wore a pedometer for 7 consecutive days. RESULTS: The average number of steps/day reported by the entire group was 3,939 +/- 232. White participants (n = 48) were older (p = 0.019), taller (p = 0.002), had lower waist circumference (WC) (p = 0.021), HbA(1c) (p = 0.001) and FG (p = 0.007), and did not differ in average steps/day (p = 0.162) or BMI (p = 0.280) as compared with nonwhite participants (n = 94). Individuals with HbA(1c) values <7% and those with FG <100 mg/dl walked about 1,343 more steps/day than those with unfavorable HbA(1c) and/or FG values. Age, race/ethnicity, WC, BMI, log base 10 of steps/days, and type 1 and 2 diabetes medications accounted for 37.5% of the variance in inverse HbA(1c) (p < 0.001), with significant or near significant individual model contributions consisting of WC (beta = -0.316, B = -0.001, SE = 0.000, p = 0.047), BMI (beta = 0.310, B = 0.001, SE = 0.001, p = 0.050), diabetic medication (beta = -0.473, B = -0.035, SE = 0.006, p < 0.001), and log base 10 of steps/day (beta = 0.198, B = 0.019, SE = 0.010, p = 0.056). Interpretations of transformed data illustrate that greater WC and being on diabetic medications are associated with higher HbA(1c) levels. Further, there is a trend to suggest that fewer accumulated steps/day and lower BMI are associated with higher HbA(1c) concentrations. CONCLUSIONS: This study demonstrated that objectively determined walking behavior and indicators of obesity were modest predictors of chronic glucose control, after accounting for glucose-altering medications, in this multicultural sample of older adults. Further, when comparing individuals with good glucose control to those with less favorable glucose control, walking an additional 0.5-0.75 miles was associated with better glucose control.