Motor network dynamic resting state fMRI connectivity of neurotypical children in regions affected by cerebral palsy.

Background: Normative childhood motor network resting-state fMRI effective connectivity is undefined, yet necessary for translatable dynamic resting-state-network-informed evaluation in pediatric cerebral palsy. Methods: Cross-spectral dynamic causal modeling of resting-state-fMRI was investigated in 50 neurotypically developing 5- to 13-year-old children. Fully connected six-node network models per hemisphere included primary motor cortex, striatum, subthalamic nucleus, globus pallidus internus, thalamus, and contralateral cerebellum. Parametric Empirical Bayes with exhaustive Bayesian model reduction and Bayesian modeling averaging informed the model; Purdue Pegboard Test scores of hand motor behavior were the covariate at the group level to determine the effective-connectivity-functional behavior relationship. Results: Although both hemispheres exhibited similar effective connectivity of motor cortico-basal ganglia-cerebellar networks, magnitudes were slightly greater on the right, except for left-sided connections of the striatum which were more numerous and of opposite polarity. Inter-nodal motor network effective connectivity remained consistent and robust across subjects. Age had a greater impact on connections to the contralateral cerebellum, bilaterally. Motor behavior, however, affected different connections in each hemisphere, exerting a more prominent effect on the left modulatory connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. Discussion: This study revealed a consistent pattern of directed resting-state effective connectivity in healthy children aged 5-13 years within the motor network, encompassing cortical, subcortical, and cerebellar regions, correlated with motor skill proficiency. Both hemispheres exhibited similar effective connectivity within motor cortico-basal ganglia-cerebellar networks reflecting inter-nodal signal direction predicted by other modalities, mainly differing from task-dependent studies due to network differences at rest. Notably, age-related changes were more pronounced in connections to the contralateral cerebellum. Conversely, motor behavior distinctly impacted connections in each hemisphere, emphasizing its role in modulating left sided connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. Motor network effective connectivity was correlated with motor behavior, validating its physiological significance. This study is the first to evaluate a normative effective connectivity model for the pediatric motor network using resting-state functional MRI correlating with behavior and serves as a foundation for identifying abnormal findings and optimizing targeted interventions like deep brain stimulation, potentially influencing future therapeutic approaches for children with movement disorders.

Control over a mixture of policies determines change of mind topology during continuous choice.

Behavior is naturally organized into categorically distinct states with corresponding patterns of neural activity; how does the brain control those states? We propose that states are regulated by specific neural processes that implement meta-control that can blend simpler control processes. To test this hypothesis, we recorded from neurons in the dorsal anterior cingulate cortex (dACC) and dorsal premotor cortex (PMd) while macaques performed a continuous pursuit task with two moving prey that followed evasive strategies. We used a novel control theoretic approach to infer subjects' moment-to-moment latent control variables, which in turn dictated their blend of distinct identifiable control processes. We identified low-dimensional subspaces in neuronal responses that reflected the current strategy, the value of the pursued target, and the relative value of the two targets. The top two principal components of activity tracked changes of mind in abstract and change-type-specific formats, respectively. These results indicate that control of behavioral state reflects the interaction of brain processes found in dorsal prefrontal regions that implement a mixture over low-level control policies.

Transcranial focused ultrasound to human rIFG improves response inhibition through modulation of the P300 onset latency.

Response inhibition in humans is important to avoid undesirable behavioral action consequences. Neuroimaging and lesion studies point to a locus of inhibitory control in the right inferior frontal gyrus (rIFG). Electrophysiology studies have implicated a downstream event-related potential from rIFG, the fronto-central P300, as a putative neural marker of the success and timing of inhibition over behavioral responses. However, it remains to be established whether rIFG effectively drives inhibition and which aspect of P300 activity uniquely indexes inhibitory control-ERP timing or amplitude. Here, we dissect the connection between rIFG and P300 for inhibition by using transcranial-focused ultrasound (tFUS) to target rIFG of human subjects while they performed a Stop-Signal task. By applying tFUS simultaneously with different task events, we found behavioral inhibition was improved, but only when applied to rIFG simultaneously with a 'stop' signal. Improved inhibition through tFUS to rIFG was indexed by faster stopping times that aligned with significantly shorter N200/P300 onset latencies. In contrast, P300 amplitude was modulated during tFUS across all groups without a paired change in behavior. Using tFUS, we provide evidence for a causal connection between anatomy, behavior, and electrophysiology underlying response inhibition.

Semi-orthogonal subspaces for value mediate a tradeoff between binding and generalization.

When choosing between options, we must associate their values with the action needed to select them. We hypothesize that the brain solves this binding problem through neural population subspaces. To test this hypothesis, we examined neuronal responses in five reward-sensitive regions in macaques performing a risky choice task with sequential offers. Surprisingly, in all areas, the neural population encoded the values of offers presented on the left and right in distinct subspaces. We show that the encoding we observe is sufficient to bind the values of the offers to their respective positions in space while preserving abstract value information, which may be important for rapid learning and generalization to novel contexts. Moreover, after both offers have been presented, all areas encode the value of the first and second offers in orthogonal subspaces. In this case as well, the orthogonalization provides binding. Our binding-by-subspace hypothesis makes two novel predictions borne out by the data. First, behavioral errors should correlate with putative spatial (but not temporal) misbinding in the neural representation. Second, the specific representational geometry that we observe across animals also indicates that behavioral errors should increase when offers have low or high values, compared to when they have medium values, even when controlling for value difference. Together, these results support the idea that the brain makes use of semi-orthogonal subspaces to bind features together.

Abstract Value Encoding in Neural Populations But Not Single Neurons.

An important open question in neuroeconomics is how the brain represents the value of offers in a way that is both abstract (allowing for comparison) and concrete (preserving the details of the factors that influence value). Here, we examine neuronal responses to risky and safe options in five brain regions that putatively encode value in male macaques. Surprisingly, we find no detectable overlap in the neural codes used for risky and safe options, even when the options have identical subjective values (as revealed by preference) in any of the regions. Indeed, responses are weakly correlated and occupy distinct (semi-orthogonal) encoding subspaces. Notably, however, these subspaces are linked through a linear transform of their constituent encodings, a property that allows for comparison of dissimilar option types. This encoding scheme allows these regions to multiplex decision related processes: they can encode the detailed factors that influence offer value (here, risky and safety) but also directly compare dissimilar offer types. Together these results suggest a neuronal basis for the qualitatively different psychological properties of risky and safe options and highlight the power of population geometry to resolve outstanding problems in neural coding.SIGNIFICANCE STATEMENT To make economic choices, we must have some mechanism for comparing dissimilar offers. We propose that the brain uses distinct neural codes for risky and safe offers, but that these codes are linearly transformable. This encoding scheme has the dual advantage of allowing for comparison across offer types while preserving information about offer type, which in turn allows for flexibility in changing circumstances. We show that responses to risky and safe offers exhibit these predicted properties in five different reward-sensitive regions. Together, these results highlight the power of population coding principles for solving representation problems in economic choice.

Subspace orthogonalization as a mechanism for binding values to space.

When choosing between options, we must solve an important binding problem. The values of the options must be associated with information about the action needed to select them. We hypothesize that the brain solves this binding problem through use of distinct population subspaces. To test this hypothesis, we examined the responses of single neurons in five reward-sensitive regions in rhesus macaques performing a risky choice task. In all areas, neurons encoded the value of the offers presented on both the left and the right side of the display in semi-orthogonal subspaces, which served to bind the values of the two offers to their positions in space. Supporting the idea that this orthogonalization is functionally meaningful, we observed a session-to-session covariation between choice behavior and the orthogonalization of the two value subspaces: trials with less orthogonalized subspaces were associated with greater likelihood of choosing the less valued option. Further inspection revealed that these semi-orthogonal subspaces arose from a combination of linear and nonlinear mixed selectivity in the neural population. We show this combination of selectivity balances reliable binding with an ability to generalize value across different spatial locations. These results support the hypothesis that semi-orthogonal subspaces support reliable binding, which is essential to flexible behavior in the face of multiple options.

Modulation of cortical beta oscillations influences motor vigor: A rhythmic TMS-EEG study.

Previous electro- or magnetoencephalography (Electro/Magneto EncephaloGraphic; E/MEG) studies using a correlative approach have shown that ß (13-30 Hz) oscillations emerging in the primary motor cortex (M1) are implicated in regulating motor response vigor and associated with an anti-kinetic role, that is, slowness of movement. However, the functional role of M1 ß oscillations in regulation of motor responses remains unclear. To address this gap, we combined EEG with rhythmic TMS (rhTMS) delivered to M1 at the ß (20 Hz) frequency shortly before subjects performed an isometric ramp-and-hold finger force production task at three force levels. rhTMS is a novel approach that can modulate rhythmic patterns of neural activity. ß-rhTMS over M1 induced a modulation of neural oscillations to ß frequency in the sensorimotor area and reduced peak force rate during the ramp-up period relative to sham and catch trials. Interestingly, this rhTMS effect occurred only in the large force production condition. To distinguish whether the effects of rhTMS on EEG and behavior stemmed from phase-resetting by each magnetic pulse or neural entrainment by the periodicity of rhTMS, we performed a control experiment using arrhythmic TMS (arTMS). arTMS did not induce changes in EEG oscillations nor peak force rate during the rump-up period. Our results provide novel evidence that ß neural oscillations emerging the sensorimotor area influence the regulation of motor response vigor. Furthermore, our findings further demonstrate that rhTMS is a promising tool for tuning neural oscillations to the target frequency.

Discerning Seizure-Onset v. Propagation Zone: Pre-and-Post-Operative Resting-State fMRI Directionality and Boerwinkle Neuroplasticity Index.

The goal of this study was to determine resting state fMRI (rs-fMRI) effective connectivity (RSEC) capacity, agnostic of epileptogenic events, in distinguishing seizure onset zones (SOZ) from propagation zones (pZ). Consecutive patients (2.1-18.2 years old), with epilepsy and hypothalamic hamartoma, pre-operative rs-fMRI-directed surgery, post-operative imaging, and Engel class I outcomes were collected. Cross-spectral dynamic causal modelling (DCM) was used to estimate RSEC between the ablated rs-fMRI-SOZ to its region of highest connectivity outside the HH, defined as the propagation zone (pZ). Pre-operatively, RSEC from the SOZ and PZ was expected to be positive (excitatory), and pZ to SOZ negative (inhibitory), and post-operatively to be either diminished or non-existent. Sensitivity, accuracy, positive predictive value were determined for node-to-node connections. A Parametric Empirical Bayes (PEB) group analysis on pre-operative data was performed to identify group effects and effects of Engel class outcome and age. Pre-operative RSEC strength was also evaluated for correlation with percent seizure frequency improvement, sex, and region of interest size. Of the SOZ's RSEC, only 3.6% had no connection of significance to the pZ when patient models were individually reduced. Among remaining, 96% were in expected (excitatory signal found from SOZ â†’ pZ and inhibitory signal found from pZ â†’ SOZ) versus 3.6% reversed polarities. Both pre-operative polarity signals were equivalently as expected, with one false signal direction out of 26 each (3.7% total). Sensitivity of 95%, specificity 73%, accuracy of 88%, negative predictive value 88%, and positive predictive value of 88% in identifying and differentiating the SOZ and pZ. Groupwise PEB analysis confirmed SOZ â†’ pZ EC was excitatory, and pZ â†’ SOZ EC was inhibitory. Patients with better outcomes (Engel Ia vs. Ib) showed stronger inhibitory signal (pZ â†’ SOZ). Age was negatively associated with absolute RSEC bidirectionally but had no relationship with Directionality SOZ identification performance. In an additional hierarchical PEB analysis identifying changes from pre-to-post surgery, SOZ â†’ pZ modulation became less excitatory and pZ â†’ SOZ modulation became less inhibitory. This study demonstrates the accuracy of Directionality to identify the origin of excitatory and inhibitory signal between the surgically confirmed SOZ and the region of hypothesized propagation zone in children with DRE due to a HH. Thus, this method validation study in a homogenous DRE population may have potential in narrowing the SOZ-candidates for epileptogenicity in other DRE populations and utility in other neurological disorders.

The whole prefrontal cortex is premotor cortex.

We propose that the entirety of the prefrontal cortex (PFC) can be seen as fundamentally premotor in nature. By this, we mean that the PFC consists of an action abstraction hierarchy whose core function is the potentiation and depotentiation of possible action plans at different levels of granularity. We argue that the apex of the hierarchy should revolve around the process of goal-selection, which we posit is inherently a form of optimization over action abstraction. Anatomical and functional evidence supports the idea that this hierarchy originates on the orbital surface of the brain and extends dorsally to motor cortex. Accordingly, our viewpoint positions the orbitofrontal cortex in a key role in the optimization of goal-selection policies, and suggests that its other proposed roles are aspects of this more general function. Our proposed perspective will reframe outstanding questions, open up new areas of inquiry and align theories of prefrontal function with evolutionary principles. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.

Neural correlates of visual attention during risky decision evidence integration.

Value-based decision-making is presumed to involve a dynamic integration process that supports assessing the potential outcomes of different choice options. Decision frameworks assume the value of a decision rests on both the desirability and risk surrounding an outcome. Previous work has highlighted neural representations of risk in the human brain, and their relation to decision choice. Key neural regions including the insula and anterior cingulate cortex (ACC) have been implicated in encoding the effects of risk on decision outcomes, including approach and avoidance. Yet, it remains unknown whether these regions are involved in the dynamic integration processes that precede and drive choice, and their relationship with ongoing attention. Here, we used concurrent fMRI and eye-tracking to discern neural activation related to visual attention preceding choice between sure-thing (i.e. safe) and risky gamble options. We found activation in both dorsal ACC (dACC) and posterior insula (PI) scaled in opposite directions with the difference in attention to risky rewards relative to risky losses. PI activation also differentiated foveations on both risky options (rewards and losses) relative to a sure-thing option. These findings point to ACC involvement in ongoing evaluation of risky but higher value options. The role of PI in risky outcomes points to a more general evaluative role in the decision-making that compares both safe and risky outcomes, irrespective of potential for gains or losses.

Dexterous Object Manipulation Requires Context-Dependent Sensorimotor Cortical Interactions in Humans.

Dexterous object manipulation is a hallmark of human evolution and a critical skill for everyday activities. A previous work has used a grasping context that predominantly elicits memory-based control of digit forces by constraining where the object should be grasped. For this "constrained" grasping context, the primary motor cortex (M1) is involved in storage and retrieval of digit forces used in previous manipulations. In contrast, when choice of digit contact points is allowed ("unconstrained" grasping), behavioral studies revealed that forces are adjusted, on a trial-to-trial basis, as a function of digit position. This suggests a role of online feedback of digit position for force control. However, despite the ubiquitous nature of unconstrained hand-object interactions in activities of daily living, the underlying neural mechanisms are unknown. Using noninvasive brain stimulation, we found the role of primary motor cortex (M1) and somatosensory cortex (S1) to be sensitive to grasping context. In constrained grasping, M1 but not S1 is involved in storing and retrieving learned digit forces and position. In contrast, in unconstrained grasping, M1 and S1 are involved in modulating digit forces to position. Our findings suggest that the relative contribution of memory and online feedback modulates sensorimotor cortical interactions for dexterous manipulation.

Neural oscillations reflect latent learning states underlying dual-context sensorimotor adaptation.

Recent studies have suggested that individuals can form multiple motor memories when simultaneously adapting to multiple, but oppositely-oriented perturbations. These findings predict that individuals detect the change in learning context, allowing the selective initialization and update of motor memories. However, previous electrophysiological studies of sensorimotor adaptation have not identified a neural mechanism supporting the detection of a context switch and adaptation to separate contexts. Here, we tested the hypothesis that such a mechanism is identifiable through neural oscillations measured through EEG. Human participants learned to manipulate an object in two opposite contexts (mass distribution). This task was designed based on previous work showing that people can adapt to both contexts. We found that sensorimotor α and ß, and medial frontal θ frequency bands all exhibited different response patterns with respect to the error in each context. To determine whether any frequency's responses to error were distinctly related to a switch in context, we predicted single-trial EEG data from a computational learning model that can adapt to multiple contexts simultaneously based on a switching mechanism. This analysis revealed that only medial frontal θ was predicted by a component of the model state that adapts to errors based on a context switch. In contrast, α and ß were predicted by a model state that was updated from performance errors independent of the context. These findings provide novel evidence showing that sensorimotor and medial frontal oscillations are predicted by different adaptation processes, and that changes in medial frontal activity may indicate the formation of motor memories by responding to changes in learning context.

Perceived heaviness in the context of Newton's Second Law: Combined effects of muscle activity and lifting kinematics.

Researchers generally agree that perceived heaviness is based on the actions associated with unsupported holding. Psychophysical research has supported this idea, as has psychophysiological research connecting muscle activity to the perceptions of heaviness and effort. However, the role of muscle activity in the context of the resulting motions has not been investigated. In the present study, perceptions of heaviness were recorded along with the electromyogram (EMG) of the lifting muscle and peak acceleration of the lift. Consistent with predictions derived from Newton's Second Law of motion (Force=Mass × Acceleration), normal and illusory perceptions of heaviness were a function of the ratio of muscle activity to lifting acceleration. These results identify a psychophysiological mechanism for heaviness perception based on the forces and motions associated with unsupported holding.

Experimental control of scaling behavior: what is not fractal?

The list of psychological processes thought to exhibit fractal behavior is growing. Although some might argue that the seeming ubiquity of fractal patterns illustrates their significance, unchecked growth of that list jeopardizes their relevance. It is important to identify when a single behavior is and is not fractal in order to make meaningful conclusions about the processes underlying those patterns. The hypothesis tested in the present experiment is that fractal patterns reflect the enactment of control. Participants performed two steering tasks: steering on a straight track and steering on a circular track. Although each task could be accomplished by holding the steering wheel at a constant angle, steering around a curve may require more constant control, at least from a psychological standpoint. Results showed that evidence for fractal behavior was strongest for the circular track; straight tracks showed evidence of two scaling regions. We argue from those results that, going forward, the goal of the fractal literature should be to bring scaling behavior under experimental control.

Emergent complexity matching in interpersonal coordination: Local dynamics and global variability.

Rhythmic coordination with stimuli and other people's movements containing variable or unpredictable fluctuations might involve distinct processes: detecting the fluctuation structure and tuning to or matching the structure's temporal complexity. This framework predicts that global tuning and local parameter adjustments (e.g., position, velocity or phase) can operate independently during coordination (Marmelat & Delignières, 2012). Alternatively, we propose that complexity matching is a result of local phase adjustments during coordination (Delignières & Marmelat, 2014; Torre, Varlet, & Marmelat, 2013). The current study examined this relationship in a rhythmic interpersonal coordination task. Dyads coordinated swinging pendulums that differed in their uncoupled frequencies (detuning). We predicted that frequency detuning would require increased local corrections to maintain the intended phase pattern (in phase). This was expected to yield a relative phase shift accompanied by a change in period complexity and matching. Experimental data and numerical modeling of the pendulum dynamics confirmed our predictions. Increased relative phase shifts occurred simultaneously with increased dissociation between individuals' movement period complexity. This provided evidence that global complexity matching is intricately linked to local movement adjustments and is not a distinct coordination mechanism. These findings are considered with respect to dynamical and computational approaches to interpersonal coordination.

Manual coordination with intermittent targets: velocity information for prospective control.

Tracking a moving target requires that information concerning the current and future state of a target is available, allowing prospective control of the tracking effector. Eye movement research has shown that prospective visual tracking is achievable during conditions of both visible and occluded targets. The ability to track visually occluded targets has been interpreted as individuals integrating target velocity into eye movement motor plans. It has not been fully established that velocity plays a similar role in other types of tracking behavior. To examine whether target velocity is also used in manual tracking, numerical predictions and a validation experiment were conducted. Predictions indicated that, if individuals utilize target velocity during coordination, increases in visual occlusion periods should yield increased phase lag between target and hand, proportional to the occlusion period. Predictions also suggest that increased occlusion yields increased coordination variability. An experiment having participants coordinate with the same stimuli and occlusion conditions was conducted to verify the predictions. Comparison of prediction and experimental results provides strong agreement that individuals use target velocity to prospectively control coordinated movements.

Stabilizing perceptual-motor asymmetries during social coordination.

The current paper presents two studies that examine how we compensate for asymmetries during interpersonal coordination. It was predicted that destabilizing effects of asymmetries are offset through the recruitment and suppression of motor degrees-of-freedom (df). In Experiment 1, this effect was examined by having participants coordinate line movements of different orientations. Greater asymmetries between participants yielded greater spatial deviation from the intended orientation, suggesting a recruitment of df. In Experiment 2, participants coordinated circle and line movements. Results showed that line became more circular and circles became more linear, specifically along the axis of the line movements. These results suggested that df were both systematically suppressed (in the case of circle movements) and recruited (in the case of line movements) to stabilize an asymmetric coordination task.

Congruency effects in interpersonal coordination.

Research on interpersonal coordination has demonstrated that incongruent tasks lead to unintended movements in the orthogonal plane. These effects have been interpreted using both an embodied simulation and coordination dynamics approach. To distinguish between these two perspectives, two experiments examined whether this congruency effect is best defined spatially or anatomically. In the first experiment, participants coordinated congruent and incongruent rhythmic arm movements with an actor. To dissociate spatial and anatomical congruency, the actor was rotated 90° in the coronal plane for half of the trials. In the second experiment, participants coordinated movements of different limbs (leg and arm). Spatial and anatomical congruency was dissociated here by rotating the actor in the transverse plane. In both experiments, the unintended movements associated with the congruency effect emerged as a function of spatial congruency; there was no congruency effect associated with anatomical congruency. The data suggests that these unintended movements represent the recruitment of additional df necessary to stabilize an unstable form of coordination.

Interpersonal Fitts' law: when two perform as one.

Intra- and interpersonal coordination was investigated using a bimanual Fitts' law task. Participants tapped rhythmically between pairs of targets. Tapping was performed with one hand (unimanual), two hands (intrapersonal coordination), and one hand together with another participant (interpersonal coordination). The sizes and distances of targets in a pair were manipulated independently for each hand. When target difficulty was unequal across hands, movement times were similar in the coordination conditions, in violation of Fitts' law. Processing speed (measured by index of performance) increased for more difficult tasks, suggesting increased attention, even for dyads. These findings suggest that similar processes, not captured by centralized control, guide coordination for both individuals and dyads. Measures of coordination, though, still showed stronger coordination tendencies for intrapersonal coordination, indicating a possible role for centralized mechanisms.