Assessing the influence of dopamine and mindfulness on the formation of routines in visual search

Given experience in cluttered but stable visual environments, our eye‐movements form stereotyped routines that sample task‐relevant locations, while not mixing‐up routines between similar task‐settings. Both dopamine signaling and mindfulness have been posited as factors that influence the formation of such routines, yet quantification of their impact remains to be tested in healthy humans. Over two sessions, participants searched through grids of doors to find hidden targets, using a gaze‐contingent display. Within each session, door scenes appeared in either one of two colors, with each color signaling a differing set of likely target locations. We derived measures for how well target locations were learned (target‐accuracy), how routine were sets of eye‐movements (stereotypy), and the extent of interference between the two scenes (setting‐accuracy). Participants completed two sessions, where they were administered either levodopa (dopamine precursor) or placebo (vitamin C), under double‐blind counterbalanced conditions. Dopamine and trait mindfulness (assessed by questionnaire) interacted to influence both target‐accuracy and stereotypy. Increasing dopamine improved accuracy and reduced stereotypy for high mindfulness scorers, but induced the opposite pattern for low mindfulness scorers. Dopamine also disrupted setting‐accuracy invariant to mindfulness. Our findings show that mindfulness modulates the impact of dopamine on the target‐accuracy and stereotypy of eye‐movement routines, whereas increasing dopamine promotes interference between task‐settings, regardless of mindfulness. These findings provide a link between non‐human and human models regarding the influence of dopamine on the formation of task‐relevant eye‐movement routines and provide novel insights into behavior‐trait factors that modulate the use of experience when building adaptive repertoires

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Familiarity with music increases walking speed in rhythmic auditory cueing

Rhythmic auditory stimulation (RAS) is a gait rehabilitation method in which patients synchronize footsteps to a metronome or musical beats. Although RAS with music can ameliorate gait abnormalities, outcomes vary, possibly because music properties, such as groove or familiarity, differ across interventions. To optimize future interventions, we assessed how initially familiar and unfamiliar low-groove and high-groove music affected synchronization accuracy and gait in healthy individuals. We also experimentally increased music familiarity using repeated exposure to initially unfamiliar songs. Overall, familiar music elicited faster stride velocity and less variable strides, as well as better synchronization performance (matching of step tempo to beat tempo). High-groove music, as reported previously, led to faster stride velocity than low-groove music. We propose two mechanisms for familiarity's effects. First, familiarity with the beat structure reduces cognitive demands of synchronizing, leading to better synchronization performance and faster, less variable gait. Second, familiarity might have elicited faster gait by increasing enjoyment of the music, as enjoyment was higher after repeated exposure to initially low-enjoyment songs. Future studies are necessary to dissociate the contribution of these mechanisms to the observed RAS effects of familiar music on gait

The role of attention and intention in synchronization to music: effects on gait

Anecdotal accounts suggest that individuals spontaneously synchronize their movements to the 'beat' of background music, often without intending to, and perhaps even without attending to the music at all. However, the question of whether intention and attention are necessary to synchronize to the beat remains unclear. Here, we compared whether footsteps during overground walking were synchronized to the beat when young healthy adults were explicitly instructed to synchronize (intention to synchronize), and were not instructed to synchronize (no intention) (Experiment 1: intention). We also examined whether reducing participants' attention to the music affected synchronization, again when participants were explicitly instructed to synchronize, and when they were not (Experiment 2: attention/intention). Synchronization was much less frequent when no instructions to synchronize were given. Without explicit instructions to synchronize, there was no evidence of synchronization in 60% of the trials in Experiment 1, and 43% of the trials in Experiment 2. When instructed to synchronize, only 26% of trials in Experiment 1, and 14% of trials in Experiment 2 showed no evidence of synchronization. Because walking to music alters gait, we also examined how gait kinematics changed with or without instructions to synchronize, and attention to the music was required for synchronization to occur. Instructions to synchronize elicited slower, shorter, and more variable strides than walking in silence. Reducing attention to the music did not significantly affect synchronization of footsteps to the beat, but did elicit slower gait. Thus, during walking, intention, but not attention, appears to be necessary to synchronize footsteps to the beat, and synchronization elicits slower, shorter, and more variable strides, at least in young healthy adults

Anodal motor cortex stimulation paired with movement repetition increases anterograde interference but not savings

Retention of motor adaptation is evident in savings, where initial learning improves subsequent learning, and anterograde interference, where initial learning impairs subsequent learning. Previously, we proposed that use-dependent movement biases induced by movement repetition contribute to anterograde interference, but not to savings. Here, we evaluate this proposal by limiting or extending movement repetition while stimulating the motor cortex (M1) with anodal transcranial direct current stimulation (tDCS), a brain stimulation technique known to increase use-dependent plasticity when applied during movement repetition. Participants first adapted to a counterclockwise rotation of visual feedback imposed either abruptly (extended repetition) or gradually (limited repetition) in a first block (A1), during which either sham or anodal tDCS (2 mA) was applied over M1. Anterograde interference was then assessed in a second block (B) with a clockwise rotation, and savings in a third block (A2) with a counterclockwise rotation. Anodal M1 tDCS elicited more anterograde interference than sham stimulation with extended but not with limited movement repetition. Conversely, anodal M1 tDCS did not affect savings with either limited or extended repetition of the adapted movement. Crucially, the effect of anodal M1 tDCS on anterograde interference did not require large errors evoked by an abrupt perturbation schedule, as anodal M1 tDCS combined with extended movement repetition within a gradual perturbation schedule similarly increased anterograde interference but not savings. These findings demonstrate that use-dependent plasticity contributes to anterograde interference but not to savings

The modulating effects of dopamine and cathodal transcranial direct current stimulation in the supplementary motor area on the speed accuracy trade off.

All decisions involve an integral trade-off known as the ‘speed-accuracy tradeoff’ (SAT), where time pressure increases the chance of making an error. Multiple lines of evidence suggest that the superior medial frontal cortex (SMFC), specifically the supplementary motor area (SMA) plays a role in SAT performance (Berkay, Eser, Sack, Çakmak, & Balcı, 2018; Filmer, Ballard, Sewell, & Dux, 2021; Forstmann et al., 2008; Georgiev et al., 2016; Tosun, Berkay, Sack, Çakmak, & Balcı, 2017; Weigard, Beltz, Reddy, & Wilson, 2019). The SMA is a smaller portion of the SMFC, involved in self-initiated movements, movement inhibition, and task switching (Hasain et al., 2008). Functional neuroimaging data suggests that neural activity in the pre-SMA correlates with individual differences in SAT response threshold changes, and trial-to-trial variability in these changes (Forstmann et al., 2008, 2010; Mansfield et al., 2011). fMRI data further demonstrates that the strength of white matter connectivity between the pre-SMA and striatum have correlates with individual differences in SAT performance (Forstmann et al., 2008, 2010, 2011; Mansfield et al., 2011). Transcranial magnetic stimulation of the right pre-SMA provides casual evidence for the SMA’s role in SAT thresholds, where Berkay et al. (2018) demonstrated right pre-SMA inhibition leads to significantly higher response thresholds, whereas right pre-SMA excitation leads to significantly lower response thresholds. Similarly, transcranial direct current stimulation (tDCS) of the pre-SMA also altered the SAT (Filmer et al., 2021). This line of evidence supports the theory that excitatory input to motor regions, mediated by connections from the pre-supplemental motor area to the striatum, lowers the threshold for response initiation (Forstmann et al., 2008). Yet how perturbational approaches such as transcranial direct current stimulation alters SAT performance is unclear, as the mechanisms of tDCS remain to be fully understood. Increasing evidence suggests that non-invasive brain stimulation involves midbrain dopamine-dependent mechanisms. Changes in anodal and cathodal tDCS excitability and brain activity appear dependent on dopamine dosage (Monte-Silva et al., 2010; Fresnoza et al., 2014; Monte-Silva 2008; Kuo et al., 2008). Specifically, there is an inverted U-shaped relationship between dopamine dosage and changes in excitability. For example, Fresnoza et al., (2014) found anodal tDCS significantly increased, and cathodal tDCS significantly decreased excitability of the motor cortex, with this effect increasing under a medium (100mg) levodopa manipulation yet diminishing under low (25mg) and high (200mg) levodopa. Monte-Silva et al., (2008). Thus, dopamine appears to play a role in brain excitability and activity, yet due to the lack of studies examining behavioral changes, we are still limited in understanding whether dopamine plays a role in how tDCS of the pre-SMA alters the SAT

Task errors drive memories that improve sensorimotor adaptation

Traditional views of sensorimotor adaptation (i.e., adaptation of movements to perturbed sensory feedback) emphasize the role of automatic, implicit correction of sensory prediction errors. However, latent memories formed during sensorimotor adaptation, manifest as improved re-learning (e.g., savings), have recently been attributed to strategic corrections of task errors (failures to achieve task goals). To dissociate contributions of task errors and sensory prediction errors to latent sensorimotor memories, we perturbed target locations to remove or enforce task errors during learning and/or test, with male/female human participants. Adaptation improved after learning in all conditions where participants were permitted to correct task errors, and did not improve whenever we prevented correction of task errors. Thus, previous correction of task errors was both necessary and sufficient to improve adaptation. In contrast, a history of sensory prediction errors was neither sufficient nor obligatory for improved adaptation. Limiting movement preparation time showed that the latent memories driven by learning to correct task errors take at least two forms: a time-consuming but flexible component, and a rapidly expressible, inflexible component. The results provide strong support for the idea that movement corrections driven by a failure to successfully achieve movement goals underpin motor memories that manifest as savings. Such persistent memories are not exclusively mediated by time-consuming strategic processes, but also comprise a rapidly expressible but inflexible component. The distinct characteristics of these putative processes suggest dissociable underlying mechanisms, and imply that identification of the neural basis for adaptation and savings will require methods that allow such dissociations.Latent motor memories formed during sensorimotor adaptation manifest as improved adaptation when sensorimotor perturbations are re-encountered. Conflicting theories suggest that this "savings" is underpinned by different mechanisms: including a memory of successful actions; a memory of errors; or an aiming strategy to correct task errors. Here we show that learning to correct task errors is sufficient to show improved subsequent adaptation with respect to naïve performance, even when tested in the absence of task errors. In contrast, a history of sensory prediction errors is neither sufficient nor obligatory for improved adaptation. Finally, we show that latent sensorimotor memories driven by task errors comprise at least two distinct components: a time-consuming, flexible component, and a rapidly expressible, inflexible component