Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA has been shown to be efficacious in increasing (via anodal tDCS) or decreasing (via cathodal tDCS) the excitability of corticospinal projections to muscles of the hand. In this study, we examined whether tDCS at currents of 2 mA could effect similar changes in the excitability of deeper cortical structures that innervate muscles of the lower leg. Similar to the hand area, 10 min of stimulation with the anode over the leg area of the motor cortex increased the excitability of corticospinal tract projections to the tibialis anterior (TA) muscle, as reflected by an increase in the amplitude of the motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation. MEP amplitudes recorded at rest and during a background contraction were increased following anodal tDCS and remained elevated at 60 min compared to baseline values by 59 and 35%, respectively. However, in contrast to the hand, hyperpolarizing cathodal stimulation at equivalent currents had minimal effect on the amplitude of the MEPs recorded at rest or during background contraction of the TA muscle. These results suggest that it is more difficult to suppress the excitability of the leg motor cortex with cathodal tDCS than the hand area of the motor cortex.

Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1-L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5-S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.

Peripheral sensory afferents in the hand activate both excitatory and inhibitory intracortical circuits to potentially facilitate and prune descending motor commands. In this study, we characterized how afferent inputs modulate the excitability of cortical circuits in the leg area of the primary motor cortex by examining how stimulation of the tibial nerve (TN) at the ankle alters motor evoked potentials (MEPs) activated by transcranial magnetic stimulation (TMS). Resting MEPs in the tibialis anterior (TA) muscle were facilitated in response to heteronymous activation of the TN 45-50 ms earlier, whereas MEPs were inhibited at interstimulus intervals of 32.5-37.5 ms. Similar time-dependent modulation occurred in the soleus (SOL) muscle with stimulation of the homonymous posterior tibial nerve (PTN) at the knee. To determine the site of this afferent-evoked facilitation and inhibition (spinal or cortical), we compared the effects of afferent stimulation to responses evoked at subcortical sites. At interstimulus intervals where MEP facilitation was observed (near 50 ms), spinal H-reflexes and responses evoked from corticospinal tract stimulation at the brainstem were predominantly depressed by the sensory stimulus suggesting that the observed MEP facilitation was cortical in origin. At interstimulus intervals where MEP depression was observed (near 35 ms), brainstem evoked responses were depressed to a similar degree and, in contrast to the hand, this suggests that spinal rather than cortical circuits mediate short-latency afferent inhibition (SAI) of leg MEPs. When the MEP was facilitated by afferent inputs, short-interval intracortical inhibition (SICI) was reduced and intracortical facilitation (ICF) was increased, but long-interval intracortical inhibition (LICI) at a 100 ms interval was unchanged. In addition, sensory excitation increased the recruitment of early, middle and late descending corticospinal volleys as evidenced from increases in MEP facilitation at the corresponding I-wave periodicity. We propose that sensory activation from the leg has a diffuse and predominantly facilitatory effect on the leg primary motor cortex.

Changes in the strength of corticospinal projections to muscles in the upper and lower limbs are induced in conscious humans after paired associative stimulation (PAS) to the motor cortex. We tested whether an intervention of PAS consisting of 90 low-frequency (0.1-Hz) stimuli to the common peroneal nerve combined with suprathreshold transcranial magnetic stimulation (TMS) produces specific changes to the motor-evoked potentials (MEPs) in lower leg muscles if the afferent volley from peripheral stimulation is timed to arrive at the motor cortex after TMS-induced firing of corticospinal neurons. Unlike PAS in the hand, MEP facilitation in the leg was produced when sensory inputs were estimated to arrive at the motor cortex over a range of 15 to 90 ms after cortical stimulation. We examined whether this broad range of facilitation occurred as a result of prolonged subthreshold excitability of the motor cortex after a single pulse of suprathreshold TMS so that coincident excitation from sensory inputs arriving many milliseconds after TMS can occur. We found that significant facilitation of MEP responses (>200%) occurred when the motor cortex was conditioned with suprathreshold TMS tens of milliseconds earlier. Likewise, it was possible to induce strong MEP facilitation (85% at 60 min) when afferent inputs were directly paired with subthreshold TMS. We argue that in the leg motor cortex, facilitation of MEP responses from PAS occurred over a large range of interstimulus intervals as a result of the paired activation of sensory inputs with sustained, subthreshold activity of cortical neurons that follow a pulse of suprathreshold TMS.

In dairy goats, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination. However, repeated eCG treatments are followed by decreased fertility in goats inseminated at a fixed time after treatment. In this report, we show the presence of anti-eCG antibodies in plasma of treated goats. A 500 IU eCG injection induces a humoral response, with variable concentrations of anti-eCG antibody being produced in individual goats. The analysis of successive anti-eCG immune responses over several years has demonstrated the existence of different populations of goats, defined as low, medium, and high responders. By the use of two caprine microsatellites located inside (OLADRB) and outside (BM1258) the major histocompatibility complex (MHC), a significant association (p < 0.05) between the anti-eCG antibody response and some MHC-DRB alleles was found. Goats with high antibody concentrations at the time of eCG injection (> 2.5 microg/ml) exhibited a much lower kidding rate than did other females (41.3% vs. 66.7%). Lower fertility of these goats, inseminated at a fixed time after eCG treatment, might be due to the observed delay in estrus occurrence and the preovulatory LH surge.