Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa.

BACKGROUND: Impaired movement vigor (bradykinesia) is a cardinal feature of Parkinson's disease (PD) and hypothesized to result from abnormal motivational processes-impaired motivation-vigor coupling. Dopamine replacement therapy (DRT) improves bradykinesia, but the response to DRT is multifaceted, comprising a short-duration response (SDR) and a long-duration response (LDR) only manifesting with chronic treatment. Prior experiments assessing motivation-vigor coupling in PD used chronically treated subjects, obscuring the roles of the SDR and LDR. METHODS: To disambiguate the SDR and LDR, 11 de novo PD subjects (6 male [M]:5 female [F]; mean age, 67) were studied before treatment, after an acute levodopa (l-dopa) dose, and in both the practical "off" (LDR) and "on" (LDR + SDR) states after chronic stable treatment. At each visit, subjects were characterized with a standard battery including the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and an incentivized joystick task to assess motor performance in response to varying rewards. RESULTS: l-Dopa induced a robust SDR and LDR, with further improvement in the combined SDR + LDR state. At baseline, after acute treatment (SDR), and after LDR induction, subjects did not exhibit the normal increase in movement speed with increasing reward. Only in the combined SDR + LDR state was there restoration of motivation-vigor coupling. CONCLUSIONS: Although consistent with prior results in chronically treated PD subjects, the significant improvement in motor performance observed with the SDR and LDR suggests that bradykinesia is not solely secondary to deficient modulation of motivational processes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Reward Accelerates the Preparation of Goal-directed Actions under Conflict.

Our goals sometimes conflict with our prepotent habitual responses, which often leads to impaired performance on a variety of tasks. People are better at exerting cognitive control to overcome prepotent and automatic responses when they are motivated by the prospect of reward. The standard experimental paradigms used to study this phenomenon examine free RTs that allow participants to select a variety of response strategies including delaying response initiation to avoid committing errors. However, this approach makes it difficult to determine which control processes are affected by reward. Does reward lead to improved performance via the inhibition of prepotent responses or the facilitation of goal-directed processing? Here, we use a forced-response paradigm to fix response initiation and systematically vary the time available for the cognitive processing necessary for response preparation. Using a probabilistic model that dissociates the preparation of habitual and goal-directed responses, we obtain evidence across multiple experiments (n = 87 people) that reward selectively accelerates the preparation of goal-directed actions in the context of conflict.

Reward modulates cortical representations of action.

People are capable of rapid improvements in performance when they are offered a reward. The neural mechanism by which this performance enhancement occurs remains unclear. We investigated this phenomenon by offering people monetary reward for successful performance in a sequence production task. We found that people performed actions more quickly and accurately when they were offered large reward. Increasing reward magnitude was associated with elevated activity throughout the brain prior to movement. Multivariate patterns of activity in these reward-responsive regions encoded information about the upcoming action. Follow-up analyses provided evidence that action decoding in pre-SMA and other motor planning areas was improved for large reward trials and successful action decoding in SMA was associated with improved performance. These results suggest that reward may enhance performance by enhancing neural representations of action used in motor planning.

Rewards interact with explicit knowledge to enhance skilled motor performance.

From typing on a keyboard to playing the piano, many everyday skills require the ability to quickly and accurately perform sequential movements. It is well known that the availability of rewards leads to increases in motivational vigor whereby people enhance both the speed and force of their movements. However, in the context of motor skills, it is unclear whether rewards also lead to more effective motor planning and action selection. Here, we trained human participants to perform four separate sequences in a skilled motor sequencing task. Two of these sequences were trained explicitly and performed with precues that allow for the planning of movements, while the other two were trained implicitly. Immediately following the introduction of performance-contingent monetary incentives, participants improved their performance on all sequences consistent with enhancements in motivational vigor. However, there was a much larger performance boost for explicitly trained sequences. We replicated these results in a second, preregistered experiment with an independent sample. We conclude from these experiments that rewards enhance both the planning of movements as well as motivational vigor.NEW & NOTEWORTHY Offering people rewards and incentives typically improves their performance on skilled motor tasks. However, the mechanisms by which motivation impacts motor skills remains unclear. In two experiments, we show that motivation impacts motor sequencing skills in two separate ways. First, the prospect of reward speeds up the execution of all actions. Second, rewards provide an additional boost to motor planning when explicit skill knowledge can be used to prepare movements in advance.

Out of control: diminished prefrontal activity coincides with impaired motor performance due to choking under pressure.

There are three non-exclusive theoretical explanations for the paradoxical collapse of performance due to large financial incentives. It has been proposed that "choking under pressure" is either due to distraction, interference via an increase in top-down control and performance monitoring, or excessive levels of arousal in the face of large losses. Given the known neural architecture involved in executive control and reward, we used fMRI of human participants during incentivized motor performance to provide evidence to support and/or reconcile these competing models in a visuomotor task. We show that the execution of a pre-trained motor task during neuroimaging is impaired by high rewards. BOLD activity occurring prior to movement onset is increased in dorsolateral prefrontal cortex and functional connectivity between this region and motor cortex is likewise increased just prior to choking. However, the extent of this increase in functional connectivity is inversely related to a participant's propensity to choke, suggesting that a failure in exerting top-down influence on motor control underlies choking under pressure due to large incentives. These results are consistent with a distraction account of choking and suggest that frontal influences on motor activity are necessary to protect performance from vulnerability under pressure.

Disruption of dorsolateral but not ventrolateral prefrontal cortex improves unconscious perceptual memories.

Attentive encoding often leads to more accurate responses in recognition memory tests. However, previous studies have described conditions under which taxing explicit memory resources by attentional distraction improved perceptual recognition memory without awareness. These findings lead to the hypothesis that explicit memory processes mediated by the prefrontal cortex (PFC) can interfere with memory processes necessary for implicit recognition memory. The present study directly tested this hypothesis by applying transcranial magnetic stimulation separately over either dorsolateral (DLPFC) or ventrolateral PFC (VLPFC) in humans before performance of a visual memory task. Disruption of DLPFC function led to improvement in recognition accuracy only in responses in which the participant's awareness of memory retrieval was absent. However, disruption of VLPFC function led to subtle shifts in recollection and familiarity accuracy. We conclude that explicit memory processes mediated by the DLPFC can indirectly interfere with implicit recognition memory.

Lateral Prefrontal Stimulation of Active Cortex With Theta Burst Transcranial Magnetic Stimulation Affects Subsequent Engagement of the Frontoparietal Network.

BACKGROUND: A critical unanswered question about therapeutic transcranial magnetic stimulation is what patients should do during treatment to optimize its effectiveness. Here, we address this lack of knowledge in healthy participants, testing the hypotheses that stimulating the left dorsolateral prefrontal cortex (dlPFC) while participants perform a working memory task will provide stronger effects on subsequent activation, perfusion, connectivity, and performance than stimulating resting dlPFC. METHODS: After a baseline functional magnetic resonance imaging session to localize dlPFC activation and the associated frontoparietal network (FPN) engaged by an n-back task, healthy participants (N = 40, 67.5% female) underwent 3 counterbalanced sessions, separated by several weeks, during which they received intermittent theta burst stimulation (iTBS) followed by magnetic resonance imaging scans as follows: 1) iTBS to the dlPFC while resting passively (passive), 2) iTBS to the dlPFC while performing the n-back task (active), and 3) iTBS to a vertex site, while not engaged in the n-back task and resting passively (control). RESULTS: We found no difference in n-back performance between the 3 conditions. However, FPN activation was reduced while performing the n-back task in the active condition relative to the passive and control conditions. There was no differential activity in the FPN on comparing passive with control conditions, i.e., there was no effect of the site of stimulation. We found no effects of state or site of stimulation on perfusion or connectivity with the dlPFC. CONCLUSIONS: In this study, the state of the brain while receiving iTBS affected FPN activation, possibly reflecting greater efficiency of FPN network activation when participants were stimulated while engaging the FPN.

The dynamic nature of top-down signals originating from prefrontal cortex: a combined fMRI-TMS study.

The prefrontal cortex (PFC) is proposed to be the source of top-down signals that can modulate extrastriate visual processing in accordance with behavioral goals, yet little direct causal evidence for this hypothesis exists. Using theta burst transcranial magnetic stimulation, we disrupted PFC function in human participants before performing a working memory task during fMRI scanning. PFC disruption decreased the tuning of extrastriate cortex responses, coinciding with decrements in working memory performance. We also found that activity in the homologous PFC region in the nonstimulated hemisphere predicted performance following disruption. Specifically, those participants with greater homologous PFC activity and greater connectivity between this region and extrastriate cortex were the most resistant to PFC disruption. These findings provide evidence for a compensatory mechanism following insults to the brain, and insight into the dynamic nature of top-down signals originating from the PFC.

Evidence for a Causal Dissociation of the McGurk Effect and Congruent Audiovisual Speech Perception via TMS.

Congruent visual speech improves speech perception accuracy, particularly in noisy environments. Conversely, mismatched visual speech can alter what is heard, leading to an illusory percept known as the McGurk effect. This illusion has been widely used to study audiovisual speech integration, illustrating that auditory and visual cues are combined in the brain to generate a single coherent percept. While prior transcranial magnetic stimulation (TMS) and neuroimaging studies have identified the left posterior superior temporal sulcus (pSTS) as a causal region involved in the generation of the McGurk effect, it remains unclear whether this region is critical only for this illusion or also for the more general benefits of congruent visual speech (e.g., increased accuracy and faster reaction times). Indeed, recent correlative research suggests that the benefits of congruent visual speech and the McGurk effect reflect largely independent mechanisms. To better understand how these different features of audiovisual integration are causally generated by the left pSTS, we used single-pulse TMS to temporarily impair processing while subjects were presented with either incongruent (McGurk) or congruent audiovisual combinations. Consistent with past research, we observed that TMS to the left pSTS significantly reduced the strength of the McGurk effect. Importantly, however, left pSTS stimulation did not affect the positive benefits of congruent audiovisual speech (increased accuracy and faster reaction times), demonstrating a causal dissociation between the two processes. Our results are consistent with models proposing that the pSTS is but one of multiple critical areas supporting audiovisual speech interactions. Moreover, these data add to a growing body of evidence suggesting that the McGurk effect is an imperfect surrogate measure for more general and ecologically valid audiovisual speech behaviors.

Reward influences the allocation but not the availability of resources in visual working memory.

Visual working memory possesses capacity constraints limiting the availability of resources for encoding and maintaining information. Studies have shown that prospective rewards improve performance on visual working memory tasks, but it remains unclear whether rewards increase total resource availability or simply influence the allocation of resources. Participants performed a continuous report visual working memory task with oriented grating stimuli. On each trial, participants were presented with a priority cue, which signaled the item most likely to be probed, and a reward cue, which signaled the magnitude of a performance-contingent reward. We showed that rewards decreased recall error for cued items and increased recall error for noncued items. This tradeoff was due to a change in the probability of successfully encoding a cued versus a noncued item rather than a change in recall precision or the probability of binding errors. Rewards did not modulate performance when priority cues were retroactively presented after the stimulus presentation period, indicating that rewards only affect resource allocation when participants are able to engage proactive control before encoding. Additionally, reward had no effect on visual working memory performance when priority cues were absent and thus unable to guide resource allocation. These findings indicate that rewards influence the flexible allocation of resources during selection and encoding in visual working memory, but do not augment total capacity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Influence of goals on modular brain network organization during working memory.

Introduction: Top-down control underlies our ability to attend relevant stimuli while ignoring irrelevant, distracting stimuli and is a critical process for prioritizing information in working memory (WM). Prior work has demonstrated that top-down biasing signals modulate sensory-selective cortical areas during WM, and that the large-scale organization of the brain reconfigures due to WM demands alone; however, it is not yet understood how brain networks reconfigure between the processing of relevant versus irrelevant information in the service of WM. Methods: Here, we investigated the effects of task goals on brain network organization while participants performed a WM task that required participants to detect repetitions (e.g., 0-back or 1-back) and had varying levels of visual interference (e.g., distracting, irrelevant stimuli). We quantified changes in network modularity-a measure of brain sub-network segregation-that occurred depending on overall WM task difficulty as well as trial-level task goals for each stimulus during the task conditions (e.g., relevant or irrelevant). Results: First, we replicated prior work and found that whole-brain modularity was lower during the more demanding WM task conditions compared to a baseline condition. Further, during the WM conditions with varying task goals, brain modularity was selectively lower during goal-directed processing of task-relevant stimuli to be remembered for WM performance compared to processing of distracting, irrelevant stimuli. Follow-up analyses indicated that this effect of task goals was most pronounced in default mode and visual sub-networks. Finally, we examined the behavioral relevance of these changes in modularity and found that individuals with lower modularity for relevant trials had faster WM task performance. Discussion: These results suggest that brain networks can dynamically reconfigure to adopt a more integrated organization with greater communication between sub-networks that supports the goal-directed processing of relevant information and guides WM.

The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest.

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes.

Heuristics contribute to sensorimotor decision-making under risk.

Research in psychophysics argues that incentivized sensorimotor decisions (such as deciding where to reach to get a reward) maximize expected gain, suggesting that these decisions may be impervious to cognitive biases and heuristics. We tested this hypothesis in two experiments, directly comparing the predictive accuracy of an optimal model and plausible suboptimal models. We obtained strong evidence that people deviated from the optimal strategy by excessively avoiding loss regions when the potential loss was zero and failing to shift far enough away from loss regions when potential losses outweighed the potential gains. Although allowing nonlinear distortions of value and probability information improved the fit of value-maximizing models, behavior was best described by a model encapsulating a simple heuristic strategy. This suggests that visuomotor decisions are likely influenced by biases and heuristics observed in more classical economic decision-making tasks.

Interactive effects of incentive value and valence on the performance of discrete action sequences.

Incentives can be used to increase motivation, leading to better learning and performance on skilled motor tasks. Prior work has shown that monetary punishments enhance on-line performance while equivalent monetary rewards enhance off-line skill retention. However, a large body of literature on loss aversion has shown that losses are treated as larger than equivalent gains. The divergence between the effects of punishments and reward on motor learning could be due to perceived differences in incentive value rather than valence per se. We test this hypothesis by manipulating incentive value and valence while participants trained to perform motor sequences. Consistent with our hypothesis, we found that large reward enhanced on-line performance but impaired the ability to retain the level of performance achieved during training. However, we also found that on-line performance was better with reward than punishment and that the effect of increasing incentive value was more linear with reward (small, medium, large) while the effect of value was more binary with punishment (large vs not large). These results suggest that there are differential effects of punishment and reward on motor learning and that these effects of valence are unlikely to be driven by differences in the subjective magnitude of gains and losses.

Continuous Theta Burst Stimulation to the Secondary Visual Cortex at 80% Active Motor Threshold Does Not Impair Central Vision in Humans During a Simple Detection Task.

Continuous theta burst stimulation (cTBS) is a powerful form of repetitive transcranial magnetic stimulation capable of suppressing cortical excitability for up to 50 min. A growing number of studies have applied cTBS to the visual cortex in human subjects to investigate the neural dynamics of visual processing, but few have specifically examined its effects on central vision, which has crucial implications for safety and inference on downstream cognitive effects. The present study assessed the safety of offline, neuronavigated cTBS to V2 by examining its effects on central vision performance. In this single-blind, randomized sham-controlled, crossover study, 17 healthy adults received cTBS (at 80% active motor threshold) and sham to V2 1-2 weeks apart. Their central vision (≤8°) was tested at 1-min (T1) and again at 50-min (T50) post-stimulation. Effects of condition (cTBS vs. sham) and time (T1 vs. T50) on accuracy and reaction time were examined using Bayes factor. Bayes factor results suggested that cTBS did not impair stimulus detection over the entire central visual field nor subfields at T1 or T50. Our results offer the first explicit evidence supporting that cTBS applied to V2 does not create blind spots in the central visual field in humans during a simple detection task. Any subtler changes to vision and downstream visual perception should be investigated in future studies.

Theta Burst Transcranial Magnetic Stimulation of Fronto-Parietal Networks: Modulation by Mental State.

Transcranial magnetic stimulation (TMS) treats neuropsychiatric disorders, but effects of stimulation are highly state-dependent and in most therapeutic applications, mental state is not controlled. This exploratory proposal will test the broad hypothesis that when TMS, specifically intermittent theta burst stimulation (iTBS), is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. We will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated fronto-parietal network (FPN), which subserves cognitive control, an important neural and behavioral target of therapeutic TMS. After a baseline functional magnetic resonance imaging (fMRI) session, iTBS will be administered to 40 healthy subjects in three sessions over three days in a within-subjects, cross-over design: (1) dlPFC stimulation by iTBS alone, (2) dlPFC stimulation by iTBS while simultaneously performing a cognitive task, and (3) vertex (control) iTBS stimulation. Immediately after each iTBS session, we will measure blood oxygenation level-dependent (BOLD) activation during a cognitive control task ("n-back" task) and during the resting state, using BOLD connectivity and arterial spin labeling (ASL). We will test hypotheses that persisting neural changes and performance enhancement induced by iTBS to the dlPFC, compared to iTBS to the vertex, will affect the FPN, and these effects will be modulated by whether or not subjects receive iTBS when they are engaged in a cognitive control task. Demonstrating this interaction between iTBS and mental state will lay critical groundwork for future studies to show how controlling mental state during TMS can improve therapeutic effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT04010461.

Limiting motor skill knowledge via incidental training protects against choking under pressure.

The paradoxical harmful effects of motivation and incentives on skilled performance ("choking under pressure") are observed in a wide variety of motor tasks. Two theories of this phenomenon suggest that choking under pressure occurs due to maladaptive attention and top-down control, either through distraction away from the task or interference via an overreliance on controlled processing of a skilled task. A third theory, overmotivation (or overarousal), suggests that under pressure, "instinctive" or Pavlovian approach/withdrawal responses compete with the desired response. Only the two former theories predict that choking under pressure would be less likely to occur if an individual is unaware of the skill over which to assert top-down control. Here we show that only participants who train and perform with premovement cues that allowed for preparatory movement planning choke under pressure due to large monetary incentives, and that this effect is independent of the level of skill attained. We provide evidence that this might be due to increased movement variability under performance pressure. In contrast, participants trained incidentally to reduce explicit skill knowledge do not modulate performance on the basis of incentives and appear immune to choking. These results are most consistent with distraction theories of choking and suggest that training strategies that limit awareness may lead to skills that are more robust under performance pressure.

Coupling between Theta Oscillations and Cognitive Control Network during Cross-Modal Visual and Auditory Attention: Supramodal vs Modality-Specific Mechanisms.

Cortical theta band oscillations (4-8 Hz) in EEG signals have been shown to be important for a variety of different cognitive control operations in visual attention paradigms. However the synchronization source of these signals as defined by fMRI BOLD activity and the extent to which theta oscillations play a role in multimodal attention remains unknown. Here we investigated the extent to which cross-modal visual and auditory attention impacts theta oscillations. Using a simultaneous EEG-fMRI paradigm, healthy human participants performed an attentional vigilance task with six cross-modal conditions using naturalistic stimuli. To assess supramodal mechanisms, modulation of theta oscillation amplitude for attention to either visual or auditory stimuli was correlated with BOLD activity by conjunction analysis. Negative correlation was localized to cortical regions associated with the default mode network and positively with ventral premotor areas. Modality-associated attention to visual stimuli was marked by a positive correlation of theta and BOLD activity in fronto-parietal area that was not observed in the auditory condition. A positive correlation of theta and BOLD activity was observed in auditory cortex, while a negative correlation of theta and BOLD activity was observed in visual cortex during auditory attention. The data support a supramodal interaction of theta activity with of DMN function, and modality-associated processes within fronto-parietal networks related to top-down theta related cognitive control in cross-modal visual attention. On the other hand, in sensory cortices there are opposing effects of theta activity during cross-modal auditory attention.

The Effect of Disruption of Prefrontal Cortical Function with Transcranial Magnetic Stimulation on Visual Working Memory.

It is proposed that feedback signals from the prefrontal cortex (PFC) to extrastriate cortex are essential for goal-directed processing, maintenance, and selection of information in visual working memory (VWM). In a previous study, we found that disruption of PFC function with transcranial magnetic stimulation (TMS) in healthy individuals impaired behavioral performance on a face/scene matching task and decreased category-specific tuning in extrastriate cortex as measured with functional magnetic resonance imaging (fMRI). In this study, we investigated the effect of disruption of left inferior frontal gyrus (IFG) function on the fidelity of neural representations of two distinct information codes: (1) the stimulus category and (2) the goal-relevance of viewed stimuli. During fMRI scanning, subjects were presented face and scene images in pseudo-random order and instructed to remember either faces or scenes. Within both anatomical and functional regions of interest (ROIs), a multi-voxel pattern classifier was used to quantitatively assess the fidelity of activity patterns representing stimulus category: whether a face or a scene was presented on each trial, and goal relevance, whether the presented image was task relevant (i.e., a face is relevant in a "Remember Faces" block, but irrelevant in a "Remember Scenes" block). We found a reduction in the fidelity of the stimulus category code in visual cortex after left IFG disruption, providing causal evidence that lateral PFC modulates object category codes in visual cortex during VWM. In addition, we found that IFG disruption caused a reduction in the fidelity of the goal relevance code in a distributed set of brain regions. These results suggest that the IFG is involved in determining the task-relevance of visual input and communicating that information to a network of regions involved in further processing during VWM. Finally, we found that participants who exhibited greater fidelity of the goal relevance code in the non-disrupted right IFG after TMS performed the task with the highest accuracy.