scholarly journals Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

2019 ◽  
Author(s):  
Z. Mridha ◽  
J. W. de Gee ◽  
Y. Shi ◽  
R. Alkashgari ◽  
J. Williams ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Basal Forebrain ◽  
Pupil Dilation ◽  
Brain State ◽  
Brain Disorders ◽  
Treatment Resistant ◽  
Stimulation Parameters ◽  
The Moment ◽  
The Brain ◽  
Target Effects

AbstractVagus nerve stimulation (VNS) is thought to alter the state of the brain by recruiting global neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other brain disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensor for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill, and use it to show that pupil dilation is a biosensor for VNS-evoked cortical neuromodulation. In a ‘goldilocks’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in auditory cortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment titratable effects of VNS on brain state.

scholarly journals Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zakir Mridha ◽  
Jan Willem de Gee ◽  
Yanchen Shi ◽  
Rayan Alkashgari ◽  
Justin Williams ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Basal Forebrain ◽  
Pupil Dilation ◽  
Brain State ◽  
Cognitive Enhancer ◽  
Treatment Resistant ◽  
Stimulation Parameters ◽  
The Moment ◽  
Target Effects ◽  
Stimulation Of

AbstractVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an ‘optimal’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.

scholarly journals Neuroscience and the future for mental health?

2015 ◽  
Vol 25 (2) ◽  
pp. 95-100 ◽  
Author(s):  
N. Rose
Keyword(s):  
Mental Health ◽  
Mental Disorders ◽  
Mental Health Problems ◽  
Living Organism ◽  
Brain Disorders ◽  
Diagnostic Systems ◽  
Social Adversity ◽  
The Moment ◽  
The Brain

Psychiatry is in one of its regular crises. It is a crisis of its diagnostic systems despite – perhaps because – of the recurrent claims about the extent of diagnosable ‘brain disorders’. It is a crisis of its explanatory systems despite – perhaps because – of its current wager on the brain as the ultimate locus for explanations of mental disorders. It is a crisis of its therapeutic capacities despite – perhaps because – more and more people are making use of its primary mode of intervention focussed on the brain – psychiatric drugs. In this editorial, I will suggest that this triple crisis of diagnosis, explanation and therapeutics arises from the dominant reductionist approaches to the role of neurobiology in psychiatry that priorities the analysis of brain mechanisms, at the expense of an understanding of the whole living organism in its milieu, and the processes which social experience shapes neurobiology from the moment of conception if not before. I shall suggest a different approach that starts from the experience of persons coping with adversity in their forms of life. This approach does not require giving up on our search for plausible explanations of mental health problems that engage neurobiological mechanisms, but it begins from a commitment to understanding, and hence intervening in, the ways in which social adversity shapes and blights the lives of so many of our fellow citizens.

scholarly journals The Hidden Repertoire of Brain Dynamics and Dysfunction

2019 ◽  
Author(s):  
Anthony R. McIntosh ◽  
Viktor K. Jirsa
Keyword(s):  
Disease Process ◽  
Refractory Status Epilepticus ◽  
Neural System ◽  
Brain Dynamics ◽  
Brain State ◽  
Brain Disorders ◽  
Refractory Status ◽  
Neural Processes ◽  
Low Dimension ◽  
The Brain

SummaryThe purpose of this paper is to describe a framework for the understanding of rules that govern how neural system dynamics are coordinated to produce behavior. The framework, structured flows on manifolds (SFM), posits that neural processes are flows depicting system interactions that occur on relatively low-dimension manifolds, which constrain possible functional configurations. Although this is a general framework, we focus on the application to brain disorders. We first explain the Epileptor, a phenomenological computational model showing fast and slow dynamics, but also a hidden repertoire whose expression is similar to refractory status epilepticus. We suggest that epilepsy represents an innate brain state whose potential may be realized only under certain circumstances. Conversely, deficits from damage or disease processes, such as stroke or dementia, may reflect both the disease process per se and the adaptation of the brain. SFM uniquely captures both scenarios.The Hidden Repertoire of Brain Dynamics and Dysfunction

scholarly journals The hidden repertoire of brain dynamics and dysfunction

2019 ◽  
Vol 3 (4) ◽  
pp. 994-1008 ◽  
Author(s):  
Anthony R. McIntosh ◽  
Viktor K. Jirsa
Keyword(s):  
Disease Process ◽  
Refractory Status Epilepticus ◽  
Neural System ◽  
Brain State ◽  
Brain Disorders ◽  
Slow Dynamics ◽  
Refractory Status ◽  
Neural Processes ◽  
Low Dimension ◽  
The Brain

The purpose of this paper is to describe a framework for the understanding of rules that govern how neural system dynamics are coordinated to produce behavior. The framework, structured flows on manifolds (SFM), posits that neural processes are flows depicting system interactions that occur on relatively low-dimension manifolds, which constrain possible functional configurations. Although this is a general framework, we focus on the application to brain disorders. We first explain the Epileptor, a phenomenological computational model showing fast and slow dynamics, but also a hidden repertoire whose expression is similar to refractory status epilepticus . We suggest that epilepsy represents an innate brain state whose potential may be realized only under certain circumstances. Conversely, deficits from damage or disease processes, such as stroke or dementia, may reflect both the disease process per se and the adaptation of the brain. SFM uniquely captures both scenarios. Finally, we link neuromodulation effects and switches in functional network configurations to fast and slow dynamics that coordinate the expression of SFM in the context of cognition. The tools to measure and model SFM already exist, giving researchers access to the dynamics of neural processes that support the concomitant dynamics of the cognitive and behavioral processes.

8. Retrospect of Mental Philosophy (Periodical Literature.)

1880 ◽  
Vol 26 (113) ◽  
pp. 119
Author(s):  
B. F. C. Costelloe
Keyword(s):  
Periodical Literature ◽  
Main Interest ◽  
Intended Meaning ◽  
Border Line ◽  
Emotional Language ◽  
Ordinary Power ◽  
The Moment ◽  
The Brain ◽  
The Way

The first number for the year is not remarkable for any paper of striking value. Readers of the Journal will be chiefly attracted by the long and clearly written resumé of Dr. Hughlings Jackson's recent studies “On Affections of Speech from Disease of the Brain,” which is contributed by Mr. James Sully. He remarks on the great value of Dr. Jackson's attempts to classify the different forms of aphasia under the three main heads or stages of—(1) Defect of Speech, in which the patient has a full vocabulary, but confuses words; (2) Loss of Speech, in which the patient is practically speechless, and his pantomimic power is impaired as well; and (3) Loss of Language, in which, besides being speechless, he has altogether lost the power of pantomime, and even his faculty of emotional language is deeply involved in the wreck. All these states or stages again are, properly speaking, to be distinguished altogether from affections of speech in the way of loss of articulation (owing to paralysis of the tongue, &c.), or loss of vocalisation (owing to disease of the larynx); whereas the three degrees or stages of aphasia proper are due to a deep-seated and severe disorganisation of the brain. The main interest of the theory lies in the ingenious and carefully-argued analysis of the symptoms, by which Dr. Jackson arrives at the theory that as the process of destruction goes on, the superior “layers” or strata of speech fail first—those namely which involve the ordinary power of adapting sounds to the circumstances of the moment as they arise; after them fail the “more highly organized utterances” those, namely, which have in any way become automatic, such as “come on,” “wo! wo!” and even “yes” and “no,” which stand on the border-line between emotional and intellectual language; next fails the power of adapting other than vocal signs to convey an intended meaning, which is called, rather clumsily, “pantomimic propositionising;” and last of all dies out the power of uttering sounds or making signs expressive merely of emotion—a power which, of course, is not true speech at all.

scholarly journals Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Redox Homeostasis ◽  
Brain State ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

Atlas of 99mTc-HMPAO SPECT brain perfusion in pediatric brain disorders

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Saleh A Othman ◽  
Keyword(s):  
Blood Flow ◽  
Neuronal Activity ◽  
Pediatric Patients ◽  
Brain Perfusion ◽  
Brain Disorders ◽  
Hmpao Spect ◽  
Perfusion Scan ◽  
Pediatric Brain ◽  
The Brain ◽  
99Mtc Hmpao

Background: Blood flow to the brain is in parallel with brain metabolism in almost all brain disorders except in brain tumors and therefore regional cerebral blood flow can be used as a marker of metabolic brain activity and hence it is closely linked to neuronal activity, the activity distribution is presumed to reflect neuronal activity levels in different areas of the brain. Purpose: The aim of this work is to demonstrate to pediatrician in general and pediatric neurologist in particular the variations in cerebral perfusion during normal development which should be taken into consideration at the time of interpreting SPECT brain perfusion scan in different pediatric brain disorders. Method: Brain SPECT was performed 10 minutes after an intravenous injection of 11.1 MBq/kg (0.3 mCi/kg), and the minimum dose is 185 MBq (5 mCi) of 99mTc-HMPAO (4). Results: This was a retrospective analysis of SPECT brain perfusion scan of pediatric patients performed between October 2015 and December 2019 at our institution. We selected normal and abnormal studies in pediatric population with age range (5 months - 14 years). Conclusion: Although anatomic cross sectional imaging give details of neurological structural changes, SPECT perfusion mirrors indirectly both metabolic and neuronal activity changes. Therefore, accurate interpretation of SPECT perfusion will consolidate its role as part of the diagnostic protocol and used when the findings of other imaging modalities do not explain the symptoms or fail partially or completely in determining the etiology of brain disorders in pediatric patients.

scholarly journals Generation of Vascularized Brain Organoids to Study Neurovascular Interactions

2022 ◽  
Author(s):  
Zhen-Ge Luo ◽  
Xin-Yao Sun ◽  
Xiang-Chun Ju ◽  
Yang Li ◽  
Peng-Ming Zeng ◽  
...  
Keyword(s):  
Brain Development ◽  
Neural Development ◽  
Immune Cells ◽  
Aging Process ◽  
Neural Progenitors ◽  
Brain Disorders ◽  
Specific Population ◽  
Neurovascular Interactions ◽  
The Brain

The recently developed brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis, brain disorders, and aging process, limits the utility of brain organoids. In this study, we induced vessel and brain organoids respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures, and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain-barrier (BBB)-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, in particular the vasculature and microglia niche.

scholarly journals Is There a Link between Oropharyngeal Microbiome and Schizophrenia? A Narrative Review

2022 ◽  
Vol 23 (2) ◽  
pp. 846
Author(s):  
Stanislas Martin ◽  
Audrey Foulon ◽  
Wissam El Hage ◽  
Diane Dufour-Rainfray ◽  
Frédéric Denis
Keyword(s):  
Periodontal Disease ◽  
Research Team ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Future Studies ◽  
The Subject ◽  
The Moment ◽  
The Impact ◽  
The Brain

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.

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