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BOLD sensitivity to baseline perfusion and blood volume is a well-acknowledged fMRI confound. Vascular correction techniques based on cerebrovascular reactivity (CVR) might reduce variance due to baseline cerebral blood volume, however this is predicated on an invariant linear relationship between CVR and BOLD signal magnitude. Cognitive paradigms have relatively low signal, high variance and involve spatially heterogenous cortical regions; it is therefore unclear whether the BOLD response magnitude to complex paradigms can be predicted by CVR. The feasibility of predicting BOLD signal magnitude from CVR was explored in the present work across two experiments using different CVR approaches. The first utilized a large database containing breath-hold BOLD responses and 3 different cognitive tasks. The second experiment, in an independent sample, calculated CVR using the delivery of a fixed concentration of carbon dioxide and a different cognitive task. An atlas-based regression approach was implemented for both experiments to evaluate the shared variance between task-invoked BOLD responses and CVR across the cerebral cortex. Both experiments found significant relationships between CVR and task-based BOLD magnitude, with activation in the right cuneus (R² = 0.64) and paracentral gyrus (R² = 0.71), and the left pars opercularis (R² = 0.67), superior frontal gyrus (R² = 0.62) and inferior parietal cortex (R² = 0.63) strongly predicted by CVR. The parietal regions bilaterally were highly consistent, with linear regressions significant in these regions for all four tasks. Group analyses showed that CVR correction increased BOLD sensitivity. Overall, this work suggests that BOLD signal response magnitudes to cognitive tasks are predicted by CVR across different regions of the cerebral cortex, providing support for the use of correction based on baseline vascular physiology. [ABSTRACT FROM AUTHOR]

BOLD sensitivity to baseline perfusion and blood volume is a well-acknowledged fMRI confound. Vascular correction techniques based on cerebrovascular reactivity (CVR) might reduce variance due to baseline cerebral blood volume, however this is predicated on an invariant linear relationship between CVR and BOLD signal magnitude. Cognitive paradigms have relatively low signal, high variance and involve spatially heterogenous cortical regions; it is therefore unclear whether the BOLD response magnitude to complex paradigms can be predicted by CVR. The feasibility of predicting BOLD signal magnitude from CVR was explored in the present work across two experiments using different CVR approaches. The first utilized a large database containing breath-hold BOLD responses and 3 different cognitive tasks. The second experiment, in an independent sample, calculated CVR using the delivery of a fixed concentration of carbon dioxide and a different cognitive task. An atlas-based regression approach was implemented for both experiments to evaluate the shared variance between task-invoked BOLD responses and CVR across the cerebral cortex. Both experiments found significant relationships between CVR and task-based BOLD magnitude, with activation in the right cuneus (R2 = 0.64) and paracentral gyrus (R2 = 0.71), and the left pars opercularis (R2 = 0.67), superior frontal gyrus (R2 = 0.62) and inferior parietal cortex (R2 = 0.63) strongly predicted by CVR. The parietal regions bilaterally were highly consistent, with linear regressions significant in these regions for all four tasks. Group analyses showed that CVR correction increased BOLD sensitivity. Overall, this work suggests that BOLD signal response magnitudes to cognitive tasks are predicted by CVR across different regions of the cerebral cortex, providing support for the use of correction based on baseline vascular physiology.

Background and objectives: Obesity is a risk factor for cognitive decline. Probable mechanisms involve inflammation and cerebrovascular dysfunction, leading to diminished cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). The hippocampus, crucially involved in memory processing and thus relevant to many types of dementia, poses a challenge in studies of perfusion and CVR, due to its location, small size, and complex shape. We examined the relationships between body mass index (BMI) and hippocampal resting CBF and CVR to carbon dioxide (CVRCO2) in a group of cognitively normal middle-aged and older adults. Methods: Our study was a retrospective analysis of prospectively collected data. Subjects were enrolled for studies assessing the role of hippocampal hemodynamics as a biomarker for AD among cognitively healthy elderly individuals (age > 50). Participants without cognitive impairment, stroke, and active substance abuse were recruited between January 2008 and November 2017 at the NYU Grossman School of Medicine, former Center for Brain Health. All subjects underwent medical, psychiatric, and neurological assessments, blood tests, and MRI examinations. To estimate CVR, we increased their carbon dioxide levels using a rebreathing protocol. Relationships between BMI and brain measures were tested using linear regression. Results: Our group (n = 331) consisted of 60.4% women (age 68.8 ± 7.5 years; education 16.8 ± 2.2 years) and 39.6% men (age 70.4 ± 6.4 years; education 16.9 ± 2.4 years). Approximately 22% of them (n = 73) were obese. BMI was inversely associated with CVRCO2 (β = -0.12, unstandardized B = -0.06, 95% CI -0.11, -0.004). A similar relationship was observed after excluding subjects with diabetes and insulin resistance (β = -0.15, unstandardized B = -0.08, 95% CI -0.16, -0.000). In the entire group, BMI was more strongly related to hippocampal CVRCO2 in women (β = -0.20, unstandardized B = -0.08, 95% CI -0.13, -0.02). Discussion: These findings lend support to the notion that obesity is a risk factor for hippocampal hemodynamic impairment and suggest targeting obesity as an important prevention strategy. Prospective studies assessing the effects of weight loss on brain hemodynamic measures and inflammation are warranted. [ABSTRACT FROM AUTHOR]

Functional and metabolic neural changes in Type 2 diabetes mellitus (T2DM) can be associated with poor cognitive performances. Here we analyzed the functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients. Thirty-three patients (70 _ 6 years, 15 males) with recent T2DM diagnosis and 18 healthy control (HC) subjects (65 _ 9 years, 9 males) were enrolled in a brain MRI study to identify the potential effects of T2DM on NVC. T2DM patients were either drug-naive (n = 19) or under treatment with metformin (n = 14) since less than 6 months. Arterial spin labeling and blood oxygen level dependent resting-state functional MRI (RS-fMRI) images were combined to derive NVC measures in brain regions and large-scale networks in a standard brain parcelation. Altered NVC values in T2DM patients were correlated with cognitive performances spanning several neurological domains using Spearman correlation coefficients. Compared to HC, T2DM patients had reduced NVC in the default mode network (DMN) and increased NVC in three regions of the dorsal (DAN) and salience-ventral (SVAN) attention networks. NVC abnormalities in DAN and SVAN were associated with reduced visuo-spatial cognitive performances. A spatial pattern of NVC reduction in the DMN, accompanied by isolated regional NVC increases in DAN and SVAN, could reflect the emergence of (defective) compensatory processes in T2DM patients in response to altered neurovascular conditions. Overall, this pattern is reminiscent of neural abnormalities previously observed in Alzheimer's disease, suggesting that similar neurobiological mechanisms, secondary to insulin resistance and manifesting as NVC alterations, might be developing in T2DM pathology. [ABSTRACT FROM AUTHOR]

Functional and metabolic neural changes in Type 2 diabetes mellitus (T2DM) can be associated with poor cognitive performances. Here we analyzed the functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients. Thirty-three patients (70 ± 6 years, 15 males) with recent T2DM diagnosis and 18 healthy control (HC) subjects (65 ± 9 years, 9 males) were enrolled in a brain MRI study to identify the potential effects of T2DM on NVC. T2DM patients were either drug-naive (n = 19) or under treatment with metformin (n = 14) since less than 6 months. Arterial spin labeling and blood oxygen level dependent resting-state functional MRI (RS-fMRI) images were combined to derive NVC measures in brain regions and large-scale networks in a standard brain parcelation. Altered NVC values in T2DM patients were correlated with cognitive performances spanning several neurological domains using Spearman correlation coefficients. Compared to HC, T2DM patients had reduced NVC in the default mode network (DMN) and increased NVC in three regions of the dorsal (DAN) and salience-ventral (SVAN) attention networks. NVC abnormalities in DAN and SVAN were associated with reduced visuo-spatial cognitive performances. A spatial pattern of NVC reduction in the DMN, accompanied by isolated regional NVC increases in DAN and SVAN, could reflect the emergence of (defective) compensatory processes in T2DM patients in response to altered neurovascular conditions. Overall, this pattern is reminiscent of neural abnormalities previously observed in Alzheimer’s disease, suggesting that similar neurobiological mechanisms, secondary to insulin resistance and manifesting as NVC alterations, might be developing in T2DM pathology.

Background and objectivesObesity is a risk factor for cognitive decline. Probable mechanisms involve inflammation and cerebrovascular dysfunction, leading to diminished cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). The hippocampus, crucially involved in memory processing and thus relevant to many types of dementia, poses a challenge in studies of perfusion and CVR, due to its location, small size, and complex shape. We examined the relationships between body mass index (BMI) and hippocampal resting CBF and CVR to carbon dioxide (CVRCO2) in a group of cognitively normal middle-aged and older adults.MethodsOur study was a retrospective analysis of prospectively collected data. Subjects were enrolled for studies assessing the role of hippocampal hemodynamics as a biomarker for AD among cognitively healthy elderly individuals (age > 50). Participants without cognitive impairment, stroke, and active substance abuse were recruited between January 2008 and November 2017 at the NYU Grossman School of Medicine, former Center for Brain Health. All subjects underwent medical, psychiatric, and neurological assessments, blood tests, and MRI examinations. To estimate CVR, we increased their carbon dioxide levels using a rebreathing protocol. Relationships between BMI and brain measures were tested using linear regression.ResultsOur group (n = 331) consisted of 60.4% women (age 68.8 ± 7.5 years; education 16.8 ± 2.2 years) and 39.6% men (age 70.4 ± 6.4 years; education 16.9 ± 2.4 years). Approximately 22% of them (n = 73) were obese. BMI was inversely associated with CVRCO2 (β = −0.12, unstandardized B = −0.06, 95% CI −0.11, −0.004). A similar relationship was observed after excluding subjects with diabetes and insulin resistance (β = −0.15, unstandardized B = −0.08, 95% CI −0.16, −0.000). In the entire group, BMI was more strongly related to hippocampal CVRCO2 in women (β = −0.20, unstandardized B = −0.08, 95% CI −0.13, −0.02).DiscussionThese findings lend support to the notion that obesity is a risk factor for hippocampal hemodynamic impairment and suggest targeting obesity as an important prevention strategy. Prospective studies assessing the effects of weight loss on brain hemodynamic measures and inflammation are warranted.

Older adults typically experience a decline in cognitive function, but improvements in physical health and lifestyle can be neuroprotective across the human lifespan. The primary objective of this study is to advance our basic understanding of how cardiorespiratory fitness and neurophysiological attributes relate to cognitive decline. While cerebral blood flow (CBF) is critical for the supply of nutrients to the tissue, the brain's major neurotransmitters (i.e., gamma-aminobutyric acid, GABA, and glutamateglutamine complex, Glx) are closely linked to oxidative metabolism. Within the context of flow-metabolism coupling, the critical question is how these neurophysiological parameters interplay, resulting in cognitive decline. Further, how cardiorespiratory fitness may impact aging neurophysiology and cognition is not well understood. To address these questions, we recruited 10 younger and 12 older cognitively intact participants to collect GABA and Glx using magnetic resonance spectroscopy (MRS), CBF using pseudo-continuous arterial spin labeling Magnetic Resonance Imaging (MRI), VO2max as a measure of cardiorespiratory fitness using the YMCA submax test, and cognitive and motor-cognitive measures using a battery of behavioral assessments. We observed expected differences in GABA+, Glx, and CBF between younger and older participants in pre-SMA, a frontal domain-general region. When GABA+ and Glx were related to CBF via multiple linear regression, Glx was identified as the main contributor to the model. For higher-order executive function (i.e., inhibition versus color naming), GABA-Glx-CBF interaction was critical in younger, while only Glx was involved in older participants. For unimanual motor dexterity, GABA-Glx interaction was the common denominator across both groups, but younger participants' brain also engages CBF. In terms of selective motor inhibition, CBF from younger participants was the only major neurophysiological factor. In terms of fitness, cardiorespiratory fitness was significantly related to GABA, Glx, and motor performance when combining cohorts, but no groupspecific relationships were observed. Taken together, our results indicate that Glx and CBF coupling decreases with aging, perhaps due to altered glial oxidative metabolism. Our data suggest that GABA, Glx, and CBF are engaged and weighted differently for different cognitive measures sensitized to aging, and higher fitness allows for a more efficient metabolic shift that facilitates improved performance on cognitive-motor tasks. [ABSTRACT FROM AUTHOR]

Older adults typically experience a decline in cognitive function, but improvements in physical health and lifestyle can be neuroprotective across the human lifespan. The primary objective of this study is to advance our basic understanding of how cardiorespiratory fitness and neurophysiological attributes relate to cognitive decline. While cerebral blood flow (CBF) is critical for the supply of nutrients to the tissue, the brain’s major neurotransmitters (i.e., gamma-aminobutyric acid, GABA, and glutamate-glutamine complex, Glx) are closely linked to oxidative metabolism. Within the context of flow-metabolism coupling, the critical question is how these neurophysiological parameters interplay, resulting in cognitive decline. Further, how cardiorespiratory fitness may impact aging neurophysiology and cognition is not well understood. To address these questions, we recruited 10 younger and 12 older cognitively intact participants to collect GABA and Glx using magnetic resonance spectroscopy (MRS), CBF using pseudo-continuous arterial spin labeling Magnetic Resonance Imaging (MRI), VO2max as a measure of cardiorespiratory fitness using the YMCA submax test, and cognitive and motor-cognitive measures using a battery of behavioral assessments. We observed expected differences in GABA+, Glx, and CBF between younger and older participants in pre-SMA, a frontal domain-general region. When GABA+ and Glx were related to CBF via multiple linear regression, Glx was identified as the main contributor to the model. For higher-order executive function (i.e., inhibition versus color naming), GABA*Glx*CBF interaction was critical in younger, while only Glx was involved in older participants. For unimanual motor dexterity, GABA*Glx interaction was the common denominator across both groups, but younger participants’ brain also engages CBF. In terms of selective motor inhibition, CBF from younger participants was the only major neurophysiological factor. In terms of fitness, cardiorespiratory fitness was significantly related to GABA, Glx, and motor performance when combining cohorts, but no group-specific relationships were observed. Taken together, our results indicate that Glx and CBF coupling decreases with aging, perhaps due to altered glial oxidative metabolism. Our data suggest that GABA, Glx, and CBF are engaged and weighted differently for different cognitive measures sensitized to aging, and higher fitness allows for a more efficient metabolic shift that facilitates improved performance on cognitive-motor tasks.

Background: Depression is common in Alzheimer's disease (AD) with an unclear neural mechanism. This study aimed to investigate the underlying cerebral perfusion associated with depression in AD and evaluate its clinical significance.Method: Twenty-one AD patients and 21 healthy controls (HCs) were enrolled in this study. The depressive symptom was defined according to the Hamilton Depression Rating Scale (HAMD). Nine patients were diagnosed as AD with depression symptoms (HAMD >7). Three-dimensional pseudocontinuous arterial spin labeling MR imaging was conducted to measure regional cerebral blood flow (CBF). Neuropsychological tests covered cognition and depressive scores. Between-group comparisons on clinical variables and regional CBFs, relationship between regional CBF and depressive score, and identification of AD patients with depression were performed using covariance analysis, linear regression, and receiver operating characteristic (ROC) analysis, respectively.Results: Compared with HCs, AD patients without depression exhibited lower gray matter CBF (p = 0.016); compared with AD patients without depression, AD patients with depression had higher CBF in the right supplementary motor area (39.23 vs. 47.91 ml/100 g/min, p = 0.017) and right supramarginal gyrus (35.54 vs. 43.85 ml/100 g/min, p = 0.034). CBF in the right supplementary motor area was correlated with depressive score (β = 0.46, p = 0.025). The combination of CBF in the right supplementary motor area and supramarginal gyrus and age could identify AD patients with depression from those without depression with a specificity of 100%, sensitivity of 66.67%, accuracy of 85.71%, and area under the curve of 0.87.Conclusions: Our findings suggested that hyperperfusion of the right supplementary motor area and right supramarginal gyrus were associated with depression syndrome in AD, which could provide a potential neuroimaging marker to evaluate the depression state in AD.

Background: Depression is common in Alzheimer's disease (AD) with an unclear neural mechanism. This study aimed to investigate the underlying cerebral perfusion associated with depression in AD and evaluate its clinical significance. Method: Twenty-one AD patients and 21 healthy controls (HCs) were enrolled in this study. The depressive symptom was defined according to the Hamilton Depression Rating Scale (HAMD). Nine patients were diagnosed as AD with depression symptoms (HAMD >7). Three-dimensional pseudocontinuous arterial spin labeling MR imaging was conducted to measure regional cerebral blood flow (CBF). Neuropsychological tests covered cognition and depressive scores. Between-group comparisons on clinical variables and regional CBFs, relationship between regional CBF and depressive score, and identification of AD patients with depression were performed using covariance analysis, linear regression, and receiver operating characteristic (ROC) analysis, respectively. Results: Compared with HCs, AD patients without depression exhibited lower gray matter CBF (p = 0.016); compared with AD patients without depression, AD patients with depression had higher CBF in the right supplementary motor area (39.23 vs. 47.91 ml/100 g/min, p = 0.017) and right supramarginal gyrus (35.54 vs. 43.85 ml/100 g/min, p = 0.034). CBF in the right supplementary motor area was correlated with depressive score (β = 0.46, p = 0.025). The combination of CBF in the right supplementary motor area and supramarginal gyrus and age could identify AD patients with depression from those without depression with a specificity of 100%, sensitivity of 66.67%, accuracy of 85.71%, and area under the curve of 0.87. Conclusions: Our findings suggested that hyperperfusion of the right supplementary motor area and right supramarginal gyrus were associated with depression syndrome in AD, which could provide a potential neuroimaging marker to evaluate the depression state in AD. [ABSTRACT FROM AUTHOR]

Sportive chokes are neck compression techniques applied with the goal of ending a fight by causing loss of consciousness (LOC) or voluntary submission prior to LOC. Time to LOC has been established in compliant volunteers but not in trained resisting opponents. The objective of this study was to determine the time to LOC following full establishment of chokes in trained resisting opponents. A secondary objective was to describe timing to LOC in separate choke categories. An internally validated panel of 17 sportive choking experts evaluated 89 choke sequences; 81 were included as chokes to LOC. Overall, chokes in our sample had a mean time from the establishment of a choke to LOC of 9.0 s [95% CI = 8.3, 9.9]. The choking categories of neck-only chokes and arm-in chokes were virtually identical to one another: neck-only M = 8.9 s [95% CI = 8.0–10.2]; arm-in M = 9.0 s [8.1–10.3]. These times to LOC correlate with previous studies using compliant volunteers. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF), oxygen metabolism (CMRO), and glucose metabolism (CMRGlc) were measure using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is imparied and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy. [ABSTRACT FROM AUTHOR]

Pericytes are essential for normal brain function, but many aspects of their physiology remain enigmatic due to a lack of tools to genetically target this cell population. Here, we characterize brain pericytes using two existing Cre-recombinase driver mouse lines that can serve distinct purposes in cerebrovascular research. One line expresses an inducible version of Cre under the NG2 proteoglycan promoter, which provides the sparse labeling necessary to define the morphology of single cells. These mice reveal structural differences between pericytes adjacent to arterioles versus those broadly distributed in the capillary bed that may underlie differential roles in control of vessel caliber. A second line expresses Cre constitutively under the platelet-derived growth factor receptor β promoter and provides continuous, highly specific and near-complete labeling of pericytes and myocytes along the entire cerebrovasculature. This line provides a three-dimensional view of pericyte distribution along the cortical angioarchitecture following optical clearing of brain tissue. In combination with recent reporter lines for expression of optogenetic actuators and activity-sensitive probes, these mice may be key tools for studying pericyte biology in the intact brain.