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1.
Proc Natl Acad Sci U S A ; 119(50): e2208867119, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36469769

RESUMEN

As a critical node connecting the forebrain with the midbrain, the lateral habenula (LHb) processes negative feedback in response to aversive events and plays an essential role in value-based decision-making. Compulsive drug use, a hallmark of substance use disorder, is attributed to maladaptive decision-making regarding aversive drug-use-related events and has been associated with dysregulation of various frontal-midbrain circuits. To understand the contributions of frontal-habenula-midbrain circuits in the development of drug dependence, we employed a rat model of methamphetamine self-administration (SA) in the presence of concomitant footshock, which has been proposed to model compulsive drug-taking in humans. In this longitudinal study, functional MRI data were collected at pretraining baseline, after 20 d of long-access SA phase, and after 5 d of concomitant footshock coupled with SA (punishment phase). Individual differences in response to punishment were quantified by a "compulsivity index (CI)," defined as drug infusions at the end of punishment phase, normalized by those at the end of SA phase. Functional connectivity of LHb with the frontal cortices and substantia nigra (SN) after the punishment phase was positively correlated with the CI in rats that maintained drug SA despite receiving increasing-intensity footshock. In contrast, functional connectivity of the same circuits was negatively correlated with CI in rats that significantly reduced SA. These findings suggest that individual differences in compulsive drug-taking are reflected by alterations within frontal-LHb-SN circuits after experiencing the negative consequences from SA, suggesting these circuits may serve as unique biomarkers and potential therapeutic targets for individualized treatment of addiction.


Asunto(s)
Habénula , Metanfetamina , Trastornos Relacionados con Sustancias , Humanos , Ratas , Animales , Habénula/fisiología , Estudios Longitudinales , Conducta Compulsiva , Lóbulo Frontal/diagnóstico por imagen
2.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-34675078

RESUMEN

We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.


Asunto(s)
Analgésicos Opioides/efectos adversos , Cuerpo Estriado/fisiología , Motivación , Oxicodona/efectos adversos , Corteza Prefrontal/fisiología , Síndrome de Abstinencia a Sustancias/fisiopatología , Animales , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/diagnóstico por imagen , Ratas , Ratas Sprague-Dawley
3.
J Clin Nurs ; 33(5): 1976-1994, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38450810

RESUMEN

AIM: To identify and appraise the quality of evidence of transitional care interventions on quality of life in lung cancer patients. BACKGROUND: Quality of life is a strong predictor of survival. The transition from hospital to home is a high-risk period for patients' readmission and death, which seriously affect their quality of life. DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and CINAHL databases were searched from inception to 22 October 2022. The primary outcome was quality of life. Statistical analysis was conducted using Review Manager 5.4, results were expressed as standard mean difference (SMD) with a 95% confidence interval (CI). The risk of bias of the included studies was assessed using the Cochrane risk of bias assessment tool. This study was complied with PRISMA guidelines and previously registered in PROSPERO (CRD42023429464). RESULTS: Fourteen randomized controlled trials were included consisting of a total of 1700 participants, and 12 studies were included in the meta-analysis. It was found that transitional care interventions significantly improved quality of life (SMD = 0.21, 95% CI: 0.02 to 0.40, p = .03) and helped reduce symptoms (SMD = -0.65, 95% CI: -1.13 to -0.18, p = .007) in lung cancer patients, but did not significantly reduce anxiety and depression, and the effect on self-efficacy was unclear. CONCLUSIONS: This study shows that transitional care interventions can improve quality of life and reduce symptoms in patients, and that primarily educational interventions based on symptom management theory appeared to be more effective. But, there was no statistically significant effect on anxiety and depression. RELEVANCE TO CLINICAL PRACTICE: This study provides references for the application of transitional care interventions in the field of lung cancer care, and encourages nurses and physicians to apply transitional care plans to facilitate patients' safe transition from hospital to home. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.


Asunto(s)
Neoplasias Pulmonares , Cuidado de Transición , Humanos , Calidad de Vida , Neoplasias Pulmonares/terapia , Ansiedad , Trastornos de Ansiedad
4.
J Adv Nurs ; 79(8): 2802-2814, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37139550

RESUMEN

AIM: To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. METHODS: Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. RESULTS: Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. CONCLUSIONS: Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. RELEVANCE TO CLINICAL PRACTICE: It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. IMPACT: The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Automanejo , Humanos , China , Internet , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Telemedicina
5.
Proc Natl Acad Sci U S A ; 116(18): 9066-9071, 2019 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-30988198

RESUMEN

Substance use disorders (SUDs) impose severe negative impacts upon individuals, their families, and society. Clinical studies demonstrate that some chronic stimulant users are able to curtail their drug use when faced with adverse consequences while others continue to compulsively use drugs. The mechanisms underlying this dichotomy are poorly understood, which hampers the development of effective individualized treatments of a disorder that currently has no Food and Drug Administration-approved pharmacological treatments. In the present study, using a rat model of methamphetamine self-administration (SA) in the presence of concomitant foot shocks, thought to parallel compulsive drug taking by humans, we found that SA behavior correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal "go" circuit and a decreased prelimbic cortex-ventrolateral striatal "stop" circuit. Critically, this correlation was seen only in rats who continued to self-administer at a relatively high rate despite receiving foot shocks of increasing intensity. While the stop circuit functional connectivity became negative after repeated SA in all rats, "shock-resistant" rats showed strengthening of this negative connectivity after shock exposure. In contrast, "shock-sensitive" rats showed a return toward their baseline levels after shock exposure. These results may help guide novel noninvasive brain stimulation therapies aimed at restoring the physiological balance between stop and go circuits in SUDs.


Asunto(s)
Conducta Compulsiva/fisiopatología , Castigo/psicología , Trastornos Relacionados con Sustancias/psicología , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Conectoma/métodos , Cuerpo Estriado/fisiopatología , Modelos Animales de Enfermedad , Electrochoque/métodos , Masculino , Metanfetamina/farmacología , Corteza Prefrontal/fisiopatología , Ratas , Ratas Sprague-Dawley , Autoadministración , Trastornos Relacionados con Sustancias/fisiopatología
6.
Holist Nurs Pract ; 36(4): E27-E37, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35708563

RESUMEN

This meta-analysis was conducted to systematically evaluate the efficacy and safety of auricular acupressure on sleep quality in patients with lung cancer. Nine articles with a total of 802 patients were retrieved after searching on 11 electronic databases. Results of the meta-analysis showed that auricular acupressure improved sleep score (standard mean difference: -0.80, 95% confidence intervals: -1.30 to -0.30, P = .002) and reduced sleep disturbance rate (risk ratio: 0.65, 95% confidence intervals: 0.51-0.84, P = .001) and sleep medicine usage (risk ratio: 0.26, 95% confidence intervals: 0.11-0.65, P = .004) significantly. Our review suggests that auricular acupressure is effective and relatively safe in improving sleep quality among patients with lung cancer.


Asunto(s)
Acupresión , Neoplasias Pulmonares , Trastornos del Sueño-Vigilia , Acupresión/métodos , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Calidad del Sueño , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/terapia
7.
Cereb Cortex ; 30(8): 4297-4305, 2020 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-32239141

RESUMEN

The CA3 and CA1 principal cell fields of the hippocampus are vulnerable to aging, and age-related dysfunction in CA3 may be an early seed event closely linked to individual differences in memory decline. However, whether the differential vulnerability of CA3 and CA1 is associated with broader disruption in network-level functional interactions in relation to age-related memory impairment, and more specifically, whether CA3 dysconnectivity contributes to the effects of aging via CA1 network connectivity, has been difficult to test. Here, using resting-state fMRI in a group of aged rats uncontaminated by neurodegenerative disease, aged rats displayed widespread reductions in functional connectivity of CA3 and CA1 fields. Age-related memory deficits were predicted by connectivity between left CA3 and hippocampal circuitry along with connectivity between left CA1 and infralimbic prefrontal cortex. Notably, the effects of CA3 connectivity on memory performance were mediated by CA1 connectivity with prefrontal cortex. We additionally found that spatial learning and memory were associated with functional connectivity changes lateralized to the left CA3 and CA1 divisions. These results provide novel evidence that network-level dysfunction involving interactions of CA3 with CA1 is an early marker of poor cognitive outcome in aging.


Asunto(s)
Envejecimiento/fisiología , Región CA1 Hipocampal/fisiología , Región CA3 Hipocampal/fisiología , Vías Nerviosas/fisiología , Corteza Prefrontal/fisiología , Animales , Mapeo Encefálico , Imagen por Resonancia Magnética , Masculino , Memoria/fisiología , Ratas , Ratas Long-Evans , Aprendizaje Espacial/fisiología
8.
J Neurosci ; 39(25): 5028-5037, 2019 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-30992371

RESUMEN

Although 60% of the US population have tried smoking cigarettes, only 16% smoke regularly. Identifying this susceptible subset of the population before the onset of nicotine dependence may encourage targeted early interventions to prevent regular smoking and/or minimize severity. While prospective neuroimaging in human populations can be challenging, preclinical neuroimaging models before chronic nicotine administration can help to develop translational biomarkers of disease risk. Chronic, intermittent nicotine (0, 1.2, or 4.8 mg/kg/d; N = 10-11/group) was administered to male Sprague Dawley rats for 14 d; dependence severity was quantified using precipitated withdrawal behaviors collected before, during, and following forced nicotine abstinence. Resting-state fMRI functional connectivity (FC) before drug administration was subjected to a graph theory analytical framework to form a predictive model of subsequent individual differences in nicotine dependence. Whole-brain modularity analysis identified five modules in the rat brain. A metric of intermodule connectivity, participation coefficient, of an identified insular-frontal cortical module predicted subsequent dependence severity, independent of nicotine dose. To better spatially isolate this effect, this module was subjected to a secondary exploratory modularity analysis, which segregated it into three submodules (frontal-motor, insular, and sensory). Higher FC among these three submodules and three of the five originally identified modules (striatal, frontal-executive, and sensory association) also predicted dependence severity. These data suggest that predispositional, intrinsic differences in circuit strength between insular-frontal-based brain networks before drug exposure may identify those at highest risk for the development of nicotine dependence.SIGNIFICANCE STATEMENT Developing biomarkers of individuals at high risk for addiction before the onset of this brain-based disease is essential for prevention, early intervention, and/or subsequent treatment decisions. Using a rodent model of nicotine dependence and a novel data-driven, network-based analysis of resting-state fMRI data collected before drug exposure, functional connections centered on an intrinsic insular-frontal module predicted the severity of nicotine dependence after drug exposure. The predictive capacity of baseline network measures was specific to inter-regional but not within-region connectivity. While insular and frontal regions have consistently been implicated in nicotine dependence, this is the first study to reveal that innate, individual differences in their circuit strength have the predictive capacity to identify those at greatest risk for and resilience to drug dependence.


Asunto(s)
Corteza Cerebral/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Nicotina/administración & dosificación , Síndrome de Abstinencia a Sustancias/diagnóstico por imagen , Tabaquismo/diagnóstico por imagen , Animales , Corteza Cerebral/efectos de los fármacos , Lóbulo Frontal/efectos de los fármacos , Neuroimagen Funcional , Pruebas Genéticas , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/efectos de los fármacos , Nicotina/efectos adversos , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad
9.
Cereb Cortex ; 29(1): 119-133, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29161352

RESUMEN

Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to examine large-scale brain network organization and function. However, the neurophysiological basis of this spontaneous brain activity as detected by resting-state functional Magnetic Resonance Imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and blood oxygenation level-dependent (BOLD) fMRI were simultaneously recorded in the rat striatum along with local pharmacological manipulation of striatal activity. Results demonstrate that delta (δ) band LFP power negatively, while beta (ß) and gamma (γ) band LFPs positively correlated with BOLD fluctuation. Furthermore, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of δ LFPs significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduced ventral striatal functional connectivity, δ LFP-BOLD correlation, and the PAC effect. These data suggest that different frequency bands of the LFP contribute distinctively to BOLD spontaneous fluctuation and that PAC is the organizing mechanism through which low frequency LFPs orchestrate neural activity that underlies resting state functional connectivity.


Asunto(s)
Ritmo Delta/fisiología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/diagnóstico por imagen , Consumo de Oxígeno/fisiología , Descanso/fisiología , Estriado Ventral/diagnóstico por imagen , Animales , Masculino , Red Nerviosa/metabolismo , Ratas , Ratas Sprague-Dawley , Estriado Ventral/metabolismo
10.
Cereb Cortex ; 28(3): 924-935, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28108494

RESUMEN

Network analyses of structural connectivity in the brain have highlighted a set of highly connected hubs that are densely interconnected, forming a "rich-club" substrate in diverse species. Here, we demonstrate the existence of rich-club organization in functional brain networks of rats. Densely interconnected rich-club regions are found to be distributed in multiple brain modules, with the majority located within the putative default mode network. Rich-club members exhibit high wiring cost (as measured by connection distance) and high metabolic running cost (as surrogated by cerebral blood flow), which may have evolved to achieve high network communications to support efficient brain functions. Furthermore, by adopting a forepaw electrical stimulation paradigm, we find that the rich-club organization of the rat functional network remains almost the same as in the resting state, whereas path motif analysis reveals significant differences, suggesting the rat brain reorganizes its topological routes by increasing locally oriented shortcuts but reducing rich-club member-involved paths to conserve metabolic running cost during unimodal stimulation. Together, our results suggest that the neuronal system is organized and dynamically operated in an economic way to balance between cost minimization and topological/functional efficiency.


Asunto(s)
Encéfalo/fisiología , Conectoma/métodos , Modelos Neurológicos , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Animales , Encéfalo/diagnóstico por imagen , Estimulación Eléctrica , Miembro Anterior/inervación , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Oxígeno/sangre , Ratas , Ratas Sprague-Dawley
11.
Proc Natl Acad Sci U S A ; 113(43): 12286-12291, 2016 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-27791017

RESUMEN

Changes in the functional connectivity (FC) of large-scale brain networks are a prominent feature of brain aging, but defining their relationship to variability along the continuum of normal and pathological cognitive outcomes has proved challenging. Here we took advantage of a well-characterized rat model that displays substantial individual differences in hippocampal memory during aging, uncontaminated by slowly progressive, spontaneous neurodegenerative disease. By this approach, we aimed to interrogate the underlying neural network substrates that mediate aging as a uniquely permissive condition and the primary risk for neurodegeneration. Using resting state (rs) blood oxygenation level-dependent fMRI and a restrosplenial/posterior cingulate cortex seed, aged rats demonstrated a large-scale network that had a spatial distribution similar to the default mode network (DMN) in humans, consistent with earlier findings in younger animals. Between-group whole brain contrasts revealed that aged subjects with documented deficits in memory (aged impaired) displayed widespread reductions in cortical FC, prominently including many areas outside the DMN, relative to both young adults (Y) and aged rats with preserved memory (aged unimpaired, AU). Whereas functional connectivity was relatively preserved in AU rats, they exhibited a qualitatively distinct network signature, comprising the loss of an anticorrelated network observed in Y adults. Together the findings demonstrate that changes in rs-FC are specifically coupled to variability in the cognitive outcome of aging, and that successful neurocognitive aging is associated with adaptive remodeling, not simply the persistence of youthful network dynamics.


Asunto(s)
Envejecimiento/fisiología , Envejecimiento Cognitivo/fisiología , Hipocampo/fisiología , Degeneración Nerviosa/fisiopatología , Animales , Sangre , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatología , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Memoria/fisiología , Degeneración Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Ratas
12.
Proc Natl Acad Sci U S A ; 113(31): E4541-7, 2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27439860

RESUMEN

The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN. In this study, we sought to identify constituents of the rat DMN using resting-state functional MRI (rs-fMRI) and diffusion tensor imaging. After identifying DMN using a group-level independent-component analysis on the rs-fMRI data, modularity analyses fractionated the DMN into an anterior and a posterior subsystem, which were further segregated into five modules. Diffusion tensor imaging tractography demonstrates a close relationship between fiber density and the functional connectivity between DMN regions, and provides anatomical evidence to support the detected DMN subsystems. Finally, distinct modulation was seen within and between these DMN subcomponents using a neurocognitive aging model. Taken together, these results suggest that, like the human DMN, the rat DMN can be partitioned into several subcomponents that may support distinct functions. These data encourage further investigation into the neurobiological mechanisms of DMN processing in preclinical models of both normal and disease states.


Asunto(s)
Encéfalo/fisiología , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Descanso/fisiología , Animales , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Imagen de Difusión Tensora/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Modelos Animales , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Ratas Sprague-Dawley
13.
IEEE Trans Magn ; 54(5)2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-30344336

RESUMEN

Transcranial magnetic stimulation (TMS) is one of the most widely used noninvasive brain stimulation method. It has been utilized for both treatment and diagnosis of many neural diseases, such as neuropathic pain and loss of function caused by stroke. Existing TMS tools cannot deliver focused electric field to targeted penetration depth even though many important neurological disorders are originated from there. A breakthrough is needed to achieve noninvasive, focused brain stimulation. We demonstrated using magnetic shield to achieve magnetic focusing without sacrificing significant amount of throughput. The shield is composed of multiple layers of copper ring arrays, which utilize induced current to generate counter magnetic fields. We experimentally set up a two-pole stimulator system to verify device simulation. A transient magnetic field probe was used for field measurements. The focusing effect highly depends on the geometric design of shield. A tight focal spot with a diameter of smaller than 5mm (plotted in Matlab contour map) can be achieved by using copper ring arrays. With properly designed array structures and rings locations, the combined original and induced counter fields can produce a tightly focused field distribution with enhanced field strength at a depth 7.5mm beyond the shield plane, which is sufficient to reach many deep and critical parts of a mouse brain.

14.
Anesthesiology ; 127(6): 976-988, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28938276

RESUMEN

BACKGROUND: The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not. METHODS: Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats. RESULTS: Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats. CONCLUSIONS: We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.


Asunto(s)
Dexmedetomidina/administración & dosificación , Gadolinio DTPA/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Isoflurano/administración & dosificación , Transducción de Señal/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Anestésicos por Inhalación/administración & dosificación , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hipocampo/diagnóstico por imagen , Hipnóticos y Sedantes/administración & dosificación , Isoenzimas/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Imagen por Resonancia Magnética/métodos , Ratas , Ratas Endogámicas F344 , Transducción de Señal/fisiología
15.
Cereb Cortex ; 26(2): 683-694, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25331598

RESUMEN

Resting-state magnetic resonance imaging (rsMRI) is thought to reflect ongoing spontaneous brain activity. However, the precise neurophysiological basis of rsMRI signal remains elusive. Converging evidence supports the notion that local field potential (LFP) signal in the high-frequency range correlates with fMRI response evoked by a task (e.g., visual stimulation). It remains uncertain whether this relationship extends to rsMRI. In this study, we systematically modulated LFP signal in the whisker barrel cortex (WBC) by unilateral deflection of rat whiskers. Results show that functional connectivity between bilateral WBC was significantly modulated at the 2 Hz, but not at the 4 or 6 Hz, stimulus condition. Electrophysiologically, only in the low-frequency range (<5 Hz) was the LFP power synchrony in bilateral WBC significantly modulated at 2 Hz, but not at 4- or 6-Hz whisker stimulation, thus distinguishing these 2 experimental conditions, and paralleling the findings in rsMRI. LFP power synchrony in other frequency ranges was modulated in a way that was neither unique to the specific stimulus conditions nor parallel to the fMRI results. Our results support the hypothesis that emphasizes the role of low-frequency LFP signal underlying rsMRI.


Asunto(s)
Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Vibrisas/inervación , Animales , Biofisica , Dexmedetomidina/farmacología , Electroencefalografía , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Análisis de Fourier , Lateralidad Funcional/efectos de los fármacos , Lateralidad Funcional/fisiología , Hipnóticos y Sedantes/farmacología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Oxígeno/sangre , Estimulación Física , Ratas , Ratas Sprague-Dawley
16.
Proc Natl Acad Sci U S A ; 110(10): 4093-8, 2013 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-23431137

RESUMEN

Chronic drug administration induces neuroplastic changes within brain circuits regulating cognitive control and/or emotions. Following repeated pairings between drug intake and environmental cues, increased sensitivity to or salience of these contextual cues provoke conscious or unconscious craving and enhance susceptibility to relapse. To explore brain circuits participating in such experience-induced plasticity, we combined functional MRI with a preclinical drug vs. food self-administration (SA) withdrawal model. Specifically, two groups of rats were trained to associate odor cues with the availability of i.v. cocaine or oral sucrose, respectively. After 20 d of cocaine or sucrose SA followed by prolonged (30 d) forced abstinence, animals were presented with odor cues previously associated with or without (S+/S-) reinforcer (cocaine/sucrose) availability while undergoing functional MRI scans. ANOVA results demonstrate that a learning effect distinguishing S+ from S- was seen in the insula and nucleus accumbens, with the insula response reflecting the individual history of cocaine SA intake. A main effect of group, distinguishing cocaine from sucrose, was seen in the medial prefrontal cortex (infralimbic, prelimbic, and cingulate cortex) and dorsolateral striatum. Critically, only the dorsomedial striatum demonstrated a double dissociation between the two SA groups and learning (S+ vs. S-). These findings demonstrate altered cortico-limbic-striatal reward-related processing to learned, environment reward-associated contextual odor cues, which may serve as potential biomarkers for therapeutic interventions.


Asunto(s)
Núcleo Caudado/fisiología , Cocaína/administración & dosificación , Recompensa , Animales , Trastornos Relacionados con Cocaína/fisiopatología , Trastornos Relacionados con Cocaína/psicología , Señales (Psicología) , Aprendizaje Discriminativo/fisiología , Imagen por Resonancia Magnética , Masculino , Modelos Neurológicos , Modelos Psicológicos , Plasticidad Neuronal/fisiología , Odorantes , Ratas , Ratas Long-Evans , Autoadministración , Olfato/fisiología , Corteza Visual/fisiología
17.
Proc Natl Acad Sci U S A ; 109(10): 3979-84, 2012 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-22355129

RESUMEN

The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function(s) remains poorly understood. We show that rats possess a DMN that is broadly similar to the DMNs of nonhuman primates and humans. Our data suggest that, despite the distinct evolutionary paths between rodent and primate brain, a well-organized, intrinsically coherent DMN appears to be a fundamental feature in the mammalian brain whose primary functions might be to integrate multimodal sensory and affective information to guide behavior in anticipation of changing environmental contingencies.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/metabolismo , Animales , Conducta Animal , Encéfalo/patología , Encéfalo/fisiología , Haplorrinos , Humanos , Imagen por Resonancia Magnética/métodos , Modelos Anatómicos , Modelos Biológicos , Vías Nerviosas , Ratas , Especificidad de la Especie
18.
J Neurosci ; 33(42): 16796-804, 2013 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-24133280

RESUMEN

Resting-state functional MRI is a powerful tool that is increasingly used as a noninvasive method for investigating whole-brain circuitry and holds great potential as a possible diagnostic for disease. Despite this potential, few resting-state studies have used animal models (of which nonhuman primates represent our best opportunity of understanding complex human neuropsychiatric disease), and no work has characterized networks in awake, truly resting animals. Here we present results from a small New World monkey that allows for the characterization of resting-state networks in the awake state. Six adult common marmosets (Callithrix jacchus) were acclimated to light, comfortable restraint using individualized helmets. Following behavioral training, resting BOLD data were acquired during eight consecutive 10 min scans for each conscious subject. Group independent component analysis revealed 12 brain networks that overlap substantially with known anatomically constrained circuits seen in the awake human. Specifically, we found eight sensory and "lower-order" networks (four visual, two somatomotor, one cerebellar, and one caudate-putamen network), and four "higher-order" association networks (one default mode-like network, one orbitofrontal, one frontopolar, and one network resembling the human salience network). In addition to their functional relevance, these network patterns bear great correspondence to those previously described in awake humans. This first-of-its-kind report in an awake New World nonhuman primate provides a platform for mechanistic neurobiological examination for existing disease models established in the marmoset.


Asunto(s)
Encéfalo/fisiología , Callithrix/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Descanso/fisiología , Vigilia/fisiología , Animales , Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino
19.
Magn Reson Med ; 72(5): 1311-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24301336

RESUMEN

PURPOSE: Despite the efforts that have been devoted to detecting the transient magnetic fields generated by neuronal firing, the conclusion that a functionally relevant signal can be measured with MRI is still controversial. For human studies of neuronal current MRI (nc-MRI), the blood-oxygen-level-dependent (BOLD) effect remains an irresolvable confound. For tissue studies where hemoglobin is removed, natural sensory stimulation is not possible. This study investigates the feasibility of detecting a physiologically induced nc-MRI signal in vivo in a BOLD-free environment. METHODS: The cephalopod mollusc Octopus bimaculoides has vertebrate-like eyes, large optic lobes (OLs), and blood that does not contain hemoglobin. Visually evoked potentials were measured in the octopus retina and OL by electroretinogram and local field potential. nc-MRI scans were conducted at 9.4 Tesla to capture these activities. RESULTS: Electrophysiological recording detected strong responses in the retina and OL in vivo; however, nc-MRI failed to demonstrate any statistically significant signal change with a detection threshold of 0.2° for phase and 0.2% for magnitude. Experiments in a dissected eye-OL preparation yielded similar results. CONCLUSION: These findings in a large hemoglobin-free nervous system suggest that sensory evoked neuronal magnetic fields are too weak for direct detection with current MRI technology.


Asunto(s)
Potenciales Evocados Visuales/fisiología , Imagen por Resonancia Magnética/métodos , Retina/fisiología , Animales , Imagen Eco-Planar , Electrorretinografía , Femenino , Procesamiento de Imagen Asistido por Computador , Octopodiformes , Estimulación Luminosa
20.
Complement Ther Clin Pract ; 55: 101849, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522328

RESUMEN

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Calidad de Vida , Estudios Prospectivos , Disnea
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