No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

The ventral tegmental area (VTA) and its dopaminergic (DA) mesocorticolimbic projections are thought to be essential in the brain’s reward neurocircuitry. In humans and animal experimental subjects, mild electrical VTA stimulation increases dopamine levels and can induce euphoria. Paradoxically, aversive stimuli activate VTA neurons and forebrain DA activity, and excessive electrical stimulation of the VTA exaggerates fearfulness. Research suggests that experimental manipulation of either the amygdala or the VTA has similar effects on the acquisition and expression of Pavlovian conditioned fear. Recently it was demonstrated that electrical stimulation of the amygdala produced fear extinction deficits in rats. Fear extinction involves the progressive dissipation of conditioned fear responses by repeated non-reinforced exposure to a conditioned stimulus (CS). Maladaptive states of fear in fear-related anxiety disorders, such as post-traumatic stress disorders (PTSD) or specific phobias are thought to reflect fear extinction learning deficits. The primary purpose of the present study was to examine the effects of intra-VTA stimulation on fear extinction learning. Using fear-potentiated startle as a behavioural index of conditioned fear, it was found that 120 VTA stimulations paired or unpaired with non-reinforced CS presentations impaired the extinction of conditioned fear. This effect was not apparent in rats that received electrical stimulation of the substantia nigra (SN), suggesting that not all midbrain regions respond similarly. Electrical stimulation parameters did not have aversive affects because rats failed to show fear conditioning when electrical VTA stimulation was used as the unconditioned stimulus. Also, VTA stimulation did not alter conditioned fear expression in non-extinguished animals. Based on the results it is suggested that VTA activation disinhibited conditioned fear responding. Therefore, VTA neuronal excitation by aversive stimuli may play a role in fear-related anxiety disorders thought to reflect extinction learning deficits.

Neuromuscular electrical stimulation (NMES) has become an increasingly popular rehabilitative treatment approach for swallowing disorders (dysphagia). However, its precise effects on swallowing biomechanics and measures of swallowing neurophysiology are unclear. Clearly defined NMES treatment protocols that have been corroborated by thorough empirical research are lacking. The primary objective of this research programme was therefore to establish optimal NMES treatment parameters for the anterior hyo-mandibular (submental) musculature, a muscle group that is critically involved in the oral and pharyngeal phases of swallowing. Based on previous research, the primary hypothesis was that various NMES treatment protocols would have differential effects of either enhancing or inhibiting the excitability of corticobulbar projections to this muscle group. The research paradigm used to test this hypothesis was an evaluation of MEP amplitude and onset latency, recorded in the functional context of volitional contraction of the submental musculature (VC) and contraction of this muscle group during the pharyngeal phase of volitional swallowing (VPS, volitional pharyngeal swallow). Outcome measures were recorded before and at several time points after each NMES treatment trial. This methodology is similar to, but improved upon, research paradigms previously reported. Changes in corticobulbar excitability in response to various NMES treatment protocols were recorded in a series of experiments. Ten healthy research participants were recruited into a study that evaluated the effects of event-related NMES, whereas 15 healthy research participants were enrolled in a study that investigated the effects of non-event-related NMES. In a third cohort of 35 healthy research participants, task-dependent differences in corticobulbar excitability were evaluated during three conditions of submental muscle contraction: VC, VPS and submental muscle contraction during the pharyngeal phase of reflexive swallowing (RPS, reflexive pharyngeal swallowing). Event-related NMES induced frequency-depended changes in corticobulbar excitability. NMES administered at 80 Hz facilitated MEP amplitude, whereas NMES at 5 Hz and 20 Hz inhibited MEP amplitude. No changes were observed after NMES at 40 Hz. Maximal excitatory or inhibitory changes occurred 60 min post-treatment. Changes in MEP amplitude in response to event-related NMES were only observed when MEPs were recorded during the VC condition, whereas MEPs recorded during the VPS condition remained unaffected. Non-event-related NMES did not affect MEP amplitude in either of the muscle contraction conditions. Similarly, MEP onset latencies remained unchanged across all comparisons. MEPs were detected most consistently during the VC contraction condition. They were less frequently detected and were smaller in amplitude for the VPS condition and they were infrequently detected during pre-activation by RPS. The documented results indicate that event-related NMES has a more substantial impact on MEP amplitude than non-event-related NMES, producing excitatory and inhibitory effects. Comparison of MEPs recorded during VC, VPS and RPS suggests that different neural networks may govern the motor control of submental muscle activation during these tasks. This research programme is the first to investigate the effects of various NMES treatment protocols on the excitability of submental corticobulbar projections. It provides important new information for the use of NMES in clinical rehabilitation practices and our understanding of the neural networks governing swallowing motor control.

Supporters of a nutritional supplement, β-Hydroxy-β-Methylbutyrate (HMB) supplementation, claim that it will increase the muscular strength gains and lean muscle mass gains seen during a resistance training program. It has been suggested that HMB supplementation does this by preventing muscle damage or by regenerating damaged muscle cell membranes. However, no research has evaluated the effect of HMB supplementation on low frequency fatigue. Therefore, the purpose of this study was to determine if three weeks of HMB supplementation could attenuate the effects of low frequency fatigue caused by eccentric muscle contractions of the tibialis anterior muscle. A total of 33 healthy recreationally active subjects (18 males, 15 females; 23.2 ± 4.3 yr) were recruited for this study. All subjects preformed 4 sets of 25 eccentric contractions of the tibialis anterior muscle through a range of motion of 30 degrees. Recovery measures were taken for 20 minutes after the fatigue protocol and at 48 and 96 hours of recovery. The recovery measures included: Maximum voluntary contraction peak torque, 10 Hz peak torque, 50 Hz peak torque, 10/50 Hz peak torque ratio, and EMG measurements. Each subject served as their own control and limbs were randomly assigned to pre-supplement or post-supplement limbs. Following the pre-supplement fatigue protocol and recovery measures each subject completed three weeks of 3g/day HMB supplementation. After the supplementation period the post-supplement fatigue protocol was completed and recovery measures were taken. The 10 Hz peak torque and the 10/50 Hz torque ratio in the pre-supplement limb was still significantly reduced at the 96-hour recovery measurement time, indicating that it was still showing low frequency muscle fatigue at this time. Furthermore, the post-supplement limb, recovered from the fatigue protocol faster, and did not show any signs of low frequency muscle fatigue at the 48-hour recovery measurement time. In addition the pre-supplement limb had significant maximum voluntary contraction torque deficit at the 48-hour recovery measurement time and the post-supplement limb showed no significant deficits. The main findings of this study were that three weeks of HMB supplementation attenuated low frequency fatigue and maximum voluntary contraction torque reduction after an eccentric fatigue protocol.

We have developed a high-throughput system of closed-loop electrical stimulation and optical recording that facilitates the rapid characterization of extracellular stimulus-evoked neural activity. The ability to selectively stimulate a neuron is a defining characteristic of next-generation neural prostheses. Greater stimulus control and differential activation of specific neuronal populations allows for prostheses that better mimic their biological counterparts. In our system, we deliver square current pulses using a microelectrode array; automated real-time image processing of high-speed digital video identifies the neuronal response; and a feedback controller alters the applied stimulus to achieve a targeted response. The system controller performs directed searches within the strength-duration (SD) stimulus parameter space to build probabilistic neuronal activation curves. An important feature of this closed-loop system is a reduction in the number of stimuli needed to derive the activation curves when compared to the more commonly used open-loop system: this allows the closed-loop system to spend more time probing stimulus regions of interest in the multi-parameter waveform space, facilitating high resolution analysis. The stimulus-evoked activation data were well-fit to a sigmoid model in both the stimulus strength (current) and duration (pulse width) slices through the waveform space. The 2-D analysis produced a set of probability isoclines corresponding to each neuron-electrode pairing, which were fit to the SD threshold model described by Lapique (1907). We show that stimulus selectivity within a given neuron pair is possible in the one-parameter search space by using multiple stimulation electrodes. Additionally, by applying simultaneous stimuli to adjacent electrodes, the interaction between stimuli alters the neuronal activation threshold. The interaction between simultaneous multi-electrode multi-parameter stimulus waveforms creates an opportunity for increased stimulus selectivity within a population. We demonstrated that closed-loop imaging and micro-stimulation technology enable the study of neuronal excitation across a large parameter space, which is requisite for controlling neuronal activation in next generation clinical solutions.