Biology subjects

McInnes, A. N.

Publications and source records attributed to McInnes, A. N..

7 recordsLinked to original sources

bioRxiv2026

Prefrontal cortical pathways mediating cognitive control enhancement from internal capsule stimulation

BackgroundDeep brain stimulation (DBS) targeting the ventral internal capsule/ventral striatum (VCVS) is an effective treatment for several psychiatric disorders, but clinical responses often vary amongst patients likely due to an incomplete mechanistic understanding of the brain pathways mediating response. VCVS DBS can improve cognitive control, a core deficit in multiple psychiatric disorders. Here, we investigated which prefrontal cortical pathway(s) in the internal capsule are associated with improving cognitive control during VCVS DBS. MethodsFour participants with bilateral VCVS DBS completed the Multi-Source Interference Task (MSIT) under 27 stimulation settings varying by side (left/right lead), electrode, amplitude, and frequency. Each condition included 100 trials and response time (RT) assessed task performance. Personalized pathway activation models quantified axonal recruitment across 11 segmented prefrontal cortical fiber bundles per brain hemisphere. Associations between pathway activation and task RT were analyzed to identify circuits linked to improved cognitive control performance. ResultsRight-sided VCVS stimulation produced greater improvements in cognitive control (reductions in MSIT RT) than left-sided stimulation. Activation of right dorsal prefrontal cortical pathways connected to the dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) most strongly predicted faster MSIT RTs, whereas no left-sided pathways were associated with performance changes. ConclusionsThese findings suggest that the effects of VCVS DBS on cognitive control are primarily mediated by right dorsal prefrontal cortical axons projecting from the dlPFC and dmPFC. Targeting these pathways may improve stimulation strategies and outcomes for psychiatric disorders characterized by impaired cognitive control.

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bioRxiv2025

Cognitive state dependent enhancement of cognitive control with transcranial magnetic stimulation

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), yet variability of therapeutic responses remains high. A key contributor to this variability may be state-dependent effects of brain stimulation, where activity in underlying circuits can shape the propagation of TMS-evoked activity. Thus, constraining the target circuits state by engaging cognition may make TMS effects more consistent. ObjectiveWe tested whether TMS effects on cognitive control, a transdiagnostic construct implicated across psychiatric disorders and a putative mediator of TMS efficacy, are state-dependent. MethodsParticipants (N = 25) completed a context-dependent behavioural assay of cognitive control before and after we delivered rTMS to the prefrontal cortex (PFC). During rTMS, participants performed either the cognitive control task (active-state TMS), or performed a context-independent perceptual task (control-state TMS). We assessed changes in downstream behavioural metrics of circuit function, as well as neural indices of cognitive control measured from electroencephalography (EEG). ResultsrTMS enhanced downstream readouts of cognitive control only when stimulation was delivered concurrent with the cognitive control task. Similarly, only active-state TMS modulated theta band oscillatory activity, which is thought to be a marker of cognitive control engagement ConclusionThese findings demonstrate that TMS effects on cognitive control are state-dependent, in which endogenous engagement of PFC-anchored networks can shape the magnitude and functional relevance of TMS-induced plasticity. Considering cognitive states during TMS may therefore offer a framework to enhance and/or accelerate TMS therapeutic effects.

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bioRxiv2023

Psychometric validation and clinical correlates of an experiential foraging task

Measuring the function of decision-making systems is a central goal of computational psychiatry. Individual measures of decisional function could be used to describe neurocognitive profiles that underpin psychopathology and offer insights into deficits that are shared across traditional diagnostic classes. However, there are few demonstrably reliable and mechanistically relevant metrics of decision making that can accurately capture the complex overlapping domains of cognition whilst also quantifying the heterogeneity of function between individuals. The WebSurf task is a reverse-translational human experiential foraging paradigm which indexes naturalistic and clinically relevant decision-making. To determine its potential clinical utility, we examined the psychometric properties and clinical correlates of behavioural parameters extracted from WebSurf in an initial exploratory experiment and a pre-registered validation experiment. Behaviour was stable over repeated administrations of the task, as were individual differences. The ability to measure decision making consistently supports the potential utility of the task in predicting an individuals propensity for response to psychiatric treatment, in evaluating clinical change during treatment, and in defining neurocognitive profiles that relate to psychopathology. Specific aspects of WebSurf behaviour also correlate with anhedonic and externalising symptoms. Importantly, these behavioural parameters may measure dimensions of psychological variance that are not captured by traditional rating scales. WebSurf and related paradigms might therefore be useful platforms for computational approaches to precision psychiatry.

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bioRxiv2023

From Inhibition to Excitation and Why: The Role of Temporal Urgency in Modulating Corticospinal Activity

Previous research on movement preparation identified a period of corticospinal suppression about 200 ms prior to movement initiation. This phenomenon has been observed for different types of motor tasks typically used to investigate movement preparation (e.g., reaction time, self-initiated, and anticipatory actions). However, we recently discovered that this phenomenon is not observed when actions must be initiated under time pressure. In the present study, we investigated urgency effects on corticospinal suppression throughout the time course of an anticipatory timing task. Participants were required to perform timing actions under two urgency scenarios, high and low, and we applied single-pulse transcranial magnetic stimulation at different times during the time course of preparation. We analysed the time course of excitability under high and low scenarios in relation to expected and actual movement onset times. Our results confirmed our earlier findings that corticospinal suppression is not observed when participants perform actions under high urgency scenarios. In addition, we found no evidence that this preparatory suppression could be shifted in time to occur later under high urgency scenarios. Moreover, we found evidence that responses prepared under high urgency are more likely to be disrupted by external events (e.g., TMS pulses). These results suggest that preparatory suppression might be a strategy employed by the central nervous system to shield motor actions from interference of external events (e.g., loud sounds) when time allows. Given these data, we propose conceptual models that could account for the absence of preparatory suppression under time pressure to act.

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bioRxiv2021

Premovement inhibition protects motor actions from interference

Shortly before movement initiation, the corticospinal system undergoes a transient suppression. This phenomenon has been observed across a range of motor tasks, suggesting that it may be a obligatory component of movement preparation. We probed whether this was also the case when the urgency to perform a motor action was high, in a situation where little time was available to engage in preparatory processes. We controlled the urgency of an impending motor action by increasing or decreasing the foreperiod duration in an anticipatory timing task. Transcranial magnetic stimulation (TMS; experiment one) or a loud acoustic stimulus (LAS; experiment two) were used to examine how corticospinal and subcortical excitability were modulated during motor preparation. Preparatory inhibition of the corticospinal tract was absent when movement urgency was high, though motor actions were initiated on time. In contrast, subcortical circuits were progressively inhibited as the time to prepare increased. Interestingly, movement force and vigour were reduced by both TMS and the LAS when movement urgency was high, and enhanced when movement urgency was low. Our findings indicate that preparatory inhibition may not be a obligatory component of motor preparation. The behavioural effects we observed in the absence of preparatory inhibition were induced by both TMS and the LAS, suggesting that accessory sensory stimulation may disrupt motor output when such stimulation is presented in the absence of preparatory inhibition. We conclude that preparatory inhibition may be an adaptive strategy which can serve to protect the prepared motor action from external interference.

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bioRxiv2021

Engagement of the contralateral limb can enhance the facilitation of motor output by loud acoustic stimuli

When intense sound is presented during light muscle contraction, inhibition of the corticospinal tract is observed. During action preparation, this effect is reversed, with sound resulting in excitation of the corticospinal tract. We investigated how the combined maintenance of a muscle contraction during preparation for a ballistic action impacts the magnitude of the facilitation of motor output by a loud acoustic stimulus (LAS) - a phenomenon known as the StartReact effect. Participants executed ballistic wrist flexion movements and a LAS was presented simultaneously with the imperative signal in a subset of trials. We examined whether the force level or muscle used to maintain a contraction during preparation for the ballistic response impacted reaction time and/or the force of movements triggered by the LAS. These contractions were sustained either ipsilaterally or contralaterally to the ballistic response. The magnitude of facilitation by the LAS was greatest when low force flexion contractions were maintained in the limb contralateral to the ballistic response during preparation. There was little change in facilitation when contractions recruited the contralateral extensor muscle, or when they were sustained in the same limb that executed the ballistic response. We conclude that a larger network of neurons which may be engaged by a contralateral sustained contraction prior to initiation may be recruited by the LAS, further contributing to the motor output of the response. These findings may be particularly applicable in stroke rehabilitation where engagement of the contralesional side may increase the benefits of a LAS to the functional recovery of movement.

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bioRxiv2020

Cumulative distribution functions: An alternative approach to examine the triggering of prepared motor actions in the StartReact effect

There has been much debate concerning whether startling sensory stimuli can activate a fast-neural pathway for movement triggering (StartReact) which is different from that of voluntary movements. Activity in sternocleidomastoid (SCM) electromyogram is suggested to indicate activation of this pathway. We evaluated whether SCM activity can accurately identify trials which may differ in their neurophysiological triggering and assessed the use of cumulative distribution functions (CDFs) of reaction time (RT) data to identify trials with the shortest RTs for analysis. Using recent datasets from the StartReact literature, we examined the relationship between RT and SCM activity. We categorised data into short/longer RT bins using CDFs and used linear mixed effects models to compare potential conclusions that can be drawn when categorising data on the basis of RT versus on the basis of SCM activity. The capacity of SCM to predict RT is task-specific, making it an unreliable indicator of distinct neurophysiological mechanisms. Classification of trials using CDFs is capable of capturing potential task- or muscle-related differences in triggering whilst avoiding the pitfalls of the traditional SCM activity based classification method. We conclude that SCM activity is not always evident on trials that show the early triggering of movements seen in the StartReact phenomenon. We further propose that a more comprehensive analysis of data may be achieved through the inclusion of CDF analyses. These findings have implications for future research investigating movement triggering as well as for potential therapeutic applications of StartReact.

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