Parkinson’s disease is a progressive neurological disorder characterized by tremors, stiffness, slow movements, and balance issues. One of the most noticeable symptoms of Parkinson’s is tremors, which are involuntary, uncontrollable shaking or trembling of part of the body. Understanding where and how tremors start in the brain is an important area of Parkinson’s research.
What causes tremors in Parkinson’s disease?
Parkinson’s tremors are caused by the death of nerve cells in a part of the brain called the substantia nigra. The substantia nigra is located in an area of the brain called the basal ganglia, which helps control and coordinate movement. In Parkinson’s, nerve cells in the substantia nigra start to die off and the cells can no longer produce enough of a chemical called dopamine. Dopamine acts as a messenger between the substantia nigra and another part of the basal ganglia called the striatum. When dopamine levels drop, communication between these two areas becomes impaired. This disruption in signaling leads to the motor symptoms of Parkinson’s, including tremors.
The basal ganglia-thalamocortical circuit
To understand where tremors originate, it helps to understand the basics of how the basal ganglia, thalamus, and motor cortex control movement as part of a circuit:
- The basal ganglia receives input from the cerebral cortex and helps select appropriate movements.
- The basal ganglia then signals the thalamus to initiate and execute the movement.
- The thalamus relays this information to the motor cortex which activates the necessary muscles to move.
- The cerebellum fine-tunes this process.
In Parkinson’s disease, the death of dopamine producing cells in the substantia nigra leads to abnormal signaling in this circuit resulting in impaired movement.
The origins of tremors in the basal ganglia
Within the basal ganglia, tremors are believed to arise from dysfunctional activity in an area called the subthalamic nucleus. The subthalamic nucleus is another part of the basal ganglia that helps control and modulate movement. In Parkinson’s disease, the loss of dopamine input from the substantia nigra causes the subthalamic nucleus to become overactive. Instead of generating normal control signals, the subthalamic nucleus starts transmitting excess, abnormal signals which lead to tremors.
Research also indicates another part of the basal ganglia called the globus pallidus internus may be involved. The abnormal activity in the subthalamic nucleus gets relayed through the globus pallidus internus and then onto the thalamus, creating oscillations or tremor-like discharges.
The role of the thalamus
The excess signals generated in the basal ganglia eventually reach an area of the thalamus called the ventral intermediate nucleus. This region acts as a gateway and relays information from the basal ganglia up to the motor cortex which initiates movement. The abnormal oscillations from the basal ganglia cause involuntary, rhythmic bursts of activity in the ventral intermediate nucleus. These bursts are then transmitted to the motor cortex, causing the muscles to contract repeatedly in time with the oscillatory signals, resulting in tremors.
How do signals from the basal ganglia reach the cortex?
There are two main pathways that convey signals from the basal ganglia up to the motor cortex:
- Direct pathway – transmits signals directly from the basal ganglia to the thalamus and then the motor cortex to facilitate wanted movements.
- Indirect pathway – relays signals through an extra step to inhibit unnecessary movements.
In Parkinson’s disease, there is an imbalance between these two pathways. The direct pathway becomes underactive, making it harder to initiate movements. At the same time, the indirect pathway is overactive, leading to too much inhibition of movement. Both can contribute to tremors and other Parkinson’s symptoms.
Direct pathway in tremors
The direct pathway normally helps trigger a movement by disinhibiting the thalamus through signals sent from the substantia nigra. In Parkinson’s, the death of dopamine producing cells in the substantia nigra reduces excitatory signals along this pathway. As a result, the thalamus is over-inhibited, making it harder to activate the motor cortex and initiate movement. When a movement is attempted, there is excessive inhibition leading to abnormal signaling and tremors.
Indirect pathway in tremors
In the indirect pathway, overactivity and abnormal signaling likely contribute to tremors. Increased inhibition of the globus pallidus internus and subthalamic nucleus from this pathway exacerbate the overexcitability of the subthalamic nucleus. The resulting excess signals transmitted to the thalamus overload the motor cortex with erratic commands, manifesting as tremors.
How do changes in neural oscillations relate to tremors?
Groups of neurons communicate through synchronized electrical rhythms called neural oscillations. Research suggests that excess oscillations at certain frequencies may drive Parkinson’s tremor:
- 4-6 Hz – Correlates with resting tremor which occurs when muscles are relaxed.
- 8-30 Hz – Linked to action/postural tremor that happens during movement.
In Parkinson’s, the loss of dopamine and subsequent changes in the basal ganglia lead to abnormalities in these neural oscillations. Instead of generating controlled signals, the affected networks get locked into pathological, rhythmic firing patterns that manifest as tremors.
Changes in beta and gamma frequencies
Two frequency bands in particular – beta (13-30 Hz) and gamma (30-100 Hz) – appear to be involved. Studies show increased synchronization of neural activity in the beta frequency in Parkinson’s disease. Excess beta activity is linked to worse motor impairment. Gamma oscillations are also altered. The normal interplay between beta and gamma waves becomes disrupted, which may contribute to tremors.
Are certain regions of the brain more involved in tremors?
Neuroimaging studies indicate that tremors likely involve complex interactions between multiple parts of the brain, not just the basal ganglia. However, some areas that may play a greater role include:
- Primary motor cortex – Increased excitability here is associated with tremor severity.
- Cerebellum – Connections between the cerebellum and motor cortex seem important for tremor generation.
- Brainstem – The inferior olivary nucleus transmits oscillatory signals that may reinforce tremor circuits.
- Thalamus – Abnormal thalamic rhythms drive oscillatory activity.
So while tremors originate from dysfunctional signaling in the basal ganglia, they also involve an interconnected network across motor control regions of the brain.
What types of tremors are there in Parkinson’s?
There are several types of tremors associated with Parkinson’s disease:
Resting tremor
- Occurs when muscles are relaxed and the body part is fully supported
- Most common; affects 70-80% of people
- Typically starts on one side, often in the hand or fingers
- 4-6 Hz oscillation frequency
Postural/action tremor
- Happens during voluntary movement or when holding a position against gravity
- Lower frequency than resting tremor (8-30 Hz range)
- Can impair coordination during activities
Kinetic tremor
- Occurs with intentional voluntary movement like writing or drawing
- Often overlaps with postural tremor
- Adds a jerky quality to motor actions
Tremor of voice/jaw
- Involves the muscles of the larynx and jaw
- Leads to a shaky, tremulous voice and other speech issues
How are tremors evaluated and measured?
Doctors use a variety of methods to evaluate the severity and impact of Parkinson’s tremors on a patient’s daily activities:
Clinical evaluation
- Assess tremor at rest, with posture, and during kinetic movements
- Note which body parts are affected
- Test motor skills like handwriting, drawing spirals, and pouring water
- Identify factors that improve or worsen tremor
Tremor rating scales
- Use validated scales like the Fahn-Tolosa-Marin Tremor Rating Scale
- Rate tremor amplitude, frequency, and functional impact
- Can help track progression over time
Accelerometers
- Portable motion sensors worn by patient
- Objectively measure tremor frequency, amplitude and variability
- Capture tremor during normal daily activity
EMG
- Measures muscle electrical activity via electrodes on the skin
- Helps distinguish between types of tremor
- Records minor tremors not visible to the naked eye
How are Parkinson’s tremors treated?
Tremor treatment aims to reduce symptoms and improve daily function. Options include:
Medications
- Levodopa – Replaces lost dopamine, often helps alleviate tremors along with other Parkinson’s symptoms.
- Dopamine agonists – Mimic dopamine effects by stimulating receptors.
- Anticholinergics – Block acetylcholine signaling to reduce tremors.
- Beta blockers – May reduce tremors by blocking adrenaline.
Deep brain stimulation
- Surgically implanted electrodes deliver electrical pulses to interrupt abnormal brain signaling patterns.
- Often targets the ventral intermediate nucleus of the thalamus or subthalamic nucleus.
- Can reduce tremor severity by 50% or more when medications are not fully effective.
Focused ultrasound
- Non-invasive approach using focused ultrasound waves to lesion parts of the thalamus.
- Helps disrupt tremor circuits without needing implanted devices.
- Significantly improves tremor within 3 months in many patients.
Therapy
- Physical therapy to improve strength, balance and daily functioning.
- Occupational therapy to adapt activities and environment.
- Speech therapy for voice and swallowing issues.
| Treatment | How it Works | Benefits | Drawbacks |
|---|---|---|---|
| Medications | Increase dopamine activity in the brain or reduce acetylcholine signaling | First line treatment, oral administration, some improvement in most | Side effects, decreased efficacy over time (“wearing off”) |
| DBS Surgery | Electrically stimulates brain regions involved in tremors | Markedly reduces tremor in many people not responsive to meds | Invasive, risk of complications, programming challenges |
| Focused Ultrasound | Focused sound waves thermally ablate tremor-related brain tissue | Non-invasive, no implanted device required | Potential risks include headache, balance issues |
| Therapy | Improves strength, balance and adaptations for daily activities | Non-invasive, benefits overall function | Requires ongoing effort for continued progress |
What is the prognosis for Parkinson’s tremors?
The prognosis for Parkinson’s tremors depends on several factors:
- Age of onset – Young onset PD often progresses faster.
- Stage of disease – Tremor often worsens with advancing Parkinson’s.
- Responsiveness to medication – Some tremors are very levodopa responsive.
- Other symptoms – More rigidity and bradykinesia correlates with worsening tremor.
- Therapies used – DBS and ultrasound thalamotomy significantly improve treatment resistant tremor.
While disabling tremors are common, symptoms are treatable in most patients, especially in the early stages. However, Parkinson’s is a progressive disease so symptoms tend to worsen over time. Ongoing management with medications, therapy, brain stimulation, and medications can help maximize quality of life.
Conclusion
Parkinson’s tremor originates from dysfunctional signaling between the basal ganglia, thalamus, and motor cortex. While many brain regions interact to generate tremors, they often start due to excess oscillations from the subthalamic nucleus and globus pallidus that get relayed through the thalamus up to the cortex. Neuroimaging and neurophysiological studies continue to uncover more about the neural circuits underlying different types of Parkinson’s tremors. Targeting these pathways with medications, electrical stimulation, ultrasound ablation, and therapies can help manage tremors and improve motor function.