Learning volition: A longitudinal study of developing intentional awareness in Tourette syndrome

Tourette syndrome (TS) is characterized by the presence of involuntary movements (tics) which are, at least partly, generated within ‘voluntary’ motor pathways. Here we reassess 16 TS patients (age 19 ± 2.3 years) who participated in a mental chronometry study of volition 5.5 years previously (Ganos C et al. Cortex. 2015 Mar.; 64:47–54), and 16 age-matched controls. Participants estimated the time of their own voluntary movements (Libet's M judgement), or of conscious intention to make voluntary movements (Libet's W judgement), in separate blocks. We considered M judgement as a control condition. Therefore, the experience of an intention to move occurring prior to actual movement onset, as measured by the W-M gap, was taken as the cardinal feature of volition. Time estimates of the TS group did not differ significantly from controls, for either M or W judgement. Further, M and W time estimates in the TS group had not changed significantly between the two assessments. However, exploratory analyses revealed a strong relation between disease duration and the development of M- and W-judgements: the longer was the disease duration, the less was the developmental increase in the W-M gap (linear regression, p = .003). In conclusion, our results suggest compromised development of experience of volition in developing TS patients. The developmental difficulty in processing internal premotor signals for voluntary actions could reflect the chronic persistence of tics from adolescence to adulthood

Oculogyric crises: Etiology, pathophysiology and therapeutic approaches

Oculogyric crisis (OGC) describes the clinical phenomenon of sustained dystonic, conjugate and typically upward deviation of the eyes lasting from seconds to hours. It was initially observed in patients with postencephalitic parkinsonism, but since then a number of conditions have been associated with OGC. These include drug-induced reactions, hereditary and sporadic movement disorders, and focal brain lesions. Here, we systematically review the literature and discuss the spectrum of disorders associated with OGC in order to aid clinicians place this rare but distinctive clinical sign into the appropriate diagnostic context. We also provide a brief synthesis of putative pathophysiological mechanisms, as well as therapeutic recommendations based on the literature and our own experience

Dopamine boosts intention and action awareness in Parkinson’s disease

Dopaminergic deficiency in Parkinson’s disease (PD) has been associated with underactivation of the supplementary motor area and a reduction of voluntary actions. In these patients, awareness of intention to act has been shown to be delayed. However, delayed awareness of intention to act has also been shown in patients with hyperdopaminergic states and an excess of unwilled movements, as in Tourette’s, and in patients with functional movement disorders. Hence, the role of dopamine in the awareness of intention and action remains unclear. 36 PD patients were tested ON and OFF dopaminergic medication and compared with 35 healthy age-matched controls. In addition, 17 PD patients with subthalamic deep brain stimulation (DBS) were tested ON medication and ON and OFF stimulation. Participants judged either the moment a self-generated action was performed, or the moment the urge to perform the action was felt, using the “Libet method”. Temporal judgments of intention and action awareness were comparable between unmedicated PD patients and controls. Dopaminergic medication boosted anticipatory awareness of both intentions and actions in PD patients, relative to an unmedicated condition. The difference between ON/OFF DBS was not statistically reliable. Functional improvement of motor ability in PD through dopaminergic supplementation leads to earlier awareness of both intention, and of voluntary action

High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation.

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted

Quantifying Whole Transcriptome Size, a Prerequisite for Understanding Transcriptome Evolution Across Species: An Example from a Plant Allopolyploid

Evolutionary biologists are increasingly comparing gene expression patterns across species. Due to the way in which expression assays are normalized, such studies provide no direct information about expression per gene copy (dosage responses) or per cell and can give a misleading picture of genes that are differentially expressed. We describe an assay for estimating relative expression per cell. When used in conjunction with transcript profiling data, it is possible to compare the sizes of whole transcriptomes, which in turn makes it possible to compare expression per cell for each gene in the transcript profiling data set. We applied this approach, using quantitative reverse transcriptase-polymerase chain reaction and high throughput RNA sequencing, to a recently formed allopolyploid and showed that its leaf transcriptome was approximately 1.4-fold larger than either progenitor transcriptome (70% of the sum of the progenitor transcriptomes). In contrast, the allopolyploid genome is 94.3% as large as the sum of its progenitor genomes and retains ≥93.5% of the sum of its progenitor gene complements. Thus, “transcriptome downsizing” is greater than genome downsizing. Using this transcriptome size estimate, we inferred dosage responses for several thousand genes and showed that the majority exhibit partial dosage compensation. Homoeologue silencing is nonrandomly distributed across dosage responses, with genes showing extreme responses in either direction significantly more likely to have a silent homoeologue. This experimental approach will add value to transcript profiling experiments involving interspecies and interploidy comparisons by converting expression per transcriptome to expression per genome, eliminating the need for assumptions about transcriptome size

A Genome-Wide Survey of Switchgrass Genome Structure and Organization

The perennial grass, switchgrass (Panicum virgatum L.), is a promising bioenergy crop and the target of whole genome sequencing. We constructed two bacterial artificial chromosome (BAC) libraries from the AP13 clone of switchgrass to gain insight into the genome structure and organization, initiate functional and comparative genomic studies, and assist with genome assembly. Together representing 16 haploid genome equivalents of switchgrass, each library comprises 101,376 clones with average insert sizes of 144 (HindIII-generated) and 110 kb (BstYI-generated). A total of 330,297 high quality BAC-end sequences (BES) were generated, accounting for 263.2 Mbp (16.4%) of the switchgrass genome. Analysis of the BES identified 279,099 known repetitive elements, >50,000 SSRs, and 2,528 novel repeat elements, named switchgrass repetitive elements (SREs). Comparative mapping of 47 full-length BAC sequences and 330K BES revealed high levels of synteny with the grass genomes sorghum, rice, maize, and Brachypodium. Our data indicate that the sorghum genome has retained larger microsyntenous regions with switchgrass besides high gene order conservation with rice. The resources generated in this effort will be useful for a broad range of applications

Interspecific introgression mediates adaptation to whole genome duplication

Adaptive gene flow is a consequential phenomenon across all kingdoms. While recognition is increasing, examples lack of bidirectional gene flow mediating adaptations at loci that manage core processes. We previously discovered concerted molecular changes among interacting members of meiotic machinery controlling crossover number upon adaptation to whole genome duplication (WGD) in Arabidopsis arenosa. Here we conduct a population genomic study to test the hypothesis that adaptation to WGD has been mediated by adaptive gene flow between A. arenosa and A. lyrata. We find that A. lyrata underwent WGD more recently than A. arenosa, suggesting that pre-adapted alleles have rescued nascent A. lyrata, but we also detect gene flow in the opposite direction at functionally interacting loci under the most extreme levels of selection. These data indicate that bidirectional gene flow allowed for survival after WGD and that the merger of these species is greater than the sum of their parts