High torsional energy disulfides : relationship between cross-strand disulfides and right-handed staples

Redox-active disulfides are capable of being oxidized and reduced under physiological conditions. The enzymatic role of redox-active disulfides in thiol-disulfide reductases is well-known, but redox-active disulfides are also present in non-enzymatic protein structures where they may act as switches of protein function. Here, we examine disulfides linking adjacent β-strands (cross-strand disulfides), which have been reported to be redox-active. Our previous work has established that these cross-strand disulfides have high torsional energies, a quantity likely to be related to the ease with which the disulfide is reduced. We examine the relationship between conformations of disulfides and their location in protein secondary structures. By identifying the overlap between cross-strand disulfides and various conformations, we wish to address whether the high torsional energy of a cross-strand disulfide is sufficient to confer redox activity or whether other factors, such as the presence of the cross-strand disulfide in a strained β-sheet, are required.

TMS stimulus-response asymmetry in left- and right handed individuals

There have been inconsistencies in the literature regarding asymmetrical neural control and results of experiments using TMS techniques. Therefore, the aim of this study was to further our understanding of the neural relationships that may underlie performance asymmetry with respect to the distal muscles of the hand using a TMS stimulus–response curve technique. Twenty-four male subjects (12 right handed, 12 left handed) participated in a TMS stimulus–response (S–R) curve trial. Focal TMS was applied over the motor cortex to find the optimal position for the first dorsal interossei muscle and to determine rest threshold (RTh). Seven TMS intensities ranging from 90 to 150 % of RTh were delivered in 10 % increments. One single TMS block consisted of 16 stimuli at each intensity. Peak-to-peak amplitudes were measured and the S–R curve generated. In right-handed subjects, the mean difference in slopes between the right and left hand was −0.011 ± 0.03, while the mean difference between hands in left-handed subjects was −0.049 ± 0.08. Left-handed normalized data in right handers displayed a mean of 1.616 ± 1.019 (two-tailed t test p < 0.05). The left-handed group showed a significant change in the normalized slope as indicated by a mean of 1.693 ± 0.149 (two-tailed t test p < 0.00006). The results found in this study reinforce previous work which suggests that there is an asymmetry in neural drive that exists in both left- and right-handed individuals. However, the results show that the non-dominant motor hemisphere displays a greater amount of excitability than the dominant, which goes against the conventional dogma. This asymmetry indicates that the non-dominant hemisphere may have a higher level of excitation or a lower level of inhibition for both groups of participants.

Priming vs. rhyming : orthographic and phonological representations in the left and right hemispheres

The right cerebral hemisphere has long been argued to lack phonological processing capacity. Recently, however, a sex difference in the cortical representation of phonology has been proposed, suggesting discrete left hemisphere lateralization in males and more distributed, bilateral representation of function in females. To evaluate this hypothesis and shed light on sex differences in the phonological processing capabilities of the left and right hemispheres, we conducted two experiments. Experiment 1 assessed phonological activation implicitly (masked homophone priming), testing 52 (M = 25, F = 27; mean age 19.23 years, SD 1.64 years) strongly right-handed participants. Experiment 2 subsequently assessed the explicit recruitment of phonology (rhyme judgement), testing 50 (M = 25, F = 25; mean age 19.67 years, SD 2.05 years) strongly right-handed participants. In both experiments the orthographic overlap between stimulus pairs was strictly controlled using DICE [Brew, C., & McKelvie, D. (1996). Word-pair extraction for lexicography. In K. Oflazer & H. Somers (Eds.), Proceedings of the second international conference on new methods in language processing (pp. 45–55). Ankara: VCH], such that pairs shared (a) high orthographic and phonological similarity (e.g., not–KNOT); (b) high orthographic and low phonological similarity (e.g., pint–HINT); (c) low orthographic and high phonological similarity (e.g., use–EWES); or (d) low orthographic and low phonological similarity (e.g., kind–DONE). As anticipated, high orthographic similarity facilitated both left and right hemisphere performance, whereas the left hemisphere showed greater facility when phonological similarity was high. This difference in hemispheric processing of phonological representations was especially pronounced in males, whereas female performance was far less sensitive to visual field of presentation across both implicit and explicit phonological tasks. As such, the findings offer behavioural evidence indicating that though both hemispheres are capable of orthographic analysis, phonological processing is discretely lateralised to the left hemisphere in males, but available in both the left and right hemisphere in females.

A possible anatomical and biomechanical explanation of the 10% rule used in the clinical assessment of prehensile hand movements and handed dominance

Abstract
A current doctrine in the dynamometric approach to determine lateralization of hand function states that in 10% of cases, the non-dominant hand will be stronger than the dominant hand. In this study, a novel MRI based modelling approach was applied to the first dorsal introsseus muscle (FDI), to determine whether the 10% rule may be applied to the FDI and may be partially explained by the arrangement of the anatomical components of the FDI.

Methods
Initially the force generated by the thumb segment during an isometric pushing task in the horizontal plane was measured from 25 strongly right-handed young males. Nine of these participants then had structural magnetic resonance imaging (sMRI) of the thumb and index osseous compartment. A modelling technique was developed to extract the muscle data and quantify the muscle line of action onto to the first metacarpal bone segment in order to quantify the muscle force at the point of momentary rotation – equilibrium.

Results
Eight of 25 subjects exhibited stronger force from the left hand. Six out of nine subjects from the MRI possessed significantly greater angles of attachment of the index osseous compartment on the left (non-dominant) hand. These six subjects also generated greater maximal isometric forces from the FDI of the left side. There was a significantly greater muscle volume for the right FDI muscle as compared to the left as measured from the reconstructed MRI slice data.

Conclusions
The calculated force produced by the muscle is related to the angle of attachment of the muscle to bone in the index osseous compartment. The MRI findings indicate that the 10% rule may be anatomically and biomechanically explained.

The Influence of Task Characteristics on the Intermanual Asymmetry of Motor Overflow

The two studies reported here were designed to test the proposition that greater motor overflow occurs when movements are performed by the non-dominant hand. Unlike previous studies using normal adults, the task in these studies did not require force production. In the first study, a group of 19 right-handed participants performed unweighted finger lifting. That the frequency of motor overflow occurrence was the same regardless of which hand performed the task, did not support findings from other studies where tasks involving force production resulted in more overflow when performed by the non-dominant hand. To investigate further the influence of task characteristics on motor overflow occurrence, in the second study participants were required to remember and reproduce a prescribed sequence of four finger lifts. Left- and right-handed participants ( N =30) performed both single and sequenced finger lifting. The relative frequency of motor overflow (unintended lifts of fingers of the passive hand) was compared between hand preference groups, active hand and task type (single/sequenced). Contrary to the expectation that motor overflow would be greater for the sequenced finger lifting task, overflow was exhibited with a significantly greater frequency on single finger lifting. This finding indicates that task characteristics influence the pattern of overflow occurrence in normal adults. The task used in this study did not involve force production and did not result in an intermanual asymmetry of motor overflow. This contrasts with findings from other studies requiring adults to exert forces where greater overflow occurred when the non-dominant hand was active. However, this study confirms previous findings which show that left-handers produce greater overflow compared to right-handers regardless of the task being performed and the hand performing the task.

Foot-targeting in reaching and grasping

Foot positioning was investigated when right-handed (Experiment One) and left handed adults (Experiment Two) stopped walking to grasp a stationary 70 mm ball at shoulder height. In both experiments centroid location formed by the toe and heel coordinates relative to the object was highly consistent within a target-location condition, demonstrating a foot-targeting phenomenon. Centroid location in the anterior-posterior direction was uninfluenced by grasping hand but the centroid shifted right for left hand grasps and left for right hand grasps. With the target either centrally located or on the same side as the dominant hand, foot positioning brought the grasping hand closer to the target in the medial-lateral direction. When the target object was aligned with the shoulder opposite the dominant hand both groups adopted foot positions to the left of the target. Thus, neither group adopted optimal foot position when the target was located opposite their dominant hand. Foot orientation angle relative to the target was also influenced by choice of grasping hand. Collectively, the findings demonstrate a close association between grasping hand and foot position when approaching to reach and grasp an object but also suggest that foot-dominance may influence medial-lateral centroid location.

Motor-unit coherence and its relation with synchrony are influenced by training

The purpose of the study was to quantify the strength of motor-unit coherence from the left and right first dorsal interosseous muscles in untrained, skill-trained (musicians), and strength-trained (weightlifters) individuals who had long-term specialized use of their hand muscles. The strength of motor-unit coherence was quantified from a total of 394 motor-unit pairs in 13 subjects using data from a previous study in which differences were found in the strength of motor-unit synchronization depending on training status. In the present study, we found that the strength of motor-unit coherence was significantly greater in the left compared with the right hand of untrained right-handed subjects with the largest differences observed between 21 and 24 Hz. The strength of motor-unit coherence was lower in both hands of skill-trained subjects (21–27 Hz) and the right (skilled) hand of untrained subjects (21–24 Hz), whereas the largest motor-unit coherence was observed in both hands of strength-trained subjects (3–9 and 21–27 Hz). A strong curvilinear association was observed between motor-unit synchronization and the integral of coherence at 10–30 Hz in all motor-unit pairs (r² = 0.77), and was most pronounced in strength-trained subjects (r² = 0.90). Furthermore, this association was accentuated when using synchronization data with broad peaks (>11 ms), suggesting that the 10- to 30-Hz coherence is due to oscillatory activity in indirect branched common inputs. The altered coherence with training may be due to an interaction between cortical inhibition and the number of direct common inputs to motor neurons in skill- or strength-trained hands.

Gender-common and -specific neuroanatomical basis of human anxiety-related personality traits

Exploration of the relationships between regional brain volume and anxiety-related personality traits is important for understanding preexisting vulnerability to depressive and anxiety disorders. However, previous studies on this topic have employed relatively limited sample sizes and/or image processing methodology, and they have not clarified possible gender differences. In the present study, 183 (male/female: 117/66) right-handed healthy individuals in the third and fourth decades of life underwent structural magnetic resonance imaging scans and Temperament and Character Inventory. Neuroanatomical correlates of individual differences in the score of harm avoidance (HA) were examined throughout the entire brain using voxel-based morphometry. We found that higher scores on HA were associated with smaller regional gray matter volume in the right hippocampus, which was common to both genders. In contrast, female-specific correlation was found between higher anxiety-related personality traits and smaller regional brain volume in the left anterior prefrontal cortex. The present findings suggest that smaller right hippocampal volume underlies the basis for higher anxiety-related traits common to both genders, whereas anterior prefrontal volume contributes only in females. The results may have implications for why susceptibility to stress-related disorders such as anxiety disorders and depression shows gender and/or individual differences.

Reduced planum temporale volume and delusional behaviour in patients with schizophrenia

The structural abnormality of planum temporale (PT), a part of the superior temporal heteromodal association cortex involved in auditory and language processing, has been implicated in the pathophysiology of schizophrenia. However, its relationship to clinical manifestations remains unclear. Magnetic resonance images were obtained from 17 right-handed Japanese men with schizophrenia and from 22 age-, handedness-, and parental socioeconomic-status-matched healthy Japanese men in order to manually evaluate grey matter volumes of Heschl’s gyrus (HG) and PT. Psychiatric symptoms were assessed using positive and negative syndrome scale among the patients. Compared with healthy participants, patients with schizophrenia were associated with a statistically significant PT grey matter volume reduction without left or right lateralization, whereas HG volume was preserved. Smaller right PT volume was significantly correlated with more severe delusional behaviour in the patients. Previous investigations have focused on smaller-than-normal left PT in the pathophysiology of schizophrenia; however, the present results suggest a possible role of the right PT, which is involved in social cognition such as understanding the intentions of others, in the production of psychotic experiences in patients with schizophrenia.

Does the longer application of anodal-transcranial direct current stimulaton increase corticomotor excitability further? A pilot study

Introduction: Anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1) has been shown to be effective in increasing corticomotor excitability.
　
Methods: We investigated whether longer applications of a-tDCS coincide with greater increases in corticomotor excitability compared to shorter application of a-tDCS. Ten right-handed healthy participants received one session of a-tDCS (1mA current) with shorter (10 min) and longer (10+10 min) stimulation durations applied to the left M1 of extensor carpi radialis muscle (ECR). Corticomotor excitability following application of a-tDCS was assessed at rest with transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) and compared with baseline data for each participant.
　
Results: MEP amplitudes were increased following 10 min of a-tDCS by 67% (p = 0.001) with a further increase (32%) after the second 10 min of a-tDCS (p = 0.005). MEP amplitudes remained elevated at 15 min post stimulation compared to baseline values by 65% (p = 0.02).
　
Discussion: The results demonstrate that longer application of a-tDCS within the recommended safety limits, increases corticomotor excitability with after effects of up to 15 minutes post stimulation.

Anodal tDCS applied during strength training enhances motor cortical plasticity

Purpose:
The objective of this study was to assess the effect of anodal transcranial direct current stimulation (a-tDCS) on voluntary dynamic strength and cortical plasticity when applied during a 3-wk strength training program for the wrist extensors.

Methods:
Thirty right-handed participants were randomly allocated to the tDCS, sham, or control group. The tDCS and sham group underwent 3 wk of heavy-load strength training of the right wrist extensors, with 20 min of a-tDCS (2 mA) or sham tDCS applied during training (double blinded). Outcome measures included voluntary dynamic wrist extension strength, muscle thickness, corticospinal excitability, short-interval intracortical inhibition (SICI), and silent period duration.

Results:
Maximal voluntary strength increased in both the tDCS and sham groups (14.89% and 11.17%, respectively, both P < 0.001). There was no difference in strength gain between the two groups (P = 0.229) and no change in muscle thickness (P = 0.15). The tDCS group demonstrated an increase in motor-evoked potential amplitude at 15%, 20%, and 25% above active motor threshold, which was accompanied by a decrease in SICI during 50% maximal voluntary isometric contraction and 20% maximal voluntary isometric contraction (all P < 0.05). Silent period decreased for both the tDCS and sham groups (P < 0.001).

Conclusion:
The application of a-tDCS in combination with strength training of the wrist extensors in a healthy population did not provide additional benefit for voluntary dynamic strength gains when compared with standard strength training. However, strength training with a-tDCS appears to differentially modulate cortical plasticity via increases in corticospinal excitability and decreases in SICI, which did not occur following strength training alone

Association between mitochondrial DNA 10398A>G polymorphism and the volume of amygdala

Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders.

Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

The performance of a repetitive index finger flexion–extension task at maximal voluntary rate (MVR) begins to decline just a few seconds into the task and we have previously postulated that this breakdown has a central origin. To test this hypothesis, we have combined two objectives; to determine whether motor practice can lessen the performance deterioration in an MVR task, and whether further gains can be achieved with a transcranial magnetic stimulation (TMS) protocol that increases corticomotor excitability (CME). Eleven right-handed subjects participated in a randomized crossover study design that consisted of a 15-min interventional TMS at I-wave periodicity (ITMS) and single-pulsed Sham intervention prior to six 10-s practice sets of a repetitive finger flexion–extension task at MVR. Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. The starting movement rate, and the percentage decline in rate by the end of the MVR were quantitated. Training of the MVR task improved the sustainability of the task by reducing the decline in movement rate. CME increased steadily after each training bout, and this increase was maintained up to 20 min after the last bout. ITMS further increased CME, and was associated with an increase in both the starting rate of the MVR task and its sustainability, when compared to Sham. The results implicate central motor processes in the performance and sustainability of the MVR task, and indicate that MVR kinematics can improve with short-term training and with non-invasive neuro-modulation.

Exploring associations between gaze patterns and putative human mirror neuron system activity

The human mirror neuron system (MNS) is hypothesized to be crucial to social cognition. Given that key MNS-input regions such as the superior temporal sulcus are involved in biological motion processing, and mirror neuron activity in monkeys has been shown to vary with visual attention, aberrant MNS function may be partly attributable to atypical visual input. To examine the relationship between gaze pattern and interpersonal motor resonance (IMR; an index of putative MNS activity), healthy right-handed participants aged 18-40 (n = 26) viewed videos of transitive grasping actions or static hands, whilst the left primary motor cortex received transcranial magnetic stimulation. Motor-evoked potentials recorded in contralateral hand muscles were used to determine IMR. Participants also underwent eyetracking analysis to assess gaze patterns whilst viewing the same videos. No relationship was observed between predictive gaze and IMR. However, IMR was positively associated with fixation counts in areas of biological motion in the videos, and negatively associated with object areas. These findings are discussed with reference to visual influences on the MNS, and the possibility that MNS atypicalities might be influenced by visual processes such as aberrant gaze pattern.