No description available.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to assess the integrity neuronal circuits in the motor cortex, both at the intrahemispheric and interhemispheric level. In the present study, TMS was used to examine age-related modulation of corticospinal function. Participants underwent hand function testing to examine possible links between TMS measures and manual ability. Participants consisted of healthy young (n=13) and senior (n=17) right-handed individuals. Hand function testing consisted of a battery of tests administered bilaterally to assess each participant’s dexterity, strength, movement speed and reaction time. The following TMS measures were assessed bilaterally: resting motor threshold, recruitment curve and silent periods of the contralateral and ipsilateral hand. Both young and senior subjects showed significant intermanual differences in most behavioral measures, favoring their dominant right hand. There was an age-related difference in TMS measures indicating a decline in intrahemispheric excitability and interhemispheric inhibition. A general trend linking specific TMS measures in the active state with age-related changes in hand function on the dominant hand was found. Our results suggest that TMS markers of corticospinal excitability can be used to predict declining hand function with age and thus could provide an early diagnosis of pathological aging.

The corticospinal tract (CST), which carries commands from the cerebral cortex to the spinal cord, is vital to fine motor control. Spinal cord injury (SCI) often damages CST axons, causing loss of motor function, most notably in the hands and legs. Our preliminary work in rats suggests that CST circuitry is complex: neurons whose axons project to the lower cervical spinal cord, which directly controls hand function, also send axon collaterals to other locations in the nervous system and may engage parallel motor systems. To inform research into repair of SCI, we therefore aimed to map the entire projection pattern, or “connectome,” of such cervically-projecting CST axons. In this study, we mapped the corticospinal connectome of the Rhesus macaque - an animal model more similar to humans, and therefore more clinically relevant for examining SCI. Comparison of the Rhesus macaque and rat CST connectome, and extrapolation to the human CST connectome, may improve targeting of treatments and rehabilitation after human SCI. To selectively trace cervically-projecting CST motor axons, a virus encoding a Cre-recombinase-dependent tracer (AAV-DIO-gCOMET) was injected into the hand motor cortex, and a virus encoding Cre-recombinase (AAV-Cre) was injected into the C8 level of the spinal cord. In this intersectional approach, the gCOMET virus infects many neurons in the cortex, but gCOMET expression is not turned on unless the nucleus also contains Cre-recombinase, which must be retrogradely transported from axon terminals in the C8 spinal cord. Thus, gCOMET is only expressed in neurons that project to the C8 spinal cord, and it proceeds to fill the entire neuron, including all axon collaterals. Any gCOMET-labeled axon segments observed in other regions of the nervous system are therefore collaterals of cervically-projecting axons. gCOMET-positive axons were immunohistochemically labeled, and axon density was quantified using a fluorescence microscope and Fiji/ImageJ software. Specific regions of interest were chosen for analysis because of their known relevance in motor function in humans, and for comparison to results of a similar study in rats. Results in the first monkey have revealed both similarities and differences between the monkey and rodent CST connectome. Analyses of additional monkeys are ongoing. The final results will provide detailed information about differences between rodent and primate CST, will serve as a baseline for examining changes in the CST connectome after SCI, and will provide guidance for studies targeting treatment and functional recovery after SCI.

No description available.

The series of experiments comprising this thesis investigate how neural inputs arising from higher motor centres (e.g., the motor cortex) and the periphery are translated into a variety of activation patterns of alpha motoneurones during the performance of various muscle contraction types. The thesis consists of six chapters, with the first chapter providing an introduction to the research program, and the final chapter giving a summary of the main research findings. Chapter 2 to 5 each represent stand-alone scientific works. The study presented in Chapter 2 examined whether the soleus (SOL) H-reflex is modulated during shortening contractions in a manner that has been observed for isometric contractions. It was revealed that no significant correlation was found between the SOL H-reflex and increasing plantar flexion torque during shortening contractions (ρ = −0.07, P = 0.15), while a strong positive correlation was observed for the isometric conditions (ρ = 0.99, P < 0.01). Furthermore, no modulation in the H-reflexes via paired stimuli in voluntary shortening contractions suggested that the level of homosynaptic post-activation depression (HPAD) did not change in response to the varying levels of activation in voluntary shortening contractions. Therefore, Ia-excitatory input is likely to be reduced during shortening contractions at increasing intensities, possibly due to a centrally regulated increase in presynaptic inhibition. The study described in Chapter 3 investigated corticospinal-evoked responses in triceps surae muscles during voluntary contractions at varying strengths. Motor-evoked potentials (MEPs) and cervicomedullary motor-evoked potentials (CMEPs) were elicited in the SOL and medial gastrocnemius (MG) muscles using magnetic stimulation over the motor cortex and cervicomedullary junction during voluntary plantar flexions with the torque ranging from 0 to 100% of a maximal voluntary contraction (MVC). In both SOL and MG, MEP and CMEP amplitudes [normalized to maximal M wave (Mmax)] showed an increase, followed by a plateau, over the greater part of the contraction range with responses increasing from 0.2 to 6% of Mmax for SOL and from 0.3 to 10% of Mmax for MG. It was suggested that increases in the evoked responses from the triceps surae muscle over a greater range of contraction strengths than for upper limb muscles, probably stems from differences in the pattern of motor unit recruitment and rate coding for these muscles, and the strength of the corticospinal input. In Chapter 4, in an attempt to investigate how the recruitment and rate coding of motor unit organisation can affect the responsiveness of gross evoked potentials to artificial excitatory stimuli, a computer simulation was performed based upon a physiologically plausible model of the motoneurone. The simulation revealed that the force level where the evoked response commences to decline corresponds approximately to the upper limit of recruitment of motor units. This observation was consistent no matter whether firing rates for low-threshold units exceed those for high-threshold units. Since the simulated results were consistent with previous observations in both individual (single motor unit) and population (motoneurone pool) terms, the proposed model is physiologically plausible and can be useful to predict the evoked EMG response via artificial stimulation protocols, thereby inferring the underlying neural mechanisms occurring at the motoneurone pool during voluntary movements. The study presented in Chapter 5 determined the recruitment range and discharge behaviours in the SOL motor units, and examined the possible influence of persistent inward currents (PICs) on SOL motor unit recruitment and discharge rates. Forty-two clearly identified motor units from five subjects revealed that soleus motor units are recruited progressively from rest to contraction strengths close to 95% of MVC, with low-threshold motor units discharging action potentials slower at their recruitment and with a lower peak rate than later recruited high-threshold units. This observation is in contrast to the ‘onion skin phenomenon’ often reported for the upper limb muscles. Based on positive correlations of the peak discharge rates, initial rates and recruitment order of the units with the magnitude of the onset-offset hysteresis (i.e., a difference in discharge rate between recruitment and de-recruitment) and not PIC contribution, we conclude that discharge behaviours among motor units appear to be related to a variation in an intrinsic property other than PICs.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22886号 / 医博第4680号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 井上 治久, 教授 伊佐 正 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23461号 / 理博第4755号 / 新制||理||1682(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 高田 昌彦, 准教授 宮地 重弘, 教授 古市 剛史 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM