Background: Disruptions in central autonomic processes in people with epilepsy have been studied ... more Background: Disruptions in central autonomic processes in people with epilepsy have been studied through evaluation of heart rate variability (HRV). Decreased HRV appears in epilepsy compared to healthy controls, suggesting a shift in autonomic balance toward sympathetic dominance; recent studies have associated HRV changes with seizure severity and outcome of interventions. However, the processes underlying these autonomic changes remain unclear. We examined the nature of these changes by assessing alterations in whole-brain functional connectivity, and relating those alterations to HRV.Methods: We examined regional brain activity and functional organization in 28 drug-resistant epilepsy patients and 16 healthy controls using resting-state functional magnetic resonance imaging (fMRI). We employed an HRV state-dependent functional connectivity (FC) framework with low and high HRV states derived from the following four cardiac-related variables: 1. RR interval, 2. root mean square of...
SummaryObjectiveThe processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusi... more SummaryObjectiveThe processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusive, but centrally mediated cardiovascular or respiratory collapse is suspected. Volume changes in brain areas mediating recovery from extreme cardiorespiratory challenges may indicate failure mechanisms and allow prospective identification of SUDEP risk.MethodsWe retrospectively imaged SUDEP cases (n = 25), patients comparable for age, sex, epilepsy syndrome, localization, and disease duration who were high‐risk (n = 25) or low‐risk (n = 23), and age‐ and sex‐matched healthy controls (n = 25) with identical high‐resolution T1‐weighted scans. Regional gray matter volume, determined by voxel‐based morphometry, and segmentation‐derived structure sizes were compared across groups, controlling for total intracranial volume, age, and sex.ResultsSubstantial bilateral gray matter loss appeared in SUDEP cases in the medial and lateral cerebellum. This was less prominent in high‐risk subjects and ...
Objective: To characterize regional brain metabolic differences in patients at high risk of sudde... more Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cere...
Heart failure patients show substantial gray matter loss in brain areas that mediate autonomic co... more Heart failure patients show substantial gray matter loss in brain areas that mediate autonomic control. Those injuries may lead to the aberrant autonomic patterns found in the syndrome. The purpose of this study was to determine if functional responses in the brain to an autonomic challenge would differ from normal patterns and would appear in areas of previously-demonstrated gray matter loss. We subjected 6 heart failure patients (left ventricular ejection fraction 0.15 +/- 0.08; age 49 +/- 12 years) and 16 controls (age 48 +/- 11 years) to a forehead cold pressor challenge that would enhance sympathetic outflow and assessed functional magnetic resonance image signals over the entire brain during a 54-second baseline and 90-second challenge. Application of the cold stimulus elicited aberrant responses in the anterior and posterior hypothalamus, bilateral amygdala, hippocampus, cerebellar cortex, insular cortex, mid/posterior cingulate cortex, right ventral frontal cortex, and temporal and frontal cortices. Many of the areas neighbored or overlaid regions of previously demonstrated gray matter damage. Both classical autonomic control regions, as well as brain areas modulating these sites showed deficient responses, some of which appeared to be of an overdampened or underdampened nature. The findings suggest that the earlier demonstrated changes in brain structure in heart failure result in aberrant functional neural responses; these dysfunctions may contribute to progression of the pathology in heart failure.
Heart failure (HF) is associated with aberrant autonomic nervous system (ANS) activity, with alte... more Heart failure (HF) is associated with aberrant autonomic nervous system (ANS) activity, with altered responses to blood pressure and breathing challenges that appear to reflect abnormal central nervous system function. The authors used functional magnetic resonance imaging (fMRI) to determine whether the Valsalva maneuver, an ANS challenge, would show abnormal responses in ANS regulatory areas of the brain in HF. Brain fMRI signal changes in 5 HF patients (left ventricular ejection fraction, 0.15+/-0.08; age, 50+/-10 years) and 14 controls (age, 47+/-11 years) were assessed during 3 successive Valsalva maneuvers. The hypothalamus, hippocampus, putamen, amygdala, mid-cingulate, right insula, and cerebellar cortex showed exaggerated and phase-shifted fMRI responses in HF; other areas showed inverted signals from those found in controls. Central ANS control areas have altered phase, extent, and direction of responses to Valsalva maneuvers in a small sample of HF patients. These findings suggest that therapeutics that address neuroprotective aspects may be useful interventions for the condition.
ABSTRACT Respiratory signals may provide information on the cause of Sudden Infant Death Syndrome... more ABSTRACT Respiratory signals may provide information on the cause of Sudden Infant Death Syndrome (SLDS). One pattern found in breathing signals is an amplitude modulation of the primary breathing frequency, a modulation that is non-stationary in nature. Rhythmicity, a novel measure based on the wavelet transform, has been developed to assess the impact of amplitude modulation on respiration. Rhythmicity was evaluated for epochs of breathing during quiet sleep that exhibited amplitude modulation from five infants who succumbed to SIDS and five controls matched by age, gender and birth weight. The extent of amplitude modulation in breathing was greater for infants who later died from SIDS, compared with their matched controls. Further studies can now focus on amplitude modulation of breathing to provide information on mechanisms underlying SIDS
Background: Disruptions in central autonomic processes in people with epilepsy have been studied ... more Background: Disruptions in central autonomic processes in people with epilepsy have been studied through evaluation of heart rate variability (HRV). Decreased HRV appears in epilepsy compared to healthy controls, suggesting a shift in autonomic balance toward sympathetic dominance; recent studies have associated HRV changes with seizure severity and outcome of interventions. However, the processes underlying these autonomic changes remain unclear. We examined the nature of these changes by assessing alterations in whole-brain functional connectivity, and relating those alterations to HRV.Methods: We examined regional brain activity and functional organization in 28 drug-resistant epilepsy patients and 16 healthy controls using resting-state functional magnetic resonance imaging (fMRI). We employed an HRV state-dependent functional connectivity (FC) framework with low and high HRV states derived from the following four cardiac-related variables: 1. RR interval, 2. root mean square of...
SummaryObjectiveThe processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusi... more SummaryObjectiveThe processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusive, but centrally mediated cardiovascular or respiratory collapse is suspected. Volume changes in brain areas mediating recovery from extreme cardiorespiratory challenges may indicate failure mechanisms and allow prospective identification of SUDEP risk.MethodsWe retrospectively imaged SUDEP cases (n = 25), patients comparable for age, sex, epilepsy syndrome, localization, and disease duration who were high‐risk (n = 25) or low‐risk (n = 23), and age‐ and sex‐matched healthy controls (n = 25) with identical high‐resolution T1‐weighted scans. Regional gray matter volume, determined by voxel‐based morphometry, and segmentation‐derived structure sizes were compared across groups, controlling for total intracranial volume, age, and sex.ResultsSubstantial bilateral gray matter loss appeared in SUDEP cases in the medial and lateral cerebellum. This was less prominent in high‐risk subjects and ...
Objective: To characterize regional brain metabolic differences in patients at high risk of sudde... more Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cere...
Heart failure patients show substantial gray matter loss in brain areas that mediate autonomic co... more Heart failure patients show substantial gray matter loss in brain areas that mediate autonomic control. Those injuries may lead to the aberrant autonomic patterns found in the syndrome. The purpose of this study was to determine if functional responses in the brain to an autonomic challenge would differ from normal patterns and would appear in areas of previously-demonstrated gray matter loss. We subjected 6 heart failure patients (left ventricular ejection fraction 0.15 +/- 0.08; age 49 +/- 12 years) and 16 controls (age 48 +/- 11 years) to a forehead cold pressor challenge that would enhance sympathetic outflow and assessed functional magnetic resonance image signals over the entire brain during a 54-second baseline and 90-second challenge. Application of the cold stimulus elicited aberrant responses in the anterior and posterior hypothalamus, bilateral amygdala, hippocampus, cerebellar cortex, insular cortex, mid/posterior cingulate cortex, right ventral frontal cortex, and temporal and frontal cortices. Many of the areas neighbored or overlaid regions of previously demonstrated gray matter damage. Both classical autonomic control regions, as well as brain areas modulating these sites showed deficient responses, some of which appeared to be of an overdampened or underdampened nature. The findings suggest that the earlier demonstrated changes in brain structure in heart failure result in aberrant functional neural responses; these dysfunctions may contribute to progression of the pathology in heart failure.
Heart failure (HF) is associated with aberrant autonomic nervous system (ANS) activity, with alte... more Heart failure (HF) is associated with aberrant autonomic nervous system (ANS) activity, with altered responses to blood pressure and breathing challenges that appear to reflect abnormal central nervous system function. The authors used functional magnetic resonance imaging (fMRI) to determine whether the Valsalva maneuver, an ANS challenge, would show abnormal responses in ANS regulatory areas of the brain in HF. Brain fMRI signal changes in 5 HF patients (left ventricular ejection fraction, 0.15+/-0.08; age, 50+/-10 years) and 14 controls (age, 47+/-11 years) were assessed during 3 successive Valsalva maneuvers. The hypothalamus, hippocampus, putamen, amygdala, mid-cingulate, right insula, and cerebellar cortex showed exaggerated and phase-shifted fMRI responses in HF; other areas showed inverted signals from those found in controls. Central ANS control areas have altered phase, extent, and direction of responses to Valsalva maneuvers in a small sample of HF patients. These findings suggest that therapeutics that address neuroprotective aspects may be useful interventions for the condition.
ABSTRACT Respiratory signals may provide information on the cause of Sudden Infant Death Syndrome... more ABSTRACT Respiratory signals may provide information on the cause of Sudden Infant Death Syndrome (SLDS). One pattern found in breathing signals is an amplitude modulation of the primary breathing frequency, a modulation that is non-stationary in nature. Rhythmicity, a novel measure based on the wavelet transform, has been developed to assess the impact of amplitude modulation on respiration. Rhythmicity was evaluated for epochs of breathing during quiet sleep that exhibited amplitude modulation from five infants who succumbed to SIDS and five controls matched by age, gender and birth weight. The extent of amplitude modulation in breathing was greater for infants who later died from SIDS, compared with their matched controls. Further studies can now focus on amplitude modulation of breathing to provide information on mechanisms underlying SIDS
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