The human motor cortex microcircuit: insights for neurodegenerative disease

Abstract

The human motor cortex is selectively vulnerable in a number of neurodegenerative diseases. In this review McColgan et al. integrate layer-specific physiology and pathobiology in the motor cortex thereby generating hypotheses that can be tested in humans using ultra-high resolution neuroimaging techniques. Glossary Anti-sense oligonucleotide therapies-These are single stranded DNA molecules, which bind to target pre-mRNA and recruit RNAse H causing degradation of the complex. This approach has already been applied to a number of neurodegenerative disease including Huntington's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Alzheimer's disease. Fusiform-This refers to a spindle shape, which is wide in the middle and tapers at both ends. Piriform-This refers to a pear shape, from the latin from pirum "pear" and forma "shape". 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-This is a compound which can cross the blood brain barrier were it is then converted into 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin, which causes selective and permanent destruction of dopaminergic neurons in the substania nigra. Vibrotactile discrimination-This is an experimental design were stimuli of two different frequencies are applied to the hand and the participant is asked to discriminate between the low and high frequency stimuli. Infragranular layers-These are cortical layers 5 and 6, which are below the granular layer 4 in the neocortex. Supergranular layers-These are cortical layers 1 to 3, which are above the granular layer 4 in the neocortex. Hyperkinetic-This relates to increased or excessive movement, such as tremor in Parkinson's disease or chorea in Huntington's disease Hypokinetic-This relates to reduced or slowed movement, such as reduced fine finger movements and rigidity seen in Parkinson's disease. Magnetic resonance spectroscopy-This technique detects radiofrequency electromagnetic signals that are produced by the atomic nuclei within molecules. It can be used to obtain measures of chemicals in the brain, such as N-acetylasparate, creatine, glutamate and GABA.

Diffusion Tensor Imaging in Parkinson's Disease and Parkinsonian Syndrome: A Systematic Review

“…The classical pathophysiological model of PD and recent updates have been established based on experimental and clinical studies (138)(139)(140)(141), which consists of functional disabilities of two main pathways: an "indirect circuit, " which interconnects neocortex-putamen-external pallidum/subthalamic nucleus-SN, and a "direct circuit, " which interconnects neocortex-putameninternal pallidum-SN-thalamus-neocortex. Under the conditions of PD, the reduced dopamine (results from neuronal loss in the SN) inhibits the indirect pathway, resulting in slow movement, and excites the direct pathway that may lead to unwanted movement such as resting tremor.…”

Circuit Mechanisms of L-DOPA-Induced Dyskinesia (LID)

“…IT neurons preferentially target both ipsilateral striatum and contralateral striatum as well as the cortex. Therefore, IT neurons include both corticostriatal and corticocortical projections, whereas PT neurons preferentially connect brainstem, spinal cord, and ipsilateral striatum (McColgan et al, 2020). In addition, it has been suggested that IT neurons express D 1 receptors and preferentially target dSPNs, whereas PT neurons express D 2 receptors and preferentially connect iSPN in the striatum (Shepherd, 2013), but this hypothesis is challenged by other studies; it has shown that IT and PT neurons project to both iSPN and dSPN in the striatum (Kress et al, 2013).…”

Molecular and microstructural biomarkers of neuroplasticity in neurodegenerative disorders through preclinical and diffusion magnetic resonance imaging studies

“…On a more technical viewpoint, due to the current significant disparity between dMRI voxel dimensions and cellular structures, there is a limited appraisal of the profound microcircuit changes within the GM and its architectural alterations (McColgan et al, 2020). The application of current diffusion models in medicine or biology has raised many questions ins the scientific community (Calamante, 2019;Little and Holloway, 2007).…”