Meeting #7: Goals and Objectives with Jackie drVries

Goals of Research Team

1. Define what (excessive fragmentary) hypnic jerking is by developing and testing SOVM 

(Sleep-onset Oscillatory Vasomotor Myoclonus) hypothesis:

It’s like the orchestra at sleep onset has lost its conductor- the gap junctions and ion channels can’t keep time. Gap junctions are like the conductor’s baton of the orchestra — keeping infraslow oscillations in time across neurons, astrocytes, vessels, and CSF flow. In the absence of the conductor, timing breaks down: vessels dilate too long, REM intrudes too early, and jerks appear as the 'bad notes' that wake the system. 

2. Establish recognition of SOVM:

   -A clear name for the condition.

   -More appropriate treatment strategies.

   -Inclusion in ICD and formal recognition as a sleep disorder.

Objectives

• Genetics Study of Ion channels and moderator variants (In progress, publication pending)

  
  

  - Cohort: ~45 WGS participants; 28 genomes returned to date. Pipeline: Coordinate with Erika (Sequencing.com) and LG for raw data transfer for analysis; centralize de-identified data to place in Google Drive. Targets: Curate variants in ion channels, RAAS, cerebrovascular/CSF-regulation genes.

  
  

  - Gap junction science: Explore role of astrocytic/neuronal connexins in synchronizing infraslow oscillations and vascular coupling at sleep onset.

  
  

  - Mapping: Genotype ↔ phenotype correlation (sleep features, autonomic markers, imaging, treatment response).

• SOVM Assessmebt: Improve sleep study

-Current limitations: 1. PSGs include EMG leads but are designed for staging and PLMs, not oscillatory/vascular instability at sleep onset. 2. Missed signals: vascular tone changes, autonomic lag (BP, HRV), CSF/ISF oscillations.

-Needed: A multimodal framework combining EEG + EMG + autonomic/vascular measures (BP, HRV, flow). Exploration with Neurosom

• Explore Treatments

-Repurposing medications that address ion channel dysfunction and gap junction modification

-Explore oscillatory synchrony through ISF Neurofeedback (Infra-Slow Frequency) intervention: Targets ultra-low brain rhythms (<0.1 Hz) linked to autonomic control, thalamocortical oscillations, sleep transitions, and blood/CSF flow. How this maps onto SOVM: potential for addressing oscillatory instability at sleep onset—helping re-stabilize vascular timing, reduce excitability, and smooth REM/NREM boundaries. Mechanisms: HRV and vagal tone improvement, strengthens cerebrovascular coupling, consolidates sleep stages. Caveats: Highly individualized; requires slow titration in sensitive patients; evidence base smaller but promising.

- Tools: Sanford Registry, Sequencing cohort, Manton Center results, anchor case (see Manuscript).

- Short-range goals: publish theoretical framework and case reviews.

- Long-range goals: diagnostic criteria; translational pathways