Withdrawal of Life-Sustaining Therapy in Intensive Care Unit Patients Following Out-Of-Hospital Cardiac Arrest: An Australian Metropolitan ICU Experience

Objective: To determine factors associated with withdrawal of life-sustaining therapy (WLST) in intensive care unit (ICU) patients following out-of-hospital cardiac arrest (OHCA).Methods: A retrospective review of ICU data from patient clinical records following OHCA was conducted from January 2010 to December 2015. Demographic features, cardiac arrest characteristics, clinical attributes and targeted temperature management were compared between patients with and without WLST. We dichotomised WLST into early (ICU length of stay <72 hours) and late (ICU length of stay ≥72 hours). Factors independently associated with WLST were determined by multivariable binary logistic regression using a backward elimination method, and results were depicted as odds ratios (OR) with 95% confidence intervals (CI).Results: The study selection criteria resulted in a cohort of 260 ICU patients post-OHCA, with a mean age of 58 years and the majority were males (178, 68%); 151 patients (58%) died, of which 145 (96%) underwent WLST, with the majority undergoing early WLST (89, 61%). Status myoclonus was the strongest independent factor associated with early WLST (OR 38.90, 95% CI 4.55–332.57; p < 0.001). Glasgow Coma Scale (GCS) motor response of <4 on day 3 post-OHCA was the strongest factor associated with delayed WLST (OR 91.59, 95% CI 11.66–719.18; p < 0.0001).Conclusion: The majority of deaths in ICU patients post-OHCA occurred following early WLST. Status myoclonus and a GCS motor response of <4 on day 3 post-OHCA are independently associated with WLST.

Deep Brain Stimulation and Treatment Outcomes of Young- and Late-Onset (≤55 Years) Parkinson's Disease: A Population-Based Study

Background: No studies have reported the rate of motor complications (MC) and response to medical and surgical treatment in a population-based cohort of young-onset Parkinson's Disease (YOPD) patients and a cohort of sex-matched late-onset Parkinson's Disease (LOPD).Objective: To assess the outcomes of dopaminergic treatment in YOPD and LOPD, explore treatment-induced MC, medical adjustment, and rate of deep brain stimulation (DBS).Methods: We used the expanded Rochester Epidemiology Project (eREP) to investigate a population-based cohort of YOPD between 2010 and 2015 in 7 counties in Minnesota. Cases with onset ≤55 years of age were included as YOPD. An additional sex-matched cohort of LOPD (onset at ≥56 years of age) was included for comparison. All medical records were reviewed to confirm the diagnoses.Results: In the seven counties 2010–15, there were 28 YOPD patients, which were matched with a LOPD cohort. Sixteen (57%) YOPD had MC, as compared to 9 (32%) LOPD. In YOPD, 9 had motor fluctuations (MF) and Levodopa-induced dyskinesia (LID) together, whereas 3 had LID only and 4 MF only. In LOPD, 3 had MF and LID, 3 MF only, and 3 LID only. Following medical treatment for MC, 6/16 YOPD (38%) and 3/9 (33%) LOPD had symptoms resolution. In YOPD, 11/16 (69%) were considered for DBS implantation, in LOPD they were 2/9 (22%), but only 7 (6 YOPD and 1 LOPD) underwent the procedure. YOPD had significantly higher rates in both DBS candidacy and DBS surgery (respectively, p = 0.03 and p = 0.04). Among DBS-YOPD, 5/6 (83%) had positive motor response to the surgery; the LOPD case had a poor response. We report the population-based incidence of both YOPD with motor complications and YOPD undergoing DBS, which were 1.17 and 0.44 cases per 100,000 person-years, respectively.Conclusion: Fifty-seven percent of our YOPD patients and 32% of the LOPD had motor complications. Roughly half of both YOPD and LOPD were treatment resistant. YOPD had higher rates of DBS candidacy and surgery. Six YOPD and 1 LOPD underwent DBS implantation and most of them had a positive motor response after the surgery.

The Stop Signal Task for Measuring Behavioral Inhibition in Mice With Increased Sensitivity and High-Throughput Operation

Ceasing an ongoing motor response requires action cancelation. This is impaired in many pathologies such as attention deficit disorder and schizophrenia. Action cancelation is measured by the stop signal task that estimates how quickly a motor response can be stopped when it is already being executed. Apart from human studies, the stop signal task has been used to investigate neurobiological mechanisms of action cancelation overwhelmingly in rats and only rarely in mice, despite the need for a genetic model approach. Contributing factors to the limited number of mice studies may be the long and laborious training that is necessary and the requirement for a very loud (100 dB) stop signal. We overcame these limitations by employing a fully automated home-cage-based setup. We connected a home-cage to the operant box via a gating mechanism, that allowed individual ID chipped mice to start sessions voluntarily. Furthermore, we added a negative reinforcement consisting of a mild air puff with escape option to the protocol. This specifically improved baseline inhibition to 94% (from 84% with the conventional approach). To measure baseline inhibition the stop is signaled immediately with trial onset thus measuring action restraint rather than action cancelation ability. A high baseline allowed us to measure action cancelation ability with higher sensitivity. Furthermore, our setup allowed us to reduce the intensity of the acoustic stop signal from 100 to 70 dB. We constructed inhibition curves from stop trials with daily adjusted delays to estimate stop signal reaction times (SSRTs). SSRTs (median 88 ms) were lower than reported previously, which we attribute to the observed high baseline inhibition. Our automated training protocol reduced training time by 17% while also promoting minimal experimenter involvement. This sensitive and labor efficient stop signal task procedure should therefore facilitate the investigation of action cancelation pathologies in genetic mouse models.

Electrical stimulation–induced speech-related negative motor responses in the lateral frontal cortex

OBJECTIVE Speech arrest is a common but crucial negative motor response (NMR) recorded during intraoperative brain mapping. However, recent studies have reported nonspeech-specific NMR sites in the ventral precentral gyrus (vPrCG), where stimulation halts both speech and ongoing hand movement. The aim of this study was to investigate the spatial relationship between speech-specific NMR sites and nonspeech-specific NMR sites in the lateral frontal cortex. METHODS In this prospective cohort study, an intraoperative mapping strategy was designed to identify positive motor response (PMR) sites and NMR sites in 33 consecutive patients undergoing awake craniotomy for the treatment of left-sided gliomas. Patients were asked to count, flex their hands, and simultaneously perform these two tasks to map NMRs. Each site was plotted onto a standard atlas and further analyzed. The speech and hand motor arrest sites in the supplementary motor area of 2 patients were resected. The 1- and 3-month postoperative language and motor functions of all patients were assessed. RESULTS A total of 91 PMR sites and 72 NMR sites were identified. NMR and PMR sites were anteroinferiorly and posterosuperiorly distributed in the precentral gyrus, respectively. Three distinct NMR sites were identified: 24 pure speech arrest (speech-specific NMR) sites (33.33%), 7 pure hand motor arrest sites (9.72%), and 41 speech and hand motor arrest (nonspeech-specific NMR) sites (56.94%). Nonspeech-specific NMR sites and speech-specific NMR sites were dorsoventrally distributed in the vPrCG. For language function, 1 of 2 patients in the NMA resection group had language dysfunction at the 1-month follow-up but had recovered by the 3-month follow-up. All patients in the NMA resection group had fine motor dysfunction at the 1- and 3-month follow-ups. CONCLUSIONS The study results demonstrated a functional segmentation of speech-related NMRs in the lateral frontal cortex and that most of the stimulation-induced speech arrest sites are not specific to speech. A better understanding of the spatial distribution of speech-related NMR sites will be helpful in surgical planning and intraoperative mapping and provide in-depth insight into the motor control of speech production.

Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson’s Disease

Background: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson’s disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. Methods: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson’s Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. Results: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. Conclusion: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.

The influence of vitality forms on action perception and motor response

During the interaction with others, action, speech, and touches can communicate positive, neutral, or negative attitudes. Offering an apple can be gentle or rude, a caress can be kind or rushed. These subtle aspects of social communication have been named vitality forms by Daniel Stern. Although they characterize all human interactions, to date it is not clear whether vitality forms expressed by an agent may affect the action perception and the motor response of the receiver. To this purpose, we carried out a psychophysics study aiming to investigate how perceiving different vitality forms can influence cognitive and motor tasks performed by participants. In particular, participants were stimulated with requests made through a physical contact or vocally and conveying rude or gentle vitality forms, and then they were asked to estimate the end of a passing action observed in a monitor (action estimation task) or to perform an action in front of it (action execution task) with the intention to pass an object to the other person presented in the video. Results of the action estimation task indicated that the perception of a gentle request increased the duration of a rude action subsequently observed, while the perception of a rude request decreased the duration of the same action performed gently. Additionally, during the action execution task, accordingly with the perceived vitality form, participants modulated their motor response.

Motor response vigour and fixations reflect subjective preferences during intertemporal choice

Value-based decision-making is of central interest in cognitive neuroscience and psychology, as well as in the context of neuropsychiatric disorders characterised by decision-making impairments. Studies examining (neuro-)computational mechanisms underlying choice behaviour typically focus on participants' decisions. However, there is increasing evidence that option valuation might also be reflected in motor response vigour and eye movements, implicit measures of subjective utility. To examine motor response vigour and visual fixation correlates of option valuation in intertemporal choice, we set up a task where the participants selected an option by pressing a grip force transducer, simultaneously tracking fixation shifts between options. As outlined in our preregistration (https://osf.io/k6jct), we used hierarchical Bayesian parameter estimation to model the choices assuming hyperbolic discounting, compared variants of the softmax and drift diffusion model, and assessed the relationship between response vigour and the estimated model parameters. The behavioural data were best explained by a drift diffusion model specifying a non-linear scaling of the drift rate by the subjective value differences. Replicating previous findings (Green et al., 1997; Wagner et al., 2020a), we found a magnitude effect for temporal discounting, such that higher rewards were discounted less. This magnitude effect was further reflected in response vigour, such that stronger forces were exerted in the high vs. the low magnitude condition. Bayesian hierarchical linear regression further revealed higher grip forces, faster response times and a lower number of fixation shifts for trials with higher subjective value differences. Our data suggest that subjective utility or implicit valuation is reflected in response vigour during intertemporal choice. Taking into account response vigour might thus provide deeper insight into decision-making, reward valuation and maladaptive changes in these processes, e.g. in the context of neuropsychiatric disorders.