Neural Circuit involved in Idiopathic Nystagmus Syndrome Based on fMRI

Abstract

Purpose: : Idiopathic Nystagmus Syndrome (INS) is characterized by early onset alternating series of slow and rapid eye movements which can manifest in different waveforms and genetic lines. The neural circuitry of INS is not known.

Methods: : A novel fMRI method was utilized to identify the neural circuitry for INS in humans by use of a GE 3T MRI scanner utilizing FEAT-FSL and FILM time series analysis with a cluster significance threshold of P=.01. The null point, a gaze position with minimal nystagmus, was utilized as the "off" condition and a gaze position with robust nystagmus was utilized as the "on" condition. Standard on-off fMRI sequence was employed whereby a fixation point alternated between the null and robust nystagmus positions. Eye movements were recorded with an fMRI compatible eye tracker (ASL) and observed in real time to ensure subject compliance and to quantify oculomotor function in "on" and "off" states. INS subjects (N= 4) included three family members (mother and two daughters) with autosomal dominant INS as well as age and gender matched normal controls (N=3).

Results: : Three of four INS subjects demonstrated significant increased activation of the Declive of the Cerebellum while no normal subjects, under identical conditions, showed activation of the Declive. Both groups showed significant activation in the occipital lobe (Brodmann Areas 17, 18, 19, Cuneus).

Conclusions: : A novel fMRI method demonstrated that the Declive of the Cerebellum is actively involved in INS. These are the first results to identify the Cerebellum, and specifically the Declive, as a possible site for the oculomotor dysfunction associated with INS.

Keywords: nystagmus • eye movements • eye movements: saccades and pursuits