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Galea, J.

Publications and source records attributed to Galea, J..

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Competitive pre-ordering during planning persists in kinematically fused sequential movements

Results in human and non-human primates have shown that elements of a movement sequence are pre-ordered in parallel competitively before execution, a process known as competitive queueing (CQ). However, it is unclear whether the preplanning of individual movements persists in continuous skilled actions that involve greater biomechanical integration and is associated with the formation of new motor primitives (neural fusion). We investigated how kinematics impact sequence planning in a handwriting-like task asking whether fusing velocity curves between adjacent movements affects movement preparation. Participants were trained and tested for two days to perform two sequences of four sequential centre-out-and-back movements from memory in a delayed sequence production task using a stylus on a Wacom tablet. To manipulate kinematic fusion between subsequent strokes, participants were assigned to one of three groups that were trained to perform the sequences either with acute, right or obtuse angles between sequential targets. Probe trials assessed the availability of constituent movement elements for fast and accurate execution towards each target during planning. Movement elements associated with later sequence positions were less available than earlier movements, regardless of kinematic fusion, in line with CQ findings for discrete typing sequences in humans. Importantly, a more pronounced CQ gradient was associated with higher fusion, faster initiation and greater accuracy of sequence production. These findings indicate that kinematically fused sequential actions do not result in the formation of new movement primitives (neural fusion) with a single movement plan. Instead, they continue to be planned separately and are associated with skilled performance. New & NoteworthyUsing a handwriting-like sequencing task, we manipulated kinematic fusion through target geometry and examined the relative availability of individual movements towards targets as a marker of competitive queuing (CQ) during planning. Contrary to the assumption that behavioural fusion reflects their neural fusion of movements into a new motor primitive, we show that even under high levels of fusion, the underlying sequence elements remain competitively pre-ordered by their sequence position benefitting performance.

neuroscience↗

The Neurochemical Mechanisms Underlying the Enhancing Effects of Rewards and Punishments on Motor Performance

Monetary rewards and punishments enhance motor performance and are associated with corticospinal excitability (CSE) increases within the motor cortex (M1) during movement preparation. However, such CSE changes have unclear origins; they could stem from increased glutamatergic (GLUTergic) facilitation and/or decreased type A gamma-aminobutyric acid (GABAA)-mediated inhibition within M1. To investigate this, paired-pulse transcranial magnetic stimulation was used to assess GLUTergic facilitation and GABAA inhibition within M1 whilst participants prepared to execute 4-element finger-press sequences. Behaviourally, rewards and punishments enhanced both reaction and movement times. Neurochemically, regardless of rewards or punishments, a digit-specific increase in GLUTergic facilitation and digit-unspecific decrease in GABAA inhibition occurred during preparation as movement onset approached. In parallel, both rewards and punishments non-specifically increased GLUTergic facilitation, but only rewards non-specifically decreased GABAA inhibition during preparation. This suggests that, to enhance performance, rewards both increase GLUTergic facilitation and decrease GABAA inhibition whilst punishments selectively increase GLUTergic facilitation. A control experiment revealed that such changes were not observed post-movement as participants processed reward and punishment feedback, indicating they were selective to movement preparation. Collectively, these results map the neurochemical changes in M1 by which incentives enhance motor performance.

neuroscience↗

Sensorimotor feedback loops are selectively sensitive to reward

Although it is well established that motivational factors such as earning more money for performing well improve motor performance, how the motor system implements this improvement remains unclear. For instance, feedback-based control, which uses sensory feedback from the body to correct for errors in movement, improves with greater reward. But feedback control encompasses many feedback loops with diverse characteristics such as the brain regions involved and their response time. Which specific loops drive these performance improvements with reward is unknown, even though their diversity makes it unlikely that they are contributing uniformly. We systematically tested the effect of reward on the latency (how long for a corrective response to arise?) and gain (how large is the corrective response?) of seven distinct sensorimotor feedback loops in humans. Only the fastest feedback loops were insensitive to reward, and the earliest reward-driven changes were consistently an increase in feedback gains, not a reduction in latency. Rather, a reduction of response latencies only tended to occur in slower feedback loops. These observations were similar across sensory modalities (vision and proprioception). Our results may have implications regarding feedback control performance in athletic coaching. For instance, coaching methodologies that rely on reinforcement or "reward shaping" may need to specifically target aspects of movement that rely on reward-sensitive feedback responses.

neuroscience↗

Isoniazid preventive therapy protects against tuberculosis among household contacts of isoniazid-resistant patients.

BackgroundThe World Health Organization recommends the use of isoniazid (INH) alone or combination INH and rifapentine therapy to treat latent tuberculosis infection (LTBI) in groups at high risk of tuberculosis (TB) progression. The recent rise of INH- and multi-drug resistant (MDR) TB has complicated the choice of LTBI treatment regimen. We examine the risk of TB disease among household contacts (HHCs) who received INH after being exposed to patients with drug-sensitive, INH-resistant, or MDR tuberculosis. MethodsIn this prospective cohort study conducted Between September 2009 and August 2012 in Lima, Peru, we identified 4,500 index TB patients and measured incident TB disease in their 14,044 HHCs over a one-year follow-up period. HHCs under 19 years of age were offered INH preventive therapy (IPT). We used a Cox frailty proportional hazards model to evaluate whether the effect of IPT on incident TB disease varied by the resistance profile of the index case. We repeated the analyses in a second independent dataset. FindingsAmong 4,216 HHCs under 19 years of age, 2,106 (50%) initiated IPT at enrolment. The protective effect of INH was more extreme in HHCs exposed to drug-sensitive (Hazard Ratio [95% confidence interval]=0{middle dot}2[0{middle dot}20-0{middle dot}50]) and to MDR-TB (0{middle dot}26[0{middle dot}08-0{middle dot}77]) compared to those exposed to mono-INH-resistant (0{middle dot}80[0{middle dot}23 to 2{middle dot}79]). Among those who received at least three months of INH, effectiveness increased across all three groups (INH-sensitive:0{middle dot}20 [0{middle dot}10 to 040]; MDR:0{middle dot}16 [0 02-127]; mono-INH-resistant:0{middle dot}72 [0{middle dot}16-3{middle dot}16]). In the second independent study, TB occurred in none of the 76 HHCs who received IPT compared to 3% (8/273) of those who did not. InterpretationWe found that IPT use is associated with reduced incidence of TB disease among contacts of MDR-TB patients. This finding suggests that INH may have role in the management of MDR-LTBI. FundingNational Institutes of Health and the National Institute of Allergy and Infectious Diseases CETR (U19AI109755) and TBRU (U19AI111224)

epidemiology↗

RESISTANCE AT NO COST: THE TRANSMISSIBILITY AND POTENTIAL FOR DISEASE PROGRESSION OF DRUG-RESISTANT M. TUBERCULOSIS

BackgroundThe future trajectory of drug resistant tuberculosis strongly depends on the fitness costs of drug resistance mutations. Here, we measured the association of phenotypic drug resistance and the risk of TB infection and disease among household contacts (HHCs) of patients with pulmonary TB.\n\nMethodsWe evaluated 12767 HHCs of patients with drug sensitive and resistant pulmonary TB at baseline, two, six, and 12 months to ascertain infection status and to determine whether they developed tuberculosis disease. We also assessed the impact of drug resistance phenotype on the likelihood that a TB strain shared a genetic fingerprint with at least one other TB patient in the cohort.\n\nFindingsAmong 3339 TB patients for whom were DST available, 1274 (38%) had TB that was resistant to at least one drug and 478 (14*3%) had multi-drug resistant (MDR) TB, i.e. TB resistant to both INH and rifampicin. Compared to HHCs of drug sensitive TB patients, those exposed to a patient with MDR-TB had an 8% (95% CI: 4-13%) higher risk of infection by the end of follow up. We found no statistically significant difference in the relative hazard of incident TB disease among HHCs exposed to MDR-TB compared to DS-TB (Adjusted HR 1*28 [(95% CI: *9-1*83]). Patients with MDR-TB were more likely to be part of a genetic cluster than were DS-TB patients.\n\nInterpretationClinical strains of MDR M. tuberculosis are neither less transmissible than drug sensitive strains nor less likely to cause disease. (ClinicalTrials.gov number, NCT00676754)\n\nFundingNational Institutes of Health: NIH/NIAID CETR U19AI109755\n\nStatementAll authors have seen the manuscript and approved the manuscript.

epidemiology↗