scholarly journals The Inert Brain: Explaining Neural Inertia as Post-anaesthetic Sleep Inertia

2021 ◽  
Vol 15 ◽  
Author(s):  
Andrea I. Luppi ◽  
Lennart R. B. Spindler ◽  
David K. Menon ◽  
Emmanuel A. Stamatakis
Keyword(s):  
Executive Control ◽  
Anaesthetic Induction ◽  
Elderly Individuals ◽  
Impaired Performance ◽  
Control Networks ◽  
Sleep Inertia ◽  
Drug Doses ◽  
Lower Drug ◽  
The Brain ◽  
Different Levels

“Neural inertia” is the brain’s tendency to resist changes in its arousal state: it is manifested as emergence from anaesthesia occurring at lower drug doses than those required for anaesthetic induction, a phenomenon observed across very different species, from invertebrates to mammals. However, the brain is also subject to another form of inertia, familiar to most people: sleep inertia, the feeling of grogginess, confusion and impaired performance that typically follows awakening. Here, we propose a novel account of neural inertia, as the result of sleep inertia taking place after the artificial sleep induced by anaesthetics. We argue that the orexinergic and noradrenergic systems may be key mechanisms for the control of these transition states, with the orexinergic system exerting a stabilising effect through the noradrenergic system. This effect may be reflected at the macroscale in terms of altered functional anticorrelations between default mode and executive control networks of the human brain. The hypothesised link between neural inertia and sleep inertia could explain why different anaesthetic drugs induce different levels of neural inertia, and why elderly individuals and narcoleptic patients are more susceptible to neural inertia. This novel hypothesis also enables us to generate several empirically testable predictions at both the behavioural and neural levels, with potential implications for clinical practice.

A Novel Intranasal Spray Device for the Administration of Nanoparticles to Rodents

2015 ◽  
Vol 9 (4) ◽  
Author(s):  
Justin E. Piazza ◽  
Chao Zhu ◽  
P. Ravi Selvaganapathy ◽  
Todd R. Hoare ◽  
Saransh B. Jain ◽  
...  
Keyword(s):  
Drug Carriers ◽  
Poly Ethylene Glycol ◽  
Pressure Fields ◽  
Dose Control ◽  
Fine Spray ◽  
Drug Doses ◽  
Lower Drug ◽  
Poly Ethylene ◽  
The Brain ◽  
Local Side

Experimental intranasal (IN) delivery of nanoparticle (NP) drug carriers is typically performed using a pipette with or without anesthesia, a technique that may be a poor simulation of practical IN administration of drug-loaded NPs in humans. Existing IN spray devices suffer from drawbacks in terms of variability in dose-control and spray duration as well as the application of nonuniform pressure fields when a NP-formulated drug is aerosolized. Furthermore, existing spray devices require large volumes that may not be available or may be prohibitively expensive to prepare. In response, we have developed a novel pneumatically driven IN spray device for the administration of NPs, which is capable of administering extremely small quantities (50–100 μl) of NP suspension in a fine spray that disperses the NPs uniformly onto the tissue. This device was validated using haloperidol-loaded Solanum tuberosum lectin (STL)-functionalized, poly(ethylene glycol)–block-poly(d,l-lactic-co-glycolic acid) (PEG–PLGA) NPs targeted for delivery to the brain for schizophrenia treatment. A pneumatic pressure of 100 kPa was found to be optimal to produce a spray that effectively aerosolizes NP suspensions and delivers them evenly to the olfactory epithelium. IN administration of STL-functionalized NPs using the IN spray device increased brain tissue haloperidol concentrations by a factor of 1.2–1.5× compared to STL-functionalized NPs administered IN with a pipette. Such improved delivery enables the use of lower drug doses and thus offers both fewer local side-effects and lower costs without compromising therapeutic efficacy.

Neurospect Findings in Patients Exposed to Neurotoxic Chemicals

1994 ◽  
Vol 10 (4-5) ◽  
pp. 561-571
Author(s):  
Gunnar Heuser ◽  
Ismael Mena ◽  
Francisca Alamos
Keyword(s):  
Elderly Patients ◽  
Qualitative Analysis ◽  
Right Hemisphere ◽  
Young Patients ◽  
Chronic Fatigue ◽  
Psychiatric Symptomatology ◽  
Elderly Individuals ◽  
Parietal Lobes ◽  
The Right ◽  
The Brain

Exposures to neurotoxic chemicals such as pesticides, glues, solvents, etc. are known to induce neurologic and psychiatric symptomatology. We report on 41 patients 16 young patients (6 males, 10 females, age 34 8 yrs.) and 25 elderly patients (9 males, 16 females, age 55 7 yrs). Fifteen of them were exposed to pesticides, and 29 to solvents. They were studied with quantitative and qualitative analysis of regional cerebral bood flow (rCBF), performed with 30 mCi of Xe-133 by inhalation, followed by 30 mCi of Tc-HMPAO given intravenously. Imaging was performed with a brain dedicated system, distribution of rCBF was assessed with automatic ROI definition, and HMPAO was normalized to maximal pixel activity in the brain. Results of Xe rCBF are expressed as mean and S.D. in ml/min/100g, and HMPAO as mean and S.D. uptake per ROI, and compared with age-matched controls 10 young and 20 elderly individuals. Neurotoxics HMPAO Uptake Young Elderly R. Orbital frontal R. Dorsal frontal .70 .66 p < 0.05 R. Temporal .64 p < 0.001 R. Parietal .66 .66 We conclude that patients exposed to chemicals present with diminished CBF, worse in the right hemisphere, with random presentation of areas of hypoperfusion, more prevalent in the dorsal frontal and parietal lobes. These findings are significantly different from observations in patients with chronic fatigue and depression, suggesting primary cortical effect, possibly due to a vasculitis process.

scholarly journals Using electrodermal activity to validate multilevel pain stimulation in healthy volunteers evoked by thermal grills

2020 ◽  
Vol 319 (3) ◽  
pp. R366-R375
Author(s):  
Hugo F. Posada-Quintero ◽  
Youngsun Kong ◽  
Kimberly Nguyen ◽  
Cara Tran ◽  
Luke Beardslee ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Electrodermal Activity ◽  
Pain Scale ◽  
Potential Harm ◽  
Electric Pulses ◽  
Stimulation Level ◽  
Highly Correlated ◽  
The Brain ◽  
Different Levels ◽  
Assessment Research

We have tested the feasibility of thermal grills, a harmless method to induce pain. The thermal grills consist of interlaced tubes that are set at cool or warm temperatures, creating a painful “illusion” (no tissue injury is caused) in the brain when the cool and warm stimuli are presented collectively. Advancement in objective pain assessment research is limited because the gold standard, the self-reporting pain scale, is highly subjective and only works for alert and cooperative patients. However, the main difficulty for pain studies is the potential harm caused to participants. We have recruited 23 subjects in whom we induced electric pulses and thermal grill (TG) stimulation. The TG effectively induced three different levels of pain, as evidenced by the visual analog scale (VAS) provided by the subjects after each stimulus. Furthermore, objective physiological measurements based on electrodermal activity showed a significant increase in levels as stimulation level increased. We found that VAS was highly correlated with the TG stimulation level. The TG stimulation safely elicited pain levels up to 9 out of 10. The TG stimulation allows for extending studies of pain to ranges of pain in which other stimuli are harmful.

scholarly journals Active information maintenance in working memory by a sensory cortex

2018 ◽  
Author(s):  
Xiaoxing Zhang ◽  
Wenjun Yan ◽  
Wenliang Wang ◽  
Hongmei Fan ◽  
Ruiqing Hou ◽  
...  
Keyword(s):  
Working Memory ◽  
Piriform Cortex ◽  
Delay Period ◽  
Sensory Cortex ◽  
Critical Function ◽  
Impaired Performance ◽  
Anterior Piriform Cortex ◽  
Electrophysiological Recordings ◽  
Dual Task Paradigm ◽  
The Brain

SummaryWorking memory is a critical function of the brain to maintain and manipulate information over delay periods of seconds. Sensory areas have been implicated in working memory; however, it is debated whether the delay-period activity of sensory regions is actively maintaining information or passively reflecting top-down inputs. We hereby examined the anterior piriform cortex, an olfactory cortex, in head-fixed mice performing a series of olfactory working memory tasks. Information maintenance is necessary in these tasks, especially in a dual-task paradigm in which mice are required to perform another distracting task while actively maintaining information during the delay period. Optogenetic suppression of the piriform cortex activity during the delay period impaired performance in all the tasks.Furthermore, electrophysiological recordings revealed that the delay-period activity of the anterior piriform cortex encoded odor information with or without the distracting task.Thus, this sensory cortex is critical for active information maintenance in working memory.

scholarly journals Attention controls multisensory perception via 2 distinct mechanisms at different levels of the cortical hierarchy

PLoS Biology ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. e3001465
Author(s):  
Ambra Ferrari ◽  
Uta Noppeney
Keyword(s):  
Causal Inference ◽  
Causal Structure ◽  
Multisensory Perception ◽  
Spatial Representations ◽  
Perceptual Inference ◽  
Sensory Signals ◽  
Cortical Hierarchy ◽  
Parietal Cortices ◽  
The Brain ◽  
Different Levels

To form a percept of the multisensory world, the brain needs to integrate signals from common sources weighted by their reliabilities and segregate those from independent sources. Previously, we have shown that anterior parietal cortices combine sensory signals into representations that take into account the signals’ causal structure (i.e., common versus independent sources) and their sensory reliabilities as predicted by Bayesian causal inference. The current study asks to what extent and how attentional mechanisms can actively control how sensory signals are combined for perceptual inference. In a pre- and postcueing paradigm, we presented observers with audiovisual signals at variable spatial disparities. Observers were precued to attend to auditory or visual modalities prior to stimulus presentation and postcued to report their perceived auditory or visual location. Combining psychophysics, functional magnetic resonance imaging (fMRI), and Bayesian modelling, we demonstrate that the brain moulds multisensory inference via 2 distinct mechanisms. Prestimulus attention to vision enhances the reliability and influence of visual inputs on spatial representations in visual and posterior parietal cortices. Poststimulus report determines how parietal cortices flexibly combine sensory estimates into spatial representations consistent with Bayesian causal inference. Our results show that distinct neural mechanisms control how signals are combined for perceptual inference at different levels of the cortical hierarchy.

scholarly journals The neural bases of resilient cognitive systems: Evidence of variable neuro-displacement in the semantic system

2019 ◽  
Author(s):  
JeYoung Jung ◽  
Grace E. Rice ◽  
Matthew A. Lambon Ralph
Keyword(s):  
Executive Control ◽  
Semantic Network ◽  
Neural System ◽  
Cognitive Systems ◽  
Dynamic Changes ◽  
Representational System ◽  
Control Networks ◽  
Domain Specific ◽  
Research Goal ◽  
Higher Cognitive Functions

AbstractThe purpose of this study was to initiate exploration of an equally-important research goal: what are the neurocomputational mechanisms that make these cognitive systems “well engineered” and thus resilient across a range of performance demands and to mild levels of perturbation or even damage? We achieved this aim by investigating the neural dynamics of the semantic network with two task difficulty manipulations. We found that intrinsic resilience-related mechanisms were observed in both the domain-specific semantic representational system and the parallel executive control networks. Functional connectivity between these regions was also increased and these increases were related to better semantic task performance. Our results suggest that higher cognitive functions are made resilient by flexible, dynamic changes (variable neuro-displacement) across both domain-specific and multi-demand networks. Our findings provide strong evidence that the compensatory functional alterations in the impaired brain might reflect intrinsic mechanisms of a well-engineered neural system.

scholarly journals Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

2019 ◽  
Author(s):  
Dick R Nässel ◽  
Dennis Pauls ◽  
Wolf Huetteroth
Keyword(s):  
Expression Pattern ◽  
Internal State ◽  
Neurosecretory Cells ◽  
Higher Order ◽  
Specific Expression ◽  
Specific Expression Pattern ◽  
Pleiotropic Functions ◽  
Pleiotropic Actions ◽  
The Brain ◽  
Different Levels

Neuropeptides constitute a large and diverse class of signaling molecules that are produced by many types of neurons, neurosecretory cells, endocrines and other cells. Many neuropeptides display pleiotropic actions either as neuromodulators, co-transmitters or circulating hormones, while some play these roles concurrently. Here, we highlight pleiotropic functions of neuropeptides and different levels of neuropeptide signaling in the brain, from context-dependent orchestrating signaling by higher order neurons, to local executive modulation in specific circuits. Additionally, orchestrating neurons receive peptidergic signals from neurons conveying organismal internal state cues and relay these to executive circuits. We exemplify these levels of signaling with four neuropeptides, SIFamide, short neuropeptide F, allatostatin-A and leucokinin, each with a specific expression pattern and level of complexity in signaling.

A Three-Component-System Hypothesis of Psychosis

1989 ◽  
Vol 155 (S5) ◽  
pp. 37-39 ◽  
Author(s):  
Hinderk M. Emrich
Keyword(s):  
Human Brain ◽  
Causative Factor ◽  
Microscopic Level ◽  
Point Of View ◽  
Component System ◽  
Pathogenetic Factor ◽  
Pet Scans ◽  
The Brain ◽  
Different Levels

Hypotheses as to the pathogenesis of schizophrenia can be discussed at different levels of a possible manifestation of the causative factor: the macroscopic-morphological, the microscopic-morphological, and the molecular. Some abnormalities have been observed on all of them: e.g. increased ventricular-brain ratios in CT, hypofrontality in SPECT and in glucographic PET-scans, and other macromorphological abnormalities (for reviews cf. Bogerts 1984; Mundt, 1986; Bogerts et al, 1987), gliosis on a microscopic level (Stevens, 1982), and an increased dopamine-binding in in vivo receptor studies (PET as well as in post-mortem studies; Cazzullo, 1988). However, the diversity and variability of these findings point to the view that rather than there being a single distinct pathogenetic factor responsible for the pathogenesis of schizophrenic psychoses, a constitutional disposition exists, which can be described as a functional dysequilibrium within the human brain. From this point of view, schizophrenia would not appear as an inherited disorder of metabolism, but as a weakness of a neurobiological ‘system’, i.e. as an interactional disorder of a complex of networks, in which the interaction between different substructures is labile in such a way that under special conditions (e.g. ‘stress’), a decompensation (functional breakdown) results. In this sense, ‘vulnerability’ to schizophrenia may be interpreted as a consequence of a constitutional deficiency of the brain which results in an inability to stabilise, under specially challenging conditions, the interaction between different substructures of the human brain. Before this ‘functional dysequilibrium-hypothesis’ (which is a special form of a constitutional structural deficiency-hypothesis) is discussed, and before the question is raised as to which are the relevant dysequilibrated components, some indication will be given as to why such an hypothesis appears plausible.

Resilience

2019 ◽  
pp. 286-303 ◽  
Author(s):  
Rebecca Alexander ◽  
Justine Megan Gatt
Keyword(s):  
Well Being ◽  
Neural Systems ◽  
Dynamic Interactions ◽  
Control Networks ◽  
Effective Interventions ◽  
Adaptive Recovery ◽  
The Brain ◽  
Insight Into ◽  
Over Time

Resilience refers to the process of adaptive recovery following adversity or trauma. It is likely to include an intertwined series of dynamic interactions between neural, developmental, environmental, genetic, and epigenetic factors over time. Neuroscientific research suggests the potential role of the brain’s threat and reward systems, as well as executive control networks. Developmental research provides insight into how the environment may affect these neural systems across the lifespan towards greater risk or resilience to stress. Genetic work has revealed numerous targets that alter key neurochemical systems in the brain to influence mental health. Current challenges include ambiguities in the definition and measurement of resilience and a simplified focus on resilience as the absence of psychopathology, irrespective of levels of positive mental functioning. Greater emphasis on understanding the protective aspects of resilience and related well-being outcomes are important to delineate the unique neurobiological factors that underpin this process, so that effective interventions can be developed to assist vulnerable populations and resilience promotion.

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