The ability to cancel a motor response is critical for optimal functioning in various facets of daily life. Hence, efficient inhibitory motor control is a key function throughout the lifespan. Considering the fact tha...The ability to cancel a motor response is critical for optimal functioning in various facets of daily life. Hence, efficient inhibitory motor control is a key function throughout the lifespan. Considering the fact that inhibitory motor function gradually declines with advancing age, it is not surprising that the study of motor inhibition in this age group is gaining considerable interest. In general, we can distinguish between two prominent types of motor inhibition, namely proactive and reactive inhibition. Whereas the anticipation for upcoming stops(proactive inhibition) appears readily preserved at older age, the ability to stop an already planned or initiated action(reactive inhibition) generally declines with advancing age. The differential impact of aging on proactive and reactive inhibition at the behavioral level prompts questions about the neural architecture underlying both types of inhibitory motor control. Here we will not only highlight the underlying structural brain properties of proactive and reactive inhibitory control but we will also discuss recent developments in brain-behavioral approaches, namely the registration of neurochemical compounds using magnetic resonance spectroscopy. This technique allows for the direct detection of the primary inhibitory neurotransmitter in the brain, i.e., γ-aminobutyric acid, across the broader cortical/subcortical territory, thereby opening new perspectives for better understanding the neural mechanisms mediating efficient inhibitory control in the context of healthy aging. Ultimately, these insights may contribute to the development of interventions specifically designed to counteract age-related declines in motor inhibition.展开更多
The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal cli...The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal clinical observation. Patients with chronic pain syndromes or chronic musculoskeletal pain often have low serum levels of vitamin D and testos-terone. Mining for relevant information in Pub Med, Medline and Cochrane Systems Review, three concepts repeatedly emerge that provide a common context for understanding the mechanics of these diverse sys-tems—epigenetic, homeostasis and neuroplasticity. Viewing homeostasis within the framework of epigenetics allows reasoned speculation as to how various human systems interact to maintain integrity and function, while simultaneously responding in a plastic manner to external stimuli. Cell signaling supports normal function by regulating synaptic activity, but can also effect plastic change in the central and peripheral nervous system. This is most commonly achieved by post-translational remodeling of chromatin. There is thus persistent epigenetic change in protein synthesis with all the related downstream effects but without disruption of normal DNA se-quencing. In itself, this may be considered an example of genomic homeo-stasis. Epigenetic mechanisms in nociception and analgesia are active in the paleospinothalamic and neospinothalamic tracts at all levels. Physiologic response to a nociceptive insult, whether mechanical, inflammatory or ischemic, is provided by cell signaling that is significantly enhanced through epigenetic mechanisms at work in nociceptors, Gamma-Aminobutyric Acid (GABA) and glutamate receptors, voltage gated receptors, higher order neurons in the various dorsal horn laminae and proximal nociceptive pro-cessing centers in the brainstem and cortex. The mediators of these direct or epigenetic effects are various ligands also active in signaling, such as free radicals, substance P, a variety of cytokines, growth factors and G proteins, stress responsive proteins, matrix and structural proteins such as reelin and the Jmjd3 gene/enzyme. Calcitriol, the vitamin D receptor and vitamin D Responsive Elements collectively determine regulatory effects of this secosteroid hormone. Agents of homeostasis and plasticity include various D-system specific cytochrome enzymes (CYP 24, CYP 27 A1, B1), as well as more widely active enzymes and protein cell signalers (Jmjd3, Calbindin, BMP), many of which play a role in the nociceptive system. While the highlighted information represents an understanding of complex systems that is currently in its infancy, there are clear results from reliable research at a foundational level. These results are beginning to tell a compelling tale of the homeostasis and plasticity inherent in vitamin D and nociception systems.展开更多
基金supported by the Research Foundation Flanders(G089818N to SPS)+6 种基金the Excellence of Science grant(EOS,30446199,MEMODYN to SPS)the KU Leuven Research Fund(C16/15/070 to SPS)the postdoctoral fellowship from the Research Fund KU Leuven(PDM/18/180 to LP)an aspirant fellowship of the Research Foundation–Flanders(FWO)to CM
文摘The ability to cancel a motor response is critical for optimal functioning in various facets of daily life. Hence, efficient inhibitory motor control is a key function throughout the lifespan. Considering the fact that inhibitory motor function gradually declines with advancing age, it is not surprising that the study of motor inhibition in this age group is gaining considerable interest. In general, we can distinguish between two prominent types of motor inhibition, namely proactive and reactive inhibition. Whereas the anticipation for upcoming stops(proactive inhibition) appears readily preserved at older age, the ability to stop an already planned or initiated action(reactive inhibition) generally declines with advancing age. The differential impact of aging on proactive and reactive inhibition at the behavioral level prompts questions about the neural architecture underlying both types of inhibitory motor control. Here we will not only highlight the underlying structural brain properties of proactive and reactive inhibitory control but we will also discuss recent developments in brain-behavioral approaches, namely the registration of neurochemical compounds using magnetic resonance spectroscopy. This technique allows for the direct detection of the primary inhibitory neurotransmitter in the brain, i.e., γ-aminobutyric acid, across the broader cortical/subcortical territory, thereby opening new perspectives for better understanding the neural mechanisms mediating efficient inhibitory control in the context of healthy aging. Ultimately, these insights may contribute to the development of interventions specifically designed to counteract age-related declines in motor inhibition.
文摘The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal clinical observation. Patients with chronic pain syndromes or chronic musculoskeletal pain often have low serum levels of vitamin D and testos-terone. Mining for relevant information in Pub Med, Medline and Cochrane Systems Review, three concepts repeatedly emerge that provide a common context for understanding the mechanics of these diverse sys-tems—epigenetic, homeostasis and neuroplasticity. Viewing homeostasis within the framework of epigenetics allows reasoned speculation as to how various human systems interact to maintain integrity and function, while simultaneously responding in a plastic manner to external stimuli. Cell signaling supports normal function by regulating synaptic activity, but can also effect plastic change in the central and peripheral nervous system. This is most commonly achieved by post-translational remodeling of chromatin. There is thus persistent epigenetic change in protein synthesis with all the related downstream effects but without disruption of normal DNA se-quencing. In itself, this may be considered an example of genomic homeo-stasis. Epigenetic mechanisms in nociception and analgesia are active in the paleospinothalamic and neospinothalamic tracts at all levels. Physiologic response to a nociceptive insult, whether mechanical, inflammatory or ischemic, is provided by cell signaling that is significantly enhanced through epigenetic mechanisms at work in nociceptors, Gamma-Aminobutyric Acid (GABA) and glutamate receptors, voltage gated receptors, higher order neurons in the various dorsal horn laminae and proximal nociceptive pro-cessing centers in the brainstem and cortex. The mediators of these direct or epigenetic effects are various ligands also active in signaling, such as free radicals, substance P, a variety of cytokines, growth factors and G proteins, stress responsive proteins, matrix and structural proteins such as reelin and the Jmjd3 gene/enzyme. Calcitriol, the vitamin D receptor and vitamin D Responsive Elements collectively determine regulatory effects of this secosteroid hormone. Agents of homeostasis and plasticity include various D-system specific cytochrome enzymes (CYP 24, CYP 27 A1, B1), as well as more widely active enzymes and protein cell signalers (Jmjd3, Calbindin, BMP), many of which play a role in the nociceptive system. While the highlighted information represents an understanding of complex systems that is currently in its infancy, there are clear results from reliable research at a foundational level. These results are beginning to tell a compelling tale of the homeostasis and plasticity inherent in vitamin D and nociception systems.