Differences in resting state functional connectivity underlie visuomotor performance declines in older adults with a genetic risk (APOE ε4) for Alzheimer's disease.

Introduction: Non-standard visuomotor integration requires the interaction of large networks in the brain. Previous findings have shown that non-standard visuomotor performance is impaired in individuals with specific dementia risk factors (family history of dementia and presence of the APOE ε4 allele) in advance of any cognitive impairments. These findings suggest that visuomotor impairments are associated with early dementia-related brain changes. The current study examined the underlying resting state functional connectivity (RSFC) associated with impaired non-standard visuomotor performance, as well as the impacts of dementia family history, sex, and APOE status. Methods: Cognitively healthy older adults (n = 48) were tested on four visuomotor tasks where reach and gaze were increasingly spatially dissociated. Participants who had a family history of dementia or the APOE ε4 allele were considered to be at an increased risk for AD. To quantify RSFC within networks of interest, an EPI sequence sensitive to BOLD contrast was collected. The networks of interest were the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), and frontoparietal control network (FPN). Results: Individuals with the ε4 allele showed abnormalities in RSFC between posterior DMN nodes that predicted poorer non-standard visuomotor performance. Specifically, multiple linear regression analyses revealed lower RSFC between the precuneus/posterior cingulate cortex and the left inferior parietal lobule as well as the left parahippocampal cortex. Presence of the APOE ε4 allele also modified the relationship between mean DAN RSFC and visuomotor control, where lower mean RSFC in the DAN predicted worse non-standard visuomotor performance only in APOE ε4 carriers. There were otherwise no effects of family history, APOE ε4 status, or sex on the relationship between RSFC and visuomotor performance for any of the other resting networks. Conclusion: The preliminary findings provide insight into the impact of APOE ε4-related genetic risk on neural networks underlying complex visuomotor transformations, and demonstrate that the non-standard visuomotor task paradigm discussed in this study may be used as a non-invasive, easily accessible assessment tool for dementia risk.

Differences in structural MRI and diffusion tensor imaging underlie visuomotor performance declines in older adults with an increased risk for Alzheimer's disease.

Introduction: Visuomotor impairments have been demonstrated in preclinical AD in individuals with a positive family history of dementia and APOE e4 carriers. Previous behavioral findings have also reported sex-differences in performance of visuomotor tasks involving a visual feedback reversal. The current study investigated the relationship between grey and white matter changes and non-standard visuomotor performance, as well as the effects of APOE status, family history of dementia, and sex on these brain-behavior relationships. Methods: Older adults (n = 49) with no cognitive impairments completed non-standard visuomotor tasks involving a visual feedback reversal, plane-change, or combination of the two. Participants with a family history of dementia or who were APOE e4 carriers were considered at an increased risk for AD. T1-weighted anatomical scans were used to quantify grey matter volume and thickness, and diffusion tensor imaging measures were used to quantify white matter integrity. Results: In APOE e4 carriers, grey and white matter structural measures were associated with visuomotor performance. Regression analyses showed that visuomotor deficits were predicted by lower grey matter thickness and volume in areas of the medial temporal lobe previously implicated in visuomotor control (entorhinal and parahippocampal cortices). This finding was replicated in the diffusion data, where regression analyses revealed that lower white matter integrity (lower FA, higher MD, higher RD, higher AxD) was a significant predictor of worse visuomotor performance in the forceps minor, forceps major, cingulum, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF). Some of these tracts overlap with those important for visuomotor integration, namely the forceps minor, forceps major, SLF, IFOF, and ILF. Conclusion: These findings suggest that measuring the dysfunction of brain networks underlying visuomotor control in early-stage AD may provide a novel behavioral target for dementia risk detection that is easily accessible, non-invasive, and cost-effective. The results also provide insight into the structural differences in inferior parietal lobule that may underlie previously reported sex-differences in performance of the visual feedback reversal task.

Cognitive-Motor Integration Performance Is Affected by Sex, APOE Status, and Family History of Dementia.

BACKGROUND: Cognitive-motor integration (CMI) involves concurrent thought and action which requires the interaction of large brain networks. Given that early-stage dementia involves neural network dysfunction, deficits in CMI may prove useful for early dementia detection. OBJECTIVE: Our research objective was to investigate sex-related differences in the ability to integrate rules into action. METHODS: Based on family medical history, we recruited male and female participants both with and without dementia risk factors. Participants did not demonstrate cognitive impairment at the time of testing. Participants were tested on four increasingly dissociated visuomotor tasks (eye and hand movements were made in different spatial planes and/or visual feedback was reversed). RESULTS: We observed significantly greater hand movement endpoint error scores and corrective path lengths in at-risk females compared to at-risk males in the most complex CMI condition (plane-change + feedback reversal). Multiple regression analyses revealed both sex and family history as significant predictors of worse performance in a CMI condition requiring visual feedback reversal. Further, the regression analyses provided preliminary evidence that having an APOEɛ4 allele was a significant predictor of poorer CMI performance in the two plane-change CMI conditions. CONCLUSION: These data suggest that underlying brain networks controlling simultaneous thought and action may differ between the sexes in ways that may be clinically relevant in dementia progression. Preliminary data also suggest an important connection between APOE variant and CMI performance in individuals at risk of developing dementia.

The Contribution of Different Cortical Regions to the Control of Spatially Decoupled Eye-Hand Coordination.

Our brain's ability to flexibly control the communication between the eyes and the hand allows for our successful interaction with the objects located within our environment. This flexibility has been observed in the pattern of neural responses within key regions of the frontoparietal reach network. More specifically, our group has shown how single-unit and oscillatory activity within the dorsal premotor cortex (PMd) and the superior parietal lobule (SPL) change contingent on the level of visuomotor compatibility between the eyes and hand. Reaches that involve a coupling between the eyes and hand toward a common spatial target display a pattern of neural responses that differ from reaches that require eye-hand decoupling. Although previous work examined the altered spiking and oscillatory activity that occurs during different types of eye-hand compatibilities, they did not address how each of these measures of neurological activity interacts with one another. Thus, in an effort to fully characterize the relationship between oscillatory and single-unit activity during different types of eye-hand coordination, we measured the spike-field coherence (SFC) within regions of macaque SPL and PMd. We observed stronger SFC within PMdr and superficial regions of SPL (areas 5/PEc) during decoupled reaches, whereas PMdc and regions within SPL surrounding medial intrapareital sulcus had stronger SFC during coupled reaches. These results were supported by meta-analysis on human fMRI data. Our results support the proposal of altered cortical control during complex eye-hand coordination and highlight the necessity to account for the different eye-hand compatibilities in motor control research.

Adults at Increased Alzheimer's Disease Risk Display Cognitive-Motor Integration Impairment Associated with Changes in Resting-State Functional Connectivity: A Preliminary Study.

BACKGROUND: Many neuroimaging parameters have demonstrated utility as biomarkers in preclinical AD, including resting-state functional connectivity in the default mode network. However, neuroimaging is not a practical, cost effective screening instrument. OBJECTIVE: Here we investigate the relationship between performance on a cognitive-motor integration assessment and alterations in resting-state functional connectivity in an at-risk population. METHODS: Three groups of ten adults (young: mean age = 26.6 ± 2.7, low AD risk: mean age = 58.7 ± 5.6, and high AD risk: mean age = 58.5 ± 6.9) performed a simple cognitive-motor integration task using a dual-touchscreen laptop and also underwent functional magnetic resonance imaging at rest. RESULTS: We found poorer cognitive-motor integration performance in high AD risk participants, as well as an association with lower resting-state functional connectivity in this group. CONCLUSION: These findings provide novel insight into underlying AD-related brain alterations associated with a behavioral assessment that can be easily administered clinically.

Sagittal plane lumbar loading when navigating an obstacle and carrying a load.

The current study quantified lumbar loading while carrying an anterior load mass and navigating an obstacle. Eight healthy male participants walked down a walkway and crossed an obstacle under three randomised LOAD conditions; empty-box (2 KG), five kilogram (5 KG) and ten kilogram (10 KG). Each walk was assessed at two events: left foot mid-stance (LMS) and right toe-crossing (TC) to characterise any changes from approach to crossing. Measures of interest included: trunk pitch, L4/L5 joint moment, compression, joint anterior-posterior shear and erector spinae activation. Findings demonstrate that obstacle crossing extended posture by 50, 41, 44%, respectively for each carried load magnitude. Further, these results indicate that shear rather than compressive loading may be an important consideration during crossing due to increase by 8, 9, 22% from LMS to TC for each load magnitude tested. These results provide insight into sagittal lumbar loading when navigating an obstacle while carrying a load. Practitioner Summary: The risk of carrying while navigating obstacles on the lumbar spine is not completely understood. The forces at the lumbar spine while simultaneously carrying and obstacle crossing were analysed. Data indicate that carrying and obstacle crossing influence lumbar shear loads, thereby moderately increasing the relative risk at lumbar spine.

Diffusion tensor imaging correlates of cognitive-motor decline in normal aging and increased Alzheimer's disease risk.

Alzheimer's disease (AD) is typically associated with impairments in memory and other aspects of cognition, while deficits in complex movements are commonly observed later in the course of the disease. Recent studies, however, have indicated that subtle deteriorations in visuomotor control under cognitively demanding conditions may in fact be an early identifying feature of AD. Our previous work has shown that the ability to perform visuomotor tasks that rely on visual-spatial and rule-based transformations is disrupted in prodromal and preclinical AD. Here, in a sample of 30 female participants (10 young: mean age = 26.6 ± 2.7, 10 low AD risk: mean age = 58.7 ± 5.6, and 10 high AD risk: mean age = 58.5 ± 6.9), we test the hypothesis that these cognitive-motor impairments are associated with early AD-related brain alterations. Using diffusion-weighted magnetic resonance imaging, we examined changes in white matter (WM) integrity associated with normal aging and increased AD risk, and assessed the relationship between these underlying WM alterations and cognitive-motor performance. Our whole-brain analysis revealed significant age-related declines in WM integrity, which were more widespread in high relative to low AD risk participants. Furthermore, analysis of mean diffusivity measures within isolated WM clusters revealed a stepwise decline in WM integrity across young, low AD risk, and high AD risk groups. In support of our hypothesis, we also observed that lower WM integrity was associated with poorer cognitive-motor performance. These results are the first to demonstrate a relationship between AD-related WM alterations and impaired cognitive-motor control. The application of these findings may provide a novel clinical strategy for the early detection of individuals at increased AD risk.

Visuomotor impairments in older adults at increased Alzheimer's disease risk.

BACKGROUND AND OBJECTIVE: Recent evidence suggests that visuomotor behaviors may be disrupted in the very early stages of Alzheimer's disease (AD). Here we propose that using kinematic measures under conditions that place demands on visual-spatial and cognitive-motor processing may provide an effective behavioral means to detect subtle changes associated with AD risk. METHODS: To this end, we have tested 22 young adults (mean age = 26.4 ± 4.1) and 22 older adults (mean age = 64.3 ± 10.1) at low AD, and 22 older adults (mean age = 67.7 ± 11.3) at high AD risk (i.e., strong family history or diagnosis of mild cognitive impairment). Kinematic measures were acquired on four visuomotor transformation tasks (standard, feedback reversal, plane dissociated, and plane dissociated + feedback reversal) using a dual-touchscreen tablet. RESULTS: Comparing participants at increased AD risk with both young and old healthy control groups revealed significant performance disruptions in at-risk individuals as task demands increased. Furthermore, we were able to discriminate between individuals at high and low AD risk with a classification accuracy of 86.4% (sensitivity: 81.8%, specificity: 90.9%). CONCLUSION: We suggest that the impairments observed in individuals at increased AD risk may reflect inherent brain alteration and/or early neuropathology disrupting the reciprocal communication between hippocampal, parietal, and frontal brain regions required to successfully prepare and update complex reaching movements. Such impairment has the potential to affect activities of daily living, and may serve as a sensitive measure of functional ability in at-risk adults.

Decoupling the actions of the eyes from the hand alters beta and gamma synchrony within SPL.

Eye-hand coordination is crucial for our ability to interact with the world around us. However, much of the visually guided reaches that we perform require a spatial decoupling between gaze direction and hand orientation. These complex decoupled reaching movements are in contrast to more standard eye and hand reaching movements in which the eyes and the hand are coupled. The superior parietal lobule (SPL) receives converging eye and hand signals; however, what is yet to be understood is how the activity within this region is modulated during decoupled eye and hand reaches. To address this, we recorded local field potentials within SPL from two rhesus macaques during coupled vs. decoupled eye and hand movements. Overall we observed a distinct separation in synchrony within the lower 10- to 20-Hz beta range from that in the higher 30- to 40-Hz gamma range. Specifically, within the early planning phase, beta synchrony dominated; however, the onset of this sustained beta oscillation occurred later during eye-hand decoupled vs. coupled reaches. As the task progressed, there was a switch to low-frequency and gamma-dominated responses, specifically for decoupled reaches. More importantly, we observed local field potential activity to be a stronger task (coupled vs. decoupled) and state (planning vs. execution) predictor than that of single units alone. Our results provide further insight into the computations of SPL for visuomotor transformations and highlight the necessity of accounting for the decoupled eye-hand nature of a motor task when interpreting movement control research data.

Differences in spectral profiles between rostral and caudal premotor cortex when hand-eye actions are decoupled.

The aim of this research was to understand how the brain controls voluntary movement when not directly interacting with the object of interest. In the present study, we examined the role of premotor cortex in this behavior. The goal of this study was to characterize the oscillatory activity within the caudal and rostral subdivisions of dorsal premotor cortex (PMdc and PMdr) with a change from the most basic reaching movement to one that involves a simple dissociation between the actions of the eyes and hand. We were specifically interested in how PMdr and PMdc respond when the eyes and hand are decoupled by moving along different spatial planes. We recorded single-unit activity and local field potentials within PMdr and PMdc from two rhesus macaques during performance of two types of visually guided reaches. During the standard condition, a visually guided reach was performed whereby the visual stimulus guiding the movement was the target of the reach itself. During the nonstandard condition, the visual stimulus provided information about the direction of the required movement but was not the target of the motor output. We observed distinct task-related and topographical differences between PMdr and PMdc. Our results support functional differences between PMdr and PMdc during visually guided reaching. PMdr activity appears more involved in integrating the rule-based aspects of a visually guided reach, whereas PMdc is more involved in the online updating of the decoupled reach. More broadly, our results highlight the necessity of accounting for the nonstandard nature of a motor task when interpreting movement control research data.

Neural activity in superior parietal cortex during rule-based visual-motor transformations.

Cognition allows for the use of different rule-based sensorimotor strategies, but the neural underpinnings of such strategies are poorly understood. The purpose of this study was to compare neural activity in the superior parietal lobule during a standard (direct interaction) reaching task, with two nonstandard (gaze and reach spatially incongruent) reaching tasks requiring the integration of rule-based information. Specifically, these nonstandard tasks involved dissociating the planes of reach and vision or rotating visual feedback by 180°. Single unit activity, gaze, and reach trajectories were recorded from two female Macaca mulattas. In all three conditions, we observed a temporal discharge pattern at the population level reflecting early reach planning and on-line reach monitoring. In the plane-dissociated task, we found a significant overall attenuation in the discharge rate of cells from deep recording sites, relative to standard reaching. We also found that cells modulated by reach direction tended to be significantly tuned either during the standard or the plane-dissociated task but rarely during both. In the standard versus feedback reversal comparison, we observed some cells that shifted their preferred direction by 180° between conditions, reflecting maintenance of directional tuning with respect to the reach goal. Our findings suggest that the superior parietal lobule plays an important role in processing information about the nonstandard nature of a task, which, through reciprocal connections with precentral motor areas, contributes to the accurate transformation of incongruent sensory inputs into an appropriate motor output. Such processing is crucial for the integration of rule-based information into a motor act.

Glycemic management in medical and surgical patients in the non-ICU setting.

Hyperglycemia is commonly observed in hospitalized patients with and without previously known diabetes and is associated with adverse outcomes. For this reason, measurement of blood glucose (BG) is recommended for all patients at admission. Measurement of an A1C identifies patients with either newly recognized diabetes or uncontrolled diabetes. Current guidelines advise fasting and premeal BG <140 mg/dl, with maximal random BG <180 mg/dl for the majority of noncritically ill patients. Rational use of basal bolus insulin (BBI) regimens is effective in achieving these glycemic goals, with low risk for hypoglycemia. The safety of BBI relies upon provider knowledge for initiation and adjustment of insulin doses for changes in nutritional status or use of medications affecting glucose metabolism. Smooth transition of care to the outpatient setting is facilitated by providing oral and written instructions regarding timing and dosing of insulin, as well as education in basic skills for home management.

Attentional demands associated with obstacle crossing while carrying a load.

The extent to which different locomotor tasks require cognitive control is not well characterized. In this article, the authors consider the potential increase in attentional demands associated with carrying an anterior load while clearing an obstacle. Nine healthy male volunteers participated in 80 walking trials, 20 in each of 4 conditions: 1 no load condition (NL) and 3 carrying conditions (2KG, 5KG, and 10KG). Of the 20 trials in each condition, 12 included a probe reaction time (PRT) test during lead limb obstacle crossing, which was used to measure cognitive load. A load-dependent increase in PRT was observed, with PRT in the 2KG condition being significantly greater than in the NL condition, and PRT in the 5KG and 10KG conditions being significantly greater than in the 2KG condition. These results suggested that cognitive load was increased when: (a) the obstacle was occluded from vision by the load, and (b) the magnitude of load was increased.