Neural connectivity predicts deep brain stimulation success in essential tremor

Discover how groundbreaking insights into thalamic connectivity are reshaping treatment approaches for essential tremor, paving the way for personalized and more effective DBS therapies.

Study: Corticothalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor. Image Credit: K_E_N / Shutterstock.com

In a recent study published in the journal Brain, researchers investigate the neural mechanisms underlying essential tremors, specifically the cortical-thalamic-tremor network. By analyzing brain and tremor signals, the researchers elucidate how specific neural connectivity patterns predict the efficacy of deep brain stimulation (DBS) in tremor suppression.

What is an essential tumor?

Essential tremor is a prevalent neurological condition that causes rhythmic shaking, which can significantly impact daily activities. It is characterized by dynamic interactions between motor regions that act as oscillators, creating the tremor. Despite these observations, the pathological mechanisms involved in essential tumors remain unclear.

Essential tremor treatments primarily consist of DBS, which often target the ventralis intermediate nucleus (VIM) of the thalamus. This method has varied effectiveness across individuals. Non-invasive methods, such as transcranial magnetic or electrical stimulation, have also been explored; however, their outcomes are inconsistent.

These therapeutic challenges indicate a limited understanding of the complex neural networks involved in essential tremor. Previous studies have focused on isolated brain regions, which has prevented researchers from gaining comprehensive insights into the interconnections within brain regions. Understanding how neural pathways, especially cortico-thalamic networks, drive essential tremor is critical to improving interventions.

About the study

In the present study, researchers record the neural activity of individuals with essential tremor to understand the underlying mechanisms of the condition.

A total of 15 patients diagnosed with essential tremor who previously underwent DBS electrode implantation targeting the VIM of the thalamus or posterior subthalamic area (PSA) were included in the analysis. Neural recordings were performed within one to five days after surgery when the electrodes were temporarily externalized.

Study participants completed a posture-holding task when DBS was switched on and off. During the task, brain activity was recorded using local field potentials from the thalamus and electroencephalograms (EEGs) from cortical sites.

Hand tremor signals were measured using accelerometers with a tremor frequency range of three to ten Hz. Advanced signal-processing techniques, including generalized orthogonalized partial directed coherence, were used to analyze directional connectivity in cortico-thalamo-tremor networks. Neural signals were filtered, and tremor-related metrics were extracted through spectral and time-domain analyses.

Power spectral density was used to estimate tremor power, whereas various statistical models identified the correlations between tremor instability and connectivity features. Stimulation settings were individually adjusted to optimize clinical benefits while minimizing side effects. Furthermore, the volume of tissue activated during DBS was mapped to anatomical regions using imaging data, which allowed the researchers to correlate neural connectivity with stimulation effects.

The connectivity patterns were compared when DBS was switched on to those when it was off to isolate outgoing and incoming pathways between brain regions and tremor signals. Additionally, data from bilateral electrode placements enabled analysis of cross-hemispheric interactions in the study.

Study findings

Tremor suppression with DBS was closely linked to specific neural connectivity patterns within cortico-thalamic networks. Efferent or outgoing connectivity from the contralateral thalamus to hand tremor was identified as a key predictor of baseline tremor power and the effectiveness of DBS. Furthermore, increased connectivity involving the contralateral thalamus correlated with greater tremor suppression during DBS, thus highlighting its role as one of the central drivers of essential tremor.

Afferent or incoming connectivity from the hand tremor back to the ipsilateral thalamus was stronger than the connectivity to the contralateral thalamus. Connectivity patterns also revealed lateralized and bidirectional interactions within the thalamic-tremor network.

Stronger cross-hemispheric interactions were associated with more unstable tremors. Cortical involvement was not a strong predictor of DBS outcomes; however, it contributed to tremor dynamics through feedback mechanisms. Several tremor characteristics, such as power and stability, were also found to independently predict thalamic-tremor connectivity strength.

Patients with more stable tremors and higher baseline power experienced greater DBS efficacy, thus indicating the role of distinct network dynamics in different patient profiles. The connectivity between the thalamus and cortex at tremor frequencies was predictive of DBS effects, although thalamo-cortical and cortico-thalamic pathways appeared to function independently.

Conclusions

The study findings demonstrate the importance of contralateral thalamic connectivity in tremor generation, with contributions from ipsilateral and cortical circuits. In the future, researchers can use these observations to support the development of more targeted interventions that potentially incorporate multiple brain regions or adaptive stimulation techniques to enhance the effectiveness of DBS therapy.