The role of the autonomic nervous system in cerebral blood flow regulation in dementia: A review

Beishon, Lucy; Hosford, Patrick S.; Brassard, Patrice; Minhas, Jatinder S; Robinson, Thompson; Haunton, Victoria J.; Panerai, Ronney B.

doi:10.1016/j.autneu.2022.102985

Cited by 17 publications

(21 citation statements)

References 115 publications

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“…Increased sympathetic activity suppresses the PNS, which contributes to the gut dysbiosis, elevating inflammation and sympathetic activity [ 21 ]. The PNS suppression is linked to memory impairment, which progresses to neurodegenerative diseases, including Alzheimer’s disease [ 18 , 22 ]. Bacteroides decreased, and Clostridium, Escherichia , and Lactobacillus increased in rats injected with scopolamine.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Gut Microbiota in Memory Impairment and Alzheimer’s Disease via the Inhibition of the Parasympathetic Nervous System

Park

2022

IJMS

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The gut microbiota has been demonstrated to play a critical role in maintaining cognitive function via the gut-brain axis, which may be related to the parasympathetic nervous system (PNS). However, the exact mechanism remains to be determined. We investigated that patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) could exhibit an altered gut microbiota through the suppression of the PNS, compared to the healthy individuals, using the combined gut microbiota data from previous human studies. The hypothesis was validated in rats to suppress the PNS by scopolamine injections. The human fecal bacterial FASTA/Q files were selected and combined from four different AD studies (n = 410). All rats had a high-fat diet and treatments for six weeks. The MD rats had memory impairment by scopolamine injection (2 mg/kg body weight; MD, Control) or no memory impairment by saline injection. The scopolamine-injected rats had a donepezil intake as the positive group. In the optimal model generated from the XGboost analysis, Blautia luti, Pseudomonas mucidoiens, Escherichia marmotae, and Gemmiger formicillis showed a positive correlation with MCI while Escherichia fergusonii, Mycobacterium neglectum, and Lawsonibacter asaccharolyticus were positively correlated with AD in the participants with enterotype Bacteroides (ET-B, n = 369). The predominant bacteria in the AD group were negatively associated in the networking analysis with the bacteria in the healthy group of ET-B participants. From the animal study, the relative abundance of Bacteroides and Bilophilia was lower, and that of Escherichia, Blautia, and Clostridium was higher in the scopolamine-induced memory deficit (MD) group than in the normal group. These results suggest that MCI was associated with the PNS suppression and could progress to AD by exacerbating the gut dysbiosis. MCI increased Clostridium and Blautia, and its progression to AD elevated Escherichia and Pseudomonas. Therefore, the modulation of the PNS might be linked to an altered gut microbiota and brain function, potentially through the gut-brain axis.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Gut Microbiota in Memory Impairment and Alzheimer’s Disease via the Inhibition of the Parasympathetic Nervous System

Park

2022

IJMS

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“…AD patients show parietal activation de cits compared to healthy older subjects during visuospatial process in, but not during a color discrimination control task (Agbangla et al, 2017). The impact of the ANA signal as recorded by GSR in our experiments is evidenced by the higher resting vagal tone being associated with improved cognitive function (Beishon et al, 2022). The prevailing pattern of autonomic disturbances in dementia is one of elevated sympathetic and depressed vagal activity.…”

Section: Brain Neural Activitymentioning

confidence: 52%

Artificial neural network analysis of Prefrontal fNIRS Blood Oxygenation Recordings

Ehleben¹,

Horschig²,

Acker³

2023

Preprint

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Noninvasive functional near infra-red spectroscopy (fNIRS) measuring brain oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) is a promising technique for studying dementia diseases. fNIRS signals are determined by cerebral and extracerebral factors as for instance neuronal activity, degree of neurovascular coupling (NVC), blood flow dependency on heart rate (HR), ventilation controlling blood oxygenation (SaO2) or autonomic nerve activity (ANA). These factors regulate different body functions such as vascular resistance in coordination with the brain. The simultaneous measurement of as many as possible anatomical and physiological factors during fNIRS of the brain is a prerequisite to interpret fNIRS signals with respect to the degree of brain tissue oxygenation. We measured brain O2Hb-HHb relation by fNIRS and four bipolar EEG recordings simultaneously with HR, blood volume changes, SaO2 and galvanic skin resistance as ANA marker. We analyzed the EEG recordings by a Fourier power analysis (delta, theta, alpha, beta, gamma frequencies). All modalities together resulted finally in 24 parameters. We investigated their probable influence on the fNIRS brain O2Hb-HHb signal. The importance of each parameter for the fNIRS signal was assessed by nonlinear regression using an artificial neural network (ANN) analysis as a new tool of fNIRS signal interpretation. We applied fNIRS to 5 healthy control patients and to 5 patients with brain disorders (BD) known to have a disturbed NVC as for instance described for Alzheimer disease. The fNIRS recordings of brain O2Hb and HHb of control patients responding to different task challenges like breath holding, odor presentation, skin touching or listening to music is mainly influenced by SaO2 and HR changes masking NVC signals due to low EEG power frequency activities as assessed by ANN. The fNIRS recordings of brain O2Hb and HHb changes of BD patients responding to the different task challenges, however, is mainly influenced by high gamma and low theta EEG power frequencies as expression of high NVC activity. Brain O2Hb-HHb relation in response to different task challenges is significantly reduced in BD patients hinting to a disturbed brain blood microcirculation. These strategies might be useful to follow up the therapeutic success cognition deficiencies in general medicine ambulance.

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“…Significantly, short-duration (<3 min) tDCS can have physiological effects in terms of the response to tES onset, which has been discussed in prior studies ( 41 , 58 ), where biological effects can extend beyond intended transient sensations ( 57 ). For example, sensory stimulation can also evoke arousal ( 6 ) with brain response ( 59 ) that can be relevant in acute stroke therapy ( 60 ) and cognitive impairment ( 61 ). However, sensory stimulation can have both beneficial and detrimental effects, viz., the potential risk from increased metabolic demand ( 60 ), where a mechanistic understanding will require physiologically detailed modeling, invasive animal studies, and systems biology approaches ( 41 ).…”

Section: Perspective On the Effects Of Transcranial Electrical Stimul...mentioning

confidence: 99%

“…The therapeutic effects of tES on brain metabolism are relevant in dementia ( 61 ) since the early stage of Alzheimer's disease (AD) shares molecular and cellular features, including insulin resistance and mitochondrial dysfunctions ( 85 ), where AD has been called “type 3 diabetes” ( 86 – 88 ). Elevated glucose levels during long-standing diabetes have been shown to induce structural and functional changes in different proteins in the body, including albumin, globulins, fibrinogen, and collagens ( 89 ).…”

Section: Perspective On the Effects Of Transcranial Electrical Stimul...mentioning

confidence: 99%

“…Both the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of AD ( 90 ). Also, cross-linking of proteins by advanced glycation end products in the vessel wall increases vascular stiffness, and modification of extracellular matrix proteins decreases pericyte adherence which can lead to neurovascular uncoupling ( 61 ) and reduced oxygen supply in the brain ( 91 ). Then, accelerated cognitive decline is postulated because of changes in small vessel structure and function, specifically expansion of the basement membrane and a loss of vascular cells ( 92 ).…”

Section: Perspective On the Effects Of Transcranial Electrical Stimul...mentioning

confidence: 99%

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Perspective: Disentangling the effects of tES on neurovascular unit

Arora

Dutta

2023

Front. Neurol.

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Transcranial electrical stimulation (tES) can modulate the neurovascular unit, including the perivascular space morphology, but the mechanisms are unclear. In this perspective article, we used an open-source “rsHRF toolbox” and an open-source functional magnetic resonance imaging (fMRI) transcranial direct current stimulation (tDCS) data set to show the effects of tDCS on the temporal profile of the haemodynamic response function (HRF). We investigated the effects of tDCS in the gray matter and at three regions of interest in the gray matter, namely, the anodal electrode (FC5), cathodal electrode (FP2), and an independent site remote from the electrodes (PZ). A “canonical HRF” with time and dispersion derivatives and a finite impulse response (FIR) model with three parameters captured the effects of anodal tDCS on the temporal profile of the HRF. The FIR model showed tDCS onset effects on the temporal profile of HRF for verum and sham tDCS conditions that were different from the no tDCS condition, which questions the validity of the sham tDCS (placebo). Here, we postulated that the effects of tDCS onset on the temporal profile of HRF are subserved by the effects on neurovascular coupling. We provide our perspective based on previous work on tES effects on the neurovascular unit, including mechanistic grey-box modeling of the effects of tES on the vasculature that can facilitate model predictive control (MPC). Future studies need to investigate grey-box modeling of online effects of tES on the neurovascular unit, including perivascular space, neurometabolic coupling, and neurovascular coupling, that can facilitate MPC of the tES dose-response to address the momentary (“state”) and phenotypic (“trait”) factors.

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The role of the autonomic nervous system in cerebral blood flow regulation in dementia: A review

Cited by 17 publications

References 115 publications

Modulation of the Gut Microbiota in Memory Impairment and Alzheimer’s Disease via the Inhibition of the Parasympathetic Nervous System

Modulation of the Gut Microbiota in Memory Impairment and Alzheimer’s Disease via the Inhibition of the Parasympathetic Nervous System

Artificial neural network analysis of Prefrontal fNIRS Blood Oxygenation Recordings

Perspective: Disentangling the effects of tES on neurovascular unit

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