Telehealth Intervention Programs for Seniors: An Observational Study of a Community-Embedded Health Monitoring Initiative.

Background:Chronic disease in older adults is estimated to account for 84% of annual health care spending in the United States, with many preventable costs expected to rise as the population continues to age.Introduction:Telehealth Intervention Programs for Seniors (TIPS) is a community-embedded program targeting low-income older adults, providing weekly assessment of vital signs and subjective wellness, and wrap-around aging services.Materials and Methods:TIPS recruited 765 volunteers over 55 years, who were Medicaid and/or Medicare eligible. Data were collected from 2014 to 2016 [median enrollment 343 days (105-435)] using 12 TIPS sites. This observational study evaluated the efficacy of TIPS by measuring within-subject changes in self-reported hospital visits and <30-day readmissions, before and during TIPS participation. Data of 617 participants (median age 74.3; interquartile range 16) were analyzed.Results:Self-reported hospital visits were reduced by 28.9% (p = 0.0013). Medicare participants benefited the most, with a 50% (p < 0.0001) reduction in hospital visits, and a 75.5% (p = 0.017) reduction in <30-day readmissions. Multivariate analysis revealed that participants (1) Medicaid-registered (odds ratio [OR] = 2.72, 95% confidence interval [CI] 0.392-1.611), (2) reporting feeling unwell (OR = 1.33, 95% CI 0.118-0.459), and (3) living alone (OR = 2.34, 95% CI 0.115-1.592) were significantly more likely than other participants to experience a hospital visit.Discussion:TIPS demonstrates that community-embedded health services can reduce rates of hospital visits in older adults.Conclusion:The success of TIPS highlights the potential of successfully deployed remote patient-monitoring initiatives in reducing the utilization of costly health services.

Intracranial cortical responses during visual-tactile integration in humans.

Sensory integration of touch and sight is crucial to perceiving and navigating the environment. While recent evidence from other sensory modality combinations suggests that low-level sensory areas integrate multisensory information at early processing stages, little is known about how the brain combines visual and tactile information. We investigated the dynamics of multisensory integration between vision and touch using the high spatial and temporal resolution of intracranial electrocorticography in humans. We present a novel, two-step metric for defining multisensory integration. The first step compares the sum of the unisensory responses to the bimodal response as multisensory responses. The second step eliminates the possibility that double addition of sensory responses could be misinterpreted as interactions. Using these criteria, averaged local field potentials and high-gamma-band power demonstrate a functional processing cascade whereby sensory integration occurs late, both anatomically and temporally, in the temporo-parieto-occipital junction (TPOJ) and dorsolateral prefrontal cortex. Results further suggest two neurophysiologically distinct and temporally separated integration mechanisms in TPOJ, while providing direct evidence for local suppression as a dominant mechanism for synthesizing visual and tactile input. These results tend to support earlier concepts of multisensory integration as relatively late and centered in tertiary multimodal association cortices.

Cortical feature analysis and machine learning improves detection of "MRI-negative" focal cortical dysplasia.

Focal cortical dysplasia (FCD) is the most common cause of pediatric epilepsy and the third most common lesion in adults with treatment-resistant epilepsy. Advances in MRI have revolutionized the diagnosis of FCD, resulting in higher success rates for resective epilepsy surgery. However, many patients with histologically confirmed FCD have normal presurgical MRI studies ('MRI-negative'), making presurgical diagnosis difficult. The purpose of this study was to test whether a novel MRI postprocessing method successfully detects histopathologically verified FCD in a sample of patients without visually appreciable lesions. We applied an automated quantitative morphometry approach which computed five surface-based MRI features and combined them in a machine learning model to classify lesional and nonlesional vertices. Accuracy was defined by classifying contiguous vertices as "lesional" when they fell within the surgical resection region. Our multivariate method correctly detected the lesion in 6 of 7 MRI-positive patients, which is comparable with the detection rates that have been reported in univariate vertex-based morphometry studies. More significantly, in patients that were MRI-negative, machine learning correctly identified 14 out of 24 FCD lesions (58%). This was achieved after separating abnormal thickness and thinness into distinct classifiers, as well as separating sulcal and gyral regions. Results demonstrate that MRI-negative images contain sufficient information to aid in the in vivo detection of visually elusive FCD lesions.

Structural brain imaging in children and adolescents following prenatal cocaine exposure: preliminary longitudinal findings.

The brain morphometry of 21 children, who were followed from birth and underwent structural brain magnetic resonance imaging at 8-10 years, was studied. This cohort included 11 children with prenatal cocaine exposure (CE) and 10 noncocaine-exposed children (NCE). We compared the CE versus NCE groups using FreeSurfer to automatically segment and quantify the volume of individual brain structures. In addition, we created a pediatric atlas specifically for this population and demonstrate the enhanced accuracy of this approach. We found an overall trend towards smaller brain volumes among CE children. The volume differences were significant for cortical gray matter, the thalamus and the putamen. Here, reductions in thalamic and putaminal volumes showed a robust inverse correlation with exposure levels, thus highlighting effects on dopamine-rich brain regions that form key components of brain circuitry known to play important roles in behavior and attention. Interestingly, head circumferences (HCs) at birth as well as at the time of imaging showed a tendency for smaller size among CE children. HCs at the time of imaging correlated well with the cortical volumes for all subjects. In contrast, HCs at birth were predictive of the cortical volume only for the CE group. A subgroup of these subjects (6 CE, 4 NCE) was also scanned at 13-15 years of age. In subjects who were scanned twice, we found that the trend for smaller structures continued into teenage years. We found that the differences in structural volumes between the CE and NCE groups are largely diminished when the HCs are controlled for or matched by study design. Participants in this study were drawn from a unique longitudinal cohort and, while the small sample size precludes strong conclusions regarding the longitudinal findings reported, the results point to reductions in HCs and in specific brain structures that persist through teenage years in children who were exposed to cocaine in utero.

Individual differences in verbal abilities associated with regional blurring of the left gray and white matter boundary.

Blurring of the cortical gray and white matter border on MRI is associated with normal aging, pathological aging, and the presence of focal cortical dysplasia. However, it remains unclear whether normal variations in signal intensity contrast at the gray and white matter junction reflect the functional integrity of subjacent tissue. This study explores the relationship between verbal abilities and gray and white matter contrast (GWC) in healthy human adults. Participants were scanned at 3 T MRI and administered standardized measures of verbal expression and verbal working memory. GWC was estimated by calculating the non-normalized T1 image intensity contrast above and below the cortical gray/white matter interface. Spherical averaging and whole-brain correlational analyses were performed. Sulcal regions exhibited higher contrast compared to gyral regions. We found a strongly lateralized and regionally specific profile with reduced verbal expression abilities associated with blurring in left hemisphere inferior frontal cortex and temporal pole. Reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomical substrates of cognition in healthy and diseased populations.

Individualized localization and cortical surface-based registration of intracranial electrodes.

In addition to its widespread clinical use, the intracranial electroencephalogram (iEEG) is increasingly being employed as a tool to map the neural correlates of normal cognitive function as well as for developing neuroprosthetics. Despite recent advances, and unlike other established brain-mapping modalities (e.g. functional MRI, magneto- and electroencephalography), registering the iEEG with respect to neuroanatomy in individuals-and coregistering functional results across subjects-remains a significant challenge. Here we describe a method which coregisters high-resolution preoperative MRI with postoperative computerized tomography (CT) for the purpose of individualized functional mapping of both normal and pathological (e.g., interictal discharges and seizures) brain activity. Our method accurately (within 3mm, on average) localizes electrodes with respect to an individual's neuroanatomy. Furthermore, we outline a principled procedure for either volumetric or surface-based group analyses. We demonstrate our method in five patients with medically-intractable epilepsy undergoing invasive monitoring of the seizure focus prior to its surgical removal. The straight-forward application of this procedure to all types of intracranial electrodes, robustness to deformations in both skull and brain, and the ability to compare electrode locations across groups of patients makes this procedure an important tool for basic scientists as well as clinicians.

Default mode network abnormalities in idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.

Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety.

Functional neuroimaging implicates hyperactivity of amygdala-orbitofrontal circuitry as a common neurobiological mechanism underlying the development of anxiety. Less is known about anxiety-related structural differences in this network. In this study, a sample of healthy adults with no history of anxiety disorders completed a 3T MRI scan and self-report mood inventories. Post-processing quantitative MRI image analysis included segmentation and volume estimation of subcortical structures, which were regressed on anxiety inventory scores, with depression scores used to establish discriminant validity. We then used a quantitative vertex-based post-processing method to correlate (1) anxiety scores and (2) left amygdala volumes with cortical thickness across the whole cortical mantle. Left amygdala volumes predicted anxiety, with decreased amygdala volume associated with higher anxiety on both state and trait anxiety measures. A negative correlation between left amygdala volume and cortical thickness overlapped with a positive correlation between anxiety and cortical thickness in left lateral orbitofrontal cortex. These results suggest a structural anxiety network that corresponds with a large body of evidence from functional neuroimaging. Such findings raise the possibility that structural abnormalities may result in a greater vulnerability to anxiety or conversely that elevated anxiety symptoms may result in focal structural changes.

Phonetically irregular word pronunciation and cortical thickness in the adult brain.

Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high-resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to-phonemic conversion.

Impact of breast milk on intelligence quotient, brain size, and white matter development.

Although observational findings linking breast milk to higher scores on cognitive tests may be confounded by factors associated with mothers' choice to breastfeed, it has been suggested that one or more constituents of breast milk facilitate cognitive development, particularly in preterms. Because cognitive scores are related to head size, we hypothesized that breast milk mediates cognitive effects by affecting brain growth. We used detailed data from a randomized feeding trial to calculate percentage of expressed maternal breast milk (%EBM) in the infant diet of 50 adolescents. MRI scans were obtained (mean age=15 y 9 mo), allowing volumes of total brain (TBV) and white and gray matter (WMV, GMV) to be calculated. In the total group, %EBM correlated significantly with verbal intelligence quotient (VIQ); in boys, with all IQ scores, TBV and WMV. VIQ was, in turn, correlated with WMV and, in boys only, additionally with TBV. No significant relationships were seen in girls or with gray matter. These data support the hypothesis that breast milk promotes brain development, particularly white matter growth. The selective effect in males accords with animal and human evidence regarding gender effects of early diet. Our data have important neurobiological and public health implications and identify areas for future mechanistic study.

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Regional white matter volume differences in nondemented aging and Alzheimer's disease.

Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline.

Feasibility of multi-site clinical structural neuroimaging studies of aging using legacy data.

The application of advances in biomedical computing to medical imaging research is enabling scientists to conduct quantitative clinical imaging studies using data collected across multiple sites to test new hypotheses on larger cohorts, increasing the power to detect subtle effects. Given that many research groups have valuable existing (legacy) data, one goal of the Morphometry Biomedical Informatics Research Network (BIRN) Testbed is to assess the feasibility of pooled analyses of legacy structural neuroimaging data in normal aging and Alzheimer's disease. The present study examined whether such data could be meaningfully reanalyzed as a larger combined data set by using rigorous data curation, image analysis, and statistical modeling methods; in this case, to test the hypothesis that hippocampal volume decreases with age and to investigate findings of hippocampal asymmetry. This report describes our work with legacy T1-weighted magnetic resonance (MR) and demographic data related to normal aging that have been shared through the BIRN by three research sites. Results suggest that, in the present application, legacy MR data from multiple sites can be pooled to investigate questions of scientific interest. In particular, statistical analyses suggested that a mixed-effects model employing site as a random effect best fits the data, accounting for site-specific effects while taking advantage of expected comparability of age-related effects. In the combined sample from three sites, significant age-related decline of hippocampal volume and right-dominant hippocampal asymmetry were detected in healthy elderly controls. These expected findings support the feasibility of combining legacy data to investigate novel scientific questions.

Abnormal cortical folding patterns within Broca's area in schizophrenia: evidence from structural MRI.

We compared cortical folding patterns between patients with schizophrenia and demographically-matched healthy controls in prefrontal and temporal regions of interest. Using the Freesurfer (http://surfer.nmr.mgh.harvard.edu) cortical surface-based reconstruction methodology, we indirectly ascertained cortical displacement and convolution, together, by measuring the degree of metric distortion required to optimally register cortical folding patterns to an average template. An area within the pars triangularis of the left inferior frontal gyrus (Broca's area) showed significantly reduced metric distortion in the patient group relative to the control group (p=0.0352). We discuss these findings in relation to the neurodevelopmental hypothesis and language dysfunction in schizophrenia.

The functional and structural significance of the frontal shift in the old/new ERP effect.

There is a lack of studies mapping electrophysiological event-related potentials (ERPs) to structural neuroanatomical characteristics. The aim of the present study was to integrate electrophysiological memory-related activity with cortical and hippocampal volume, as well as psychometric memory performance, in a life-span sample. More specifically, we wanted to investigate the functional significance of the often-observed frontal shift of ERP amplitude with increasing age and whether neuroanatomical characteristics can explain this shift. Sixty six healthy participants (20-78 years) went through a neuropsychological examination, MRI scans, and a visual recognition ERP task with verbal stimuli. The results showed that ERPs elicited in the recognition memory task (the old/new effect) correlated significantly with cortical volume, but not with hippocampal volume. Large cortex predicted more differentiated ERP activity and not just larger amplitude in general, implying more distinct and efficient retrieval. Furthermore, ERP amplitude, cortical volume, and hippocampal volume all predicted scores on a composite memory scale. All these relationship were dependent upon the common influence of age. Finally, the participants with the most anterior distribution of activity showed the poorest recognition memory performance. Neither cortical nor hippocampal volume were related to this frontal shift. It is concluded that the distribution of activity along the anterior-posterior axis in a memory paradigm may have functional but not neuroanatomical volumetric correlates. The functional correlates need not be restricted to the older age groups.

Effects of age on volumes of cortex, white matter and subcortical structures.

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.

Cortical volume and speed-of-processing are complementary in prediction of performance intelligence.

The rationale for the present study was to investigate the relationship between cortical volume, the latency of the ERP component P3a (as a measure of speed-of-processing), and performance intelligence (not adjusted for age differences). Seventy-one participants aged 20-88 years underwent a visual 3-stimuli oddball ERP task, an MRI-scan, and intelligence testing. P3a latency and cortical volume shared 9% variance (p<.05) and both were significantly related to performance intelligence (R2=.26 and .40, respectively). The amount of explained variance increased significantly (to R2=.51) when both measures were used as simultaneous predictors. When a path diagram was constructed including age as an exogenous variable, P3a latency and cortical volume both significantly predicted performance intelligence, but were no longer related to one another. The main conclusion from the study is that speed and size are complementary in prediction of performance intelligence, and the theoretical implications are discussed.

Orbitofrontal thickness, retention of fear extinction, and extraversion.

People differ in their personality traits and in their ability to modulate fear. Does our personality determine how well we extinguish conditioned fear responses? Or is the opposite true? Herein, we examine the relationships between personality traits, memory for fear extinction, and cortical thickness as a measure of brain structure. We found that in healthy humans, extinction retention and thickness of the medial orbitofrontal cortex are positively correlated with extraversion. Path analysis indicates that extinction retention mediates the relationship between the medial orbitofrontal cortex thickness and extraversion, thereby illustrating one path through which brain structure influences personality.

Meditation experience is associated with increased cortical thickness.

Previous research indicates that long-term meditation practice is associated with altered resting electroencephalogram patterns, suggestive of long lasting changes in brain activity. We hypothesized that meditation practice might also be associated with changes in the brain's physical structure. Magnetic resonance imaging was used to assess cortical thickness in 20 participants with extensive Insight meditation experience, which involves focused attention to internal experiences. Brain regions associated with attention, interoception and sensory processing were thicker in meditation participants than matched controls, including the prefrontal cortex and right anterior insula. Between-group differences in prefrontal cortical thickness were most pronounced in older participants, suggesting that meditation might offset age-related cortical thinning. Finally, the thickness of two regions correlated with meditation experience. These data provide the first structural evidence for experience-dependent cortical plasticity associated with meditation practice.

Cortical thickness abnormalities associated with dyslexia, independent of remediation status.

Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the "reading network." Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same "double hit" of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status.