Great Scott! Could time travel be a movement disorder?

Who hasn’t seen “Back to the Future”?  A great movie about a kid named Marty McFly, played by Michael J. Fox, whose goal is to go back to the future after he repairs the damage he inadvertently caused when he is accidentally sent back in time.  Michael J. Fox would star in this movie and its two sequels and propel them to cult movie status, before he was diagnosed in 1991 with Parkinson’s disease, a degenerative neurological condition. Parkinson’s disease would eventually sideline him as a mainstream “on-screen” actor, and cause him to stick to voice-work as his main acting roles.

Parkinson’s disease, along with many other movement disorders is characterized by degeneration of neuron function in the central nervous system and physically presents itself in the form of decreasing muscle control in the patient.  In addition to this primary symptom, Parkinson’s disease patients can also experience other recurring symptoms, including depression, dementia, speech issues and poor sleep.

What is Parkinson’s disease at the base level? What causes the progressive loss of motor control in patients?  Recent research into the neurocircuitry of this disease has revealed quite a bit of information on the pathology of this disease and its progression.

The basis of Parkinson’s disease lies in the basal ganglia located in the forebrain, with many connections stretching out to other structures such as the thalamus and the cerebral cortex (Figure 1).  The basal ganglia are a group of functionally similar nuclei that work in conjunction with each other to convey output signals to targets such as the cerebral cortex, superior colliculus, and the lateral habenular nucleus.  Within these basal ganglia is where Parkinson’s disease develops.

Figure 1.  Basal ganglia and related structures of the brain.  Image from Henkel, 1998.

Figure 1. Basal ganglia and related structures of the brain. Image from Henkel, 1998.

The predominant feature of Parkinson’s disease is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), a primary input to the basal ganglia, which sends signals to the striatum.  It is this reduction in dopamine transmission that defines idiopathic Parkinson’s disease.

This decrease in dopamine signaling can be caused by reduced dopamine synthesis, altered dopamine release from neurons, or a problem with dopamine binding to post-synaptic neurons, preventing dopamine from causing an effect.  The loss in dopamine signaling in the basal ganglia is incredibly important due to their function as the motor control center of the brain.  When the frontal cortex sends a signal to the basal ganglia, such as “pick up the penny”, the basal ganglia send signals outward which decide “how to pick up the penny”; that is, what muscles need to contract and relax in order to pick up the penny.  This signal from the basal ganglia goes back to the cortex via the thalamus.  Interruptions in this signaling pathway can cause these messages to become corrupted, and the planned muscle movements to become distorted.

In a more technical sense, neurodegeneration of the SNc leads to changes within the basal ganglia nuclei that result in an overall increase in the output of the interior globus pallidus (GPi) and the substantia nigra pars reticulata (SNr).  The increased output of these two nuclei causes the inhibition of the ventral lateral thalamus (VL) and the ventral anterior thalamus (VA).  The VL and the VA signal to the motor cortices, which completes the regulatory circuitry of the basal ganglia.  Thus, it is specifically VA/VL inhibition which causes reduced motor control.

Figure 2. Thick lines indicate increased output, and thin arrows indicate decreased output patterns present in Parkinson’s disease. Black lines indicate inhibitory actions, and lines in red indicate excitatory actions.

The image above helps to visualize the previous concepts (Figure 2).  Thicker lines indicate increased output, and thin arrows indicate decreased output patterns present in Parkinson’s disease. Black lines indicate inhibitory actions, and lines in red indicate excitatory actions.  Note that, with loss of SNc function, the cascade of effects causes decreased VL/VA function, which leads to loss of motor control.

Decreased dopamine signaling in the basal ganglia can lead to a subsequent decrease in muscle control.  However, with recent treatment protocols and advances in modern medicine, this degeneration of muscle control can be slowed down leading to increased patient quality of life.  Treatment of this condition focuses around modulating the dopamine imbalance.  More dopamine leads to increased signaling in the SNc, which can provide patients of the disease with symptom relief.

For more information about monitoring of dopamine levels in patients, please check out this paper: Validation of an ELISA for urinary dopamine: applications in monitoring treatment of dopamine-related disorders.

Guest author: Ken Gorsegner is a member of the Clinical Support & Education Department at NeuroScience, Inc. and the resident expert in autoimmune disorders.

References:
Henkel, John (July-August 1998). “Parkinson’s Disease: New Treatments Slow Onslaught of Symptoms“. FDA Consumer: p. 17.
Oluigbo, Chima O, and Ali RRezai. (2011). Addressing neurological disorders with neuromodulation. IEEE Transactions on Biomedical Engineering, 58(7): 1907-17.
Wichmann, Thomas and Delong, Mahlon. (2002). Neurocircuitry of Parkinson’s Disease. Neuropsychopharmacology: The Fifth Generation of Progress.
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One Response to Great Scott! Could time travel be a movement disorder?

  1. Rosemary Flynn says:

    Would love you to discuss idiopathic dystonia, also a movement disorder but not neurodegenerative. It is quite incapacitating, functionally limiting and painful! Sometimes a symptom of other neurological conditions but often just its own disease/disorder. Suggestions on supportive therapies sorely needed. They understand dystonia much less than Parkinson’s and many other conditions. Not sure if it involves an excess or deficiency of dopamine or even if dopamine involved at all.

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