Benjamin Zimmerman

Battery-free, stretchable optoelectronic systems for wireless optical characterization of the skin

Stretchable, wireless health monitoring patches to evaluate heart rate, blood oximetry, UV exposure, and skin coloration. Recent advances in materials, mechanics, and electronic device design are rapidly establishing the foundations for health monitoring technologies that have “skin-like” properties, with options in chronic (weeks) integration with the epidermis. The resulting capabilities in physiological sensing greatly exceed those possible with conventional hard electronic systems, such as those found in wrist-mounted wearables, because of the intimate skin interface. However, most examples of such emerging classes of devices require batteries and/or hard-wired connections to enable operation. The work reported here introduces active optoelectronic systems that function without batteries and in an entirely wireless mode, with examples in thin, stretchable platforms designed for multiwavelength optical characterization of the skin. Magnetic inductive coupling and near-field communication (NFC) schemes deliver power to multicolored light-emitting diodes and extract digital data from integrated photodetectors in ways that are compatible with standard NFC-enabled platforms, such as smartphones and tablet computers. Examples in the monitoring of heart rate and temporal dynamics of arterial blood flow, in quantifying tissue oxygenation and ultraviolet dosimetry, and in performing four-color spectroscopic evaluation of the skin demonstrate the versatility of these concepts. The results have potential relevance in both hospital care and at-home diagnostics.

Cardiorespiratory fitness mediates the effects of aging on cerebral blood flow.

The brains vasculature is likely to be subjected to the same age-related physiological and anatomical changes affecting the rest of the cardiovascular system. Since aerobic fitness is known to alleviate both cognitive and volumetric losses in the brain, it is important to investigate some of the possible mechanisms underlying these beneficial changes. Here we investigated the role that estimated cardiorespiratory fitness (eCRF) plays in determining the relationship between aging and cerebral blood flow (CBF) in a group of older adults (ages 55–85). Using arterial spin labeling to quantify CBF, we found that blood flow in the gray matter was positively correlated with eCRF and negatively correlated with age. Subsequent analyses revealed that eCRF fully mediated the effects of age on CBF in the gray matter, but not in the white matter. Additionally, regional measures of CBF were related to regional measures of brain volume. These findings provide evidence that age-related effects on cerebrovascular health and perfusion in older adults are largely influenced by their eCRF levels.

Taking the pulse of aging: Mapping pulse pressure and elasticity in cerebral arteries with optical methods

Cerebrovascular support is crucial for healthy cognitive and brain aging. Arterial stiffening is a cause of reduced brain blood flow, a predictor of cognitive decline, and a risk factor for cerebrovascular accidents and Alzheimers disease. Arterial health is influenced by lifestyle factors, such as cardiorespiratory fitness (CRF). We investigated new noninvasive optical measures of cerebrovascular health, which provide estimates of arterial pulse parameters (pulse pressure, transit time, and compliance/elasticity) within specific cerebral arteries and cortical regions, and low-resolution maps of large superficial cerebral arteries. We studied naturally occurring variability in these parameters in adults (aged 55-87), and found that these indices of cerebrovascular health are negatively correlated with age and positively with CRF and gray and white matter volumes. Further, regional pulse transit time predicts specific neuropsychological performance.

Mapping cerebral pulse pressure and arterial compliance over the adult lifespan with optical imaging

Cerebrovascular health is important for maintaining a high level of cognitive performance, not only in old age, but also throughout the lifespan. Recently, it was first demonstrated that diffuse optical imaging measures of pulse amplitude and arterial compliance can provide estimates of cerebral arterial health throughout the cortex, and were associated with age, estimated cardiorespiratory fitness (eCRF), neuroanatomy and cognitive function in older adults (aged 55–87). The current study replicates and extends the original findings using a broader age range (a new adult sample aged 18–75), longer recording periods (360 s), and a more extensive optical montage (1536 channels). These methodological improvements represent a 5-fold increase in recording time and a 4-fold increase in coverage compared to the initial study. Results show that reliability for both pulse amplitude and compliance measures across recording blocks was very high (r(45) = .99 and .75, respectively). Pulse amplitude and pulse pressure were shown to correlate with age across the broader age range. We also found correlations between arterial health and both cortical and subcortical gray matter volumes. Additionally, we replicated the correlations between arterial compliance and age, eCRF, global brain atrophy, and cognitive flexibility. New regional analyses revealed that higher performance on the operation span (OSPAN) working memory task was associated with greater localized arterial compliance in frontoparietal cortex, but not with global arterial compliance. Further, greater arterial compliance in frontoparietal regions was associated with younger age and higher eCRF. These associations were not present in the visual cortex. The current study not only replicates the initial one in a sample including a much wider age range, but also provides new evidence showing that frontoparietal regions may be especially vulnerable to vascular degeneration during brain aging, with potential functional consequences in cognition.

Optical measures of changes in cerebral vascular tone during voluntary breath holding and a Sternberg memory task

The human cerebral vasculature responds to changes in blood pressure and demands for oxygenation via cerebral autoregulation. Changes in cerebrovascular tone (vasoconstriction and vasodilation) also mediate the changes in blood flow measured by the BOLD fMRI signal. This cerebrovascular reactivity is known to vary with age. In two experiments, we demonstrate that cerebral pulse parameters measured using optical imaging can quantify changes in cerebral vascular tone, both globally and locally. In experiment 1, 51 older adults (age range=55-87) performed a voluntary breath-holding task while cerebral pulse amplitude measures were taken. We found significant pulse amplitude variations across breath-holding periods, indicating vasodilation during, and vasoconstriction after breath holding. The breath-holding index (BHI), a measure of cerebrovascular reactivity (CVR) was derived and found to correlate with age. BHI was also correlated with performance in the Modified Mini-Mental Status Examination, even after controlling for age and education. In experiment 2, the same participants performed a Sternberg task, and changes in regional pulse amplitude between high (set-size 6) and low (set-size 2) task loads were compared. Only task-related areas in the fronto-parietal network (FPN) showed significant reduction in pulse amplitude, indicating vasodilation. Non-task-related areas such as the somatosensory and auditory cortices did not show such reductions. Taken together, these experiments suggest that optical pulse parameters can index changes in brain vascular tone both globally and locally, using both physiological and cognitive load manipulations.

Comparing Aging and Fitness Effects on Brain Anatomy

Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors.

Working Memory and Aging: A Review

Abstract In this chapter, we review research on the sensory and working memory changes that typically accompany normal aging, with the view that an examination of individual differences over the lifespan can illuminate some of the mechanisms underlying working memory processes. We also discuss the theoretical frameworks used to interpret these age-related changes and provide an integrated view encompassing both behavioral and brain imaging data. Behavioral data show age-related changes in both the maintenance and attention-control aspects of working memory, suggesting a balance change between the top-down and bottom-up processing streams. Brain imaging studies provide evidence for anatomical and functional changes in the brain networks associated with working memory and the top-down control of attention.In this chapter, we review research on the sensory and working memory changes that typically accompany normal aging, with the view that an examination of individual differences over the lifespan can illuminate some of the mechanisms underlying working memory processes. We also discuss the theoretical frameworks used to interpret these age-related changes and provide an integrated view encompassing both behavioral and brain imaging data. Behavioral data show age-related changes in both the maintenance and attention-control aspects of working memory, suggesting a balance change between the top-down and bottom-up processing streams. Brain imaging studies provide evidence for anatomical and functional changes in the brain networks associated with working memory and the top-down control of attention.

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

&NA; Aging is often accompanied by changes in brain anatomy and cerebrovascular health. However, the specific relationship between declines in regional cortical volumes and loss of cerebral arterial elasticity is less clear, as only global or very localized estimates of cerebrovascular health have been available. Here we employed a novel tomographic optical method (pulse‐DOT) to derive local estimates of cerebral arterial elasticity and compared regional volumetric estimates (obtained with FreeSurfer) with optical arterial elasticity estimates from the same regions in 47 healthy adults (aged 18–75). Between‐subject analyses revealed a global correlation between cortical volume and cortical arterial elasticity, which was a significant mediator of the association between age and cortical volume. Crucially, a novel within‐subject analysis highlighted the spatial association between regional variability in cortical volumes and arterial elasticity in the same regions. This association strengthened with age. Gains in the predictability of cortical volumes from arterial elasticity data were obtained by sharpening the resolution up to individual cortical regions. These results indicate that some of the variance of sub‐clinical age‐related brain atrophy is associated with differences in the status of cerebral arteries, and can help explain the unique patterns of brain atrophy found within each individual. HighlightsPulse‐DOT is a new optical method for mapping arterial status in the brain.Aging is accompanied by arterial stiffening and brain volumetric changes.Arterial stiffness mediates age effects on brain volume.Regional variability in arterial stiffness and in volume are associated.

Dissociating tinnitus patients from healthy controls using resting-state cyclicity analysis and clustering

Chronic tinnitus is a common and sometimes debilitating condition that lacks scientific consensus on physiological models of how the condition arises as well as any known cure. In this study, we applied a novel cyclicity analysis, which studies patterns of leader-follower relationships between two signals, to resting state functional magnetic resonance imaging (rs-fMRI) data of brain regions acquired from subjects with and without tinnitus. Using the output from the cyclicity analysis, we were able to differentiate between these two groups with 58-67% accuracy using a partial least squares discriminant analysis. Stability testing yielded a 70% classification accuracy for identifying individual subjects’ data across sessions one week apart. Additional analysis revealed that the pairs of brain regions that contributed most to the dissociation between tinnitus and controls were those connected to the amygdala. In the controls, there were consistent temporal patterns across frontal, parietal, and limbic regions and amygdalar activity, whereas in tinnitus subjects, this pattern was much more variable. Our findings demonstrate a proof-of-principle for the use of cyclicity analysis of rs-fMRI data to better understand functional brain connectivity and to use it as a tool for the differentiation of patients and controls who may differ on specific traits. AUTHOR SUMMARY Chronic tinnitus is a common, yet poorly understood, condition without a known cure. Understanding differences in the functioning of brains of tinnitus patients and controls may lead to better knowledge regarding the physiology of the condition and to subsequent treatments. There are many ways to characterize relationships between neural activity in different parts of the brain. Here, we apply a novel method, called cyclicity analysis, to functional MRI data obtained from tinnitus patients and controls over a period of wakeful rest. Cyclicity analysis lends itself to interpretation as analysis of temporal orderings between elements of time-series data; it is distinct from methods like periodicity analysis or time correlation analysis in that its theoretical underpinnings are invariant to changes in time-scales of the generative process. In this proof-of-concept study, we use the feature generated from the cyclicity analysis of the fMRI data to investigate group level differences between tinnitus patients and controls. Our findings indicate that temporal ordering of regional brain activation is much more consistent in the control population than in tinnitus population. We also apply methods of classification from machine learning to differentiate between the two populations with moderate amount of success.Chronic tinnitus is a common and sometimes debilitating condition that lacks scientific consensus on physiological models of how the condition arises as well as any known cure. In this study, we applied a novel cyclicity analysis, which studies patterns of leader-follower relationships between two signals, to resting-state functional magnetic resonance imaging (rs-fMRI) data of brain regions acquired from subjects with and without tinnitus. Using the output from the cyclicity analysis, we were able to differentiate between these two groups with 58–67% accuracy by using a partial least squares discriminant analysis. Stability testing yielded a 70% classification accuracy for identifying individual subjects’ data across sessions 1 week apart. Additional analysis revealed that the pairs of brain regions that contributed most to the dissociation between tinnitus and controls were those connected to the amygdala. In the controls, there were consistent temporal patterns across frontal, parietal, and limbic regions and amygdalar activity, whereas in tinnitus subjects, this pattern was much more variable. Our findings demonstrate a proof-of-principle for the use of cyclicity analysis of rs-fMRI data to better understand functional brain connectivity and to use it as a tool for the differentiation of patients and controls who may differ on specific traits.Author SummaryChronic tinnitus is a common, yet poorly understood, condition without a known cure. Understanding differences in the functioning of brains of tinnitus patients and controls may lead to better knowledge regarding the physiology of the condition and to subsequent treatments. There are many ways to characterize relationships between neural activity in different parts of the brain. Here, we apply a novel method, called cyclicity analysis, to functional MRI data obtained from tinnitus patients and controls over a period of wakeful rest. Cyclicity analysis lends itself to interpretation as analysis of temporal orderings between elements of time-series data; it is distinct from methods like periodicity analysis or time correlation analysis in that its theoretical underpinnings are invariant to changes in time scales of the generative process. In this proof-of-concept study, we use the feature generated from the cyclicity analysis of the fMRI data to investigate group level differences between tinnitus patients and controls. Our findings indicate that temporal ordering of regional brain activation is much more consistent in the control population than in tinnitus population. We also apply methods of classification from machine learning to differentiate between the two populations with moderate amount of success.

Noninvasive imaging of cerebral blood volume in piglets with vascular occupancy MR imaging and inflow vascular space occupancy with dynamic subtraction

Accurate quantitative non-invasive assessments of arterial cerebral blood volume (aCBV) can greatly benefit the study of cerebral vascular health in both humans and in animal models. In recent years, progress has been made in the techniques available to quantify CBV with magnetic resonance imaging (MRI). Here, we compared a non-invasive technique, measuring inflowing vascular space occupancy with dynamic subtraction (iVASO-ds) with a contrast-based vascular space occupancy measurement in piglets. In addition, we measured how the iVASO-ds derived aCBV changed with piglet development from 4 weeks to 8 weeks. Our results indicate that there is a significant correlation between the non-invasive iVASO-ds derived aCBV and CBV quantified using a gadolinium contrast agent, despite the contrast-based method providing significantly higher estimates of CBV resulting from challenges inherent to using the contrast-based technique. In addition, it was possible to see significant increases in blood volume across 4 weeks to 8 weeks in pig development with the non-invasive technique. Our results suggest that the non-invasive technique, iVASO-ds can assess aCBV in the developing piglet, both cross-sectionally and longitudinally, and has significant advantages over the contrast-based quantification method.