PREP2 Algorithm Predictions Are Correct at 2 Years Poststroke for Most Patients

Background. The PREP2 algorithm combines clinical and neurophysiological measures to predict upper-limb (UL) motor outcomes 3 months poststroke, using 4 prediction categories based on Action Research Arm Test (ARAT) scores. The algorithm was accurate at 3 months for 75% of participants in a previous validation study. Objective. This study aimed to evaluate whether PREP2 predictions made at baseline are correct 2 years poststroke. We also assessed whether patients’ UL performance remained stable, improved, or worsened between 3 months and 2 years after stroke. Methods. This is a follow-up study of 192 participants recruited and assessed in the original PREP2 validation study. Participants who completed assessments 3 months poststroke (n = 157) were invited to complete follow-up assessments at 2 years poststroke for the present study. UL outcomes were assessed with the ARAT, upper extremity Fugl-Meyer Scale, and Motor Activity Log. Results. A total of 86 participants completed 2-year follow-up assessments in this study. PREP2 predictions made at baseline were correct for 69/86 (80%) participants 2 years poststroke, and PREP2 UL outcome category was stable between 3 months and 2 years poststroke for 71/86 (83%). There was no difference in age, stroke severity, or comorbidities among patients whose category remained stable, improved, or deteriorated. Conclusions. PREP2 algorithm predictions made within days of stroke are correct at both 3 months and 2 years poststroke for most patients. Further investigation may be useful to identify which patients are likely to improve, remain stable, or deteriorate between 3 months and 2 years

Uncoupling response inhibition

The ability to prevent unwanted movement is fundamental to human behavior. When healthy adults must prevent a subset of prepared actions, execution of the remaining response is markedly delayed. We hypothesized that the delay may be sensitive to the degree of similarity between the prevented and continued actions. Fifteen healthy participants performed an anticipatory response inhibition task that required bilateral index finger extension or thumb abduction with homogeneous digit pairings, or a heterogeneous pairing of a combination of the two movements. We expected that the uncoupling of responses required for selective movement prevention would be more difficult with homogeneous (same digit, homologous muscles) than heterogeneous pairings (different digits, nonhomologous muscles). Measures of response times (and asynchrony between digits) during action execution, stopping performance, and electromyography from EIP (index finger extension) and APB (thumb abduction) were analyzed. As expected, selective trials produced a delay in the remaining movement compared with execution trials. Successful performance in the selective condition occurred via suppression of the entire prepared response and subsequent selective reinitiation of the remaining component. Importantly, the delayed reinitiation of motor output was sensitive to the degree of similarity between responses, occurring later but at a faster rate with homogeneous digits. There were persistent aftereffects from the selective condition on the motor system, which indicated greater levels of inhibition and a higher gain were necessary to successfully perform selective trials with homogeneous pairings. Overall, the results support a model of inhibition of a unitary response and selective reinitiation, rather than selective inhibition. </jats:p

The fall and rise of corticomotor excitability with cancellation and reinitiation of prepared action

The sudden cancellation of a motor action, known as response inhibition (RI), is fundamental to human motor behavior. The behavioral selectivity of RI can be studied by cueing cancellation of only a subset of a planned response, which markedly delays the remaining executed components. The present study examined neurophysiological mechanisms that may contribute to these delays. In two experiments, human participants received single- and paired-pulse transcranial magnetic stimulation while performing a bimanual anticipatory response task. Participants performed most trials bimanually (Go trials) and were sometimes cued to cancel the response with one hand while responding with the other (Partial trials). Motor evoked potentials were recorded from left first dorsal interosseous (FDI) as a measure of corticomotor excitability (CME) during Go and Partial trials. CME was temporally modulated during Partial trials in a manner that reflected anticipation, suppression, and subsequent initiation of a reprogrammed response. There was an initial increase in CME, followed by suppression 175 ms after the stop signal, even though the left hand was not cued to stop. A second increase in excitability occurred prior to the (delayed) response. We propose an activation threshold model to account for nonselective RI. To investigate the inhibitory component of our model, we investigated short-latency intracortical inhibition (sICI), but results indicated that sICI cannot fully explain the observed temporal modulation of CME. These neurophysiological and behavioural results indicate that the default mode for reactive partial cancellation is suppression of a unitary response, followed by response reinitiation with an inevitable time delay. </jats:p

Multisensory attention training for treatment of tinnitus

Spiegel, D. P. et al. Multisensory attention training for treatment of tinnitus. Sci. Rep. 5, 10802; doi: 10.1038/srep10802 (2015).Tinnitus is the conscious perception of sound with no physical sound source. Some models of tinnitus pathophysiology suggest that networks associated with attention, memory, distress and multisensory experience are involved in tinnitus perception. The aim of this study was to evaluate whether a multisensory attention training paradigm which used audio, visual, and somatosensory stimulation would reduce tinnitus. Eighteen participants with predominantly unilateral chronic tinnitus were randomized between two groups receiving 20 daily sessions of either integration (attempting to reduce salience to tinnitus by binding with multisensory stimuli) or attention diversion (multisensory stimuli opposite side to tinnitus) training. The training resulted in small but statistically significant reductions in Tinnitus Functional Index and Tinnitus Severity Numeric Scale scores and improved attentional abilities. No statistically significant improvements in tinnitus were found between the training groups. This study demonstrated that a short period of multisensory attention training reduced unilateral tinnitus, but directing attention toward or away from the tinnitus side did not differentiate this effect.This work was supported by a grant from Links Research and Grants Corporation to G.D.S

Implementing biomarkers to predict motor recovery after stroke

BACKGROUND: There is growing interest in using biomarkers to predict motor recovery and outcomes after stroke. The PREP2 algorithm combines clinical assessment with biomarkers in an algorithm, to predict upper limb functional outcomes for individual patients. To date, PREP2 is the first algorithm to be tested in clinical practice, and other biomarker-based algorithms are likely to follow. PURPOSE: This review considers how algorithms to predict motor recovery and outcomes after stroke might be implemented in clinical practice. FINDINGS: There are two tasks: first the prediction information needs to be obtained, and then it needs to be used. The barriers and facilitators of implementation are likely to differ for these tasks. We identify specific elements of the Consolidated Framework for Implementation Research that are relevant to each of these two tasks, using the PREP2 algorithm as an example. These include the characteristics of the predictors and algorithm, the clinical setting and its staff, and the healthcare environment. CONCLUSIONS: Active, theoretically underpinned implementation strategies are needed to ensure that biomarkers are successfully used in clinical practice for predicting motor outcomes after stroke, and should be considered in parallel with biomarker developmen

Task-Dependent Interaction between Parietal and Contralateral Primary Motor Cortex during Explicit versus Implicit Motor Imagery

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks

Recovery After Stroke: Not So Proportional After All?

The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. To the extent that this is true, recovery from stroke can be predicted accurately from baseline measures of acute post-stroke impairment alone. Reports that baseline scores explain more than 80%, and sometimes more than 90%, of the variance in the patients’ recoveries, are rapidly accumulating. Here, we show that these headline effect sizes are likely inflated. The key effects in this literature are typically expressed as, or reducible to, correlation coefficients between baseline scores and recovery (outcome scores minus baseline scores). Using formal analyses and simulations, we show that these correlations will be extreme when outcomes are less variable than baselines, which they often will be in practice regardless of the real relationship between outcomes and baselines. We show that these effect sizes are likely to be over optimistic in every empirical study that we found, which reported enough information for us to make the judgement, and argue that the same is likely to be true in other studies as well. The implication is that recovery after stroke may not be as proportional as recent studies suggest

Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole

Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists

Mirror Symmetric Bimanual Movement Priming Can Increase Corticomotor Excitability and Enhance Motor Learning

Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality in post-stroke upper limb rehabilitation