Beyond the hallmark proteinopathies of Alzheimer’s Disease (AD), complementary neurophysiological features of cortical excitability may add depth and precision to forecasting an individual's clinical trajectory along the broad continuum of disease. Transcranial Magnetic Stimulation (TMS), a versatile non-invasive brain stimulation tool, can facilitate this line of inquiry. Specifically, as a proxy for central cholinergic function, a deficit of TMS-derived short-afferent inhibition (SAI) is commonly reported in the later stages of AD. In this study, we characterized SAI across the broader continuum of cognitive aging by enrolling three distinct cohorts: 1) healthy young adults, 2) cognitively normal older adults, and 3) older adults with objectively defined preclinical cognitive impairment. The primary finding indicates that SAI was significantly diminished only in the cohort of cognitively impaired older adults. Additionally, diminished SAI was significantly associated with impaired sustained attention and working memory. As a proxy measure for central cholinergic deficits, we discuss the potential utility of diminished SAI as a supplementary biomarker that may hold diagnostic and prognostic value along the AD continuum.
Abstract The human extensor digitorum (ED) muscle gives rise distally to multiple tendons that insert onto and extend digits 2–5. It has been shown previously that the spike‐triggered average forces of motor units in ED are broadly distributed across many tendons. Such force dispersion may result from linkages between the distal tendons of ED and may limit the ability to move the fingers independently. The purpose of this study, therefore, was to determine the extent to which the connections between tendons of ED distribute force across the fingers. Stimulation of ED muscle fibers was performed at 107 different sites in four subjects. The isometric force exerted on digits 2–5 resulting from the stimulation was measured separately. Stimulus‐triggered averaging of each of the four force channels yielded the force contribution to each of the digits due to the stimulation at each site. A selectivity index from 0 (a site that distributes force equally across the fingers) to 1.0 (a site that produces force on a single finger) was computed to describe the distribution of force across the four fingers. The selectivity index resulting from electrical stimulation of ED averaged 0.70 ± 0.21. These selectivity index values were significantly greater ( P < 0.001) than those obtained for single motor units using spike‐triggered averaging. These findings suggest that linkages between the distal tendons of ED probably play only a minor role in distributing force across the fingers and, therefore, other factors must be primarily responsible for the inability to move the fingers independently. Muscle Nerve 28: 614–622, 2003
Objective. A variety of bioengineering systems are being developed to restore tactile sensations in individuals who have lost somatosensory feedback because of spinal cord injury, stroke, or amputation. These systems typically detect tactile force with sensors placed on an insensate hand (or prosthetic hand in the case of amputees) and deliver touch information by electrically or mechanically stimulating sensate skin above the site of injury. Successful object manipulation, however, also requires proprioceptive feedback representing the configuration and movements of the hand and digits. Approach. Therefore, we developed a simple system that simultaneously provides information about tactile grip force and hand aperture using current amplitude-modulated electrotactile feedback. We evaluated the utility of this system by testing the ability of eight healthy human subjects to distinguish among 27 objects of varying sizes, weights, and compliances based entirely on electrotactile feedback. The feedback was modulated by grip-force and hand-aperture sensors placed on the hand of an experimenter (not visible to the subject) grasping and lifting the test objects. We were also interested to determine the degree to which subjects could learn to use such feedback when tested over five consecutive sessions. Main results. The average percentage correct identifications on day 1 (28.5% ± 8.2% correct) was well above chance (3.7%) and increased significantly with training to 49.2% ± 10.6% on day 5. Furthermore, this training transferred reasonably well to a set of novel objects. Significance. These results suggest that simple, non-invasive methods can provide useful multisensory feedback that might prove beneficial in improving the control over prosthetic limbs.
Muscle fibers release K(+) into the interstitial space upon recruitment. Increased local interstitial K(+) concentration ([K(+)]) can cause dilation of terminal arterioles, leading to perfusion of downstream capillaries. The possibility that capillary perfusion can be regulated by vascular responses to [K(+)] was examined using a theoretical model. The model takes into account the spatial relationship between functional units of muscle fiber recruitment and capillary perfusion. Diffusion of K(+) in the interstitial space was simulated. Two hypothetical mechanisms for vascular sensing of interstitial [K(+)] were considered: direct sensing by arterioles and sensing by capillaries with stimulation of feeding arterioles via conducted responses. Control by arteriolar sensing led to poor tissue oxygenation at high levels of muscle activation. With control by capillary sensing, increases in perfusion matched increases in oxygen demand. The time course of perfusion after sudden muscle activation was considered. Predicted capillary perfusion increased rapidly within the first 5 s of muscle fiber activation. The reuptake of K(+) by muscle fibers had a minor effect on the increase of interstitial [K(+)]. Uptake by perfused capillaries was primarily responsible for limiting the increase in [K(+)] in the interstitial space at the onset of fiber activation. Vascular responses to increasing interstitial [K(+)] may contribute to the rapid increase in blood flow that is observed to occur after the onset of muscle contraction.
Motor neurons are often assumed to generate spikes in proportion to the excitatory synaptic input received. There are, however, many intrinsic properties of motor neurons that might affect this relationship, such as persistent inward currents (PICs), spike-threshold accommodation, or spike-frequency adaptation. These nonlinear properties have been investigated in reduced animal preparation but have not been well studied during natural motor behaviors because of the difficulty in characterizing synaptic input in intact animals. Therefore, we studied the influence of each of these intrinsic properties on spiking responses and muscle force using a population model of motor units that simulates voluntary contractions in human subjects. In particular, we focused on the difference in firing rate of low-threshold motor units when higher threshold motor units were recruited and subsequently derecruited, referred to as ΔF. Others have used ΔF to evaluate the extent of PIC activation during voluntary behavior. Our results showed that positive ΔF values could arise when any one of these nonlinear properties was included in the simulations. Therefore, a positive ΔF should not be considered as exclusive evidence for PIC activation. Furthermore, by systematically varying contraction duration and speed in our simulations, we identified a means that might be used experimentally to distinguish among PICs, accommodation, and adaptation as contributors to ΔF.
1. Motor unit activity was recorded with intramuscular fine wire electrodes during isometric, concentric, and eccentric activity in the human first dorsal interosseus muscle. Twenty-one units from 11 subjects were sampled. 2. During isotonic cycles of shortening and lengthening, 18 of 21 units were recruited during the concentric phase, increased their discharge rates as the concentric movement progressed, then decreased their discharge rate during the eccentric phase, and were derecruited. 3. A different pattern of recruitment was observed in recordings from three units. These units were recruited during the eccentric phase, at a time when other units were decreasing their discharge rate or being derecruited. In two of the units selectively recruited during the eccentric phase, it was possible to determine their isometric thresholds, which were higher than those of units exhibiting the more common pattern of recruitment. 4. For two of the three units exhibiting selective recruitment during eccentric contraction, the unit was recorded simultaneously with different pairs of recording wires separated by 5<10 mm. Each discharge of these units was detected by both electrodes, making it unlikely that movement artifact was responsible for the initiation or cessation of discharge. 5. The recruitment patterns observed suggest that changes in the type or distribution of synaptic inputs to motoneurons during movement can, in some instances, override pre- and postsynaptic factors that shape recruitment order in isometric conditions.
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