Nucleus accumbens and dorsal medial striatal dopamine and neural activity are essential for action sequence performance.

Separable striatal circuits have unique functions in Pavlovian and instrumental behaviors but how these roles relate to performance of sequences of actions with and without associated cues are less clear. Here, we tested whether dopamine transmission and neural activity more generally in three striatal subdomains are necessary for performance of an action chain leading to reward delivery. Male and female Long-Evans rats were trained to press a series of three spatially distinct levers to receive reward. We assessed the contribution of neural activity or dopamine transmission within each striatal subdomain when progression through the action sequence was explicitly cued and in the absence of cues. Behavior in both task variations was substantially impacted following microinfusion of the dopamine antagonist, flupenthixol, into nucleus accumbens core (NAc) or dorsomedial striatum (DMS), with impairments in sequence timing and numbers of rewards earned after NAc flupenthixol. In contrast, after pharmacological inactivation to suppress overall activity, there was minimal impact on total rewards earned. Instead, inactivation of both NAc and DMS impaired sequence timing and led to sequence errors in the uncued, but not cued task. There was no impact of dopamine antagonism or reversible inactivation of dorsolateral striatum on either cued or uncued action sequence completion. These results highlight an essential contribution of NAc and DMS dopamine systems in motivational and performance aspects of chains of actions, whether cued or internally generated, as well as the impact of intact NAc and DMS function for correct sequence performance.

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system.

Adaptive behavior in a dynamic environment often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical test to theories of dopamine's function in learning, motivation, and motor control. Yet how dopamine neurons are involved in the revaluation of cues when the world changes to alter our behavior remains unclear. Here we make use of pharmacology, in vivo electrophysiology, fiber photometry, and optogenetics to resolve the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward-seeking. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by sucrose reward by exploiting the prior, non-overlapping presentation of a separate discrete cue - an occasion setter. Only when the occasion setter's presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery. As a result, in this task we were able to dissociate the average value of the conditioned stimulus from its immediate expected value on a trial-to-trial basis. Both the activity of ventral tegmental area dopamine neurons and dopamine signaling in the nucleus accumbens were essential for rats to successfully update behavioral responding in response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward. Downstream of dopamine release, we found that single neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together these results reveal a novel mechanism within the mesolimbic dopamine system for the rapid revaluation of motivation.

Advance directives among community-dwelling stroke survivors.

OBJECTIVE: Advance directives (ADs) are integral to health care, allowing patients to specify surrogate decision-makers and treatment preferences in case of loss of capacity. The present study sought to identify determinants of ADs among stroke survivors. METHODS: In this cross-sectional study (Care Attitudes and Preferences in Stroke Survivors [CAPriSS]), community-dwelling stroke survivors were surveyed on ADs; validated scales were used to query palliative care knowledge and attitudes towards life-sustaining treatments. Logistic regression was used to determine variables associated with ADs. RESULTS: Among 562 community-dwelling stroke survivors who entered the survey after screening questions confirmed eligibility, 421 (74.9%) completed survey components with relevant variables of interest. The median age was 69 years (IQR 58-75 years); 53.7% were male; and 15.0% were Black. Two hundred and fifty-one (59.6%) respondents had ADs. Compared to stroke survivors without ADs, those with ADs were more likely to be older (median age 72 vs. 61 years; p<0.001), White (91.2% vs. 75.9%, p<0.001), and male (58.6% vs. 46.5%, p = 0.015), and reported higher education (p<0.001) and income (p = 0.011). Ninety-eight (23.3%) participants had "never heard of palliative care". Compared to participants without ADs, participants with ADs had higher Palliative Care Knowledge Scale (PaCKS) scores (median 10 [IQR 5-12] vs. 7 [IQR 0-11], p<0.001), and lower scores on the Attitudes Towards Life-Sustaining Treatments Scale (indicating a more negative attitude towards life-sustaining treatments; median 23 [IQR 18-28] vs. 29 [IQR 24-35], p<0.001). Multivariable logistic regression identified age (OR 1.62 per 10 year increase, 95% CI 1.30-2.02; p<0.001), prior advance care planning discussion with a physician (OR 1.73, 95% CI 1.04-2.86; p = 0.034), PaCKS scores (OR 1.06 per 1 point increase, 95% CI 1.01-1.12; p = 0.018), and Attitudes Towards Life-Sustaining Treatments Scale scores (OR 0.91 per 1 point increase, 95% CI 0.88-0.95; p<0.001) as variables independently associated with ADs. CONCLUSIONS: Age, prior advance care planning discussion with a physician, palliative care knowledge, and attitudes towards life-sustaining treatments were independently associated with ADs.

Practice Patterns and Attitudes Among Speech-Language Pathologists Treating Stroke Patients with Dysphagia: A Nationwide Survey.

Dysphagia management is a core component of quality stroke care. Speech-Language Pathologists (SLPs) play a key role in the management of post-stroke dysphagia. We sought to elicit perceptions, attitudes, and practice patterns regarding post-stroke dysphagia management among SLPs in the United States. We conducted a survey among SLPs registered with the American Speech-Language-Hearing Association who indicated that they care for acute stroke patients. A total of 336 participants completed the survey. Over half of the participants (58.6%) indicated that they obtain objective swallow testing in ≥ 60% of their post-stroke dysphagia patients. Almost 1 in 5 SLPs indicated that they are often unable to perform objective dysphagia testing due to limited resources (18.8% indicated resource limitations; 78.9% indicated no resources limitations; 2.4% were unsure). SLPs in hospitals without stroke center certification had higher odds of indicating limited resources compared to SLPs in certified stroke centers (OR 2.08, 95% CI 1.11-3.87). Over 75% indicated that percutaneous endoscopic gastrostomy (PEG) tubes after stroke are placed too early. SLPs who obtain objective swallow testing in ≥ 60% of patients had higher odds of indicating that PEG tubes are placed too early (OR 1.70, 95% CI 1.13-2.56). While 19.4% indicated that the optimal timing for PEG after stroke is < 7 days after admission, 25.0% indicated that the optimal timing is > 12 days. Almost 35% indicated that health care system pressures influence their recommendations, and 47.6% indicated that ≥ 25% of PEGs could be avoided if patients were given up to 7 more days for swallowing recovery.

Geographic and Regional Variability in Racial and Ethnic Disparities in Stroke Thrombolysis in the United States.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) after ischemic stroke is underutilized in racially/ethnically minoritized groups. We aimed to determine the regional and geographic variability in racial/ethnic IVT disparities in the United States. METHODS: Acute ischemic stroke admissions between 2012 and 2018 were identified in the National Inpatient Sample. Multivariable logistic regression was used to test the association between IVT and race/ethnicity, stratified by geographic region and controlling for demographic, clinical, and hospital characteristics. RESULTS: Of the 545 509 included cases, 47 031 (8.6%) received IVT. Racially/ethnically minoritized groups had significantly lower adjusted odds of IVT compared with White people in the South Atlantic region (odds ratio [OR], 0.86 [95% CI, 0.82-0.91]), the East North Central region (OR, 0.91 [95% CI, 0.85-0.97]) and the Pacific region (OR, 0.90 [95% CI, 0.85-0.96]). In the South Atlantic region, IVT use in racial/ethnic minority groups was below the national average of all racial/ethnic minority patients (P=0.002). Compared with White patients, Black patients had lower odds of IVT in the Middle Atlantic region (OR, 0.84 [95% CI, 0.78-0.91]), the South Atlantic region (OR, 0.78 [95% CI, 0.74-0.82]), and the East North Central region (OR, 0.86 [95% CI, 0.79-0.93]). In the South Atlantic region, this difference was below the national average for Black people (P<0.001). Hispanic patients had significantly lower use of IVT only in the Pacific region (OR, 0.92 [95% CI, 0.85-0.99]), while Asian/Pacific Islander patients had lower odds of IVT in the Mountain (OR, 0.76 [95% CI, 0.59-0.98]) and Pacific region (OR, 0.89 [95% CI, 0.82-0.97]). CONCLUSIONS: Racial/ethnic disparities in IVT use in the United States vary by region. Geographic hotspots of lower IVT use in racially/ethnically minoritized groups are the South Atlantic region, driven predominantly by lower use of IVT in Black patients, and the East North Central and Pacific regions.

Bleeding risk in patients with cardiac disease from ischaemic stroke reperfusion therapy: an update.

BACKGROUND: Intravenous tissue plasminogen activator (rtPA) and arterial endovascular therapy (ET) rapidly restore cerebral perfusion in eligible patients who had an acute ischaemic stroke (AIS). It is unknown whether patients who had an AIS with premorbid cardiac disease respond differently to reperfusion therapies than those without. These patients may have risk factors that worsen outcomes or may represent those who would most benefit from reperfusion therapy. OBJECTIVE: To determine whether patients who had an AIS with the most frequently encountered pre-existing cardiac conditions, atrial fibrillation (AF), heart failure (HF), left ventricular assist devices (LVADs), or taking anticoagulation for cardiac indications, are at increased risk for poor outcome, such as symptomatic intracranial haemorrhage (sICH), after reperfusion therapy. RESULTS: Although AF is an independent risk factor for poor poststroke outcomes, intravenous rtPA is not associated with increased risk of sICH for those not on anticoagulants. Likewise, HF is independently associated with mortality post stroke, yet these patients benefit from reperfusion therapies without increased rates of sICH. Patients with LVADs or who are on anticoagulation should not be given IV rtPA; however, ET remains a viable option in those who meet criteria, even patients with LVAD. CONCLUSION: There is no evidence of an increased risk for sICH after intravenous rtPA or ET for those with AF or HF. Intravenous rtPA should not be given to patients on anticoagulation or with LVADs, but ET should be offered to them when eligible. Whenever possible, future AIS reperfusion research should include patients with premorbid cardiac disease as they are frequently excluded, representing a gap in evidence.

Novel Score for Stratifying Risk of Critical Care Needs in Patients With Intracerebral Hemorrhage.

OBJECTIVE: To develop a risk prediction score identifying patients with intracerebral hemorrhage (ICH) at low risk for critical care. METHODS: We retrospectively analyzed data of 451 patients with ICH between 2010 and 2018. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting independent predictors of intensive care unit (ICU) needs according to strength of association. The risk score was tested in the validation cohort and externally validated in a dataset from another institution. RESULTS: The rate of ICU interventions was 80.3%. Systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, intraventricular hemorrhage (IVH), and ICH volume were independent predictors of critical care, resulting in the following point assignments for the Intensive Care Triaging in Spontaneous Intracerebral Hemorrhage (INTRINSIC) score: SBP 160 to 190 mm Hg (1 point), SBP >190 mm Hg (3 points); GCS 8 to 13 (1 point), GCS <8 (3 points); ICH volume 16 to 40 cm3 (1 point), ICH volume >40 cm3 (2 points); and presence of IVH (1 point), with values ranging between 0 and 9. Among patients with a score of 0 and no ICU needs during their emergency department stay, 93.6% remained without critical care needs. In an external validation cohort of patients with ICH, the INTRINSIC score achieved an area under the receiver operating characteristic curve of 0.823 (95% confidence interval 0.782-0.863). A score <2 predicted the absence of critical care needs with 48.5% sensitivity and 88.5% specificity, and a score <3 predicted the absence of critical care needs with 61.7% sensitivity and 83.0% specificity. CONCLUSION: The INTRINSIC score identifies patients with ICH who are at low risk for critical care interventions. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the INTRINSIC score identifies patients with ICH at low risk for critical care interventions.