Elucidating the complex organization of neural micro-domains in the locust Schistocerca gregaria using dMRI.

To understand brain function it is necessary to characterize both the underlying structural connectivity between neurons and the physiological integrity of these connections. Previous research exploring insect brain connectivity has typically used electron microscopy techniques, but this methodology cannot be applied to living animals and so cannot be used to understand dynamic physiological processes. The relatively large brain of the desert locust, Schistercera gregaria (Forksȧl) is ideal for exploring a novel methodology; micro diffusion magnetic resonance imaging (micro-dMRI) for the characterization of neuronal connectivity in an insect brain. The diffusion-weighted imaging (DWI) data were acquired on a preclinical system using a customised multi-shell diffusion MRI scheme optimized to image the locust brain. Endogenous imaging contrasts from the averaged DWIs and Diffusion Kurtosis Imaging (DKI) scheme were applied to classify various anatomical features and diffusion patterns in neuropils, respectively. The application of micro-dMRI modelling to the locust brain provides a novel means of identifying anatomical regions and inferring connectivity of large tracts in an insect brain. Furthermore, quantitative imaging indices derived from the kurtosis model that include fractional anisotropy (FA), mean diffusivity (MD) and kurtosis anisotropy (KA) can be extracted. These metrics could, in future, be used to quantify longitudinal structural changes in the nervous system of the locust brain that occur due to environmental stressors or ageing.

Task-specificity of unilateral anodal and dual-M1 tDCS effects on motor learning.

Task-specific effects of transcranial direct current stimulation (tDCS) on motor learning were investigated in 30 healthy participants. In a sham-controlled, mixed design, participants trained on 3 different motor tasks (Purdue Pegboard Test, Visuomotor Grip Force Tracking Task and Visuomotor Wrist Rotation Speed Control Task) over 3 consecutive days while receiving either unilateral anodal over the right primary motor cortex (M1), dual-M1 or sham stimulation. Retention sessions were administered 7 and 28 days after the end of training. In the Purdue Pegboard Test, both anodal and dual-M1 stimulation reduced average completion time approximately equally, an improvement driven by online learning effects and maintained for about 1 week. The Visuomotor Grip Force Tracking Task and the Visuomotor Wrist Rotation Speed Control Task were associated with an advantage of dual-M1 tDCS in consolidation processes both between training sessions and when testing at long-term retention; both were maintained for at least 1 month. This study demonstrates that M1-tDCS enhances and sustains motor learning with different electrode montages. Stimulation-induced effects emerged at different learning phases across the tasks, which strongly suggests that the influence of tDCS on motor learning is dynamic with respect to the functional recruitment of the distributed motor system at the time of stimulation. Divergent findings regarding M1-tDCS effects on motor learning may partially be ascribed to task-specific consequences and the effects of offline consolidation.

Pressure pain thresholds increase after preconditioning 1 Hz repetitive transcranial magnetic stimulation with transcranial direct current stimulation.

BACKGROUND: The primary motor cortex (M1) is an effective target of non-invasive cortical stimulation (NICS) for pain threshold modulation. It has been suggested that the initial level of cortical excitability of M1 plays a key role in the plastic effects of NICS. OBJECTIVE: Here we investigate whether transcranial direct current stimulation (tDCS) primed 1 Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pressure pain thresholds and if this is related to observed alterations in cortical excitability. METHOD: 15 healthy, male participants received 10 min 1 mA anodal, cathodal and sham tDCS to the left M1 before 15 min 1 Hz rTMS in separate sessions over a period of 3 weeks. Motor cortical excitability was recorded at baseline, post-tDCS priming and post-rTMS through recording motor evoked potentials (MEPs) from right FDI muscle. Pressure pain thresholds were determined by quantitative sensory testing (QST) through a computerized algometer, on the palmar thenar of the right hand pre- and post-stimulation. RESULTS: Cathodal tDCS-primed 1 Hz-rTMS was found to reverse the expected suppressive effect of 1 Hz rTMS on cortical excitability; leading to an overall increase in activity (p<0.001) with a parallel increase in pressure pain thresholds (p<0.01). In contrast, anodal tDCS-primed 1 Hz-rTMS resulted in a corresponding decrease in cortical excitability (p<0.05), with no significant effect on pressure pain. CONCLUSION: This study demonstrates that priming the M1 before stimulation of 1 Hz-rTMS modulates experimental pressure pain thresholds in a safe and controlled manner, producing a form of analgesia.

Enhanced motor learning following task-concurrent dual transcranial direct current stimulation.

OBJECTIVE: Transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has beneficial effects on motor performance and motor learning in healthy subjects and is emerging as a promising tool for motor neurorehabilitation. Applying tDCS concurrently with a motor task has recently been found to be more effective than applying stimulation before the motor task. This study extends this finding to examine whether such task-concurrent stimulation further enhances motor learning on a dual M1 montage. METHOD: Twenty healthy, right-handed subjects received anodal tDCS to the right M1, dual tDCS (anodal current over right M1 and cathodal over left M1) and sham tDCS in a repeated-measures design. Stimulation was applied for 10 mins at 1.5 mA during an explicit motor learning task. Response times (RT) and accuracy were measured at baseline, during, directly after and 15 mins after stimulation. Motor cortical excitability was recorded from both hemispheres before and after stimulation using single-pulse transcranial magnetic stimulation. RESULTS: Task-concurrent stimulation with a dual M1 montage significantly reduced RTs by 23% as early as with the onset of stimulation (p<0.01) with this effect increasing to 30% at the final measurement. Polarity-specific changes in cortical excitability were observed with MEPs significantly reduced by 12% in the left M1 and increased by 69% in the right M1. CONCLUSION: Performance improvement occurred earliest in the dual M1 condition with a stable and lasting effect. Unilateral anodal stimulation resulted only in trendwise improvement when compared to sham. Therefore, task-concurrent dual M1 stimulation is most suited for obtaining the desired neuromodulatory effects of tDCS in explicit motor learning.

Transcranial direct current stimulation (tDCS) priming of 1Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pain thresholds.

Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) modulate cortical excitability. Both techniques have been demonstrated to modulate chronic pain and experimental pain thresholds, but with inconsistent effects. Preconditioning M1 with weak tDCS (1mA) standardizes the effects of subsequent stimulation via rTMS on levels of cortical excitability. Here we examine whether 1Hz rTMS, primed with tDCS, could effectively standardize the modulation of pain thresholds. Thermal pain thresholds were determined using quantitative sensory testing (QST) of the palmar thenar of both hands in 12 healthy males pre and post tDCS - 1Hz rTMS over the hand area of the left M1. Cathodal tDCS preconditioning of 1Hz rTMS successfully reversed the normal suppressive effect of low frequency rTMS and effectively modulated cold and heat pain thresholds. Conversely, anodal tDCS - 1Hz rTMS led to a decrease in cold pain thresholds. Therefore, this study supports that preconditioning M1 using cathodal tDCS before subsequent stimulation via 1Hz rTMS facilitates the production of analgesia.

Kinematics of phonotactic steering in the walking cricket Gryllus bimaculatus (de Geer).

Female crickets, Gryllus bimaculatus, are attracted by the male calling song and approach singing males; a behaviour known as phonotaxis. Even tethered females walking on a trackball steer towards a computer-generated male song presented from their left or right side. High-speed video analysis showed how this auditory-evoked steering was integrated with walking. Typically all the front and middle legs showed kinematic adjustments during steering, with the trajectories tilted towards the side of acoustic stimulation. Furthermore, the average speed of the tarsi contralateral to song increased relative to the ipsilateral tarsi. Kinematic changes of the hind legs were small and may be a consequence of the front and middle leg adjustments. Although phonotactic steering generally led to stereotyped adjustments there were differences in the specific combination of kinematic changes in leg trajectories. The most reliable kinematic steering response was by the contralateral front leg, such that, during its swing phase the tarsus moved towards the side of acoustic stimulation through an increased forward rotation of the femur and an increased extension of the tibia. Relating the changes in tarsal positioning of each leg to the steering velocity of the animal indicated that typically the front and middle legs contralateral to song generated the turning forces. Phonotactic steering was integrated into forward walking without changes to the walking motor cycle.

The effect of externally generated loading on predictive grip force modulation.

A characteristic of skilled movement is the ability of the CNS to predict the consequences of motor commands. When we lift an object there is an anticipatory increase in grip force that prevents a grasped object from slipping. When an object is pulled from our grasp by an external force, a reflexive modulation in grip force prevents slippage. Here we examine how external perturbations to a grasped object influence anticipatory grip force during object manipulation using a bimanual task, with each hand holding a computer-controlled object. Subjects were instructed to maintain the position of the object held in the right hand. Loading was applied to this restrained object: either self-generated by the action of their left hand or externally generated by a motor. The magnitude of the grip force response to self-generated loading increased after the object was loaded, and the latency of this response remained predictive of load force. This implies that external and self-generated loading increase the anticipatory grip force response. Unlinked trials, where the subject's moved their left hand but no loading was generated on the right-hand object were used to assess the presence of purely predictive control of grip force. External loading soon after self-generated loading maintained an existing predictive response once the linkage between the subject's action and object loading had been removed. However, external loading had no influence as the existing prediction decays. Therefore, the predictive grip force response during object manipulation can be significantly modified by object loading from an external source.

Internal models for bi-manual tasks.

Co-ordinated bi-manual actions form the basis for many everyday motor skills. In this review, the internal model approach to the problem of bi-manual co-ordination is presented. Bi-manual coordinative tasks are often regarded as a hallmark of complex action. They are often associated with object manipulation, whether the holding of a single object between the two hands or holding an object in each hand. However, the task of movement and control is deceptively difficult even when we execute an action with a single hand without holding an object. The simplest voluntary action requires the problems of co-ordination, timing and interaction between neural, muscular and skeletal structures to be overcome. When we are making a movement whilst holding an object, a further requirement is that an internal model is able to predict the dynamics of the object that is being held as well as the dynamics of the motor system. There has been extensive work examining the formation of internal models when acting in novel environments. The majority of studies examine uni-lateral learning of a task generally to the participant's dominant hand. However, many everyday motor tasks are bi-manual, and the existing findings regarding the learning of internal models in uni-manual tasks and their subsequent generalization highlights the complexities that must underlie the formation of bi-manual tasks. Our ability to perform bi-manual tasks raises interesting questions about how internal models are specified for co-ordinative actions, and also for how the motor system learns to represent the properties of objects.

The cutaneous contribution to adaptive precision grip.

Only after injury, or perhaps prolonged exposure to cold that is sufficient to numb the fingers, do we suddenly appreciate the complex neural mechanisms that underlie our effortless dexterity in manipulating objects. The nervous system is capable of adapting grip forces to a wide range of object shapes, weights and frictional properties, to provide optimal and secure handling in a variety of potentially perturbing environments. The dynamic interplay between sensory information and motor commands provides the basis for this flexibility, and recent studies supply somewhat unexpected evidence of the essential role played by cutaneous feedback in maintaining and acquiring predictive grip force control. These examples also offer new insights into the adaptive control of other voluntary movements.

Spatial representation of predictive motor learning.

A key feature of skilled motor behavior is the ability of the CNS to predict the consequences of its actions. Such prediction occurs when one hand pulls on an object held in the other hand; the restraining hand generates an anticipatory increase in grip force, thereby preventing the object from slipping. When manipulating a novel object, the CNS adapts its predictive response to ensure that predictions are accurately tuned to the dynamics of the object. Here we examine whether learning to predict the consequences of an action on a novel object is restricted to the actions performed during manipulation or generalizes to novel actions. A bimanual task in which subjects held an object in each hand and the relationship between actions on one object and the motion of the other could be computer controlled from trial-to-trial was used. In four conditions we varied the spatial relationship between the direction of force subjects applied to the left-hand object and the consequent direction of motion of an object held in their right hand, which subjects were required to restrain. The results show that predictive learning was local to the direction of forces experienced during learning and that the magnitude of predictive responses was greatly reduced for novel directions of action of the left hand. The pattern of generalization shows that the representation of predictive learning is spatially local and can be approximated as having a spatially narrow Gaussian basis function.