Biology subjects

Rawji, V.

Publications and source records attributed to Rawji, V..

5 recordsLinked to original sources

bioRxiv2021

Rise-to-threshold and dynamical systems views of proactive inhibition

Successful models of movement should encompass the flexibility of the human motor system to execute movements under different contexts. One such context-dependent modulation is proactive inhibition, a type of behavioural inhibition concerned with responding with restraint. Whilst movement has classically been modelled as a rise-to-threshold process, there exists a lack of empirical evidence for this in limb movements. Alternatively, the dynamical systems view conceptualises activity during motor preparation as setting the initial state of a dynamical system, that evolves into the movement upon receipt of a trigger. We tested these models by measuring how proactive inhibition influenced movement preparation and execution in humans. We changed the orientation (PA: postero-anterior and AP: antero-posterior flowing currents) and pulse width (120 s and 30 s) of motor cortex transcranial magnetic stimulation to probe different corticospinal interneuron circuits. PA and AP interneuron circuits represent the dimensions of a state space upon which motor cortex activity unfolds during motor preparation and execution. AP30 inputs were inhibited at the go cue, regardless of proactive inhibition, whereas PA120 inputs scaled inversely with the probability of successful inhibition. When viewed through a rise-to-threshold model, proactive inhibition was implemented by delaying the trigger to move, suggesting that motor preparation and execution are independent. A dynamical systems perspective showed that proactive inhibition was marked by a shift in the distribution of interneuron networks (trajectories) during movement execution, despite normalisation for reaction time. Viewing data through the rise-to-threshold and dynamical systems models reveal complimentary mechanisms by which proactive inhibition is implemented. Key pointsO_LIWe view proactive inhibition through the rise-to-threshold and dynamical systems models. C_LIO_LIWe change the orientation (PA: postero-anterior and AP: antero-posterior flowing currents) and pulse width (120 s and 30 s) of transcranial magnetic stimulation to probe interneuron networks in motor cortex during behavioural tasks employing proactive inhibition. C_LIO_LIWhen viewed through a rise-to-threshold model, proactive inhibition was implemented by delaying the trigger to move, suggesting that motor preparation and execution are independent. C_LIO_LIA dynamical systems perspective showed that despite normalisation for reaction time, the trajectory/balance between PA120 and AP30 interneuron inputs during movement execution depended on proactive inhibition. C_LIO_LIViewing data through the rise-to-threshold and dynamical systems models reveal complimentary mechanisms by which proactive inhibition is implemented. C_LI

neuroscience↗

bioRxiv2020

Ropinirole, a dopamine agonist with high D3 affinity, reduces proactive inhibition: a double-blind, placebo-controlled study in healthy adults

Response inhibition describes the cognitive processes mediating the suppression of unwanted actions. A network involving the basal ganglia mediates two forms of response inhibition: reactive and proactive inhibition. Reactive inhibition serves to abruptly stop motor activity, whereas proactive inhibition is goal-orientated and results in slowing of motor activity in anticipation of stopping. Due to its impairment in several psychiatric disorders, the neurochemistry of response inhibition has become of recent interest. Dopamine has been posed as a candidate mediator of response inhibition due to its role in functioning of the basal ganglia and the observation that patients with Parkinsons disease on dopamine agonists develop impulse control disorders. Although the effects of dopamine on reactive inhibition have been studied, substantial literature on the role of dopamine on proactive inhibition is lacking. To fill this gap, we devised a double-blind, placebo-controlled study of 1 mg ropinirole (a dopamine agonist) on response inhibition in healthy volunteers. We found that whilst reactive inhibition was unchanged, proactive inhibition was impaired when participants were on ropinirole relative to when on placebo. To investigate how ropinirole mediated this effect on proactive inhibition, we used hierarchical drift-diffusion modelling. We found that ropinirole impaired the ability to raise the decision threshold when proactive inhibition was called upon. Our results provide novel evidence that an acute dose of ropinirole selectively reduces proactive inhibition in healthy participants. These results may help explain how ropinirole induces impulse control disorders in susceptible patients with Parkinsons disease.

neuroscience↗

bioRxiv2020

Comparison between conventional electrodes and ultrasound monitoring to measure TMS evoked muscle contraction

BackgroundTranscranial Magnetic stimulation (TMS) is a non-invasive cortical stimulation method that has been widely employed to explore cortical physiology in health and a range of diseases. At the core of many TMS protocols is the measurement of evoked muscle contractions using surface electromyography (sEMG). While sEMG is appropriate for many superficial muscles such as abductor pollicis brevis (ABP) and first dorsal interosseous (FDI), there are situations where the study of less accessible muscles may be of interest. Peripheral ultrasound is a non-invasive method that could provide a solution. We explore the relationship between TMS evoked sMEP and TMS evoked muscle contractions measured with muscle ultrasound. We hypothesise that in a healthy population, we expect a positive correlation between EMG and ultrasound measures. MethodsIn 10 participants we performed a standard TMS recruitment curve and simultaneously measured MEP and peripheral muscle ultrasound (pUS). We targeted the following muscles: biceps (BI), first dorsal interosseous (FDI), tibialis anterior (TA) and the tongue (TO). ResultsWe report a very close relationship between the MEP and pUS contraction. Resting motor threshold (RMT) measurements and recruitment curves are consistent in sEMG and pUS. A key aspect of this work is the ability to examine clinically relevant muscles that are difficult to probe using surface EMG electrodes, such as the tongue. ConclusionWe find that TMS muscle contractions can be measured with muscle ultrasound in superficial and deep muscles, enable additional, previously hard to study muscles, to be investigated. This could be valuable for allowing TMS to be used to explore a new range of muscles in disorders such as ALS. In muscles less accessible by sEMG, such as the tongue, it may be possible to use pUS as an alternative output. This may be useful in conditions such as ALS and stroke that can differentially affect the tongue.

neuroscience↗

bioRxiv2019

Short interval intracortical inhibition as measured by TMS-EEG

The diagnosis of amyotrophic lateral sclerosis (ALS) relies on involvement of both upper (UMN) lower motor neurons (LMN). Yet, there remains no objective marker of UMN involvement, limiting early diagnosis of ALS. This study establishes whether TMS combined with EEG can be used to measure short-interval intracortical inhibition (SICI) via TMS evoked potentials (TEP) in healthy volunteers - an essential first step in developing an independent marker of UMN involvement in ALS.\n\nWe hypothesised that a SICI paradigm would result in characteristic changes in the TMS-evoked EEG potentials that directly mirror the changes in MEP.\n\nTMS was delivered to the left motor cortex using single-pulse and three inhibitory stimulation paradigms. SICI was present in all three conditions. TEP peaks were reduced predominantly under the SICI 70 protocol but less so for SICI 80 and not at all for SICI 90. There was a significant negative correlation between MEPs and N45 TEP peak for SICI 70 (rho = -0.54, p = 0.04). In other words, as MEPs becomes inhibited the N45 increases. The same trend was maintained across SICI 80 and 90 (SICI 80, rho = -0.5, p = 0.06; SICI 90, rho = -0.48, p = 0.07). Additional experiments suggest these results cannot be explained by artefact.\n\nWe establish that motor cortical inhibition can be measured during a SICI 70 protocol expanding on previous work. We have carefully considered the role of artefact in TEPs and have taken a number of steps to show that artefact cannot explain these results and we suggesting the differences are cortical in origin. TMS-EEG has potential to aid early diagnosis and to further understand central and peripheral pathophysiology in MND.

neuroscience↗

bioRxiv2017

tDCS changes in motor excitability are specific to orientation of current flow

Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the cephalic cortex result in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. Here we test this idea by measuring changes in cortico-spinal excitability by Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP), following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. Current flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces none-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is through to select different afferent pathways to M1. Our results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.\n\nHighlights O_LIDirection of current flow is important for tDCS after-effects.\nC_LIO_LItDCS modulates excitability between two electrodes.\nC_LIO_LItDCS differentially modulates PA and AP inputs into M1.\nC_LI\n\nAbbreviations\n\nFundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

neuroscience↗