Gaurav Misra

Neuroimaging Evidence of Motor Control and Pain Processing in the Human Midcingulate Cortex

Human neuroimaging and virus-tracing studies in monkey predict that motor control and pain processes should overlap in anterior midcingulate cortex (aMCC), but there is currently no direct evidence that this is the case. We used a novel functional magnetic resonance imaging paradigm to examine brain activity while subjects performed a motor control task, experienced a pain-eliciting stimulus on their hand, and performed the motor control task while also experiencing the pain-eliciting stimulus. Our experiment produced 3 novel results. First, group-level analyses showed that when separate trials of motor control and pain processing were performed, overlapping functional activity was found in the same regions of aMCC, supplementary motor area (SMA), anterior insula, and putamen. Secondly, increased activity was found in the aMCC and SMA when motor control and pain processing occurred simultaneously. Thirdly, individual-level analyses showed that 93% of subjects engaged the same region of aMCC during separate trials of motor control and pain processing irrespective of differences in the sulcal/gyral morphology of the cingulate cortex across individuals. These observations provide direct evidence in humans that the same region of aMCC is engaged for motor control and pain processing.

Effects of dynein on microtubule mechanics and centrosome positioning.

When microtubules are severed by laser ablation, newly created minus ends increase in curvature, but they straighten when dynein is inhibited. It is found that cytoplasmic dynein generates tension and friction along microtubule lengths and that these forces govern the dynamics of centrosome centering.

Increased force variability in chronic stroke: contributions of force modulation below 1 Hz.

Increased force variability constitutes a hallmark of arm disabilities following stroke. Force variability is related to the modulation of force below 1 Hz in healthy young and older adults. However, whether the increased force variability observed post stroke is related to the modulation of force below 1 Hz remains unknown. Thus, the purpose of this study was to compare force modulation below 1 Hz in chronic stroke and age-matched healthy individuals. Both stroke and control individuals (N = 26) performed an isometric grip task to submaximal force levels. Coefficient of variation quantified force variability, and power spectrum density of force quantified force modulation below 1 Hz with a high resolution (0.07 Hz). Analyses indicated that force variability was greater for the stroke group compared with to healthy controls and for the paretic hand compared with the non-paretic hand. Force modulation below 1 Hz differentiated the stroke individuals and healthy controls, as well as the paretic and non-paretic hands. Specifically, stroke individuals (paretic hand) exhibited greater power ∼0.2 Hz (0.07–0.35 Hz) and lesser power ∼0.6 Hz (0.49–0.77 Hz) compared to healthy controls (non-dominant hand). Similarly, the paretic hand exhibited greater power ∼0.2 Hz, and lesser power ∼0.6 Hz than the non-paretic hand. Moreover, variability of force was strongly predicted from the modulation of specific frequencies below 1 Hz (R 2 = 0.80). Together, these findings indicate that the modulation of force below 1 Hz provides significant insight into changes in motor control after stroke.

Pain-Related Suppression of Beta Oscillations Facilitates Voluntary Movement

Abstract Increased beta oscillations over sensorimotor cortex are antikinetic. Motor‐ and pain‐related processes separately suppress beta oscillations over sensorimotor cortex leading to the prediction that ongoing pain should facilitate movement. In the current study, we used a paradigm in which voluntary movements were executed during an ongoing pain‐eliciting stimulus to test the hypothesis that a pain‐related suppression of beta oscillations would facilitate the initiation of a subsequent voluntary movement. Using kinematic measures, electromyography, and high‐density electroencephalography, we demonstrate that ongoing pain leads to shorter reaction times without affecting the kinematics or accuracy of movement. Reaction time was positively correlated with beta power prior to movement in contralateral premotor areas. Our findings corroborate the view that beta‐band oscillations are antikinetic and provide new evidence that pain primes the motor system for action. Our observations provide the first evidence that a pain‐related suppression of beta oscillations over contralateral premotor areas leads to shorter reaction times for voluntary movement.

Mechanics of Vorticella Contraction

Vorticella convallaria is one of a class of fast-moving organisms that can traverse its body size in less than a millisecond by rapidly coiling a slender stalk anchoring it to a nearby surface. The stalk houses a fiber called the spasmoneme, which winds helically within the stalk and rapidly contracts in response to calcium signaling. We have developed a coupled mechanical-chemical model of the coiling process, accounting for the coiling of the elastic stalk and the binding of calcium to the protein spasmin. Simulations of the model describe the contraction and recovery processes quantitatively. The stalk-spasmoneme system is shown to satisfy geometric constraints, which explains why the cell body sometimes rotates during contraction. The shape of the collapsing and recovering stalk bounds its effective bending stiffness. Simulations suggest that recovery from the contracted state is driven by the stalk at a rate controlled by dissociation of calcium from spasmin.

Effects of a Force Production Task and a Working Memory Task on Pain Perception

UNLABELLED The goal in the current study was to examine the analgesic effects of a pinch grip-force production task and a working memory task when pain-eliciting thermal stimulation was delivered simultaneously to the left or right hand during task performance. Control conditions for visual distraction and thermal stimulation were included, and force performance measures and working memory performance measures were collected and analyzed. Our experiments revealed 3 novel findings. First, we showed that accurate isometric force contractions elicit an analgesic effect when pain-eliciting thermal stimulation was delivered during task performance. Second, the magnitude of the analgesic effect was not different when the pain-eliciting stimulus was delivered to the left or right hand during the force task or the working memory task. Third, we found no correlation between analgesia scores during the force task and the working memory task. Our findings have clinical implications for rehabilitation settings because they suggest that acute force production by one limb influences pain perception that is simultaneously experienced in another limb. From a theoretical perspective, we interpret our findings on force and memory driven analgesia in the context of a centralized pain inhibitory response. PERSPECTIVE This article shows that force production and working memory have analgesic effects irrespective of which side of the body pain is experienced on. Analgesia scores were not correlated, however, suggesting that some individuals experience more pain relief from a force task as compared to a working memory task and vice versa.

Microstructural properties of premotor pathways predict visuomotor performance in chronic stroke

Microstructural properties of the corticospinal tract (CST) descending from the motor cortex predict strength and motor skill in the chronic phase after stroke. Much less is known about the relation between brain microstructure and visuomotor processing after stroke. In this study, individuals poststroke and age‐matched controls performed a unimanual force task separately with each hand at three levels of visual gain. We collected diffusion MRI data and used probabilistic tractography algorithms to identify the primary and premotor CSTs. Fractional anisotropy (FA) within each tract was used to predict changes in force variability across different levels of visual gain. Our observations revealed that individuals poststroke reduced force variability with an increase in visual gain, performed the force task with greater variability as compared with controls across all gain levels, and had lower FA in the primary motor and premotor CSTs. Our results also demonstrated that the CST descending from the premotor cortex, rather than the primary motor cortex, best predicted force variability. Together, these findings demonstrate that the microstructural properties of the premotor CST predict visual gain‐related changes in force variability in individuals poststroke. Hum Brain Mapp 37:2039–2054, 2016.

Dose-Response Effect of Isometric Force Production on the Perception of Pain

Isometric contractions can influence the way that we perceive pain, but conclusions on the dose-response effect of force amplitude on pain perception are limited because previous studies have not held the duration of force contractions constant while varying force amplitude. To address this issue we designed an experiment that allowed us to accurately guide the amplitude of an isometric pinch grip force contraction on a trial-by-trial basis, while a thermal pain eliciting stimulus was simultaneously delivered for the same duration to the non-contracting hand. Our results show that an increase in the amplitude of force produced by one hand corresponded with a decrease in pain perception in the opposite hand. Our observations provide novel evidence that the centralized inhibitory response that underlies analgesia is sensitive to and enhanced by stronger isometric contractions.

Beta-band activity and connectivity in sensorimotor and parietal cortex are important for accurate motor performance.

ABSTRACT Accurate motor performance may depend on the scaling of distinct oscillatory activity within the motor cortex and effective neural communication between the motor cortex and other brain areas. Oscillatory activity within the beta‐band (13–30 Hz) has been suggested to provide distinct functional roles for attention and sensorimotor control, yet it remains unclear how beta‐band and other oscillatory activity within and between cortical regions is coordinated to enhance motor performance. We explore this open issue by simultaneously measuring high‐density cortical activity and elbow flexor and extensor neuromuscular activity during ballistic movements, and manipulating error using high and low visual gain across three target distances. Compared with low visual gain, high visual gain decreased movement errors at each distance. Group analyses in 3D source‐space revealed increased theta‐, alpha‐, and beta‐band desynchronization of the contralateral motor cortex and medial parietal cortex in high visual gain conditions and this corresponded to reduced movement error. Dynamic causal modeling was used to compute connectivity between motor cortex and parietal cortex. Analyses revealed that gain affected the directionally‐specific connectivity across broadband frequencies from parietal to sensorimotor cortex but not from sensorimotor cortex to parietal cortex. These new findings provide support for the interpretation that broad‐band oscillations in theta, alpha, and beta frequency bands within sensorimotor and parietal cortex coordinate to facilitate accurate upper limb movement. Summary statement: Our findings establish a link between sensorimotor oscillations in the context of online motor performance in common source space across subjects. Specifically, the extent and distinct role of medial parietal cortex to sensorimotor beta connectivity and local domain broadband activity combine in a time and frequency manner to assist ballistic movements. These findings can serve as a model to examine whether similar source space EEG dynamics exhibit different time‐frequency changes in individuals with neurological disorders that cause movement errors. HIGHLIGHTSCortical activity and connectivity were examined during upper limb movement.Visual feedback gain led to better motor performance and increased muscle activity.Increased theta‐, alpha‐, and beta‐band desynchronization at high gain feedback.Increased parietal‐to‐motor cortex connectivity in the beta‐band at high gain feedback.Visual gain did not affect motor‐to‐parietal cortex connectivity.

Automated Classification of Pain Perception using High Density Electroencephalography Data

The translation of brief, millisecond-long pain-eliciting stimuli to the subjective perception of pain is associated with changes in theta, alpha, beta, and gamma oscillations over sensorimotor cortex. However, when a pain-eliciting stimulus continues for minutes, regions beyond the sensorimotor cortex, such as the prefrontal cortex, are also engaged. Abnormalities in prefrontal cortex have been associated with chronic pain states, but conventional, millisecond-long EEG paradigms do not engage prefrontal regions. In the current study, we collected high-density EEG data during an experimental paradigm in which subjects experienced a 4-s, low- or high-intensity pain-eliciting stimulus. EEG data were analyzed using independent component analyses, EEG source localization analyses, and measure projection analyses. We report three novel findings. First, an increase in pain perception was associated with an increase in gamma and theta power in a cortical region that included medial prefrontal cortex. Second, a decrease in lower beta power was associated with an increase in pain perception in a cortical region that included the contralateral sensorimotor cortex. Third, we used machine learning for automated classification of EEG data into low- and high-pain classes. Theta and gamma power in the medial prefrontal region and lower beta power in the contralateral sensorimotor region served as features for classification. We found a leave-one-out cross-validation accuracy of 89.58%. The development of biological markers for pain states continues to gain traction in the literature, and our findings provide new information that advances this body of work.NEW & NOTEWORTHY The development of a biological marker for pain continues to gain traction in literature. Our findings show that high- and low-pain perception in human subjects can be classified with 89% accuracy using high-density EEG data from prefrontal cortex and contralateral sensorimotor cortex. Our approach represents a novel neurophysiological paradigm that advances the literature on biological markers for pain.