Motor Phenotypes and Neuroimaging in Parkinson's Disease

Parkinson’s disease manifests through distinct motor phenotypes, most notably tremor-dominant and akinetic-rigid forms, with an intermediate postural instability and gait difficulty subtype. These phenotypes reflect divergent patterns of neural dysfunction across basal ganglia, cerebellar and cortical circuits. Advances in neuroimaging have revealed that tremor arises from aberrant oscillations within interacting basal ganglia–cortical and cerebello-thalamo-cortical loops, whereas bradykinesia and rigidity correlate with altered connectivity in striato-thalamo-cortical pathways. Functional MRI and dynamic functional connectivity analyses have mapped phenotype-specific connectomes, demonstrating that tremor-dominant patients exhibit greater cerebellar-motor network synchrony while akinetic-rigid patients show widespread parietal-limbic involvement. Structural imaging further distinguishes subcortical volume changes across subtypes, offering prognostic insight into disease progression. Together, these findings highlight the value of multimodal neuroimaging for early phenotype classification, biomarker development and personalised treatment planning, including targeted neuromodulation and circuit-based therapies.

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Motor Phenotypes and Neuroimaging in Parkinson's Disease publication trend

The graph below shows the total number of articles in motor phenotypes and neuroimaging in parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Akinetic-rigid (AR): Motor phenotype characterised by slowness of movement (bradykinesia) and muscle stiffness rather than prominent tremor.

Tremor-dominant (TD): Parkinson’s subtype in which resting tremor is the principal and most disabling motor feature.

Functional connectivity: Statistical association between activity time series of separate brain regions, typically measured with functional MRI.

Cerebello-thalamo-cortical circuit: Neural pathway linking cerebellum, thalamus and motor cortex, implicated in tremor generation.

Basal ganglia: Subcortical nuclei critical for motor control, whose dopamine-dependent loops underlie rigidity and bradykinesia.

Functional MRI (fMRI): Imaging modality that detects blood-oxygen-level-dependent signals to infer neural activity.

Graph theory: Mathematical framework for analysing brain networks by modelling regions as nodes and their connections as edges.

References

1. Integrative Brain States Facilitate the Expression of Parkinson's Tremor. Movement Disorders (2023).
2. Functional connectomes of akinetic‐rigid and tremor within drug‐naïve Parkinson's disease. CNS Neuroscience & Therapeutics (2023).
3. Modeling of cerebellar transcranial electrical stimulation effects on hand tremor in Parkinson’s disease. Frontiers in Aging Neuroscience (2023).
4. Subcortical Volumes Differ in Parkinson’s Disease Motor Subtypes: New Insights into the Pathophysiology of Disparate Symptoms. Frontiers in Human Neuroscience (2016).
5. The pathophysiology of Parkinson's disease tremor. Journal of the Neurological Sciences (2022).
6. Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern. PLOS ONE (2012).