Search PubMed⌕ Search

Biomedical subjects

S N Baker

Publications and source records attributed to S N Baker.

30 records · Page 2Linked to original sources

Emergent oscillations in a realistic network: the role of inhibition and the effect of the spatiotemporal distribution of the input.

We have simulated a network of 10,000 two-compartment cells, spatially distributed on a two-dimensional sheet; 15% of the cells were inhibitory. The input to the network was spatially delimited. Global oscillations frequently were achieved with a simple set of connectivity rules. The inhibitory neurons paced the network, whereas the excitatory neurons amplified the input, permitting oscillations at low-input intensities. Inhibitory neurons were active over a greater area than excitatory ones, forming a ring of inhibition. The oscillation frequency was modulated to some extent by the input intensity, as has been shown experimentally in the striate cortex, but predominantly by the properties of the inhibitory neurons and their connections: the membrane and synaptic time constants and the distribution of delays. In networks that showed oscillations and in those that did not, widely distributed inputs could lead to the specific recruitment of the inhibitory neurons and to near zero activity of the excitatory cells. Hence the spatial distribution of excitatory inputs could provide a means of selectively exciting or inhibiting a target network. Finally, neither the presence of oscillations nor the global spike activity provided any reliable indication of the level of excitatory output from the network.

Computer Systems↗

The importance of the cortico-motoneuronal system for control of grasp.

Our recent work has revealed new evidence of the importance of direct cortico-motoneuronal (CM) connections for voluntary control of the hand. Most of these connections are derived from corticospinal neurons located in the M1 hand area, although there are some much smaller contributions from other secondary motor areas, such as the supplementary motor area (SMA). Intracellular recordings show that 75% of upper limb motoneurons in the chloralose-anaesthetized macaque monkey receive a monosynaptic projection from the corticospinal tract; evidence for non-monosynaptic, propriospinal excitatory influences from the corticospinal tract was conspicuously lacking in these anaesthetized preparations. Moreover, in the conscious monkey, hand and arm muscle motor unit responses to corticospinal tract input are dominated by single, brief peaks compatible with monosynaptic excitation. CM excitatory post-synaptic potentials, recorded from a comparable sample of hand and arm motoneurons in anaesthetized macaque and squirrel monkeys, were found to be larger and faster rising in the macaque, which is by far the more dexterous of the two species. CM cells facilitating a given muscle in the conscious macaque are distributed over a wide region of M1 cortex, and each contributes a particular pattern of discharge during a skilled task. In addition to their direct effects on target muscles there may be weaker but potentially important effects that derive from the synchronous binding of assemblies of output neurons. Synchronous oscillations between these neurons are particularly prevalent during steady grip, but disappear during digit movement.

Animals↗

An investigation of the intrinsic circuitry of the motor cortex of the monkey using intra-cortical microstimulation.

The motor cortex contains a distributed map of muscles, with a single muscle represented over a wide cortical area. We have searched for inter-connections between distant sites projecting to common muscles by delivering pairs of 20-microA single-pulse intracortical microstimuli (ICMS) to sites separated by 1.5-2 mm in the hand-area primary motor cortex of two macaque monkeys performing a precision grip task. The facilitation of hand- and forearm-muscle rectified EMG was measured. When stimuli were delivered simultaneously, responses were quantified using a technique to correct for non-linearities inherent in the use of averaged, rectified EMG. A spatial facilitation was seen for such simultaneous stimuli; however, it was of the same magnitude as that occurring when ICMS was paired with stimulation of corticospinal axons in the pyramidal tract (PT), so that it was likely to be spinal in origin. When two such distant sites were stimulated separated by a 10- or 20-ms delay, the second response scaled with the level of background EMG in the same way as a response to the PT stimulus. By contrast, when the same site was stimulated twice with these delays, the second response showed a facilitation compared with a similarly timed PT response. There would therefore appear to be a local facilitation of the cortical output at these intervals, which is not seen between distant sites. Antidromically identified pyramidal-tract neurones (PTNs) were recorded whilst stimuli were delivered to a cortical site, with a distance between stimulating and recording electrodes of also 1.5-2 mm. The most common response was a facilitation followed by a suppression. Six of eleven PTNs showed a facilitation in their discharge following this stimulation (maximum connection strength s=0.19), 8/11 showed a suppression (maximum s=0.16). It is concluded that powerful inter-connections do exist between distributed parts of the motor output and that there is widespread cortical activation after even a single ICMS pulse. However, these inter-connections do not lead to interactions between cortical outputs following stimulation, as assessed from the EMG. It is proposed that this is likely to reflect differences in the summation of output cells to local versus remote stimulation.

Animals↗

Computer simulation of post-spike facilitation in spike-triggered averages of rectified EMG.

When the spikes of a motor cortical cell are used to compile a spike-triggered average (STA) of rectified electromyographic (EMG) activity, a post-spike facilitation (PSF) is sometimes seen. This is generally thought to be indicative of direct corticomotoneuronal (CM) connections. However, it has been claimed that a PSF could be caused by synchronization between CM and non-CM cells. This study investigates the generation of PSF using a computer model. A population of cortical cells was simulated, some of which made CM connections to a pool of 103 motoneurons. Motoneurons were simulated using a biophysically realistic model. A subpopulation of the cortical cells was synchronized together. After a motoneuron discharge, a motor unit action potential was generated; these were summed to produce an EMG output. Realistic values were used for the corticospinal and peripheral nerve conduction velocity distribution, for slowing of impulse conduction in CM terminal axons, and for the amount of cortical synchrony. STA of the rectified EMG from all cortical neurons showed PSF; however, these were qualitatively different for CM versus non-CM cells. Using an epoch analysis to determine reliability in a quantitative manner, it was shown that the onset latency of PSF did not distinguish the two classes of cells after 10,000 spikes because of high noise in the averages. The time of the PSF peak and the peak width at half-maximum (PWHM) could separate CM from synchrony effects. However, only PWHM was robust against changes in motor unit action-potential shape and duration and against changes in the width of cortical synchrony. The amplitude of PSF from a CM cell could be doubled by the presence of synchrony. It is proposed that, if a PSF has PWHM < 7 ms, this reliably indicates that the trigger is a CM cell projecting to the muscle whose EMG is averaged. In an analysis of experimental data where macaque motor cortical cells facilitated hand and forearm muscle EMG, 74% of PSFs fulfilled this criterion. The PWHM criterion could be applied to other STA studies in which it is important to exclude the effects of synchrony.

Action Potentials↗

Coherent oscillations in monkey motor cortex and hand muscle EMG show task-dependent modulation.

1. Recordings were made of local field potential (slow waves) and pyramidal tract neurone (PTN) discharge from pairs of sites separated by a horizontal distance of up to 1.5 mm in the primary motor cortex of two conscious macaque monkeys performing a precision grip task. 2. In both monkeys, the slow wave recordings showed bursts of oscillations in the 20-30 Hz range. Spectral analysis revealed that the oscillations were coherent between the two simultaneously recorded cortical sites. In the monkey from which most data were recorded, the mean frequency of peak coherence was 23.4 Hz. 3. Coherence in this frequency range was also seen between cortical slow wave recordings and rectified EMG of hand and forearm muscles active during the task, and between pairs of rectified EMGs. 4. The dynamics of the coherence were investigated by analysing short, quasi-stationary data segments aligned relative to task performance. This revealed that the 20-30 Hz coherent oscillations were present mainly during the hold phase of the precision grip task. 5. The spikes of identified PTNs were used to compile spike-triggered averages of the slow wave recordings. Oscillations were seen in 11/17 averages of the slow wave recorded on the same electrode as the triggering spike, and 11/17 averages of the slow wave recorded on the distant electrode. The mean period of these oscillations was 45.8 ms. 6. It is concluded that oscillations in the range 20-30 Hz are present in monkey motor cortex, are coherent between spatially separated cortical sites, and encompass the pyramidal tract output neurones. They are discernable in the EMG of active muscles, and show a consistent task-dependent modulation.

Animals↗

Direct and indirect corticospinal control of arm and hand motoneurons in the squirrel monkey (Saimiri sciureus).

Anatomic evidence suggests that direct corticomotoneuronal (CM) projections to hand motoneurons in the New World squirrel monkey (Saimiri sciureus) are weak or absent, but electrophysiological evidence is lacking. The nature of the corticospinal linkage to these motoneurons was therefore investigated first with the use of transcranial magnetic stimulation (TMS) of the motor cortex under ketamine sedation in five monkeys. TMS produced early responses in hand muscle electromyogram, but thresholds were high (compared with macaque monkey) and the onset latency was variable. Second, stimulation of the pyramidal tract (PT) was carried out with the use of chronically implanted electrodes in ketamine-sedated monkeys; this produced more robust responses that were markedly facilitated by repetitive stimulation, with little decrease in latency on the third compared with the first shock. Finally, postsynaptic potentials were recorded intracellularly from 93 arm and hand motoneurons in five monkeys under general chloralose anesthesia. After a single PT stimulus, the most common response was a small, slowly rising excitatory postsynaptic potential (EPSP), either alone (35 of 93 motoneurons) or followed by an inhibitory postsynaptic potential (39 of 93). The segmental delay of the early EPSPs was within the monosynaptic range (mean 0.85 ms); however, the rise time of these EPSPs was slow (mean 1.3 ms) and their amplitude was small (mean 0.74 mV). These values are significantly slower and smaller than EPSPs in a comparable sample of Old World macaque monkey motoneurons. The results show that CM connections do exist in the squirrel monkey but that they are weak and possibly located on the remote dendrites of the motoneurons. The findings are consistent with earlier anatomic studies. Repetitive PT stimulation produced large, late EPSPs in some motoneurons, suggesting that, in this species, there are relatively strong nonmonosynaptic pathways linking the corticospinal tract to hand motoneurons.

Animals↗

Task-related variation in corticospinal output evoked by transcranial magnetic stimulation in the macaque monkey.

1. A volley evoked by transcranial magnetic stimulation (TMS) over the motor cortex was recorded from the medullary pyramid in an awake monkey performing a precision grip task. It was identified as corticospinal using a collision test. 2. The volley latency was 0.50 ms, indicating that it was produced by direct activation of corticospinal neurones. 3. A mean modulation of 13% in the amplitude of this volley was seen during task performance, with the largest volley occurring during the hold phase of the task. A similar pattern of modulation was seen in the EMG responses of hand and forearm muscles to TMS. 4. No comparable modulation was observed in a volley evoked by electrical stimulation of the corticospinal fibres via chronically implanted electrodes in the cerebral peduncle. 5. The results are compatible with direct activation of the corticospinal neurones by TMS at a site close to the soma, with the probability of activation by TMS depending on the current level of cortical excitability.

Animals↗

Non-linear summation of responses in averages of rectified EMG.

Studies on the motor system commonly use averages of rectified electromyogram (EMG) to measure muscular response. The assumption is usually made that this is a linear measure of response magnitude. It is shown here using a theoretical and experimental model that averages of rectified EMG can lead to non-linearities, which are of particular importance when considering the summation of two independent responses. When responses had a highly stereotyped waveform from trial to trial, so that averages of unrectified EMG revealed a deflection from zero, in measurements from averages of rectified EMG the size of a response to two stimuli delivered together was greater than the linear sum of the responses to each stimulus delivered alone. This deviation from linearity was greatest when two responses which were small relative to the ongoing background EMG activity were combined. The total response was then as much as twice as large as the linear sum of the individual component responses. Conversely, under conditions where responses were highly variable from trial to trial, resulting in no consistent deflection being seen in an average of unrectified EMG, the summed responses in rectified and averaged EMG were smaller than expected if summation were linear. This effect was most pronounced when both component responses were relatively large; the combined response tended asymptotically to approximately 70% of the linear sum of the component responses. A practical method is presented which allows prediction of the size of a response to two stimuli given together, when measured from averages of rectified EMG, on the assumption that they act independently.

Electric Stimulation↗

Recording an identified pyramidal volley evoked by transcranial magnetic stimulation in a conscious macaque monkey.

A descending volley in response to non-invasive transcranial magnetic stimulation has been recorded from the pyramidal tract in a conscious monkey and identified by means of a collision test. The short latency of the earliest wave was inconsistent with a trans-synaptically mediated activation of pyramidal tract neurones. Considerable variability in the size of this wave was seen in response to a constant stimulus, and isoflurane anaesthetic was shown to depress it markedly. These results are consistent with direct activation of pyramidal tract neurones at a site close to the cell body.

Animals↗

HIV screening and counseling for intravenous drug abuse patients. Staff and patient attitudes.

At least one third of patients enrolled in a methadone maintenance treatment program are willing to comply voluntarily with screening for and counseling about human immunodeficiency virus (HIV). A questionnaire about knowledge, attitudes, and behavior concerning acquired immunodeficiency syndrome was answered anonymously by 79% (46) of the clinical staff and 67% (868) of the enrolled patients. On their own initiative, 21% of the patients had already received voluntary anonymous HIV screening and brief counseling, seldom discussing the result with the staff. Approximately 90% of the staff and a majority of the patients (72%) thought a voluntary HIV screening program should be offered to all patients. Almost all staff (98%), but only 50% of the patients, felt the HIV test results should be known to physicians, nurses, and counselors at the clinic. Few staff members (15%) believed that patients had changed their sex behavior; more (48%) felt that needle sharing was reduced. Patients believed methadone patients in general had changed their sex behavior (49.2%) and reduced needle sharing (62%) to prevent becoming infected. Patients reported statistically significant reductions both in number of sex partners and in personal needle sharing during the past year.

Adult↗

Emergent oscillations in a realistic network: the role of inhibition and the effect of the spatiotemporal distribution of the input.

We have simulated a network of 10,000 two-compartment cells, spatially distributed on a two-dimensional sheet; 15% of the cells were inhibitory. The input to the network was spatially delimited. Global oscillations frequently were achieved with a simple set of connectivity rules. The inhibitory neurons paced the network, whereas the excitatory neurons amplified the input, permitting oscillations at low-input intensities. Inhibitory neurons were active over a greater area than excitatory ones, forming a ring of inhibition. The oscillation frequency was modulated to some extent by the input intensity, as has been shown experimentally in the striate cortex, but predominantly by the properties of the inhibitory neurons and their connections: the membrane and synaptic time constants and the distribution of delays. In networks that showed oscillations and in those that did not, widely distributed inputs could lead to the specific recruitment of the inhibitory neurons and to near zero activity of the excitatory cells. Hence the spatial distribution of excitatory inputs could provide a means of selectively exciting or inhibiting a target network. Finally, neither the presence of oscillations nor the global spike activity provided any reliable indication of the level of excitatory output from the network.

Action Potentials↗