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1.
J Biophotonics ; 17(3): e202300347, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171947

RESUMO

Non-human primates (NHPs) are crucial models for studies of neuronal activity. Emerging photoacoustic imaging modalities offer excellent tools for studying NHP brains with high sensitivity and high spatial resolution. In this research, a photoacoustic microscopy (PAM) device was used to provide a label-free quantitative characterization of cerebral hemodynamic changes due to peripheral mechanical stimulation. A 5 × 5 mm area within the somatosensory cortex region of an adult squirrel monkey was imaged. A deep, fully connected neural network was characterized and applied to the PAM images of the cortex to enhance the vessel structures after mechanical stimulation on the forelimb digits. The quality of the PAM images was improved significantly with a neural network while preserving the hemodynamic responses. The functional responses to the mechanical stimulation were characterized based on the improved PAM images. This study demonstrates capability of PAM combined with machine learning for functional imaging of the NHP brain.


Assuntos
Técnicas Fotoacústicas , Animais , Saimiri , Técnicas Fotoacústicas/métodos , Microscopia/métodos , Hemodinâmica , Neurônios
2.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38265300

RESUMO

The rostral forelimb area (RFA) in the rat is a premotor cortical region based on its dense efferent projections to primary motor cortex. This study describes corticocortical connections of RFA and the relative strength of connections with other cortical areas. The goal was to provide a better understanding of the cortical network in which RFA participates, and thus, determine its function in sensorimotor behavior. The RFA of adult male Long-Evans rats (n = 6) was identified using intracortical microstimulation techniques and injected with the tract-tracer, biotinylated dextran amine (BDA). In post-mortem tissue, locations of BDA-labeled terminal boutons and neuronal somata were plotted and superimposed on cortical field boundaries. Quantitative estimates of terminal boutons in each region of interest were based on unbiased stereological methods. The results demonstrate that RFA has dense connections with primary motor cortex and frontal cortex medial and lateral to RFA. Moderate connections were found with insular cortex, primary somatosensory cortex (S1), the M1/S1 overlap zone, and lateral somatosensory areas. Cortical connections of RFA in rat are strikingly similar to cortical connections of the ventral premotor cortex in non-human primates, suggesting that these areas share similar functions and allow greater translation of rodent premotor cortex studies to primates.


Assuntos
Córtex Motor , Ratos , Masculino , Animais , Vias Neurais/fisiologia , Ratos Long-Evans , Córtex Motor/fisiologia , Membro Anterior/fisiologia , Primatas , Mapeamento Encefálico
3.
J Biol Chem ; 299(11): 105318, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37797699

RESUMO

Collagen IV scaffold is a primordial innovation enabling the assembly of a fundamental architectural unit of epithelial tissues-a basement membrane attached to polarized cells. A family of six α-chains (α1 to α6) coassemble into three distinct protomers that form supramolecular scaffolds, noted as collagen IVα121, collagen IVα345, and collagen IVα121-α556. Chloride ions play a pivotal role in scaffold assembly, based on studies of NC1 hexamers from mammalian tissues. First, Cl- activates a molecular switch within trimeric NC1 domains that initiates protomer oligomerization, forming an NC1 hexamer between adjoining protomers. Second, Cl- stabilizes the hexamer structure. Whether this Cl--dependent mechanism is of fundamental importance in animal evolution is unknown. Here, we developed a simple in vitro method of SDS-PAGE to determine the role of solution Cl- in hexamer stability. Hexamers were characterized from 34 animal species across 15 major phyla, including the basal Cnidarian and Ctenophora phyla. We found that solution Cl- stabilized the quaternary hexamer structure across all phyla except Ctenophora, Ecdysozoa, and Rotifera. Further analysis of hexamers from peroxidasin knockout mice, a model for decreasing hexamer crosslinks, showed that solution Cl- also stabilized the hexamer surface conformation. The presence of sufficient chloride concentration in solution or "chloride pressure" dynamically maintains the native form of the hexamer. Collectively, our findings revealed that chloride pressure on the outside of cells is a primordial innovation that drives and maintains the quaternary and conformational structure of NC1 hexamers of collagen IV scaffolds.


Assuntos
Cloretos , Colágeno Tipo IV , Animais , Camundongos , Subunidades Proteicas/análise , Estrutura Terciária de Proteína , Colágeno Tipo IV/química , Membrana Basal , Mamíferos
4.
Neurorehabil Neural Repair ; 37(6): 384-393, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36636754

RESUMO

BACKGROUND: After an acquired injury to the motor cortex, the ability to generate skilled movements is impaired, leading to long-term motor impairment and disability. While rehabilitative therapy can improve outcomes in some individuals, there are no treatments currently available that are able to fully restore lost function. OBJECTIVE: We previously used activity-dependent stimulation (ADS), initiated immediately after an injury, to drive motor recovery. The objective of this study was to determine if delayed application of ADS would still lead to recovery and if the recovery would persist after treatment was stopped. METHODS: Rats received a controlled cortical impact over primary motor cortex, microelectrode arrays were implanted in ipsilesional premotor and somatosensory areas, and a custom brain-machine interface was attached to perform the ADS. Stimulation was initiated either 1, 2, or 3 weeks after injury and delivered constantly over a 4-week period. An additional group was monitored for 8 weeks after terminating ADS to assess persistence of effect. Results were compared to rats receiving no stimulation. RESULTS: ADS was delayed up to 3 weeks from injury onset and still resulted in significant motor recovery, with maximal recovery occurring in the 1-week delay group. The improvements in motor performance persisted for at least 8 weeks following the end of treatment. CONCLUSIONS: ADS is an effective method to treat motor impairments following acquired brain injury in rats. This study demonstrates the clinical relevance of this technique as it could be initiated in the post-acute period and could be explanted/ceased once recovery has occurred.


Assuntos
Transtornos Motores , Masculino , Animais , Ratos , Fatores de Tempo , Transtornos Motores/etiologia , Transtornos Motores/terapia , Córtex Motor , Lesões Encefálicas Traumáticas/complicações , Recuperação de Função Fisiológica , Comportamento Animal , Terapia por Estimulação Elétrica
5.
J Neurosci Methods ; 384: 109767, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36493978

RESUMO

BACKGROUND: Cortical electrical stimulation is a versatile technique for examining the structure and function of cortical regions and for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. NEW METHOD: Here, we sought to use intracortical microstimulation (ICMS) in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex. Neural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing. RESULTS: Multi-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomical connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state. COMPARISON WITH EXISTING METHODS: Previous imaging studies investigating cross-regional responses to stimulation are limited to utilizing indirect hemodynamic responses and thus lack the temporal specificity of ICMS-evoked responses. CONCLUSIONS: These results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity, enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.


Assuntos
Estimulação Elétrica , Estimulação Elétrica/métodos
6.
Photoacoustics ; 25: 100326, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35028289

RESUMO

The investigation of neuronal activity in non-human primate models is of critical importance due to their genetic similarity to human brains. In this study, we tested the feasibility of using photoacoustic imaging for the detection of cortical and subcortical responses due to peripheral electrical stimulation in a squirrel monkey model. Photoacoustic computed tomography and photoacoustic microscopy were applied on squirrel monkeys for real-time deep subcortical imaging and optical-resolution cortical imaging, respectively. The electrically evoked hemodynamic changes in primary somatosensory cortex, premotor cortices, primary motor cortex, and underlying subcortical areas were measured. Hemodynamic responses were observed in both cortical and subcortical brain areas at the cortices during external stimulation, demonstrating the feasibility of photoacoustic technique for functional imaging of non-human primate brain.

7.
J Neurosci Methods ; 361: 109283, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34237383

RESUMO

BACKGROUND: Technological advances in developing experimentally controlled models of traumatic brain injury (TBI) are prevalent in rodent models and these models have proven invaluable in characterizing temporal changes in brain and behavior after trauma. To date no long-term studies in non-human primates (NHPs) have been published using an experimentally controlled impact device to follow behavioral performance over time. NEW METHOD: We have employed a controlled cortical impact (CCI) device to create a focal contusion to the hand area in primary motor cortex (M1) of three New World monkeys to characterize changes in reach and grasp function assessed for 3 months after the injury. RESULTS: The CCI destroyed most of M1 hand representation reducing grey matter by 9.6 mm3, 12.9 mm3, and 15.5 mm3 and underlying corona radiata by 7.4 mm3, 6.9 mm3, and 5.6 mm3 respectively. Impaired motor function was confined to the hand contralateral to the injury. Gross hand-use was only mildly affected during the first few days of observation after injury while activity requiring skilled use of the hand was impaired over three months. COMPARISON WITH EXISTING METHOD(S): This study is unique in establishing a CCI model of TBI in an NHP resulting in persistent impairments in motor function evident in volitional use of the hand. CONCLUSIONS: Establishing an NHP model of TBI is essential to extend current rodent models to the complex neural architecture of the primate brain. Moving forward this model can be used to investigate novel therapeutic interventions to improve or restore impaired motor function after trauma.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Córtex Motor , Animais , Modelos Animais de Doenças , Força da Mão , Primatas
8.
Artigo em Inglês | MEDLINE | ID: mdl-33806314

RESUMO

BACKGROUND: Sexting is an increasingly common phenomenon among adolescents and young adults. Some studies have investigated the role of personality traits in different sexting behaviors within mainstream personality taxonomies like Big Five and HEXACO. However, very few studies have investigated the role of maladaptive personality factors in sexting. Therefore, the present study investigated the relationship between Dark Triad Personality Traits and experimental (i.e., sharing own sexts), risky (i.e., sexting under substance use and with strangers), and aggravated sexting (i.e., non-consensual sexting and sexting under pressure) across 11 countries. METHODS: An online survey was completed by 6093 participants (Mage = 20.35; SDage = 3.63) from 11 different countries which covered four continents (Europe, Asia, Africa, and America). Participants completed the Sexting Behaviors Questionnaire and the 12-item Dark Triad Dirty Dozen scale. RESULTS: Hierarchical regression analyses showed that sharing own sexts was positively predicted by Machiavellianism and Narcissism. Both risky and aggravated sexting were positively predicted by Machiavellianism and Psychopathy. CONCLUSIONS: The present study provided empirical evidence that different sexting behaviors were predicted by Dark Triad Personality Traits, showing a relevant role of Machiavellianism in all kinds of investigated sexting behaviors. Research, clinical, and education implications for prevention programs are discussed.


Assuntos
Transtorno da Personalidade Antissocial , Maquiavelismo , Adolescente , África , Transtorno da Personalidade Antissocial/epidemiologia , Ásia , Europa (Continente) , Humanos , Personalidade , Adulto Jovem
9.
Antonie Van Leeuwenhoek ; 113(1): 83-99, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31531746

RESUMO

In the last decade there has been increased interest in the manipulation of rhizosphere microbial communities in soilless systems (hydroponics) through the addition of plant growth promoting microbes (PGPMs) to increase plant nutrition, lower plant stress response, and control pathogens. This method of crop management requires documenting patterns in communities living in plant roots throughout the growing season to inform decisions on timing of application and composition of the supplemental PGPM consortium. As a contribution to this effort, we measured changes in the bacterial community through early succession (first 26 days) in plant root biofilms growing in an indoor commercial aeroponic system where roots were sprayed with a mist of nutrient-amended water. By 12 days following seed germination, a root-associated community had established that was distinct from the source communities found circulating in the system. Successional patterns in the community over the following 2 weeks (12-26 days) included changes in abundance of bacterial groups that have been documented in published literature as able to utilize plant root exudates, release plant hormones, or augment nutrient availability. Six bacterial families/genera (Hydrogenophilaceae, Rhizobium, Legionellaceae, Methylophilus, Massilia, or Herbaspirillum) were the most abundant in each root sample, comprising 8-37% of the microbiome. Given the absence of soil-associated microbial communities in hydroponic systems, they provide an ideal design for isolating plant-microbial interactions and identifying key components possibly contributing to plant health.


Assuntos
Microbiota/genética , Rizosfera , Microbiologia do Solo , Herbaspirillum/classificação , Herbaspirillum/genética , Hydrogenophilaceae/classificação , Hydrogenophilaceae/genética , Legionellaceae/classificação , Legionellaceae/genética , Methylophilus/classificação , Methylophilus/genética , Rhizobium/classificação , Rhizobium/genética
10.
Clin Toxicol (Phila) ; 58(8): 837-842, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31829049

RESUMO

Background: Therapeutic use, overdose and recreational abuse of bupropion are increasing. The purpose of this study was to describe the incidence and outcomes of bupropion exposures reported to the Ontario Poison Centre in Canada, and to identify predictors of seizures.Methods: This was a retrospective, chart review of bupropion exposures reported to the Ontario Poison Centre between 2013 and 2015. Extracted variables included demographics, formulation and dose of bupropion ingested, co-ingestants, timing of exposure, provided treatments, clinical characteristics on presentation (i.e. tachycardia, ECG changes), onset of seizures following exposure, and clinical outcomes (i.e. admission to hospital, ICU admission, intubation, death). Data were compared between patients who had a benzodiazepine co-ingestion and those that had a seizure using descriptive statistics. A multivariable logistic regression was then conducted to determine predictors of seizure.Results: In this study, there were 1,065 reported bupropion overdoses. Among patients with reported outcomes, 51.9% of patients had episodes of tachycardia, (23.9% of patients had ECG changes, and 17.3% of patients experienced a seizure. The dose of bupropion ingested was significantly associated with the odds of seizure, with a 13% increased odds of seizure for every 20 mg/kg increase in bupropion dose (Odds Ratio [OR] = 1.13, 95% CI = 1.05-1.21). Co-ingestion of benzodiazepines reduced the odds of seizure by over 60% (OR = 0.32, 95% CI = 0.15-0.69).Conclusion: Our findings contribute to the existing clinical toxicology literature by describing specific characteristics and outcomes of patients with acute bupropion overdoses. Patients were less likely to experience a seizure if they had co-ingested benzodiazepines.

11.
Clin Toxicol (Phila) ; 58(7): 736-741, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31621422

RESUMO

Background: Poisoning in pregnancy can cause maternal and neonatal morbidity and mortality, but few data detail such events. Herein, we describe poisoning exposures in pregnant women identified by a large Canadian Poison Centre.Methods: This retrospective study evaluated poisoning exposures in pregnant women aged 12-60 years, reported to the Ontario Poison Centre from 2010 to 2017. Exposures were identified from the Poison Centre database by calls received, in which the patient was also reported to be pregnant. We collected patient demographics (age, trimester, and location), as well as information about the poisoning exposure (number and type of substances, route of exposure, reason for exposure, decontamination, and treatment recommendations).Results: There were 1716 cases of poisoning exposures during pregnancy over the eight-year study period, representing 0.28% of all 619,539 calls over the period. Median maternal age was 29 years (IQR 25-33), and exposures were most frequent in the second trimester of pregnancy (41%). Unintentional exposures (n = 1397) accounted for 81% of all calls. Of the 18% of calls (n = 305) for intentional exposures, 71% (n = 219) were suspected attempted suicides. Intentional exposures were more frequent in the first (OR 2.64, 95% CI 1.85-3.76) and second trimesters (OR 1.61, 95% CI 1.13-2.28), relative to third trimester. The associated risk of intentional exposures was more likely in women aged ≤19 years (OR 21.41, 95% CI 12.75-35.94) and 20-29 years (OR 3.72, 95% CI 2.70-5.14), relative to women ≥30 years old.Conclusions: Intentional poisoning exposures in pregnancy most commonly involve young women in the first two trimesters. Population-based studies are needed to further examine risk factors for overdose, poisoning, and self-harm in pregnancy, as well as perinatal outcomes.


Assuntos
Overdose de Drogas/epidemiologia , Centros de Controle de Intoxicações/estatística & dados numéricos , Intoxicação/epidemiologia , Complicações na Gravidez/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Bases de Dados Factuais , Feminino , Humanos , Ontário , Gravidez , Trimestres da Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Health Psychol Behav Med ; 7(1): 385-395, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34040857

RESUMO

Objective: This study compared the effects of yoga and mindfulness meditation on self-compassion, mindfulness, and perceived stress in college students; and explored mind-body mechanisms and predictors of stress reduction. Participants: Student participants (N = 92) were enrolled in either yoga or mindfulness meditation classes at a college in the southern United States from August through May of 2015-2016. Methods: Students participated in 50-minute classes twice a week for 10 weeks, completing self-report questionnaires during the 1st and 10th week. Results: Multiple-linear regression analysis found change in self-compassion was the strongest predictor of stress reduction. Conclusions: Increasing self-compassion may increase the efficacy of mind-body interventions. Research into mind-body mechanisms is needed to identify intervention components that most improve student well-being.

13.
West J Emerg Med ; 19(5): 808-812, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30202491

RESUMO

INTRODUCTION: The peripheral internal jugular (IJ), also called the "easy IJ," is an alternative to peripheral venous access reserved for patients with difficult intravenous (IV) access. The procedure involves placing a single-lumen catheter in the IJ vein under ultrasound (US) guidance. As this technique is relatively new, the details regarding the ease of the procedure, how exactly it should be performed, and the safety of the procedure are uncertain. Our primary objective was to determine the success rate for peripheral IJ placement. Secondarily, we evaluated the time needed to complete the procedure and assessed for complications. METHODS: This was a prospective, single-center study of US-guided peripheral IJ placement using a 2.5-inch, 18-gauge catheter on a convenience sample of patients with at least two unsuccessful attempts at peripheral IV placement by nursing staff. Peripheral IJ lines were placed by emergency medicine (EM) attending physicians and EM residents who had completed at least five IJ central lines. All physicians who placed lines for the study watched a 15-minute lecture about peripheral IJ technique. A research assistant monitored each line to assess for complications until the patient was discharged. RESULTS: We successfully placed a peripheral IJ in 34 of 35 enrolled patients (97.1%). The median number of attempts required for successful cannulation was one (interquartile range (IQR): 1 to 2). The median time to successful line placement was 3 minutes and 6 seconds (IQR: 59 seconds to 4 minutes and 14 seconds). Two lines failed after placement, and one of the 34 successfully placed peripheral IJ lines (2.9%) had a complication - a local hematoma. There were, however, no arterial punctures or pneumothoraces. Although only eight of 34 lines were placed using sterile attire, there were no line infections. CONCLUSION: Our research adds to the growing body of evidence supporting US-guided peripheral internal jugular access as a safe and convenient procedure alternative for patients who have difficult IV access.


Assuntos
Cateterismo Venoso Central/métodos , Veias Jugulares , Ultrassonografia de Intervenção , Cateterismo Venoso Central/instrumentação , Medicina de Emergência , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
J Neurophysiol ; 118(1): 47-63, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28356482

RESUMO

Stimulus-triggered averaging (StTA) of forelimb muscle electromyographic (EMG) activity was used to investigate individual forelimb muscle representation within the primary motor cortex (M1) of rhesus macaques with the objective of determining the extent of intra-areal somatotopic organization. Two monkeys were trained to perform a reach-to-grasp task requiring multijoint coordination of the forelimb. EMG activity was simultaneously recorded from 24 forelimb muscles including 5 shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles. Microstimulation (15 µA at 15 Hz) was delivered throughout the movement task and individual stimuli were used as triggers for generating StTAs of EMG activity. StTAs were used to map the cortical representations of individual forelimb muscles. As reported previously (Park et al. 2001), cortical maps revealed a central core of distal muscle (wrist, digit, and intrinsic hand) representation surrounded by a horseshoe-shaped proximal (shoulder and elbow) muscle representation. In the present study, we found that shoulder and elbow flexor muscles were predominantly represented in the lateral branch of the horseshoe whereas extensors were predominantly represented in the medial branch. Distal muscles were represented within the core distal forelimb representation and showed extensive overlap. For the first time, we also show maps of inhibitory output from motor cortex, which follow many of the same organizational features as the maps of excitatory output.NEW & NOTEWORTHY While the orderly representation of major body parts along the precentral gyrus has been known for decades, questions have been raised about the possible existence of additional more detailed aspects of somatotopy. In this study, we have investigated this question with respect to muscles of the arm and show consistent features of within-arm (intra-areal) somatotopic organization. For the first time we also show maps of how inhibitory output from motor cortex is organized.


Assuntos
Mapeamento Encefálico , Membro Anterior/inervação , Córtex Motor/fisiologia , Músculo Esquelético/inervação , Animais , Membro Anterior/fisiologia , Força da Mão , Macaca mulatta , Masculino , Músculo Esquelético/fisiologia
16.
Cereb Cortex ; 26(7): 3036-51, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26088970

RESUMO

While a large body of evidence supports the view that ipsilateral motor cortex may make an important contribution to normal movements and to recovery of function following cortical injury (Chollet et al. 1991; Fisher 1992; Caramia et al. 2000; Feydy et al. 2002), relatively little is known about the properties of output from motor cortex to ipsilateral muscles. Our aim in this study was to characterize the organization of output effects on hindlimb muscles from ipsilateral motor cortex using stimulus-triggered averaging of EMG activity. Stimulus-triggered averages of EMG activity were computed from microstimuli applied at 60-120 µA to sites in both contralateral and ipsilateral M1 of macaque monkeys during the performance of a hindlimb push-pull task. Although the poststimulus effects (PStEs) from ipsilateral M1 were fewer in number and substantially weaker, clear and consistent effects were obtained at an intensity of 120 µA. The mean onset latency of ipsilateral poststimulus facilitation was longer than contralateral effects by an average of 0.7 ms. However, the shortest latency effects in ipsilateral muscles were as short as the shortest latency effects in the corresponding contralateral muscles suggesting a minimal synaptic linkage that is equally direct in both cases.


Assuntos
Eletromiografia , Membro Posterior/fisiologia , Atividade Motora/fisiologia , Córtex Motor/fisiologia , Músculo Esquelético/fisiologia , Animais , Estimulação Elétrica , Eletrodos Implantados , Eletromiografia/métodos , Lateralidade Funcional , Macaca mulatta , Masculino , Microeletrodos , Fatores de Tempo
17.
Artigo em Inglês | MEDLINE | ID: mdl-26236229

RESUMO

Deep brain stimulation (DBS) in the pedunculopontine tegmental nucleus (PPTg) has been proposed to alleviate medically intractable gait difficulties associated with Parkinson's disease. Clinical trials have shown somewhat variable outcomes, stemming in part from surgical targeting variability, modulating fiber pathways implicated in side effects, and a general lack of mechanistic understanding of DBS in this brain region. Subject-specific computational models of DBS are a promising tool to investigate the underlying therapy and side effects. In this study, a parkinsonian rhesus macaque was implanted unilaterally with an 8-contact DBS lead in the PPTg region. Fiber tracts adjacent to PPTg, including the oculomotor nerve, central tegmental tract, and superior cerebellar peduncle, were reconstructed from a combination of pre-implant 7T MRI, post-implant CT, and post-mortem histology. These structures were populated with axon models and coupled with a finite element model simulating the voltage distribution in the surrounding neural tissue during stimulation. This study introduces two empirical approaches to evaluate model parameters. First, incremental monopolar cathodic stimulation (20 Hz, 90 µs pulse width) was evaluated for each electrode, during which a right eyelid flutter was observed at the proximal four contacts (-1.0 to -1.4 mA). These current amplitudes followed closely with model predicted activation of the oculomotor nerve when assuming an anisotropic conduction medium. Second, PET imaging was collected OFF-DBS and twice during DBS (two different contacts), which supported the model predicted activation of the central tegmental tract and superior cerebellar peduncle. Together, subject-specific models provide a framework to more precisely predict pathways modulated by DBS.

18.
J Neurophysiol ; 113(3): 937-49, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25411454

RESUMO

The cortical control of forelimb motor function has been studied extensively, especially in the primate. In contrast, cortical control of the hindlimb has been relatively neglected. This study assessed the output properties of the primary motor cortex (M1) hindlimb representation in terms of the sign, latency, magnitude, and distribution of effects in stimulus-triggered averages (StTAs) of electromyography (EMG) activity recorded from 19 muscles, including hip, knee, ankle, digit, and intrinsic foot muscles, during a push-pull task compared with data reported previously on the forelimb. StTAs (15, 30, and 60 µA at 15 Hz) of EMG activity were computed at 317 putative layer V sites in two rhesus macaques. Poststimulus facilitation (PStF) was distributed equally between distal and proximal muscles, whereas poststimulus suppression (PStS) was more common in distal muscles than proximal muscles (51/49%, respectively, for PStF; 72/28%, respectively, for PStS) at 30 µA. Mean PStF and PStS onset latency generally increased the more distal the joint of a muscle's action. Most significantly, the average magnitude of hindlimb poststimulus effects was considerably weaker than the average magnitude of effects from forelimb M1. In addition, forelimb PStF magnitude increased consistently from proximal to distal joints, whereas hindlimb PStF magnitude was similar at all joints except the intrinsic foot muscles, which had a magnitude of approximately double that of all of the other muscles. The results suggest a greater monosynaptic input to forelimb compared with hindlimb motoneurons, as well as a more direct synaptic linkage for the intrinsic foot muscles compared with the other hindlimb muscles.


Assuntos
Potencial Evocado Motor , Membro Posterior/fisiologia , Córtex Motor/fisiologia , Músculo Esquelético/fisiologia , Animais , Membro Anterior/inervação , Membro Anterior/fisiologia , Membro Posterior/inervação , Macaca mulatta , Masculino , Músculo Esquelético/inervação , Tempo de Reação
19.
J Neurosci ; 34(5): 1647-56, 2014 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-24478348

RESUMO

The delivery of high-frequency, long-duration intracortical microstimulation (HFLD-ICMS) to primary motor cortex (M1) in primates produces hand movements to a common final end-point regardless of the starting hand position (Graziano et al., 2002). We have confirmed this general conclusion. We further investigated the extent to which the (1) temporal pattern, (2) magnitude, and (3) latency of electromyographic (EMG) activation associated with HFLD-ICMS-evoked movements are dependent on task conditions, including limb posture. HFLD-ICMS was applied to layer V sites in M1 cortex. EMG activation with HFLD-ICMS was evaluated while two male rhesus macaques performed a number of tasks in which the starting position of the hand could be varied throughout the workspace. HFLD-ICMS-evoked EMG activity was largely stable across all parameters tested independent of starting hand position. The most common temporal pattern of HFLD-ICMS-evoked EMG activity (58% of responses) was a sharp rise to a plateau. The plateau level was maintained essentially constant for the entire duration of the stimulus train. The plateau pattern is qualitatively different from the largely bell-shaped patterns typical of EMG activity associated with natural goal directed movements (Brown and Cooke, 1990; Hoffman and Strick, 1999). HFLD-ICMS produces relatively fixed parameters of muscle activation independent of limb position. We conclude that joint movement associated with HFLD-ICMS occurs as a function of the length-tension properties of stimulus-activated muscles until an equilibrium between agonist and antagonist muscle force is achieved.


Assuntos
Mapeamento Encefálico , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Movimento/fisiologia , Músculo Esquelético/fisiologia , Animais , Estimulação Elétrica , Eletromiografia , Membro Anterior/inervação , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/inervação
20.
Artigo em Inglês | MEDLINE | ID: mdl-23459919

RESUMO

The cortical control of fast and slow muscles of the ankle has been the subject of numerous reports yielding conflicting results. Although it is generally agreed that cortical stimulation yields short latency facilitation of fast muscles, the effects on the slow muscle, soleus, remain controversial. Some studies have shown predominant facilitation of soleus from the cortex while others have provided evidence of differential control in which soleus is predominantly inhibited from the cortex. The objective of this study was to investigate the cortical control of fast and slow muscles of the ankle using stimulus triggered averaging (StTA) of EMG activity, which is a sensitive method of detecting output effects on muscle activity. This method also has relatively high spatial resolution and can be applied in awake, behaving subjects. Two rhesus macaques were trained to perform a hindlimb push-pull task. Stimulus triggered averages (StTAs) of EMG activity (15, 30, and 60 µA at 15 Hz) were computed for four muscles of the ankle [tibialis anterior (TA), medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus] as the monkeys performed the task. Poststimulus facilitation (PStF) was observed in both the fast muscles (TA, MG, and LG) as well as the slow muscle (soleus) and was as common and as strong in soleus as in the fast muscles. However, while poststimulus suppression (PStS) was observed in all muscles, it was more common in the slow muscle compared to the fast muscles and was as common as facilitation at low stimulus intensities. Overall, our results demonstrate that cortical facilitation of soleus has an organization that is very similar to that of the fast ankle muscles. However, cortical inhibition is organized differently allowing for more prominent suppression of soleus motoneurons.


Assuntos
Tornozelo/inervação , Tornozelo/fisiologia , Córtex Motor/fisiologia , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Estimulação Acústica/métodos , Animais , Eletromiografia/métodos , Macaca mulatta , Masculino , Músculo Esquelético/fisiologia , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia
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