Motor Cortical Physiology Research Articles

Motor Cortex Excitability Reflects the Subjective Value of Reward and Mediates Its Effects on Incentive-Motivated Performance.

Performance-based incentives tend to increase an individual's motivation, resulting in enhancements in behavioral output. While much work has focused on understanding how the brain's reward circuitry influences incentive-motivated performance, fewer studies have investigated how such reward representations act on the motor system. Here we measured motor cortical excitability with transcranial magnetic stimulation while female and male human participants performed a motoric incentive motivation task for prospective monetary gains and losses. We found that individuals' performance increased for increasing prospective gains and losses. While motor cortical excitability appeared insensitive to prospective loss, temporal features of motor cortical excitability for prospective gains were modulated by an independent measure of an individual's subjective preferences for incentive (i.e., loss aversion). Those individuals that were more loss averse had a greater motor cortical sensitivity to prospective gain, closer to movement onset. Critically, behavioral sensitivity to incentive and motor cortical sensitivity to prospective gains were both predicted by loss aversion. Furthermore, causal modeling indicated that motor cortical sensitivity to incentive mediated the relationship between subjective preferences for incentive and behavioral sensitivity to incentive. Together, our findings suggest that motor cortical activity integrates information about the subjective value of reward to invigorate incentive-motivated performance.SIGNIFICANCE STATEMENT Increasing incentives tend to increase motivation and effort. Using a motoric incentive motivation task and transcranial magnetic stimulation, we studied the motor cortical mechanisms responsible for incentive-motivated motor performance. We provide experimental evidence that motor cortical sensitivity to incentive mediates the relationship between subjective preferences for incentive and incentive-motivated performance. These results indicate that, rather than simply being a reflection of motor output, motor cortical physiology integrates information about reward value to motivate performance.

Non-invasive Brain Stimulation for Essential Tremor.

BackgroundThere is increasing interest in the use of non-invasive brain stimulation to characterize and potentially treat essential tremor (ET). Studies have used a variety of stimulation coils, paradigms, and target locations to make these observations. We reviewed the literature to compare prior studies and to evaluate the rationale and the methods used in these studies.MethodsWe performed a systematic literature search of the PubMed database using the terms “transcranial,” “noninvasive,” “brain stimulation,” “transcranial magnetic stimulation (TMS),” “transcranial direct current stimulation (tDCS),” “transcranial alternating current stimulation (tACS),” and “essential tremor.”ResultsSingle pulses of TMS to the primary motor cortex have long been known to reset tremor. Although there are relatively few studies showing alterations in motor cortical physiology, such as motor threshold, short and long intracortical inhibition, and cortical silent period, there may be some evidence of altered intracortical facilitation and cerebello-brain inhibition in ET. Repetitive TMS, theta burst stimulation, tDCS, and tACS have been applied to human subjects with tremor with some preliminary signs of tremor reduction, particularly in those studies that employed consecutive daily sessions.DiscussionA variety of stimulation paradigms and targets have been explored, with the increasing rationale an interest in targeting the cerebellum. Rigorous assessment of coil geometry, stimulation paradigm, rationale for selection of the specific anatomic target, and careful phenotypic and physiologic characterization of the subjects with ET undergoing these interventions may be critical in extending these preliminary findings into effective stimulation therapies.

Changes in Cortical Plasticity in Relation to a History of Concussion during Adolescence.

Adolescence and early adulthood is a critical period for neurophysiological development potentially characterized by an increased susceptibility to the long-term effects of traumatic brain injury. The current study investigated differences in motor cortical physiology and neuroplastic potential across a cohort of young adults with adolescent concussion history and those without. Transcranial magnetic stimulation (TMS) was used to assess motor evoked potential (MEP) amplitude, short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) before and after intermittent theta burst stimulation (iTBS). Pre-iTBS, MEP amplitude, but not SICI or ICF, was greater in the concussion history group. Post-iTBS, the expected increase in MEP amplitude and ICF was tempered in the concussion history group. Change in SICI was variable within the concussion history group. Post hoc assessment revealed that SICI was significantly lower in individuals whose concussion was not diagnosed at the time of injury compared to both those without a concussion history or whose concussion was medically diagnosed. Concussive impacts during adolescence appear to result in a persistent reduction of the ability to modulate facilitatory motor networks. Failure to report/identify concussive impacts close to injury during adolescence also appears to produce persistent change in inhibitory networks. These findings highlight the potential long-term impact of adolescent concussion upon motor cortical physiology.

P 74. Practice and stimulation induce shifts in TMS-evoked 2D movements involving multiple joints of the upper limb

Goal-directed reaching is important for activities of daily living. The population of neurons in the primary motor cortex (M1) is known to represent kinematic characteristics of reaching movements. Previous research in our laboratory used transcranial magnetic stimulation (TMS) to reveal maps of reaching within M1 that varied considerably by subject and stimulus location, but remained consistent over time, providing a substrate to assess practice-related changes in motor representation (Jones-Lush et al., 2010). We investigated how repetitive practice of goal-directed reaching movements induces use-dependent plasticity of kinematic characteristics of reaching movements encoded in M1. Healthy individuals (N = 22) sat with their arm in a robotic manipulandum while TMS was applied over M1. Movements were evoked with 120% movement threshold TMS intensity applied over M1. Two baseline measurements were obtained to establish the stability of TMS-evoked movements. Participants then practiced 3 blocks of 160 goal-directed reaching movements in a direction opposite to the baseline direction (14 cm reach 180° from baseline direction) against a 75 N m spring field. Changes in TMS-evoked arm movements were assessed after each practice block and after 5 min following the end of practice. In a second study, subthreshold M1 stimulation coordinated with voluntary reaching movement was added on alternate practice trials, with stimulation either triggered by EMG or preceding EMG by linking to the go cue. Kinematic characteristics of TMS-evoked arm movements were consistent for direction (p = 0.339) and amplitude (p = 0.881) across the two baseline measurements. Direction and the position of the point of peak velocity of TMS-evoked movements were significantly altered following training (p = 0.001 for direction, and p = 0.003 for position), and after 5-min interval following training (p = 0.0316 for direction and p = 0.01 for position). This was accompanied by significant changes in the motor evoked potentials (MEPs) of the shoulder (p = 0.04) and elbow (p = 0.02) agonist muscles indicating an association between the motor cortical physiology and kinematics of TMS-evoked movements. When stimulation was added to practice, preliminary results suggest an increased magnitude and rapidity of shift in kinematics. These findings demonstrate that repetitive practice of functional multi-joint movements modulates the motor cortical representation within M1 in a way that supports the performance of practiced reaching movements, although there are inter-individual differences that may have implications for rehabilitation. Stimulation to M1 has the potential to enhance this plasticity (Bütefisch et al., 2004), and we are currently determining the best timing paradigm to take advantage of this form of associational plasticity. Support: USPHS NIH R01 HD061462.

Interaction of Motor Training and Intermittent Theta Burst Stimulation in Modulating Motor Cortical Plasticity: Influence of BDNF Val66Met Polymorphism

Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

Neural mechanism of activity spread in the cat motor cortex and its relation to the intrinsic connectivity

Motor cortical points are linked by intrinsic horizontal connections having a recurrent network topology. However, it is not known whether neural activity can propagate over the area covered by these intrinsic connections and whether there are spatial anisotropies of synaptic strength, as opposed to synaptic density. Moreover, the mechanisms by which activity spreads have yet to be determined. To address these issues, an 8 × 8 microelectrode array was inserted in the forelimb area of the cat motor cortex (MCx). The centre of the array had a laser etched hole ∼500 μm in diameter. A microiontophoretic pipette, with a tip diameter of 2-3 μm, containing bicuculline methiodide (BIC) was inserted in the hole and driven to a depth of 1200-1400 μm from the cortical surface. BIC was ejected for ∼2min from the tip of the micropipette with positive direct current ranging between 20 and 40 nA in different experiments. This produced spontaneous nearly periodic bursts (0.2-1.0 Hz) of multi-unit activity in a radius of about 400 μm from the tip of the micropipette. The bursts of neural activity spread at a velocity of 0.11-0.24 ms⁻¹ (mean=0.14 mm ms⁻¹, SD=0.05)with decreasing amplitude.The area activated was on average 7.22 mm² (SD=0.91 mm²), or ∼92% of the area covered by the recording array. The mode of propagation was determined to occur by progressive recruitment of cortical territory, driven by a central locus of activity of some 400 μm in radius. Thus, activity did not propagate as a wave. Transection of the connections between the thalamus and MCx did not significantly alter the propagation velocity or the size of the recruited area, demonstrating that the bursts spread along the routes of intrinsic cortical connectivity. These experiments demonstrate that neural activity initiated within a small motor cortical locus (≤ 400 μm in radius) can recruit a relatively large neighbourhood in which a variety of muscles acting at several forelimb joints are represented. These results support the hypothesis that the MCx controls the forelimb musculature in an integrated and anticipatory manner based on a recurrent network topology

Columnar organization in the motor cortex

Despite many attempts to find spatial structure in the functional properties of neurons within the primary motor cortex (MI), there is still no compelling evidence for such structure despite the anatomical similarities between motor cortex and other neocortical areas. This is a longstanding puzzle in motor cortical physiology because topographic structure of function is a hallmark of primary sensory cortices including the visual, somatosensory, and auditory cortices. In particular, experimental evidence has supported the idea of vertical columns perpendicular to the cortical surface which contain neurons that share similar sensory tuning properties. Moreover, horizontal spatial structure has been observed in sensory cortices, most elegantly manifested by the pinwheel structure of orientation tuning across V1 (Bonhoeffer and Grinvald, 1991). Although early work by Asanuma provided some evidence for somatotopic, columnar organization in MI using intracortical microstimulation (Asanuma, 1975), further research by many others did not support this perspective but rather suggested distributed and overlapping representations of body parts. Namely, nearby sites in motor cortex could represent or evoke very different muscles and joints, and multiple, spatially-distributed sites could represent very similar body parts (Donoghue, Leibovic et al., 1992; Schieber and Hibbard, 1993; Sanes, Donoghue et al., 1995). By focusing on movement parameters instead of body parts, recent studies have provided evidence that a topographic organization of directional tuning does exist within the motor cortex (Amirikian and Georgopoulos, 2003; Georgopoulos, Merchant et al., 2007). However, it still remains controversial as to which movement parameters, if any, are truly encoded in single MI neurons.

Motor cortical physiology in patients and asymptomatic carriers of parkin gene mutations

Autosomal recessive parkin (PARK2) gene-related parkinsonism may be phenotypically and pathophysiologically distinct from idiopathic Parkinson's disease (PD). Furthermore, asymptomatic subjects carrying a single parkin mutation ("parkin carriers") may show striatal dopaminergic dysfunction and increased cortical movement-related activation. Here, we used transcranial magnetic stimulation (TMS) to study corticospinal and intracortical excitability in manifesting parkin patients and asymptomatic carriers. We studied resting and active motor thresholds (RMT/AMT), central motor conduction time (CMCT), active recruitment curves, short-interval intracortical inhibition (SICI) and facilitation (ICF), SICI recruitment curve, and cortical silent period (CSP) in 8 patients "off" medication, 7 carriers, and two groups of age-matched controls (n = 21). Patients had longer CMCTs compared to controls with a significant negative correlation between CMCT duration and onset age (r = -0.83, P = 0.04). Carriers had increased RMT/AMT; the time course of SICI/ICF and the duration of CSP were normal in both patients and carriers; however slight abnormalities in the recruitment of SICI were found in the carriers. Prolonged CMCT and normal cortical inhibitory mechanisms in parkin patients may be of value in the differentiation from idiopathic PD. The subclinical electrophysiological abnormalities found in carriers may represent underlying compensatory mechanisms.

Corticospinal involvement in volitional contractions

It is more than 25 years since Merton & Morton (1980) first demonstrated that it was possible to stimulate fast conducting corticospinal connections from motor cortex to spinal motoneurones in conscious humans. The initial stimulators used high-voltage electrical pulses that produced an uncomfortable twitch of scalp muscles under the stimulating electrodes. However, the advent of transcranial magnetic stimulation (TMS) made the procedure painless and it is now widely used to study motor cortical physiology. Despite its success, one thorny question remains: are the corticospinal connections activated by transcranial stimulation the same as those that are normally recruited in voluntary muscle contractions? It is undoubtedly true that the size of the response to a TMS pulse is modulated by volitional muscle contraction, but that does not mean that the outputs activated by the TMS pulse are the same as those used volitionally. So how do we tackle the question? One potential solution lies in the observation that stimulation at very low intensities, below the threshold for evoking a muscle twitch, can reduce ongoing volitional muscle activity. This is thought to occur by suppression of ongoing corticospinal excitation to motoneurones by activation of intracortical inhibitory circuits (Davey et al. 1994). The result means that TMS pulses can certainly affect volitionally produced activity in corticospinal fibres, but are these the same fibres as are activated by suprathreshold pulses? Unfortunately, the answer appeared to be no. The latency of electromyographic (EMG) suppression after a subthreshold TMS pulse had usually been found to be about 10 ms later than the onset of facilitation caused by a suprathreshold pulse. One explanation for the unusually long delay of this suppression was that in fact the TMS pulse was suppressing activity in slowly conducting corticospinal fibres, and that these, rather than the large diameter ones activated by suprathreshold pulses, were the source of volitional excitation to spinal motoneurones. However, as Butler et al. (2007) point out in this issue of The Journal of Physiology, there is one potential flaw in these measurements. They were all made in average recordings of rectified surface EMG activity. Determining the true onset of inhibition in such records is notoriously difficult because muscle action potentials recorded by the surface electrodes have a duration of about 5–10 ms (Widmer & Lund, 1989). Imagine it was possible to stop all the units firing at the same instant. Electrical activity would still continue for 5–10 ms as the final action potentials travelled down the muscle fibres, and it is this that complicates estimation of the onset of inhibition. In the present experiments, Butler et al. bypassed this problem by recording the activity of single motor units with needle electrodes, and constructing a peri-stimulus time histogram (PSTH) of discharge around the time of a TMS pulse to the motor cortex. This should give a true estimate of the difference in timing of facilitation evoked by a suprathreshold TMS pulse and inhibition produced by a subthreshold pulse. However, one last problem remained to be solved. A reliable measure of the onset of inhibition in a PSTH requires there to be a large number of counts in the baseline. Units discharge at around 10 Hz in the weak contractions that are needed to identify single motor units in human muscle. Thus, about 100 trials are needed to fill each 1 ms bin of the PSTHs used in these experiments. Since TMS pulses can be applied at about once every 5 s, this would take just under 10 min of recording. A good number of counts per bin to identify inhibition would be about 10, which would take some 1.5 h of experimenting. The solution to making the experiments tolerable for subjects is to manipulate the experimental conditions so that the onset of inhibition coincides with the expected time of firing of a unit. That way the number of counts per bin is high in the time interval of interest. This can be arranged by timing the TMS pulse with respect to the previous discharge of the unit such that the presumed onset of inhibition is about 100 ms later. With this arrangement, Butler et al. found that the difference in latency of TMS-evoked suppression was around 2 ms longer than facilitation when recordings were taken from the first dorsal interosseous muscle and 3 ms for the biceps brachii. Assuming an oligosynaptic (or even disynaptic) inhibition, this is compatible with inhibition of activity in the fast conducting fibres of the corticospinal tract. Thus, it appears that TMS is indeed likely to activate the same fast conducting corticospinal fibres as are used in volitional contractions. Perhaps more importantly, we now have a method of testing the extent of this contribution in different types of muscle contraction, from volitional finger and arm movements to walking and breathing.

News in Motor Cortical Physiology.

Motor cortical activity relates to static motor parameters (isometric force, limb position) under static conditions but predominantly to dynamic parameters (change of force, limb velocity) under dynamic conditions. This dual relation conceptually unifies the role of motor cortex in the control of isometric force and movement.

Interneuronal activity as a factor interfering with the interpretation of results from microiontophoretic studies

Transneuronal interference in microelectrophoretic studies has been investigated in the motor cortex of unanaesthetized cats. A special electrode assembly was used, which consisted of a combination of one single and a five-barrel micropipette attached in parallel, with various intertip distances. Simultaneous recordings from both electrodes were obtained. Electrode position was verified histologically at the end of each successful experiment. Our results show that transneuronal effects contribute to the results obtained from iontophoretic studies and that these effects may occassionally predominate, if favoured by conditions of substance application. These findings are discussed in relation to the significance they might have in interpreting results from iontophoretic studies and to their bearing on motor cortical physiology.