Summary: Rest quake in Parkinson’s disease is linked to dopamine activity in the caudate cell, challenging normal ideas about serotonin damage and engine symptoms. Interestingly, more dopamine was preserved in the caudate in those with stronger tremors, which highlights the sophisticated connection between neural circuits and tremor severity.
This study provides insights into PD’s various progression patterns by demonstrating that rest tremor may be studied individually from another motor symptoms. By identifying specific dopaminergic pathways involved in tremor, the findings make it possible to develop more precisely targeted therapies.
Important Information:
- Serotonin levels preserved in the caudate nucleus are related to the intensity of rest tremors.
- Vibration displays a” same-side” influence, linking brain and body in an unexpected manner.
- Tremor and other symptoms may be studied independently, which could help to develop more accurate treatments.
Origin: Champalimaud Centre for the Mysterious
Parkinson’s disease ( PD ) is a progressive neurological disorder known for its characteristic motor symptoms: tremor, rigidity, and slowness of movement. Among these, sleep tremor—a shaking that occurs when muscle are relaxed—is one of the most recognized yet least understood.
A new study from the Champalimaud Foundation, led by the Neural Wires Dysfunction Lab in collaboration with the Neuropsychiatry and Nuclear Medicine Labs, provides new insights into the complex relationship between sleep vibration and serotonin, a chemical messenger crucial to controlling activity.
The Dopamine Paradox
Dopamine decline in mental areas like the putamen, associated with motion regulation, is a well-established essence of PD. However, while some patients experience significant tremor relief with dopamine replacement therapies like L-DOPA, others see little to no improvement, or even a worsening of symptoms.
” Tremor is a common and often debilitating symptom for PD patients, but it has always been a bit of a puzzle”, says Marcelo Mendonça, one of the study’s lead authors.
” We know dopamine is involved, but the way it affects tremor is n’t as direct as with other motor symptoms”.
Less dopamine should be correlated with more severe symptoms, according to conventional wisdom. The researchers discovered the opposite to be true when it comes to rest tremor, however.
” Paradoxically, we discovered that patients who exhibit tremor have more dopamine preserved in the caudate nucleus, a part of the brain important for movement planning and cognition”, explains Mendonça.
This challenges our conventional understanding of how PD symptoms are related to dopamine.
An Overlooked Player in Tremor?
The researchers analyzed information from over 500 patients using data from patients at the Champalimaud Clinical Centre and public databases. This diverse set included wearable motion sensors that precisely measure tremor severity, DaT scans to visualize dopaminergic neurons, and clinical assessments.
” Wearable motion sensors gave us a clearer, more objective measurement of tremor”, says co-first author Pedro Ferreira.
” On the surface, patients with and without dopamine loss in the caudate seem similar. Sensors are relatively simple to use, allowing us to reliably connect symptoms to what’s happening in the brain, and they reveal subtle differences in tremor oscillations that traditional clinical rating scales might miss.
We found a clear link between dopamine function in the caudate nucleus and the caudate nucleus ‘ global severity, says Ferreira, combining imaging data with these sensor measurements.
The caudate’s dopamine activity is preserved, according to our analysis, making the tremor stronger.
The head of the Neural Circuits Dysfunction Lab, senior author Joaquim Alves da Silva, sums up the thesis:” This is the first significant study to clearly link a relationship between better-preserved caudate levels and the presence of rest tremor.”
Patients with rest tremors actually have more of these nerve endings preserved than those without tremors, according to the article”…
The study’s most intriguing findings were that the more dopamine was preserved in the caudate on one side of the brain ( each brain has its own caudate ), the more tremor there was on the same side of the body.
” This was quite unexpected”, says Alves da Silva.
” Typically, the brain’s side controls movement on the body’s other side,” says the saying. This” same-side” effect, according to their computational model, could be caused by two things: the significantly higher dopamine levels in both caudates in tremor patients and the disparate impact of PD on each side of the brain.
Challenging Conventional Classifications
This study builds on earlier research by the same team, which was published last month in Neurobiology of Disease, which demonstrated the value of treating rest tremor and other motor symptoms separately, a change from traditional methods that have combined these symptoms.
Their previous research demonstrated that rest tremor is more prevalent in patients who have “brain-first,” while those who do n’t have a “gut-first” PD, where the disease process begins in the gut and spreads to the brain, is more common.
This fresh study expands that area of study by demonstrating how specific brain regions may affect how severe rest tremors are.
” Dopamine loss in PD is not uniform—different patients may lose dopamine in distinct circuits”, notes Alves da Silva.
We are able to identify the specific neural pathways involved by focusing on rest tremor alone. Could there be a dopamine imbalance between the caudate and the putamen, for instance, to cause tremor?
It is crucial to find reliable biological correlates of each individual symptom because it will help to develop more effective, targeted treatments for their relief.
” Not all dopamine cells are alike”, adds Mendonça. ” They have different genetic makeups, connections, and functions. This implies that a patient’s symptoms might be impacted by which cells they lose or keep.
” Tremor may be caused by the loss or preservation of particular dopamine populations that connect to particular brain regions,” for instance. The wide range of symptoms experienced by PD patients may be further explained by this variation in cell type loss.
Treatment implications and upcoming research
The team is already looking ahead, says Alves da Silva”. We want to test this in animal models so we can manipulate specific cells and observe the effects of dopamine preservation in the caudate and rest tremor in humans. Because of this, it’s difficult to establish a causal link between rest tremor and dopamine preservation in caudate.
We’d like to link key nodes in the dopamine system with specific motor symptoms by using advanced imaging techniques like high-resolution dopamine PET scans and MRIs. This approach could aid in better understanding how PD symptoms differ among different patients.
The study emphasizes the value of examining PD beyond general classifications and emphasizes the need for more in-depth analyses that are based on underlying biology.
We hope to dispel the mist that surrounds the heterogeneity of PD symptoms by identifying the specific neural circuits involved, bringing about more precise interventions that can enhance the quality of life for those with the disease, Mendonça says.
About this Parkinson’s disease research news
Author: Hedi Young
Source: Champalimaud Centre for the Unknown
Contact: Hedi Young – Champalimaud Centre for the Unknown
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Integrity of dopaminergic terminals in the caudate nucleus is relevant for rest tremor in Parkinson’s disease” by Marcelo Mendonça et al. npj Parkinson’s Disease
Abstract
The caudate nucleus ‘ integration of dopaminergic terminals is important for rest tremor in Parkinson’s disease.
Resting tremor (RT ) is a Parkinson’s disease ( PD ) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson’s Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter single-photon emission computed tomography ( DaT-SPECT).
Caudate binding ratio ( CBR ), but not putamen binding ratio, was higher in RT patients. Furthermore, higher baseline CBR was linked to RT development. In the smaller cohorts, a 4–6 Hz oscillation-based metric from inertial sensors correlated with RT amplitude, distinguished controls from patients with reduced DaT binding and correlated with CBR in the latter group.
In silico modeling, which found that higher CBR in RT patients explained correlations between RT and DaT-SPECT found in a number of datasets, suggested that there may be ipsilateral correlations between CBR and RT.
These findings point to the potential pathophysiological implications of caudate dopaminergic terminal integrity as a RT trait.
