A Working Theory on the Use of Alternating Bilateral Stimulation for Treating Parkinsonian and non-Parkinsonian Tremor

A Working Theory on the Use of Alternating Bilateral Stimulation for Treating Parkinsonian and non-Parkinsonian Tremor

A Working Theory on the Use of Alternating Bilateral Stimulation for Treating Parkinsonian and non-Parkinsonian Tremor

Key Points

  • Tremors fall into two general categories – resting tremors and action tremors.
  • Resting tremors – typically associated with Parkinson’s Disease (PD) and is most noticeable when the patient is distracted and/or not moving (“at rest”).
  • Action tremors – also called intention tremors, are typically seen in patients with essential tremor (ET) and are not seen with Parkinson’s disease. They are worse when the patient is focusing on a planned, purposeful movement, such as reaching out to grasp a glass.
  • Resting tremors and action tremors are thought to be caused by different areas of the brain, which requires different treatment approaches.
  • TouchPoints, a wearable device based on bilateral alternating somatosensory stimulation, affect resting and action tremors differently.
    • Because the resting tremor of PD is likely caused by decreased electrical activity in the brain, TouchPoints would most likely be ineffective or exacerbate a resting tremor.
    • Because the action tremor of ET is likely caused by increased electrical activity in certain areas of the brain, TouchPoints would likely be effective in treating an action tremor.
  • Although different, patients can present with a mix of both types of tremor. It is more difficult to predict if and how TouchPoints will affect these patients.  

Tremors fall into two general categories - resting tremors and action tremors.  A wearable device based on bilateral alternating stimulation, TouchPoints, has shown some efficacy in treating patients with tremors, but results have been inconsistent. Given the different characteristics and etiologies of these two types of tremors, this is not surprising.

As a general rule, the tremor of Parkinson’s disease (PD) is a resting tremor, which means it is clinically worse when the patient is at rest or distracted; the neuropathophysiological cause is thought to reside in a subcortical structure that regulates movement, called the basal ganglia, and its connections with the cerebral cortex. The consensus is that the tremor associated with Parkinson’s disease results from a loss of dopaminergic neurons in the substantia nigra. This alteration of the basal ganglia circuitry results overall in increased inhibitory transmission to the cerebral cortex3.  Given the known global cortical and subcortical inhibitory effects of TouchPoints seen on post-treatment EEG (mimicking EMDR studies)4, the application of TouchPoints would likely transiently worsen a Parkinsonian tremor and/or would be ineffective in treating a PD tremor.

In contrast, an action tremor or intention tremor is worse during planned movement, such as when moving your arm to pick up a glass; the neuropathophysiological cause is thought to be rooted in the connections between the brainstem and the cerebellum, called the olivocerebellar circuit. The tremor is thought to be caused, in part, by an intrinsic central pacemaker property of the brainstem neurons and correlates with increased electrical activity, blood flow, and increased glucose metabolism in the brain stem and the cerebellum causing the characteristic 4-10 Hz frequency of essential tremor (ET)5,6Since action tremors are correlated with increased excitatory activity in this olivocerebellar circuit, the hyperpolarizing cortical and subcortical activity of alternating bilateral stimulations would likely result in improved control and tremor severity. It is also possible that the alternating bilateral stimuli provided by a device such as TouchPoints would frequency lock with the pacemaker neurons in the brainstem leading to a reduction in the amplitude of the electrical oscillations that cause the tremor of ET.

Despite the differences between resting and action tremors, elements of both types of tremor might be present in PD or ET patients. In some patients, there is considerable overlap between ET, intention tremor, and PD, and the diagnoses and timelines are far from clear. There is also likely a link between ET and PD and a certain subset of patients develop ET early on (often with a family history) and subsequently are at a higher risk for subsequently developing PD.  Obviously, in these patients with a mix of different etiologies of tremor, it becomes more difficult to predict exactly what effect alternating bilateral stimulation will have. 

This article was written by Dr. Nathan Hageman. Dr. Hageman is the Research Director at the TouchPoint Solution Dr. Hageman received a Bachelor of Science in Physics, Chemistry and Biology from Johns Hopkins University, and an MD and a Ph.D. in Neuroscience and Neuro-Engineering from UCLA with a focus in brain mapping and medical image processing. 

References

  1. Pagani M, Högberg G, Fernandez I, Siracusano A. Correlates of EMDR Therapy in Functional and Structural Neuroimaging: A Critical Summary of Recent Findings. J EMDR Pract Res. 2013;7(1):29-38. doi:10.1891/1933-3196.7.1.29
  2. Rousseau PF, El Khoury-Malhame M, Reynaud E, Zendjidjian X, Samuelian JC, Khalfa S. Neurobiological correlates of EMDR therapy effect in PTSD. Eur J Trauma Dissociation. 2019;3(2):103-111. doi:10.1016/j.ejtd.2018.07.001
  3. Okun MS. Deep-brain stimulation - Entering the era of human neural-network modulation. N Engl J Med. 2014;371(15):1369-1373. doi:10.1056/NEJMp1408779
  4. Serin A, Hageman NS, Kade E. The Therapeutic Effect of Bilateral Alternating Stimulation Tactile Form Technology on the Stress Response. J Biotechnol Biomed Sci. 2018;1(2):42-47. doi:10.14302/issn.2576-6694.jbbs-18-1887
  5. Louis ED, Lenka A. The olivary hypothesis of essential tremor: Time to lay this model to rest? Tremor and Other Hyperkinetic Movements. 2017;7. doi:10.7916/D8FF40RX
  6. Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED. Rest tremor in patients with essential tremor: Prevalence, clinical correlates, and electrophysiologic characteristics. Arch Neurol. 2003;60(3):405-410. doi:10.1001/archneur.60.3.405

A Working Theory on the Use of Alternating Bilateral Stimulation for Treating Parkinsonian and non-Parkinsonian Tremor

Key Points

  • Tremors fall into two general categories – resting tremors and action tremors.
  • Resting tremors – typically associated with Parkinson’s Disease (PD) and is most noticeable when the patient is distracted and/or not moving (“at rest”).
  • Action tremors – also called intention tremors, are typically seen in patients with essential tremor (ET) and are not seen with Parkinson’s disease. They are worse when the patient is focusing on a planned, purposeful movement, such as reaching out to grasp a glass.
  • Resting tremors and action tremors are thought to be caused by different areas of the brain, which requires different treatment approaches.
  • TouchPoints, a wearable device based on bilateral alternating somatosensory stimulation, affect resting and action tremors differently.
    • Because the resting tremor of PD is likely caused by decreased electrical activity in the brain, TouchPoints would most likely be ineffective or exacerbate a resting tremor.
    • Because the action tremor of ET is likely caused by increased electrical activity in certain areas of the brain, TouchPoints would likely be effective in treating an action tremor.
  • Although different, patients can present with a mix of both types of tremor. It is more difficult to predict if and how TouchPoints will affect these patients.  

Tremors fall into two general categories - resting tremors and action tremors.  A wearable device based on bilateral alternating stimulation, TouchPoints, has shown some efficacy in treating patients with tremors, but results have been inconsistent. Given the different characteristics and etiologies of these two types of tremors, this is not surprising.

As a general rule, the tremor of Parkinson’s disease (PD) is a resting tremor, which means it is clinically worse when the patient is at rest or distracted; the neuropathophysiological cause is thought to reside in a subcortical structure that regulates movement, called the basal ganglia, and its connections with the cerebral cortex. The consensus is that the tremor associated with Parkinson’s disease results from a loss of dopaminergic neurons in the substantia nigra. This alteration of the basal ganglia circuitry results overall in increased inhibitory transmission to the cerebral cortex3.  Given the known global cortical and subcortical inhibitory effects of TouchPoints seen on post-treatment EEG (mimicking EMDR studies)4, the application of TouchPoints would likely transiently worsen a Parkinsonian tremor and/or would be ineffective in treating a PD tremor.

In contrast, an action tremor or intention tremor is worse during planned movement, such as when moving your arm to pick up a glass; the neuropathophysiological cause is thought to be rooted in the connections between the brainstem and the cerebellum, called the olivocerebellar circuit. The tremor is thought to be caused, in part, by an intrinsic central pacemaker property of the brainstem neurons and correlates with increased electrical activity, blood flow, and increased glucose metabolism in the brain stem and the cerebellum causing the characteristic 4-10 Hz frequency of essential tremor (ET)5,6Since action tremors are correlated with increased excitatory activity in this olivocerebellar circuit, the hyperpolarizing cortical and subcortical activity of alternating bilateral stimulations would likely result in improved control and tremor severity. It is also possible that the alternating bilateral stimuli provided by a device such as TouchPoints would frequency lock with the pacemaker neurons in the brainstem leading to a reduction in the amplitude of the electrical oscillations that cause the tremor of ET.

Despite the differences between resting and action tremors, elements of both types of tremor might be present in PD or ET patients. In some patients, there is considerable overlap between ET, intention tremor, and PD, and the diagnoses and timelines are far from clear. There is also likely a link between ET and PD and a certain subset of patients develop ET early on (often with a family history) and subsequently are at a higher risk for subsequently developing PD.  Obviously, in these patients with a mix of different etiologies of tremor, it becomes more difficult to predict exactly what effect alternating bilateral stimulation will have. 

This article was written by Dr. Nathan Hageman. Dr. Hageman is the Research Director at the TouchPoint Solution Dr. Hageman received a Bachelor of Science in Physics, Chemistry and Biology from Johns Hopkins University, and an MD and a Ph.D. in Neuroscience and Neuro-Engineering from UCLA with a focus in brain mapping and medical image processing. 

References

  1. Pagani M, Högberg G, Fernandez I, Siracusano A. Correlates of EMDR Therapy in Functional and Structural Neuroimaging: A Critical Summary of Recent Findings. J EMDR Pract Res. 2013;7(1):29-38. doi:10.1891/1933-3196.7.1.29
  2. Rousseau PF, El Khoury-Malhame M, Reynaud E, Zendjidjian X, Samuelian JC, Khalfa S. Neurobiological correlates of EMDR therapy effect in PTSD. Eur J Trauma Dissociation. 2019;3(2):103-111. doi:10.1016/j.ejtd.2018.07.001
  3. Okun MS. Deep-brain stimulation - Entering the era of human neural-network modulation. N Engl J Med. 2014;371(15):1369-1373. doi:10.1056/NEJMp1408779
  4. Serin A, Hageman NS, Kade E. The Therapeutic Effect of Bilateral Alternating Stimulation Tactile Form Technology on the Stress Response. J Biotechnol Biomed Sci. 2018;1(2):42-47. doi:10.14302/issn.2576-6694.jbbs-18-1887
  5. Louis ED, Lenka A. The olivary hypothesis of essential tremor: Time to lay this model to rest? Tremor and Other Hyperkinetic Movements. 2017;7. doi:10.7916/D8FF40RX
  6. Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED. Rest tremor in patients with essential tremor: Prevalence, clinical correlates, and electrophysiologic characteristics. Arch Neurol. 2003;60(3):405-410. doi:10.1001/archneur.60.3.405

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