Derek B. Archer

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

Progression markers of Parkinson’s disease are crucial for therapeutic development. Burciu et al. validate free-water in the substantia nigra as a progression marker at one- and four-year follow-up, in an international cohort of de novo Parkinson’s disease. One-year changes in free-water predict the progression of motor symptoms over four years.

A Template and Probabilistic Atlas of the Human Sensorimotor Tracts using Diffusion MRI

The purpose of this study was to develop a high-resolution sensorimotor area tract template (SMATT) which segments corticofugal tracts based on 6 cortical regions in primary motor cortex, dorsal premotor cortex, ventral premotor cortex, supplementary motor area (SMA), pre-supplementary motor area (preSMA), and primary somatosensory cortex using diffusion tensor imaging. Individual probabilistic tractography analyses were conducted in 100 subjects using the highest resolution data currently available. Tractography results were refined using a novel algorithm to objectively determine slice level thresholds that best minimized overlap between tracts while preserving tract volume. Consistent with tracing studies in monkey and rodent, our observations show that cortical topography is generally preserved through the internal capsule, with the preSMA tract remaining most anterior and the primary somatosensory tract remaining most posterior. We combine our results into a freely available white matter template named the SMATT. We also provide a probabilistic SMATT that quantifies the extent of overlap between tracts. Finally, we assess how the SMATT operates at the individual subject level in another independent data set, and in an individual after stroke. The SMATT and probabilistic SMATT provide new tools that segment and label sensorimotor tracts at a spatial resolution not previously available.

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.

Smile without euphoria induced by deep brain stimulation: a case report

Poststroke central pain (PSCP) can be a debilitating medication-refractory disorder. We report a single case where right unilateral ventral capsule/ventral striatum (VC/VS) deep brain stimulation was used to treat PSCP and inadvertently induced a smile without euphoria. The patient was a 69 year-old woman who had a stroke with resultant dysesthesia and allodynia in her left hemibody and also a painful left hemibody dystonia. In her case, VC/VS stimulation induced a smile phenomenon, but without a euphoric sensation. This phenomenon was different from the typical smile responses we have observed in obsessive-compulsive disorder cases. This difference was considered to be possibly attributable to impairment in the emotional smile pathway.

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.

A widespread visually-sensitive functional network relates to symptoms in essential tremor

Essential tremor is a neurological syndrome of heterogeneous pathology and aetiology that is characterized by tremor primarily in the upper extremities. This tremor is commonly hypothesized to be driven by a single or multiple neural oscillator(s) within the cerebello-thalamo-cortical pathway. Several studies have found an association of blood-oxygen level-dependent (BOLD) signal in the cerebello-thalamo-cortical pathway with essential tremor, but there is behavioural evidence that also points to the possibility that the severity of tremor could be influenced by visual feedback. Here, we directly manipulated visual feedback during a functional MRI grip force task in patients with essential tremor and control participants, and hypothesized that an increase in visual feedback would exacerbate tremor in the 4-12 Hz range in essential tremor patients. Further, we hypothesized that this exacerbation of tremor would be associated with dysfunctional changes in BOLD signal and entropy within, and beyond, the cerebello-thalamo-cortical pathway. We found that increases in visual feedback increased tremor in the 4-12 Hz range in essential tremor patients, and this increase in tremor was associated with abnormal changes in BOLD amplitude and entropy in regions within the cerebello-thalamo-motor cortical pathway, and extended to visual and parietal areas. To determine if the tremor severity was associated with single or multiple brain region(s), we conducted a birectional stepwise multiple regression analysis, and found that a widespread functional network extending beyond the cerebello-thalamo-motor cortical pathway was associated with changes in tremor severity measured during the imaging protocol. Further, this same network was associated with clinical tremor severity measured with the Fahn, Tolosa, Marin Tremor Rating Scale, suggesting this network is clinically relevant. Since increased visual feedback also reduced force error, this network was evaluated in relation to force error but the model was not significant, indicating it is associated with force tremor but not force error. This study therefore provides new evidence that a widespread functional network is associated with the severity of tremor in patients with essential tremor measured simultaneously at the hand during functional imaging, and is also associated with the clinical severity of tremor. These findings support the idea that the severity of tremor is exacerbated by increased visual feedback, suggesting that designers of new computing technologies should consider using lower visual feedback levels to reduce tremor in essential tremor.

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.

Free-water and free-water corrected fractional anisotropy in primary and premotor corticospinal tracts in chronic stroke

Measures from diffusion MRI have been used to characterize the corticospinal tract in chronic stroke. However, diffusivity can be influenced by partial volume effects from free‐water, region of interest placement, and lesion masking. We collected diffusion MRI from a cohort of chronic stroke patients and controls and used a bitensor model to calculate free‐water corrected fractional anisotropy (FAT) and free water (FW) in the primary motor corticospinal tract (M1‐CST) and the dorsal premotor corticospinal tract (PMd‐CST). Region of interest analyses and whole‐tract slice‐by‐slice analyses were used to assess between‐group differences in FAT and FW in each tract. Correlations between FAT and FW and grip strength were also examined. Following lesion masking and correction for multiple comparisons, relative increases in FW were found for the stroke group in large portions of the M1‐CST and PMd‐CST in the lesioned hemisphere. FW in cortical regions was the strongest predictor of grip strength in the stroke group. Our findings also demonstrated that FAT is sensitive to the direct effects of the lesion itself, thus after controlling for the lesion, differences in FAT in nonlesioned tissue were small and generally similar between hemispheres and groups. Our observations suggest that FW may be a robust biological measurement that can be used to assess microstructure in residual white matter after stroke. Hum Brain Mapp 38:4546–4562, 2017.

Motor-Evoked Pain Increases Force Variability in Chronic Jaw Pain

Musculoskeletal pain changes how people move. Although experimental pain is associated with increases in the variability of motor output, it is not clear whether motor-evoked pain in clinical conditions is also associated with increases in variability. In the current study, we measured jaw force production during a visually guided force paradigm in which individuals with chronic jaw pain and control subjects produced force at 2% of their maximum voluntary contraction (low target force level) and at 15% of their maximum voluntary contraction (high target force level). State measures of pain were collected before and after each trial. Trait measures of pain intensity and pain interference, self-report measures of jaw function, and measures of depression, anxiety, and fatigue were also collected. We showed that the chronic jaw pain group exhibited greater force variability compared with controls irrespective of the force level, whereas the accuracy of force production did not differ between groups. Furthermore, predictors of force variability shifted from trait measures of pain intensity and pain interference at the low force level to state measures of pain intensity at the high force level. Our observations show that motor-evoked jaw pain is associated with increases in force variability that are predicted by a combination of trait measures and state measures of pain intensity and pain interference. PERSPECTIVE Chronic jaw pain is characterized by increases in variability during force production, which can be predicted by pain intensity and pain interference. This report could help clinicians better understand the long-term consequences of chronic jaw pain on the motor system.