Effects of motor preparation and spatial attention on corticospinal excitability in a delayed-response paradigm

The preparation of motor responses during the delay period of an instructed delay task is associated with sustained neural firing in the primate premotor cortex. It remains unclear how and when such preparation-related premotor activity influences the motor output system. In this study, we tested modulation of corticospinal excitability using single-pulse transcranial magnetic stimulation (TMS) during a delayed-response task. At the beginning of the delay interval participants were either provided with no information, spatial attentional information concerning location but not identity of an upcoming imperative stimulus, or information regarding the upcoming response. Behavioral data indicate that participants used all information available to them. Only when information concerning the upcoming response was provided did corticospinal excitability show differential modulation for the effector muscle compared to other task-unrelated muscles. We conclude that modulation of corticospinal excitability reflects specific response preparation, rather than non-specific event preparation

Time-Dependent Changes in Human Corticospinal Excitability Reveal Value-Based Competition for Action during Decision Processing

Our choices often require appropriate actions to obtain a preferred outcome, but the neural underpinnings that link decision making and action selection remain largely undetermined. Recent theories propose that action selection occurs simultaneously, i.e., parallel in time, with the decision process. Specifically, it is thought that action selection in motor regions originates from a competitive process that is gradually biased by evidence signals originating in other regions, such as those specialized in value computations. Biases reflecting the evaluation of choice options should thus emerge in the motor system before the decision process is complete. Using transcranial magnetic stimulation, we sought direct physiological evidence for this prediction by measuring changes in corticospinal excitability in human motor cortex during value-based decisions. We found that excitability for chosen versus unchosen actions distinguishes the forthcoming choice before completion of the decision process. Both excitability and reaction times varied as a function of the subjective value-difference between chosen and unchosen actions, consistent with this effect being value-driven. This relationship was not observed in the absence of a decision. Our data provide novel evidence in humans that internally generated value-based decisions influence the competition between action representations in motor cortex before the decision process is complete. This is incompatible with models of serial processing of stimulus, decision, and action

On the synchronization of transcranial magnetic stimulation and functional echo-planar imaging

Purpose: To minimize artifacts in echo-planar imaging (EPI) of human brain function introduced by simultaneous transcranial magnetic stimulation (TMS). Materials and Methods: Distortions due to TMS pulses (0.25 msec, 2.0 T) were studied at 2.0 T before and during EPI. Results: Best results were obtained if both the EPI section orientation and the frequency-encoding gradient were parallel to the plane of the TMS coil. Under these conditions, a TMS pulse caused image distortions when preceding the EPI sequence by less than 100 msec. Recordings with a magnetic field gradient pick-up coil revealed transient magnetic fields after TMS, which are generated by eddy currents in the TMS coil. TMS during image acquisition completely spoiled all transverse magnetizations and induced disturbances ranging from image corruption to mild image blurring, depending on the affected low and high spatial frequencies. Simultaneous TMS and radio-frequency (RF) excitation gave rise to T1- dependent signal changes that lasted for several seconds and yielded pronounced false-positive activations during functional brain mapping. Conclusion: To ensure reliable and robust combinations, TMS should be applied at least 100 msec before EPI while completely avoiding any pulses during imaging

A Future of Current Flow Modelling for Transcranial Electrical Stimulation?

Purpose of Review: Transcranialelectrical stimulation (tES) is used to non-invasively modulate brain activityin health and disease. Current flow modeling (CFM) provides estimates of whereand how much electrical current is delivered to in the brain during tES. Ittherefore holds promise as a method to reduce commonplace variability in tESdelivery and, in turn, the outcomes of stimulation. However, the adoption ofCFM has not yet been widespread and its impact on tES outcome variability isunclear. Here, we discuss the potential barriers to effective, practicalCFM-informed tES use. Recent Findings: CFMhas progressed from models based on concentric spheres to gyri-precise headmodels derived from individual MRI scans. Users can now estimate the intensityof electrical fields (E-fields), their spatial extent, and the direction ofcurrent flow in a target brain region during tES. Here. we consider the multi-dimensionalchallenge of implementing CFM to optimise stimulation dose: this requiresinformed decisions to prioritise E-field characteristics most likely to resultin desired stimulation outcomes, though the physiological consequences of themodelled current flow are often unknown. Second, we address the issue of adisconnect between predictions of E-field characteristics provided by CFMs andpredictions of the physiological consequences of stimulation which CFMs are notdesigned to address. Third, we discuss how ongoing development of CFM inconjunction with other modelling approaches could overcome these challengeswhile maintaining accessibility for widespread use. Summary: Theincreasing complexity and sophistication of CFM is a mandatory step towards dosecontrol and precise, individualised delivery of tES. However, it also riskscounteracting the appeal of tES as a straightforward, cost-effective tool forneuromodulation, particularly in clinical settings

Response repetition biases in human perceptual decisions are explained by activity decay in competitive attractor models

Animals and humans have a tendency to repeat recent choices, a phenomenon known as choice hysteresis. The mechanism for this choice bias remains unclear. Using an established, biophysically informed model of a competitive attractor network for decision making, we found that decaying tail activity from the previous trial caused choice hysteresis, especially during difficult trials, and accurately predicted human perceptual choices. In the model, choice variability could be directionally altered through amplification or dampening of post-trial activity decay through simulated depolarizing or hyperpolarizing network stimulation. An analogous intervention using transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (dlPFC) yielded a close match between model predictions and experimental results: net soma depolarizing currents increased choice hysteresis, while hyperpolarizing currents suppressed it. Residual activity in competitive attractor networks within dlPFC may thus give rise to biases in perceptual choices, which can be directionally controlled through non-invasive brain stimulation

Physiological characterisation of transcranial magnetic stimulation (TMS) using functional magnetic resonance imaging (fMRI).

Despite its widespread use, a striking lack of knowledge exists regarding the mechanism of action of transcranial magnetic stimulation (TMS). This thesis describes the physiological characterisation of repetitive TMS (rTMS) to the motor system by means of functional magnetic resonance imaging (fMRI). A detailed analysis of imaging artefacts arising from the simultaneous application of TMS-fMRI was conducted and subsequently, strategies were presented for unperturbed TMS-fMRI. Physiological responses during subthreshold high-frequency rTMS of the primary sensorimotor cortex (Ml/Sl) were visualised within distinct cortical motor regions, comprising PMd, SMA, and contralateral Ml/Sl, while no significant responses were evidenced in the area of stimulation. Repetitive TMS during or before motor behaviour illustrated the context- dependence of rTMS-induced activity changes. The first demonstration of TMS-fMRI at 3 Tesla provided evidence that subthreshold rTMS can activate distinct networks including subcortical motor regions. The subthreshold nature of rTMS was confirmed by simultaneous electromyographic recordings from the target muscle. Stimulation of the dorsal premotor cortex provided evidence that rTMS- evoked local activity changes depend on the input function. The capability of TMS to target distinct networks in the human brain was confirmed. TMS targets a set of cortical and subcortical structures. Local responses may not invariably be elicited, indicating that low levels of synaptic activity, as occurring at low-intensity stimulation, do not necessarily evoke corresponding changes in cortical haemodynamics. It is concluded that combined TMS-fMRI offers a means to assess the mechanism of action of TMS at high spatial and temporal resolution

Neural dynamics of illusory tactile pulling sensations

Directional tactile pulling sensations are integral to everyday life, but their neural mechanisms remain unknown. Prior accounts hold that primary somatosensory (SI) activity is sufficient to generate pulling sensations, with alternative proposals suggesting that amodal frontal or parietal regions may be critical. We combined high-density EEG with asymmetric vibration, which creates an illusory pulling sensation, thereby unconfounding pulling sensations from unrelated sensorimotor processes. Oddballs that created opposite direction pulls to common stimuli were compared to the same oddballs after neutral common stimuli (symmetric vibration) and to neutral oddballs. We found evidence against the sensory-frontal N140 and in favor of the midline P200 tracking the emergence of pulling sensations, specifically contralateral parietal lobe activity 264-320ms, centered on the intraparietal sulcus. This suggests that SI is not sufficient to generate pulling sensations, which instead depend on the parietal association cortex, and may reflect the extraction of orientation information and related spatial processing

High precision magnetoencephalography reveals increased right-inferior frontal gyrus beta power during response conflict

Flexibility of behavior and the ability to rapidly switch actions is critical for adaptive living in humans. It is well established that the right-inferior frontal gyrus (R-IFG) is recruited during outright action-stopping, relating to increased beta (12–30 Hz) power. It has also been posited that inhibiting incorrect response tendencies and switching is central to motor flexibility. However, it is not known if the commonly reported R-IFG beta signature of response inhibition in action-stopping is also recruited during response conflict, which would suggest overlapping networks for stopping and switching. In the current study, we analyzed high precision magnetoencephalography (hpMEG) data recorded with multiple within subject recording sessions (trials n > 10,000) from 8 subjects during different levels of response conflict. We hypothesized that a R-IFG-triggered network for response inhibition is domain general and therefore also involved in mediating response conflict. We tested whether R-IFG showed increased beta power dependent on the level of response conflict. Using event-related spectral perturbations and linear mixed modeling, we found that R-IFG beta power increased for response conflict trials. The R-IFG beta increase was specific to trials with strong response conflict, and increased R-IFG beta power related to less error. This supports a more generalized role for R-IFG beta, beyond simple stopping behavior towards response switching

Neural Signatures of Value Comparison in Human Cingulate Cortex during Decisions Requiring an Effort-Reward Trade-off

UNLABELLED: Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT: The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization

Neurodynamic Evidence Supports a Forced-Excursion Model of Decision-Making under Speed/Accuracy Instructions

Evolutionary pressures suggest that choices should be optimised to maximise rewards, by appropriately trading speed for accuracy. This speed-accuracy tradeoff (SAT) is commonly explained by variation in just the baseline-to-boundary distance, i.e. excursion, of accumulation-to-bound models of perceptual decision making. However, neural evidence is not consistent with this explanation. A compelling account of speeded choice should explain both overt behaviour and the full range of associated brain signatures. Here, we reconcile seemingly contradictory behavioural and neural findings. In two variants of the same experiment, we triangulated upon the neural underpinnings of the SAT in the human brain using both EEG and TMS. We found that distinct neural signals, namely the ERP centroparietal positivity (CPP) and a smoothed motor-evoked potential (MEP) signal, which have both previously been shown to relate to decision-related accumulation, revealed qualitatively similar average neurodynamic profiles with only subtle differences between SAT conditions. These signals were then modelled from behaviour by either incorporating traditional boundary variation or utilising a forced excursion. These model variants are mathematically equivalent, in terms of their behavioural predictions, hence providing identical fits to correct and erroneous reaction time distributions. However, the forced-excursion version instantiates SAT via a more global change in parameters and implied neural activity, a process conceptually akin to, but mathematically distinct from, urgency. This variant better captured both ERP and MEP neural profiles, suggesting that the SAT may be implemented via neural gain modulation, and reconciling standard modelling approaches with human neural data