Compulsive alcohol drinking, where intake persists regardless of adverse consequences, plays a major role in the substantial costs of alcohol use disorder. However, the processes that promote aversion-resistant drinking remain poorly understood. Compulsion-like responding has been considered automatic and reflexive and also to involve higher motivation, since drinking persists despite adversity. Thus, we used lickometry, where microstructural behavioral changes can reflect altered motivation, to test whether conflict-resistant intake [quinine-alcohol (QuiA)] reflected greater automaticity or motivation relative to alcohol-only drinking (Alc). Front-loading during QuiA and Alc suggested incentive to drink in both. However, the relationship between total licking and intake was less variable during QuiA, as was lick volume, without changes in average responding. QuiA bout organization was also less variable, with fewer licks outside of bouts (stray licks) and fewer gaps within bouts. Interestingly, QuiA avoidance of stray licking continued into short bouts, with fewer short and more medium-length bouts, which was striking given their minor impact on intake. Instead, more effort at bout onset could allow short bouts to persist longer. Indeed, while QuiA licking was overall faster, QuiA bouts were especially fast at bout initiation. However, few QuiA changes individually predicted greater intake, perhaps suggesting an overarching strategy during aversion-resistant responding. Thus, our results indicate that aversion-resistant intake exhibited less variability, where increased automaticity could decrease need for awareness, and stronger bout initiation, which might prolong responding despite adversity. This may reflect a collective strategy, which we call Head Down and Push responding that facilitates conflict-resistant, compulsion-like intake.

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The objective of this study was to evaluate proposed electroencephalographic (EEG) biomarkers of Parkinson’s disease (PD) and test their correlation with motor impairment in a new, well-characterized cohort of PD patients and controls. Sixty-four-channel EEG was recorded from 14 patients with rigid-akinetic PD with minimal tremor and from 14 age-matched healthy controls at rest and during voluntary movement. Patients were tested off and on medication during a single session. Recordings were analyzed for phase-amplitude coupling over sensorimotor cortex and for pairwise coherence from all electrode pairs in the recording montage (distributed coherence). Phase-amplitude coupling and distributed coherence were found to be elevated Off compared with On levodopa, and their reduction was correlated with motor improvement. In the Off medication state, phase-amplitude coupling was greater in sensorimotor contacts contralateral to the most affected body part and reduced by voluntary movement. We conclude that phase-amplitude coupling and distributed coherence are cortical biomarkers of the parkinsonian state that are detectable noninvasively and may be useful as objective aids for management of dopaminergic therapy. Several analytic methods may be used for noninvasive measurement of abnormal brain synchronization in PD. Calculation of phase-amplitude coupling requires only a single electrode over motor cortex. NEW & NOTEWORTHY Several EEG biomarkers of the parkinsonian state have been proposed that are related to abnormal cortical synchronization. We report several new findings in this study: correlations of EEG markers of synchronization with specific motor signs of Parkinson’s disease (PD), and demonstration that one of the EEG markers, phase-amplitude coupling, is more elevated over the more clinically affected brain hemisphere. These findings underscore the potential utility of scalp EEG for objective, noninvasive monitoring of medication state in PD.

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Excessive, binge alcohol drinking is a potent and pernicious obstacle to treating alcohol use disorder (AUD), and heavy-drinking humans are responsible for much of the substantial costs and harms of AUD. Thus, identifying key mechanisms that drive intake in higher-drinking individuals may provide important, translationally useful therapeutic interventions. Orexin-1-receptors (Ox1Rs) promote states of high motivation, and studies with systemic Ox1R inhibition suggest a particular role in individuals with higher intake levels. However, little has been known about circuits where Ox1Rs promote pathological intake, especially excessive alcohol consumption. We previously discovered that binge alcohol drinking requires Ox1Rs in medial nucleus accumbens shell (Shell), using two-bottle-choice Drinking-in-the-Dark (2bc-DID) in adult, male C57BL/6 mice. Here, we show that Shell Ox1Rs promoted intake during intermittent-access alcohol drinking as well as 2bc-DID, and that Shell inhibition with muscimol/baclofen also suppressed 2bc-DID intake. Importantly, with this large data set, we were able to demonstrate that Shell Ox1Rs and overall activity were particularly important for driving alcohol consumption in higher-drinking individuals, with little overall impact in moderate drinkers. Shell inhibition results were compared with control data combined from drug treatments that did not reduce intake, including NMDAR or PKC inhibition in Shell, Ox1R inhibition in accumbens core, and systemic inhibition of dopamine-1 receptors; these were used to understand whether more specific Shell Ox1R contributions in higher drinkers might simply result from intrinsic variability in mouse drinking. Ineffectiveness of Shell inhibition in moderate-drinkers was not due to a floor effect, since systemic baclofen reduced alcohol drinking regardless of basal intake levels, without altering concurrent water intake or saccharin consumption. Finally, alcohol intake in the first exposure predicted consumption levels weeks later, suggesting that intake level may be a stable trait in each individual. Together, our studies indicate that Shell Ox1Rs are critical mediators of binge alcohol intake in higher-drinking individuals, with little net contribution to alcohol drinking in more moderate bingers, and that targeting Ox1Rs may substantially reduce AUD-related harms.

Background: Recurrent shoulder instability results from overuse injuries that are often associated with athletic activity. Timely diagnosis and treatment are necessary to prevent further dislocations and secondary joint damage. In pediatric and adolescent patients, insurance status is a potential barrier to accessing timely care that has not yet been explored. Purpose: To examine the effect of insurance status on access to clinical consultation, surgical intervention, and surgical outcome of pediatric and adolescent patients with recurrent shoulder instability. Study Design: Cohort study; Level of evidence, 3. Methods: We conducted a retrospective review of pediatric and adolescent patients who were treated at a single tertiary children’s hospital for recurrent shoulder instability between 2011 and 2017. Patients were sorted into private and public insurance cohorts. Dates of injury, consultation, and surgery were recorded. Number of previous dislocations, magnetic resonance imaging (MRI) results, surgical findings, and postoperative complications were also noted. Delays in care were compared between the cohorts. The presence of isolated anterior versus complex labral pathology as well as bony involvement at the time of surgery was recorded. The incidences of labral pathology and secondary bony injury were then compared between the 2 cohorts. Postoperative notes were reviewed to compare rates of repeat dislocation and repeat surgery. Results: A total of 37 patients had public insurance, while 18 patients had private insurance. Privately insured patients were evaluated nearly 5 times faster than were publicly insured patients ( P < .001), and they obtained MRI scans over 4 times faster than did publicly insured patients ( P < .001). Publicly insured patients were twice as likely to have secondary bony injuries ( P = .016). Postoperatively, a significantly greater number (24.3%) of publicly insured patients experienced redislocation versus the complete absence of redislocation in the privately insured patients ( P = .022). Conclusion: Public insurance status affected access to care and was correlated with the development of secondary bony injury and a higher rate of postoperative dislocations. Clinicians should practice with increased awareness of how public insurance status can significantly affect patient outcomes by delaying access to care—particularly if delays lead to increased patient morbidity and health care costs.

Animals can capitalize on invariance in the environment by learning and automating highly consistent actions; however, they must also remain flexible and adapt to environmental changes. It remains unclear how primary motor cortex (M1) can drive precise movements, yet also support behavioral exploration when faced with consistent errors. Using a reach-to-grasp task in rats, along with simultaneous electrophysiological monitoring in M1 and dorsolateral striatum (DLS), we find that behavioral exploration to overcome consistent task errors is closely associated with tandem increases in M1 and DLS neural variability; subsequently, consistent ensemble patterning returns with convergence to a new successful strategy. We also show that compared to reliably patterned intracranial microstimulation in M1, variable stimulation patterns result in significantly greater movement variability. Our results thus indicate that motor and striatal areas can flexibly transition between two modes, reliable neural pattern generation for automatic and precise movements versus variable neural patterning for behavioral exploration.

Background-Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol.