Biology subjects

Jahanshahi, M.

Publications and source records attributed to Jahanshahi, M..

4 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

Intersection of structural and functional connectivity of the nucleus basalis of Meynert in Parkinson's disease dementia and Lewy body dementia

Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography (MEG) with the spatial resolution of MRI tractography in order to explore the intersection of functional and structural connectivity of the NBM in a unique cohort of PDD and DLB patients undergoing Deep Brain Stimulation (DBS) of this structure. We observe that NBM-cortical structural and functional connectivity correlate within spatially and spectrally segregated networks including: 1) a beta band network to supplementary motor area (SMA), where activity in the SMA was found to drive activity in the NBM, 2) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus and 3) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.

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↗

bioRxiv2019

ERP sources in middle cingulate and precuneus differentiate Parkinson's patients from healthy controls and lingual gyri sources reflect human recombinant EPO effects in a Flanker task

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson s Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low-resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO, seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus evoked by incongruent stimuli differentiated PD and HCs.

neuroscience↗