Human Brain: "Deep Brain Stimulation" (DBS) has had apparent success in (1) movement disorders and (2) neuropsychiatric conditions.
--What are the "conditions/diseases" in which DBS is helpful?
--What is the "nature of its help" in these conditions?
--What is its "mechanism of action"?
Dennis
Dennis Mazur
Dear Dennis
none of the questions that you have asked are easy to answer. I will still try to give you an brief overview of the current state of the field.
--What are the "conditions/diseases" in which DBS is helpful?
Large multicenter clinical trials have successfully reached primary endpoints repeatedly for the treatment of Parkinson's disease (targets: subthalamic nucleus and internal pallidum), Dystonia (subthalamic nucleus and internal pallidum) and essential tremor (ventral intermediate nucleus of the thalamus).
Indications currently under investigation by many centers are (non-exhaustive list): obsessive compulsive disorder (anterior limb of internal capsule/bed nucleus of stria terminalis, subthalamic nucleus, Nucleus accumbens), Tourette syndrome (centromedian/parafascicular nucleus of the thalamus, internal pallidum), treatment refractory depression (subgenual cingulate cortex, medial forebrain bundle), Parkinson's dementia (Nucleus basalis of Meynert), Alzheimer's disease (Nucleus basalis of Meynert, Fornix), cerebral palsy in children (internal pallidum) and Huntington's disease (internal pallidum)
Few case series have been described for Addiction, Anorexia nervosa and aggressive behavior among other neuropsychiatric syndromes.
Here are some reviews that can guide you:
Article Innovations in deep brain stimulation methodology: Innovatio...
Article Proceedings of the Fourth Annual Deep Brain Stimulation Thin...
--What is the "nature of its help" in these conditions?
I am not sure I am understanding this question correctly I will just state a brief sentence: That depends on the condition and the way clinical success is measured. In large clinical trials for Parkinson's disease Quality of Life and parkinsonian symptoms have been shown to improve robustly across multiple centers. Usually changes in clinical scores are tested that evaluate symptom severity in the respective condition.
--What is its "mechanism of action"?
The correct answer is that we do not know and the exact mechanism likely depends on the target and tissue properties that are affected by the electrical field. However, a lot of research has been conducted to tackle this question. The procedure is adopted from ablational neurosurgery and its effectiveness has been reported for the first time by Alim Louis Benabid during thalamotomy surgery for parkinsonian tremor in 1987. Subthalamic DBS has been adopted after a landmark paper in 1990 by Hagai Bergman, Thomas Wichmann and Mahlon DeLong (Article Reversal of Experimental Parkinsonism by Lesions of the Subt...
).Thus, deep brain stimulation has been believed to create a reversible lesion in the target, potentially through disruption of circuit communication.
This is still a widely discussed hypothesis, which is further supported by the fact that DBS suppresses aberrant oscillatory activity in target nuclei (Article High-Frequency Stimulation of the Subthalamic Nucleus Suppre...
)In cervical dystonia we could recently demonstrate that pallidal theta activity is correlated with symptom severity and the spatial distribution overlaps with the optimal target location for DBS (Article A localized pallidal physiomarker in cervical dystonia
), while we have previously shown DBS to suppress this activity.Article Deep brain stimulation suppresses pallidal low frequency act...
)The molecular mechanism of the "information block" is also a matter of debate with excitation of axonal fibers and inhibition of local cell bodies being most commonly referenced (see Article Deep Brain Stimulation
).In STN-DBS for Parkinson's disease the fact that activation of layer 5 neurons in the motor cortex resembles DBS effects that give rise to pyramidal tract axons with collaterals to the subthalamic nucleus has inspired the hypothesis that the underlying mechanism depends on antidromic stimulation of these "hyperdirect pathway" fibers leading to excitation of the motor cortex. This finding is difficult to generalize to other targets and disorders, because of the anatomical specifics in this mechanism.
I have not heard of a study that reported activation of inhibitory interneurons as a mechanism of action in DBS, but I would love to read about it because interneurons could indeed represent a feasible electrochemical translator because of their ability to spike with high frequency. However, to the best of my knowledge the internal pallidum and subthalamic nucleus have low amount of interneurons and are practically absent in rodents, where DBS is still effective for the treatment of experimental parkinsonism.
Hope this helps.
Julian
Dear Dennis
none of the questions that you have asked are easy to answer. I will still try to give you an brief overview of the current state of the field.
--What are the "conditions/diseases" in which DBS is helpful?
Large multicenter clinical trials have successfully reached primary endpoints repeatedly for the treatment of Parkinson's disease (targets: subthalamic nucleus and internal pallidum), Dystonia (subthalamic nucleus and internal pallidum) and essential tremor (ventral intermediate nucleus of the thalamus).
Indications currently under investigation by many centers are (non-exhaustive list): obsessive compulsive disorder (anterior limb of internal capsule/bed nucleus of stria terminalis, subthalamic nucleus, Nucleus accumbens), Tourette syndrome (centromedian/parafascicular nucleus of the thalamus, internal pallidum), treatment refractory depression (subgenual cingulate cortex, medial forebrain bundle), Parkinson's dementia (Nucleus basalis of Meynert), Alzheimer's disease (Nucleus basalis of Meynert, Fornix), cerebral palsy in children (internal pallidum) and Huntington's disease (internal pallidum)
Few case series have been described for Addiction, Anorexia nervosa and aggressive behavior among other neuropsychiatric syndromes.
Here are some reviews that can guide you:
Article Innovations in deep brain stimulation methodology: Innovatio...
Article Proceedings of the Fourth Annual Deep Brain Stimulation Thin...
--What is the "nature of its help" in these conditions?
I am not sure I am understanding this question correctly I will just state a brief sentence: That depends on the condition and the way clinical success is measured. In large clinical trials for Parkinson's disease Quality of Life and parkinsonian symptoms have been shown to improve robustly across multiple centers. Usually changes in clinical scores are tested that evaluate symptom severity in the respective condition.
--What is its "mechanism of action"?
The correct answer is that we do not know and the exact mechanism likely depends on the target and tissue properties that are affected by the electrical field. However, a lot of research has been conducted to tackle this question. The procedure is adopted from ablational neurosurgery and its effectiveness has been reported for the first time by Alim Louis Benabid during thalamotomy surgery for parkinsonian tremor in 1987. Subthalamic DBS has been adopted after a landmark paper in 1990 by Hagai Bergman, Thomas Wichmann and Mahlon DeLong (Article Reversal of Experimental Parkinsonism by Lesions of the Subt...
).Thus, deep brain stimulation has been believed to create a reversible lesion in the target, potentially through disruption of circuit communication.
This is still a widely discussed hypothesis, which is further supported by the fact that DBS suppresses aberrant oscillatory activity in target nuclei (Article High-Frequency Stimulation of the Subthalamic Nucleus Suppre...
)In cervical dystonia we could recently demonstrate that pallidal theta activity is correlated with symptom severity and the spatial distribution overlaps with the optimal target location for DBS (Article A localized pallidal physiomarker in cervical dystonia
), while we have previously shown DBS to suppress this activity.Article Deep brain stimulation suppresses pallidal low frequency act...
)The molecular mechanism of the "information block" is also a matter of debate with excitation of axonal fibers and inhibition of local cell bodies being most commonly referenced (see Article Deep Brain Stimulation
).In STN-DBS for Parkinson's disease the fact that activation of layer 5 neurons in the motor cortex resembles DBS effects that give rise to pyramidal tract axons with collaterals to the subthalamic nucleus has inspired the hypothesis that the underlying mechanism depends on antidromic stimulation of these "hyperdirect pathway" fibers leading to excitation of the motor cortex. This finding is difficult to generalize to other targets and disorders, because of the anatomical specifics in this mechanism.
I have not heard of a study that reported activation of inhibitory interneurons as a mechanism of action in DBS, but I would love to read about it because interneurons could indeed represent a feasible electrochemical translator because of their ability to spike with high frequency. However, to the best of my knowledge the internal pallidum and subthalamic nucleus have low amount of interneurons and are practically absent in rodents, where DBS is still effective for the treatment of experimental parkinsonism.
Hope this helps.
Julian
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