Higher Prefrontal Cortex Activity Research Articles

GAIT AUTOMATICITY AND COMMUNITY MOBILITY OF OLDER ADULTS

Abstract Gait automaticity may decline with age-related impairments in the brain. As subcortical structures supporting gait automaticity decline, the prefrontal cortex (PFC) may provide compensatory function, allowing for maintenance of mobility but with loss of efficiency. Loss of efficiency may reduce ability to navigate complex community environments and restrict community mobility. We assessed the relation between PFC activation during walking in the laboratory with self-reported and objectively measured community mobility in participants aged 65+ (n=42, mean age=76, 60% female) from a randomized trial of a physical activity intervention to improve walking speed. PFC activation was measured by functional near-infrared spectroscopy as change from quiet standing to usual pace walking. Community mobility was measured objectively by 7-day global positioning system recordings of spatial (standard deviation ellipse area (SDEa), maximum distance from home) and temporal (percent time out of home (pTOH)) characteristics. Additionally, step count was recorded from 7-day actigraphy and the Life-Space Assessment (LSA) assessed self-reported mobility. Among participants with complete data at baseline (n=27), higher PFC activation during walking was associated with smaller SDEa (beta=-0.93 (-1.72, -0.15)), less pTOH (beta=-0.45 (-0.78, -0.12)), and lower step count (beta=-346 (-575, -118)) which persisted after adjusting for age, gender, education, or gait speed. PFC activation was not associated with maximum distance or LSA. There were no significant associations at the post-intervention visits (n=39). Greater PFC activation, likely indicating reduced gait automaticity, is related to lower spatial extent, duration, and intensity of community mobility. This association may be mitigated by participation in physical activity interventions.

Runners with better cardiorespiratory fitness had higher prefrontal cortex activity during both single and exercise-executive function dual tasks: an fNIRS study.

Objective: This study investigated the relationship between executive function and prefrontal cortex oxygenation during exercise in young adults with different Cardiorespiratory fitness (CRF) levels. Methods: A total of 28 amateur runners (n = 14) and sedentary college students (n = 14) were recruited. The maximum oxygen uptake estimated for the sub-maximal intensity run (4.97 miles/h) was used to indicate the different CRF levels. After 1week, participants must complete the Stroop and 2-Back tasks in silence while performing moderate-intensity exercise. Using 19-channel functional near-infrared spectroscopic (fNIRS) to examine changes in prefrontal cortex oxyhemoglobin. Results: There was no significant difference in the correctness of the Stroop and 2-Back tasks between the two groups during exercise, but the amateur runner group showed an acceleration in reaction time. fNIRS results showed that during the exercise 2-Back task, the left dorsolateral prefrontal cortex oxyhemoglobin was higher in the amateur runner group than in the sedentary group. Conclusion: Executive function during exercise was similarly improved in participants with better fitness, suggesting that CRF provides an excellent metabolic reserve and directed allocation for cognitive tasks during exercise.

Inefficient frontal and parietal brain activation during dual-task walking in a virtual environment in older adults

Walking while performing an additional cognitive task (dual-task walking; DT walking) is a common yet highly demanding behavior in daily life. Previous neuroimaging studies have shown that performance declines from single-task (ST) to DT conditions are accompanied by increased prefrontal cortex (PFC) activity. This increment is particularly pronounced in older adults and has been explained either by compensation, dedifferentiation, or inefficient task processing in fronto-parietal circuits. However, there is only limited evidence for the hypothesized fronto-parietal activity changes measured under real-life conditions such as walking. In this study, we therefore assessed brain activity in PFC and parietal lobe (PL), to investigate whether higher PFC activation during DT walking in older adults is related to compensation, dedifferentiation, or neural inefficiency. Fifty-six healthy older adults (69.11 ± 4.19 years, 30 female) completed three tasks (treadmill walking at 1 m/s, Stroop task, Serial 3′s task) under ST and DT conditions (Walking + Stroop, Walking + Serial 3′s), and a baseline standing task. Behavioral outcomes were step time variability (Walking), Balance Integration Score BIS (Stroop), and number of correct calculations S3corr (Serial 3′s). Brain activity was measured using functional near-infrared spectroscopy (fNIRS) over ventrolateral and dorsolateral PFC (vlPFC, dlPFC) and inferior and superior PL (iPL, sPL). Neurophysiological outcome measures were oxygenated (HbO2) and deoxygenated hemoglobin (HbR). Linear mixed models with follow-up estimated marginal means contrasts were applied to investigate region-specific upregulations of brain activation from ST to DT conditions. Furthermore, the relationships of DT-specific activations across all brain regions was analyzed as well as the relationship between changes in brain activation and changes in behavioral performance from ST to DT. Data indicated the expected upregulation from ST to DT and that DT-related upregulation was more pronounced in PFC (particularly in vlPFC) than in PL regions. Activation increases from ST to DT were positively correlated between all brain regions, and higher brain activation changes predicted higher declines in behavioral performance from ST to DT. Results were largely consistent for both DTs (Stroop and Serial 3′s). These findings more likely suggest neural inefficiency and dedifferentiation in PFC and PL rather than fronto-parietal compensation during DT walking in older adults. Findings have implications for interpreting and promoting efficacy of long-term interventions to improve DT walking in older persons.

Effects of pre-exercise H2 inhalation on physical fatigue and related prefrontal cortex activation during and after high-intensity exercise.

Objective: In this study, we examined the effects of pre-exercise H2 gas inhalation on physical fatigue (PF) and prefrontal cortex (PFC) activation during and after high-intensity cycling exercise. Methods: Twenty-four young men completed four study visits. On the first two visits, the maximum workload (Wmax) of cycling exercise of each participant was determined. On each of the other two visits, participants inhaled 20 min of either H2 gas or placebo gas after a baseline test of maximal voluntary isometric contraction (MVIC) of thigh. Then participants performed cycling exercise under their maximum workload. Ratings of perceived exertion (RPE), heart rate (HR) and the PFC activation by using functional near-infrared spectroscopy (fNIRS) was measured throughout cycling exercise. The MVIC was measured again after the cycling. Results: It was observed that compared to control, after inhaling H2 gas, participants had significantly lower RPE at each workload phase (p < 0.032) and lower HR at 50% Wmax, 75% Wmax, and 100% Wmax during cycling exercise (p < 0.037); the PFC activation was also significantly increased at 75 and 100% Wmax (p < 0.011). Moreover, the H2-induced changes in PF were significantly associated with that in PFC activation, that is, those who had higher PFC activation had lower RPE at 75% Wmax (p = 0.010) and lower HR at 100% Wmax (p = 0.016), respectively. Conclusion: This study demonstrated that pre-exercise inhalation of H2 gas can alleviate PF, potentially by maintaining high PFC activation during high-intensity exercise in healthy young adults.

Exploratory fNIRS Assessment of Differences in Activation in Virtual Reality Visual Self-Expression Including With a Fragrance Stimulus

A within-subjects experimental design examined differences in functional near-infrared spectroscopy (fNIRS) assessment of prefrontal cortex (PFC) activation with two virtual reality (VR) drawing conditions (rote tracing and creative self-expression) with and without a fragrance stimulus. Participants were healthy adults and included 18 women, 6 men: age range = 18–54 years. Findings indicate significant differences such that rote tracing resulted in higher PFC activity than the creative self-expression task. Although there was no significant impact of fragrance on the overall sample, emergent differences in responsiveness to fragrance were seen by age and gender. The study suggests that repetitive tasks like rote tracing can enhance focus and the creative self-expressive tasks can reduce PFC load and induce relaxation and flow.

CAN COGNITIVE TRAINING USING A TABLET COMPUTER ENHANCE COGNITIVE FUNCTION OF HEALTHY OLDER ADULTS? AN ALTERNATING-TREATMENT DESIGN

Even though a variety of cognitive interventions have been conducted to ameliorate age-related cognitive declines, the effects of cognitive intervention using activities in everyday life are still unknown. The purpose of this study was to compare the effects between tablet computer-based productive and receptive cognitive engagement using an alternating-treatment design. Three healthy older adults performed a total of 19 sessions consisting of three baseline periods and 16 alternating training sessions. The training sessions were divided into four blocks and each block involved four treatment sessions. Productive and receptive engagements were randomly allocated to four treatment sessions. All participants alternatively received productive engagement that requires learning new practical applications and receptive engagement requiring little new learning such as listening to music. Prefrontal cortex (PFC) activity using functional near-infrared spectroscopy and executive function through the Trail Making Test were assessed at the baseline and the end of each session. All data were visually analyzed. Visual analysis results showed that the productive engagement was associated with higher PFC activity and faster performance in the Trail Making Test, compared to those utilizing receptive engagement. These results suggest that productive engagement might be effective in facilitating PFC activity and improving the executive function of healthy older adults, indicating cognitively challenging activities are more beneficial relative to nonchallenging activities.

Functional Status Is Associated With Prefrontal Cortex Activation in Gait in Subacute Stroke Patients: A Functional Near-Infrared Spectroscopy Study.

Increasing cerebral oxygenation, more precisely the overactivation of the prefrontal cortex (PFC), reflects cortical control of gait in stroke disease. Studies about the relationship between brain activation and the functional status in stroke patients remain scarce. The aim of this study was to compare brain activation, gait parameters, and cognitive performances in single and dual tasks according to the functional status in subacute stroke patients. Twenty-one subacute stroke patients were divided in two groups according to Barthel Index (“low Barthel” and “high Barthel”) and randomly performed ordered walking, cognitive task (n-back task), and dual tasks (walking + n-back task). We assessed gait performances (speed, variability) using an electronic walkway system and cerebral oxygenation (ΔO2Hb) by functional near-infrared spectroscopy. Patients with better functional status (high Barthel) showed a lower PFC activation (ΔO2Hb) and better gait parameters in single and dual tasks compared to low-Barthel patients, who exhibited decreased gait performances despite a higher PFC activation, especially in the unaffected side (P < 0.001). PFC overactivation in less functional subacute stroke patients may be due to the loss of stepping automaticity. Our results underline the interest of proposing rehabilitation programs focused on walking, especially for patients with low functional capacity.

Neurophysiological biomarkers of response inhibition and the familial risk for borderline personality disorder

Understanding of the biological factors that run in families affected with borderline personality disorder (BPD) is limited. The authors investigated the familial aggregation of neurophysiological biomarkers of response inhibition in the first-degree biological relatives of probands with BPD and associations with psychiatric diagnosis and impulsive traits. In the present study, psychiatric diagnoses and impulsive traits were measured in BPD probands (n = 86), psychiatrically affected and non-affected relatives (n = 60) and controls (n = 83). While undergoing neuroimaging using functional near-infrared spectroscopy, prefrontal cortex (PFC) activation was measured during a go/no-go response inhibition task and compared between probands, relatives and controls. Additionally, non-psychiatrically affected relatives and controls were contrasted to examine the potential impact of familial risk for BPD on response inhibition-related PFC activation in the absence of confounding psychiatric morbidity. Probands showed bilateral decreases in PFC activation during response inhibition compared to relatives and controls. Conversely, both affected and non-affected relatives displayed higher activation than controls and probands in left lateral/medial and right medial PFC, although non-affected relatives showed a lesser extent of activation than affected relatives. Probands and controls reporting greater impulsive traits displayed deactivation across the PFC during response inhibition, whereas relatives showed increased activation. In this first family study of neuroimaging biomarkers in BPD, we show that the familial risk for BPD is reflected in activation of the PFC during response inhibition, with lifetime psychiatric diagnosis and higher impulsive traits in relatives associated with larger increases in PFC activity. Higher PFC activity during response inhibition including among non-affected relatives could reflect a neurophysiological compensatory mechanism.

Prefrontal Cortex Activity and Gait in Parkinson's Disease With Cholinergic and Dopaminergic Therapy.

Degradation of striatal dopamine in Parkinson's disease (PD) may initially be supplemented by increased cognitive control mediated by cholinergic mechanisms. Shift to cognitive control of walking can be quantified by prefrontal cortex activation. Levodopa improves certain aspects of gait and worsens others, and cholinergic augmentation influence on gait and prefrontal cortex activity remains unclear. This study examined dopaminergic and cholinergic influence on gait and prefrontal cortex activity while walking in PD. A single-site, randomized, double-blind crossover trial examined effects of levodopa and donepezil in PD. Twenty PD participants were randomized, and 19 completed the trial. Participants were randomized to either levodopa + donepezil (5 mg) or levodopa + placebo treatments, with 2 weeks with treatment and a 2-week washout. The primary outcome was change in prefrontal cortex activity while walking, and secondary outcomes were change in gait and dual-task performance and attention. Levodopa decreased prefrontal cortex activity compared with off medication (effect size, -0.51), whereas the addition of donepezil reversed this decrease. Gait speed and stride length under single- and dual-task conditions improved with combined donepezil and levodopa compared with off medication (effect size, 1 for gait speed and 0.75 for stride length). Dual-task reaction time was quicker with levodopa compared with off medication (effect size, -0.87), and accuracy improved with combined donepezil and levodopa (effect size, 0.47). Cholinergic therapy, specifically donepezil 5 mg/day for 2 weeks, can alter prefrontal cortex activity when walking and improve secondary cognitive task accuracy and gait in PD. Further studies will investigate whether higher prefrontal cortex activity while walking is associated with gait changes. © 2020 International Parkinson and Movement Disorder Society.

The Association between Prefrontal Cortex Activity and Turning Behavior in People with and without Freezing of Gait

Turning elicits Freezing of Gait (FoG) episodes in people with Parkinson's disease (PD) and is thought to require higher cortical control compared to straight ahead gait. Functional near infrared spectroscopy (fNIRS) has been used to examine prefrontal cortex (PFC) activity while walking, but the relationship between PFC activity and turn performance remains unclear. The aim of this pilot study was to examine PFC activity during turning in PD and healthy controls, and to investigate the association between PFC activity and turning.Thirty-two subjects, 15 freezers (PD + FoG) and 17 non-freezers (PD − FoG), and 8 controls were asked to perform a 2-min turning-in-place test under single-task (ST) and dual-task (DT) conditions. Each participant wore an fNIRS system to measure changes in oxyhemoglobin, as measure of PFC activity, and inertial sensors to quantify turning.Our results show a significant group (p = .050), task (p = .039), and interaction (p = .047) for the PFC activity during turning. Specifically, PD + FoG show higher PFC during turning compared to the other groups; PFC activity during DT is overall different compared to ST with an opposite trend in PD + FoG compared to controls and PD − FoG. In addition, higher PFC is associated with worse FoG in PD + FoG (r = 0.57, p = .048) and with lower number of turns in PD − FoG (r = −0.70, p = .002).The increased PFC activity in PD and the association between higher PFC activity and poorer turning performance may be a sign of poor movement automaticity in PD. Although further investigations are required, these pilot findings may guide development of personalized treatments to improve motor automaticity in PD.

Pre-frontal Cortical Activity During Walking and Turning Is Reliable and Differentiates Across Young, Older Adults and People With Parkinson's Disease

Introduction: Mobility declines with age and further with neurodegenerative disorders, such as Parkinson's disease (PD). Walking and turning ability, in particular, are vital aspects of mobility that deteriorate with age and are further impaired in PD. Such deficits have been linked with reduction in automatic control of movement and the need for compensatory cognitive cortical control via the pre-frontal cortex (PFC), however the underlying neural mechanisms remain unclear. Establishing and using a robust methodology to examine PFC activity during continuous walking and turning via mobile functional near infra-red spectroscopy (fNIRS) may aid in the understanding of mobility deficits and help with development of appropriate therapeutics.This study aimed to: (1) examine test re-test reliability of PFC activity during continuous turning and walking via fNIRS measurement; and (2) compare PFC activity during continuous turning and walking in young, old and Parkinson's subjects.Methods: Twenty-five young (32.3 ± 7.5 years), nineteen older (65.4 ± 7.0 years), and twenty-four PD (69.3 ± 4.1 years) participants performed continuous walking and 360° turning-in-place tasks, each lasting 2 min. Young participants repeated the tasks a second time to allow fNIRS measurement reliability assessment. The primary outcome was PFC activity, assessed via measuring changes in oxygenated hemoglobin (HbO2) concentrations.Results: PFC activity during continuous walking and turning was moderately reproducible (Intra-class correlation coefficient = 0.67). The PD group had higher PFC activation than young and older adults during walking and turning, with significant group differences for bilateral PFC activation (p = 0.025), left PFC activation (p = 0.012), and the early period (first 40 s) of walking (p = 0.007), with greater activation required in PD. Interestingly, older adults had similar PFC activation to young adults across conditions, however older adults required greater activation than young adults during continuous turning, specifically the early period of the turning task (Cohens d = 0.86).Conclusions: PFC activity can be measured during continuous walking and turning tasks with acceptable reliability, and can differentiate young, older and PD groups. PFC activation was significantly greater in PD compared to young and older adults during walking, particularly when beginning to walk.