Biomedical subjects

Roger N Lemon

Publications and source records attributed to Roger N Lemon.

13 recordsLinked to original sources

PubMed2006

Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.

Adaptation, Physiological↗

PubMed2006

Linear encoding of muscle activity in primary motor cortex and cerebellum.

The activity of neurons in primary motor cortex (M1) and cerebellum is known to correlate with extrinsic movement parameters, including hand position and velocity. Relatively few studies have addressed the encoding of intrinsic parameters, such as muscle activity. Here we applied a generalized regression analysis to describe the relationship of neurons in M1 and cerebellar dentate nucleus to electromyographic (EMG) activity from hand and forearm muscles, during performance of precision grip by macaque monkeys. We showed that cells in both M1 and dentate encode muscle activity in a linear fashion, and that EMG signals provide predictions of neural discharge that are equally accurate to those from kinematic information under these task conditions. Neural activity in M1 was significantly more correlated with both EMG and kinematic signals than was activity in dentate nucleus. Furthermore, the analysis enabled us to look at the temporal properties of muscle encoding. Cells were broadly tuned to muscle activity as a function of the lag between spiking and EMG and there was considerable heterogeneity in the optimal delay among individual neurons. However, a single lag (40 ms) was generally sufficient to provide good fits. Finally, incorporating spike history effects in our model offered no advantage in predicting novel spike trains, reinforcing the simple nature of the muscle encoding that we observed here.

Algorithms↗

PubMed2005

Comparing the function of the corticospinal system in different species: organizational differences for motor specialization?

An appreciation of the comparative functions of the corticospinal tract is of direct relevance to the understanding of how results from animal models can advance knowledge of the human motor system and its disorders. Two critical functions of the corticospinal tract are discussed: first, the role of descending projections to the dorsal horn in the control of sensory afferent input, and second, the capacity of direct cortico-motoneuronal projections to support voluntary execution of skilled hand and finger movements. We stress that there are some important differences in corticospinal projections from different cortical regions within a particular species and that these projections support different functions. Therefore, any differences in the organization of corticospinal projections across species may well reflect differences in their functional roles. Such differences most likely reflect features of the sensorimotor behavior that are characteristic of that species. Insights into corticospinal function in different animal models are of direct relevance to understanding the human motor system, providing they are interpreted in relation to the functions they underpin in a given model. Studies in non-human primates will continue to be needed for understanding special features of the human motor system, including feed-forward control of skilled hand movements. These movements are often particularly vulnerable to neurological disease, including stroke, cerebral palsy, movement disorders, spinal injury, and motor neuron disease.

Afferent Pathways↗

PubMed2005

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

Adult↗

PubMed2004

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.

Adult↗

PubMed2004

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex.

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.

Adult↗

PubMed2004

Direct and indirect pathways for corticospinal control of upper limb motoneurons in the primate.

In the macaque monkey and in humans, the monosynaptic cortico-motoneuronal system is well developed. It allows the cortical motor areas to make an important direct contribution to the pattern of muscle activity during upper limb movements. There is, in addition, good anatomical evidence for descending corticospinal inputs being able to influence the premotoneuronal networks of the cervical spinal cord, and especially those operating at the segmental level of upper limb motoneurons. While oligosynaptic inhibition has been easy to demonstrate in the macaque, and may be a very important component of descending corticospinal control, it has proved much more difficult to detect signs of oligosynaptic excitation. In contrast, in the squirrel monkey, in which the cortico-motoneuronal system is far less developed, oligosynaptic excitation is prominent. There are important changes in the interplay between direct and indirect pathways in different primates, which may provide important clues on the nature of the corticospinal control of upper limb function.

Animals↗

PubMed2003

EEG oscillations at 600 Hz are macroscopic markers for cortical spike bursts.

The human electroencephalogram (EEG) is generated predominantly by synchronised cortical excitatory postsynaptic potentials oscillating at frequencies <100 Hz. Unusually, EEG responses to electrical nerve stimulation contain brief bursts of high-frequency (600 Hz) wavelets. Here we show, in awake monkeys, that a subset of primary somatosensory cortex single units consistently fires both bursts and single spikes phase-locked to EEG wavelets. Spike bursts were also evoked by tactile stimuli, proving that this is a natural response mode. EEG wavelets at 600 Hz may therefore permit non-invasive assessment of population spike timing in human cortex.

Animals↗

PubMed2003

Synchrony between neurons with similar muscle fields in monkey motor cortex.

Synchronous firing of motor cortex cells exhibiting postspike facilitation (PSF) or suppression (PSS) of hand muscle EMG was examined to investigate the relationship between synchrony and output connectivity. Recordings were made in macaque monkeys performing a precision grip task. Synchronization was assessed with cross-correlation histograms of the activity from 144 pairs of simultaneously recorded neurons, while spike-triggered averages of EMG defined the muscle field for each cell. Cell pairs with similar muscle fields showed greater synchronization than pairs with nonoverlapping fields. Furthermore, cells with opposing effects in the same muscles exhibited negative synchronization. We conclude that synchrony in motor cortex engages networks of neurons directly controlling the same muscle set, while inhibitory connections exist between neuronal populations with opposing output effects.

Action Potentials↗

PubMed2003

Synchronization in monkey motor cortex during a precision grip task. II. effect of oscillatory activity on corticospinal output.

Recordings from primary motor cortex (M1) during periods of steady contraction show oscillatory activity; these oscillations are coherent with the activity of contralateral muscles. We investigated synchronization of corticospinal output neurons with the oscillations, which could provide the pathway for their transmission to the spinal motoneurons. One hundred seventy-six antidromically identified pyramidal tract neurons (PTNs) were recorded from M1 in three macaque monkeys trained to perform a precision grip task. Local field potentials (LFP) were simultaneously recorded. All analysis was confined to the hold period of the task, where our previous work has shown that there is the strongest oscillatory activity. Coherence was calculated between LFP and PTN discharge. Significant coherence was seen in three bands, with frequencies of 10-14, 17-31, and 34-44 Hz. Coherence values were low, with the majority of PTN-LFP coherences having a peak lower than 0.05. The phase of coherence was approximately -pi/2 radians for each band (with LFP polarity defined as negative upward), although there was some dispersion of phase across the population of PTNs. Coherence was also calculated between pairs of PTNs that had been simultaneously recorded. Where there was significant coherence, it was also generally smaller than 0.05. The phase of PTN-PTN coherence clustered around zero radians. A computer model was constructed to assist the interpretation of the experimental results. It simulated an integrate-and-fire neuron responding to synaptic inputs. A fraction of the synaptic inputs was synchronized with a simulated LFP; the remainder were uncorrelated with it. The model showed that coherence between the LFP and the output spike train considerably underestimated the fraction of synchronized inputs. Additionally, for a given fraction of synchronized inputs, coherence was smaller for high- compared with low-frequency bins. Cell discharge rate also influenced the spike-LFP coherence: coherence was higher for simulations in which the cell discharged at a faster rate. Thus although levels of PTN-LFP coherence seen experimentally were low, a considerable proportion of the input to the PTN must be synchronized with the global oscillatory activity recorded by the LFP. The low LFP-PTN coherences do however indicate that cortical oscillations are transmitted with only low fidelity in the discharge of a single PTN. Using further computer simulations, it was demonstrated that a small population of PTNs could encode the cortical oscillatory signal effectively, since the action of averaging across the population improves the signal:noise ratio. The oscillations will therefore be effectively transmitted to spinal motoneurons, and this has important consequences for the possible role of oscillations in motor control of the hand.

Animals↗

PubMed2002

Initial demonstration of in vivo tracing of axonal projections in the macaque brain and comparison with the human brain using diffusion tensor imaging and fast marching tractography.

Diffusion tensor imaging (DTI), a magnetic resonance imaging technique, is used to infer major axonal projections in the macaque and human brain. This study investigates the feasibility of using known macaque anatomical connectivity as a "gold-standard" for the evaluation of DTI tractography methods. Connectivity information is determined from the DTI data using fast marching tractography (FMT), a novel tract-tracing (tractography) method. We show for the first time that it is possible to determine, in an entirely noninvasive manner, anatomical connection pathways and maps of an anatomical connectivity metric in the macaque brain using a standard clinical scanner and that these pathways are consistent with known anatomy. Analogous human anatomical connectivity is also presented for the first time using the FMT method, and the results are compared. The current limitations of the methodology and possibilities available for further studies are discussed.

Animals↗

PubMed2002

Interspecies comparisons for the C3-C4 propriospinal system: unresolved issues.

There are conflicting views on the functional importance of the system of C3-C4 propriospinal neurones in the macaque, although the two sets of observations from the opposing laboratories are actually quite similar, both making the system appear much weaker than its well-known equivalent in the cat. One group asserts, mainly via evidence derived from experiments with strychnine, that this is a consequence simply of inhibition of the propriospinal neurone. However, we ague here that this judgement is premature and that much more needs to be known about the neurones involved and their connectivity before the analogy with the system in the cat is safe. This is particularly important because of a similar analogy which has been made with respect to measurements in human subjects.

Animals↗

PubMed2002

Functional differences in corticospinal projections from macaque primary motor cortex and supplementary motor area.

We made a quantitative comparison of the density of macaque corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles. We also compared the action of corticospinal outputs from these two areas on 84 upper limb (mostly hand) motoneurones in chloralose-anaesthetised macaques. The hand representations of M1 and SMA were first identified using MRI and intracortical microstimulation. We made focal injections of WGA-HRP into these representations. Densitometric analysis showed that corticospinal projections from M1 were far denser and occupied a much greater proportion of the hand muscle motor nuclei than did SMA projections. Stimulation of M1 and SMA with bipolar intracortical pulses evoked monosynaptic EPSPs. These were significantly larger and more common from M1 (88% of motoneurons) than from SMA (48%). The results demonstrate corticomotoneuronal connections from both M1 and SMA, some converging upon single motoneurons. Both areas give rise to CM projections but that those from M1 are far more numerous and exert stronger excitatory effects than those from the SMA.

Animals↗