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1.
Cell ; 181(2): 396-409.e26, 2020 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-32220308

RESUMEN

Decades after the motor homunculus was first proposed, it is still unknown how different body parts are intermixed and interrelated in human motor cortical areas at single-neuron resolution. Using multi-unit recordings, we studied how face, head, arm, and leg movements are represented in the hand knob area of premotor cortex (precentral gyrus) in people with tetraplegia. Contrary to traditional expectations, we found strong representation of all movements and a partially "compositional" neural code that linked together all four limbs. The code consisted of (1) a limb-coding component representing the limb to be moved and (2) a movement-coding component where analogous movements from each limb (e.g., hand grasp and toe curl) were represented similarly. Compositional coding might facilitate skill transfer across limbs, and it provides a useful framework for thinking about how the motor system constructs movement. Finally, we leveraged these results to create a whole-body intracortical brain-computer interface that spreads targets across all limbs.


Asunto(s)
Lóbulo Frontal/fisiología , Corteza Motora/anatomía & histología , Corteza Motora/fisiología , Adulto , Mapeo Encefálico , Lóbulo Frontal/anatomía & histología , Cuerpo Humano , Humanos , Corteza Motora/metabolismo , Movimiento/fisiología
2.
Nature ; 620(7976): 1031-1036, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37612500

RESUMEN

Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text1,2 or sound3,4. Early demonstrations, although promising, have not yet achieved accuracies sufficiently high for communication of unconstrained sentences from a large vocabulary1-7. Here we demonstrate a speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant-who can no longer speak intelligibly owing to amyotrophic lateral sclerosis-achieved a 9.1% word error rate on a 50-word vocabulary (2.7 times fewer errors than the previous state-of-the-art speech BCI2) and a 23.8% word error rate on a 125,000-word vocabulary (the first successful demonstration, to our knowledge, of large-vocabulary decoding). Our participant's attempted speech was decoded  at 62 words per minute, which is 3.4 times as fast as the previous record8 and begins to approach the speed of natural conversation (160 words per minute9). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for restoring rapid communication to people with paralysis who can no longer speak.


Asunto(s)
Interfaces Cerebro-Computador , Prótesis Neurales , Parálisis , Habla , Humanos , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/rehabilitación , Corteza Cerebral/fisiología , Microelectrodos , Parálisis/fisiopatología , Parálisis/rehabilitación , Vocabulario
3.
N Engl J Med ; 391(7): 609-618, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39141853

RESUMEN

BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy. METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice. RESULTS: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours. CONCLUSIONS: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).


Asunto(s)
Esclerosis Amiotrófica Lateral , Interfaces Cerebro-Computador , Disartria , Habla , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/rehabilitación , Calibración , Equipos de Comunicación para Personas con Discapacidad , Disartria/rehabilitación , Disartria/etiología , Electrodos Implantados , Microelectrodos , Cuadriplejía/etiología , Cuadriplejía/rehabilitación
4.
Nature ; 593(7858): 249-254, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33981047

RESUMEN

Brain-computer interfaces (BCIs) can restore communication to people who have lost the ability to move or speak. So far, a major focus of BCI research has been on restoring gross motor skills, such as reaching and grasping1-5 or point-and-click typing with a computer cursor6,7. However, rapid sequences of highly dexterous behaviours, such as handwriting or touch typing, might enable faster rates of communication. Here we developed an intracortical BCI that decodes attempted handwriting movements from neural activity in the motor cortex and translates it to text in real time, using a recurrent neural network decoding approach. With this BCI, our study participant, whose hand was paralysed from spinal cord injury, achieved typing speeds of 90 characters per minute with 94.1% raw accuracy online, and greater than 99% accuracy offline with a general-purpose autocorrect. To our knowledge, these typing speeds exceed those reported for any other BCI, and are comparable to typical smartphone typing speeds of individuals in the age group of our participant (115 characters per minute)8. Finally, theoretical considerations explain why temporally complex movements, such as handwriting, may be fundamentally easier to decode than point-to-point movements. Our results open a new approach for BCIs and demonstrate the feasibility of accurately decoding rapid, dexterous movements years after paralysis.


Asunto(s)
Interfaces Cerebro-Computador , Encéfalo/fisiología , Comunicación , Escritura Manual , Humanos , Redes Neurales de la Computación , Traumatismos de la Médula Espinal , Factores de Tiempo
5.
Proc Natl Acad Sci U S A ; 121(1): e2312204121, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38157452

RESUMEN

How the human cortex integrates ("binds") information encoded by spatially distributed neurons remains largely unknown. One hypothesis suggests that synchronous bursts of high-frequency oscillations ("ripples") contribute to binding by facilitating integration of neuronal firing across different cortical locations. While studies have demonstrated that ripples modulate local activity in the cortex, it is not known whether their co-occurrence coordinates neural firing across larger distances. We tested this hypothesis using local field-potentials and single-unit firing from four 96-channel microelectrode arrays in the supragranular cortex of 3 patients. Neurons in co-rippling locations showed increased short-latency co-firing, prediction of each other's firing, and co-participation in neural assemblies. Effects were similar for putative pyramidal and interneurons, during non-rapid eye movement sleep and waking, in temporal and Rolandic cortices, and at distances up to 16 mm (the longest tested). Increased co-prediction during co-ripples was maintained when firing-rate changes were equated, indicating that it was not secondary to non-oscillatory activation. Co-rippling enhanced prediction was strongly modulated by ripple phase, supporting the most common posited mechanism for binding-by-synchrony. Co-ripple enhanced prediction is reciprocal, synergistic with local upstates, and further enhanced when multiple sites co-ripple, supporting re-entrant facilitation. Together, these results support the hypothesis that trans-cortical co-occurring ripples increase the integration of neuronal firing of neurons in different cortical locations and do so in part through phase-modulation rather than unstructured activation.


Asunto(s)
Interneuronas , Neuronas , Humanos , Hipocampo/fisiología
6.
Glob Chang Biol ; 30(6): e17344, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38837566

RESUMEN

Hosting 1460 plant and 126 vertebrate endemic species, the Great Escarpment (hereafter, Escarpment) forms a semi-circular "amphitheater" of mountains girdling southern Africa from arid west to temperate east. Since arid and temperate biota are usually studied separately, earlier studies overlooked the biogeographical importance of the Escarpment as a whole. Bats disperse more widely than other mammalian taxa, with related species and intraspecific lineages occupying both arid and temperate highlands of the Escarpment, providing an excellent model to address this knowledge gap. We investigated patterns of speciation and micro-endemism from modeled past, present, and future distributions in six clades of southern African bats from three families (Rhinolophidae, Cistugidae, and Vespertilionidae) having different crown ages (Pleistocene to Miocene) and biome affiliations (temperate to arid). We estimated mtDNA relaxed clock dates of key divergence events across the six clades in relation both to biogeographical features and patterns of phenotypic variation in crania, bacula and echolocation calls. In horseshoe bats (Rhinolophidae), both the western and eastern "arms" of the Escarpment have facilitated dispersals from the Afrotropics into southern Africa. Pleistocene and pre-Pleistocene "species pumps" and temperate refugia explained observed patterns of speciation, intraspecific divergence and, in two cases, mtDNA introgression. The Maloti-Drakensberg is a center of micro-endemism for bats, housing three newly described or undescribed species. Vicariance across biogeographic barriers gave rise to 29 micro-endemic species and intraspecific lineages whose distributions were congruent with those identified in other phytogeographic and zoogeographic studies. Although Köppen-Geiger climate models predict a widespread replacement of current temperate ecosystems in southern Africa by tropical or arid ecosystems by 2070-2100, future climate Maxent models for 13 bat species (all but one of those analyzed above) showed minimal range changes in temperate species from the eastern Escarpment by 2070, possibly due to the buffering effect of mountains to climate change.


Asunto(s)
Quirópteros , Cambio Climático , ADN Mitocondrial , Animales , Quirópteros/fisiología , Quirópteros/genética , África Austral , ADN Mitocondrial/genética , ADN Mitocondrial/análisis , Filogenia , Especiación Genética , Filogeografía , Distribución Animal
7.
Transpl Infect Dis ; 26(3): e14302, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38761053

RESUMEN

BACKGROUND: Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic. METHODS: Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke-ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non-HSCT). RESULTS: Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified. CONCLUSIONS: Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient-centered outcomes.


Asunto(s)
Bacteriemia , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neutropenia , Humanos , Neutropenia/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hematológicas/complicaciones , Estudios Retrospectivos , Bacteriemia/microbiología , Bacteriemia/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Endocarditis/microbiología , Endocarditis/complicaciones , Anciano , Ecocardiografía , Ecocardiografía Transesofágica
8.
Neurocrit Care ; 41(1): 129-145, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38286946

RESUMEN

BACKGROUND: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment. METHODS: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question. RESULTS: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed. CONCLUSIONS: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.


Asunto(s)
Interfaces Cerebro-Computador , Trastornos de la Conciencia , Humanos , Trastornos de la Conciencia/fisiopatología , Trastornos de la Conciencia/terapia , Comunicación
9.
Child Care Health Dev ; 50(1): e13213, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38105630

RESUMEN

BACKGROUND: In 2019, the World Health Organization (WHO) launched the first global movement guidelines for children that combined sleep, physical activity and screen time. Our previous research showed that adherence to age-specific guidelines for screen time was challenging for families with children in different age groups. We aimed to determine whether families with children in different age-based movement guideline categories have poorer adherence to the broader 24-h movement guidelines than those with all children in the same age category. METHODS: Data were from the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health (seventh survey, 2015) and the women's three youngest children (aged ≤12) (Mothers and their Children's Health sub-study, 2016/2017). The sample was 1787 women (families) with 4064 children (mean age 7.2 [SD 2.9]). Whether children in the family were in the same or different age-based category was determined by matching children's ages in a family against age-based guideline categories for the 24-h movement behaviours. The association between children in the family being in the same or different age-based guideline category on adherence to 24-h movement guidelines, both collectively and individually, was analysed by adjusted logistic regression (binary and multinomial). RESULTS: Families with children in the same age guideline categories had double the odds of having all children meet 24-h movement guidelines (adjusted odds ratio [OR] 1.95 [95% confidence interval, CI: 1.32, 2.86]). Families with children in the same age categories on the screen guideline had higher odds of all children meeting (2.25 [1.73, 2.93]) and lower odds of some meeting/some failing the screen guideline (0.18 [0.14, 0.25]), than families with all children in different age categories. Families with children in the same age categories on the physical activity guideline had lower odds of all children meeting (0.57 [0.43, 0.75]) or some meeting/some failing the physical activity guideline (0.08 [0.06, 0.12]). No associations were found for sleep guidelines. CONCLUSIONS: Families with multiple children may need practical advice and strategies on how to adhere to guidelines when children span age categories. This could form part of public health strategies that raise awareness of the guidelines and may improve guideline adherence.


Asunto(s)
Ejercicio Físico , Conducta Sedentaria , Niño , Humanos , Femenino , Estudios Longitudinales , Australia , Adhesión a Directriz , Sueño
10.
J Neurosci ; 42(25): 5007-5020, 2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35589391

RESUMEN

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep. A 36-year-old man with tetraplegia secondary to cervical spinal cord injury enrolled in the ongoing BrainGate brain-computer interface pilot clinical trial had two 96-channel intracortical microelectrode arrays placed chronically into left precentral gyrus. Single- and multi-unit activity was recorded while he played a color/sound sequence matching memory game. Intended movements were decoded from motor cortical neuronal activity by a real-time steady-state Kalman filter that allowed the participant to control a neurally driven cursor on the screen. Intracortical neural activity from precentral gyrus and 2-lead scalp EEG were recorded overnight as he slept. When decoded using the same steady-state Kalman filter parameters, intracortical neural signals recorded overnight replayed the target sequence from the memory game at intervals throughout at a frequency significantly greater than expected by chance. Replay events occurred at speeds ranging from 1 to 4 times as fast as initial task execution and were most frequently observed during slow-wave sleep. These results demonstrate that recent visuomotor skill acquisition in humans may be accompanied by replay of the corresponding motor cortex neural activity during sleep.SIGNIFICANCE STATEMENT Within cortex, the acquisition of information is often followed by the offline recapitulation of specific sequences of neural firing. Replay of recent activity is enriched during sleep and may support the consolidation of learning and memory. Using an intracortical brain-computer interface, we recorded and decoded activity from motor cortex as a human research participant performed a novel motor task. By decoding neural activity throughout subsequent sleep, we find that neural sequences underlying the recently practiced motor task are repeated throughout the night, providing direct evidence of replay in human motor cortex during sleep. This approach, using an optimized brain-computer interface decoder to characterize neural activity during sleep, provides a framework for future studies exploring replay, learning, and memory.


Asunto(s)
Aprendizaje/fisiología , Corteza Motora/fisiología , Sueño/fisiología , Adulto , Interfaces Cerebro-Computador , Vértebras Cervicales , Electroencefalografía/métodos , Humanos , Masculino , Proyectos Piloto , Cuadriplejía/etiología , Cuadriplejía/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatología
11.
Int J Obes (Lond) ; 47(9): 841-847, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37369781

RESUMEN

AIM: To examine the association between motherhood status (mothers, voluntarily childless, involuntarily childless) and overweight and obesity over 22 years. METHODS: A total of 4092 women aged 18-23 years were followed from 1996 to 2018. Motherhood status was defined by women's reports on their fertility, attempts to conceive, use of in vitro fertilisation and fertility hormones, and number of biological children. Associations between motherhood status and overweight and obesity were examined using generalised estimating equations models, adjusting for socio-demographic characteristics, lifestyle factors, depressive symptoms, early life factors, and polycystic ovary syndrome (PCOS). RESULTS: At age 40-45 years, 12% of women were voluntarily childless and 5% were involuntarily childless. The prevalence of overweight and obesity increased with age and women who were voluntarily or involuntarily childless had higher prevalence of obesity than mothers in all surveys. After adjusting for covariates, compared with mothers, women who were voluntarily childless had higher odds of being overweight (odds ratio [OR], 95% confidence interval [CI]: 1.29, 1.09-1.52) and obese (OR, 95% CI: 1.65, 1.29-2.12). Involuntary childlessness was not associated with being overweight (OR, 95% CI: 1.05, 0.82-1.33), and its association with obesity was attenuated after adjusting for PCOS in the final model (OR, 95% CI: 1.40, 0.99-1.98). CONCLUSIONS: Around one in nine Australian women remained voluntarily childless by their late reproductive years. On average, they had higher odds of being overweight and obese than mothers, suggesting that overweight and obesity prevention programs should consider tailoring their advice by motherhood status.


Asunto(s)
Sobrepeso , Síndrome del Ovario Poliquístico , Niño , Femenino , Humanos , Adulto , Persona de Mediana Edad , Sobrepeso/epidemiología , Sobrepeso/complicaciones , Estudios Longitudinales , Australia/epidemiología , Obesidad/epidemiología , Obesidad/complicaciones , Madres , Síndrome del Ovario Poliquístico/complicaciones
12.
Environ Sci Technol ; 57(41): 15546-15557, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37647222

RESUMEN

Unsaturated triglycerides found in food and skin oils are reactive in ambient air. However, the chemical fate of such compounds has not been well characterized in genuine indoor environments. Here, we monitored the aging of oil coatings on glass surfaces over a range of environmental conditions, using mass spectrometry, nuclear magnetic resonance (NMR), and electron paramagnetic resonance (EPR) techniques. Upon room air exposure (up to 17 ppb ozone), the characteristic ozonolysis products, secondary ozonides, were observed on surfaces near the cooking area of a commercial kitchen, along with condensed-phase aldehydes. In an office setting, ozonolysis is also the dominant degradation pathway for oil films exposed to air. However, for indoor enclosed spaces such as drawers, the depleted air flow makes lipid autoxidation more favorable after an induction period of a few days. Forming hydroperoxides as the major primary products, this radical-mediated peroxidation behavior is accelerated by indoor direct sunlight, but the initiation step in dark settings is still unclear. These results are in accord with radical measurements, indicating that indoor photooxidation facilitates radical formation on surfaces. Overall, many intermediate and end products observed are reactive oxygen species (ROS) that may induce oxidative stress in human bodies. Given that these species can be widely found on both food and household surfaces, their toxicological properties are worth further attention.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Ozono , Humanos , Ozono/análisis , Espectrometría de Masas , Aceites , Contaminación del Aire Interior/análisis , Contaminantes Atmosféricos/análisis
13.
Qual Life Res ; 32(5): 1481-1491, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36598639

RESUMEN

PURPOSE: To compare health-related quality of life (HRQoL) between mothers and females who were voluntarily or involuntarily childless, across their reproductive years. METHODS: 4100 females born in 1973-78 from the Australian Longitudinal Study on Women's Health were followed for 22 years. Motherhood status was defined by females' reports in Survey 8 (2018, 40-45 years) on their fertility, attempts to conceive, use of in vitro fertilization and fertility hormones, and number of children. HRQoL was assessed in each survey using the 36-Item Short Form Survey (SF-36). Linear mixed models were used to assess the associations between motherhood status and HRQoL. RESULTS: Over 22 years, compared with females who were voluntarily childless, mothers on average had better HRQoL (shown by scores 1.5 to 3.4 points higher on five of the eight SF-36 subscales), while females who were involuntarily childless scored 2.2 to 3.0 points lower on three of eight SF-36 subscales. Compared with females who were voluntarily childless, teen mothers (age at first birth < 20 years) scored lower on role limitations due to physical problems subscale (b = -5.5, 95% CI: -9.3, -1.6), while females with either two, or three or more children scored 1.6 to 4.8 points higher on seven of eight SF-36 subscales. CONCLUSIONS: Females who were childless had poorer HRQoL than mothers. Further research is needed to understand the underlying mechanisms, which could inform policymakers on how to reduce the health disparities and improve long-term health outcomes for females.


Asunto(s)
Madres , Calidad de Vida , Adolescente , Femenino , Humanos , Niño , Persona de Mediana Edad , Adulto Joven , Adulto , Calidad de Vida/psicología , Estudios Longitudinales , Australia , Salud de la Mujer
14.
Lancet ; 397(10284): 1545-1553, 2021 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-33894832

RESUMEN

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.


Asunto(s)
Neuroestimuladores Implantables/efectos adversos , Accidente Cerebrovascular Isquémico/complicaciones , Rehabilitación de Accidente Cerebrovascular/métodos , Extremidad Superior/fisiopatología , Estimulación del Nervio Vago/instrumentación , Anciano , Estudios de Casos y Controles , Terapia Combinada/métodos , Terapia por Ejercicio/métodos , Femenino , Humanos , Accidente Cerebrovascular Isquémico/rehabilitación , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Paresia/etiología , Recuperación de la Función/fisiología , Resultado del Tratamiento , Parálisis de los Pliegues Vocales/epidemiología
15.
Brain ; 144(11): 3291-3310, 2021 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-34347037

RESUMEN

Neuroethical questions raised by recent advances in the diagnosis and treatment of disorders of consciousness are rapidly expanding, increasingly relevant and yet underexplored. The aim of this thematic review is to provide a clinically applicable framework for understanding the current taxonomy of disorders of consciousness and to propose an approach to identifying and critically evaluating actionable neuroethical issues that are frequently encountered in research and clinical care for this vulnerable population. Increased awareness of these issues and clarity about opportunities for optimizing ethically responsible care in this domain are especially timely given recent surges in critically ill patients with prolonged disorders of consciousness associated with coronavirus disease 2019 around the world. We begin with an overview of the field of neuroethics: what it is, its history and evolution in the context of biomedical ethics at large. We then explore nomenclature used in disorders of consciousness, covering categories proposed by the American Academy of Neurology, the American Congress of Rehabilitation Medicine and the National Institute on Disability, Independent Living and Rehabilitation Research, including definitions of terms such as coma, the vegetative state, unresponsive wakefulness syndrome, minimally conscious state, covert consciousness and the confusional state. We discuss why these definitions matter, and why there has been such evolution in this nosology over the years, from Jennett and Plum in 1972 to the Multi-Society Task Force in 1994, the Aspen Working Group in 2002 and the 2018 American and 2020 European Disorders of Consciousness guidelines. We then move to a discussion of clinical aspects of disorders of consciousness, the natural history of recovery and ethical issues that arise within the context of caring for people with disorders of consciousness. We conclude with a discussion of key challenges associated with assessing residual consciousness in disorders of consciousness, potential solutions and future directions, including integration of crucial disability rights perspectives.


Asunto(s)
Discusiones Bioéticas , Trastornos de la Conciencia/clasificación , Neurología/ética , COVID-19 , Trastornos de la Conciencia/diagnóstico , Humanos , SARS-CoV-2
16.
Int J Eat Disord ; 55(11): 1565-1574, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35855598

RESUMEN

OBJECTIVE: To explore whether children of mothers with pre-pregnancy binge eating (BE) symptoms have more behavioral difficulties compared with those without and whether associations are moderated by ED symptoms and other maternal health and social factors measured during childhood. METHOD: Pre-pregnancy BE symptoms were collected by the Australian Longitudinal Study on Women's Health at Survey 1 (in 1996) and/or at Survey 2 (in 2000) using questions mapped to DSM BE criterion 1. In 2016/7, 2180 women from the 1973-78 cohort provided data on externalizing and internalizing behavior, measured by Strengths and Difficulties Questionnaire, on 4054 of their children (2-12 years) in the Mothers and their Children's Health study. Covariates were markers of other ED symptoms, sociodemographic, social support, and mental health factors collected proximally to the child outcomes. Hierarchical multivariable regression models, using generalized estimating equations accounting for clustering of children within mothers, were used. RESULTS: Pre-pregnancy BE symptoms were associated with child behavior, with associations only moderated after adjustment for proximal markers of ED (girls internalizing behavior, b (95%CI) .30 (-.02, .61); boys externalizing behavior .34 (-.04, .73)) or social support (girls externalizing behavior 0.26 (-.08, .61)). Pre-pregnancy BE symptoms were not associated with boys internalizing behavior (-.27 (-.02, 0.57)). DISCUSSION: Studies with repeated ED measures should test hypotheses that these associations vary by timing of ED measurement. Identification of young women at risk of BE symptoms pre-pregnancy, as well as when children are older, may enable health services, treatment programs, and supports to minimize longer term effects on children. PUBLIC SIGNIFICANCE STATEMENT: A history of binge eating symptoms up to 10 years pre-pregnancy in mothers is associated with behavior problems in their girls and boys at average age of 7. However, the association is moderated by behaviors of eating disorders and social support in the mothers during childhood. Identification of ED symptoms prior to pregnancy, and then after childbirth, might enable health services to intervene to maximize child and mother outcomes.


Asunto(s)
Trastorno por Atracón , Trastornos de la Conducta Infantil , Problema de Conducta , Niño , Embarazo , Masculino , Femenino , Humanos , Estudios Longitudinales , Australia , Madres/psicología , Trastornos de la Conducta Infantil/psicología
17.
Birth ; 49(4): 728-740, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35355322

RESUMEN

BACKGROUND AND OBJECTIVE: Short and long intervals between successive births are associated with adverse birth outcomes, especially in low-income and middle-income countries, yet the birth intervals in high-income countries remain relatively understudied. The aim was to examine maternal factors associated with birth intervals in Australia. METHODS: The sample comprised 6130 participants in the Australian Longitudinal Study on Women's Health who were born in 1973-1978, had two or more births, and responded to regular surveys between 1996 and 2018. Interbirth interval (IBI) was defined as the time between successive live births. Maternal factors were examined using accelerated failure time models. RESULTS: For women with only two births (n = 3802), the median time to the second birth was 34.0 months (IQR 23.1, 46.2) with shorter IBI associated with higher socioeconomic status (eg, university education (31.9 months), less income stress (31.1)), and longer IBI associated with age over 35 (39.7), fair/poor health (43.0), untreated fertility problems (45.5), miscarriage (39.4), or abortion (41.0). For women with three or more births (n = 2328), the median times to the second and third births were 31.2 months (19.9, 42.1) and 36.5 months (25.3, 50.1), respectively; some factors were consistent between the first IBI and second IBI (eg, university education and being married were associated with shorter IBI), whereas income stress was associated with longer first IBI but not with second IBI. CONCLUSIONS: Understanding maternal factors associated with birth intervals in a high-income country like Australia may enable more nuanced tailoring of guidelines for prepregnancy care.


Asunto(s)
Intervalo entre Nacimientos , Clase Social , Embarazo , Femenino , Humanos , Persona de Mediana Edad , Estudios Longitudinales , Australia/epidemiología , Escolaridad , Factores Socioeconómicos , Edad Materna
18.
Ann Surg ; 274(6): 904-912, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34402804

RESUMEN

OBJECTIVES: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. BACKGROUND: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. METHODS: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. RESULTS: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. CONCLUSION: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.


Asunto(s)
COVID-19/epidemiología , Urgencias Médicas/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Cirugía General/estadística & datos numéricos , SARS-CoV-2 , Encuestas y Cuestionarios , Adulto , Anciano , Comorbilidad , Femenino , Estudios de Seguimiento , Salud Global , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Pandemias
19.
Nat Methods ; 15(10): 805-815, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30224673

RESUMEN

Neuroscience is experiencing a revolution in which simultaneous recording of thousands of neurons is revealing population dynamics that are not apparent from single-neuron responses. This structure is typically extracted from data averaged across many trials, but deeper understanding requires studying phenomena detected in single trials, which is challenging due to incomplete sampling of the neural population, trial-to-trial variability, and fluctuations in action potential timing. We introduce latent factor analysis via dynamical systems, a deep learning method to infer latent dynamics from single-trial neural spiking data. When applied to a variety of macaque and human motor cortical datasets, latent factor analysis via dynamical systems accurately predicts observed behavioral variables, extracts precise firing rate estimates of neural dynamics on single trials, infers perturbations to those dynamics that correlate with behavioral choices, and combines data from non-overlapping recording sessions spanning months to improve inference of underlying dynamics.


Asunto(s)
Potenciales de Acción , Algoritmos , Modelos Neurológicos , Corteza Motora/fisiología , Neuronas/fisiología , Animales , Humanos , Masculino , Persona de Mediana Edad , Dinámica Poblacional , Primates
20.
Ann Neurol ; 88(4): 851-854, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32613682

RESUMEN

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness. ANN NEUROL 2020;88:851-854.


Asunto(s)
Encéfalo/diagnóstico por imagen , Coma/diagnóstico por imagen , Infecciones por Coronavirus/fisiopatología , Estado Vegetativo Persistente/diagnóstico por imagen , Neumonía Viral/fisiopatología , Recuperación de la Función , Betacoronavirus , Encéfalo/fisiopatología , COVID-19 , Coma/fisiopatología , Infecciones por Coronavirus/terapia , Electroencefalografía , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas , Pandemias , Estado Vegetativo Persistente/fisiopatología , Neumonía Viral/terapia , Pronóstico , Insuficiencia Renal/fisiopatología , Respiración Artificial , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , SARS-CoV-2 , Choque/fisiopatología
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