Functional correlates of Saccadic Eye Movement in Spinocerebellar Ataxia Type 2
Poster No:
172
Submission Type:
Abstract Submission
Authors:
Pankaj -1, S Senthil Kumaran2, Ajay Garg3, Achal Srivastava4, Ramesh Agarwal5, Ashima Nehra6
Institutions:
1All India Institute of Medical Sciences (AIIMS), New Delhi, New Delhi, New Delhi, 2All India Institute of Medical Sciences, South East Delhi, Delhi, 3All India Institute of Medical Sciences (AIIMS), New Delhi, New Delhi, 4All India institute of Medical Sciences (AIIMS), New Delhi, New Delhi, 5Jawaharlal Nehru University, New Delhi, New Delhi, 6All India Institute of Medical Sciences, New Delhi, New Delhi
First Author:
Co-Author(s):
Introduction:
Spinocerebellar ataxia type-2 (SCA 2), characterized by a CAG trinucleotide repeat expansion on the chromosome(ATXN2), is a rare form of autosomal dominant ataxia worldwide(1). Predominantly found in the Indian subcontinent it presents with gait ataxia, dysarthria, saccadic eye pursuit, tremor, hyperreflexia, dementia, and cortical and cerebellar atrophy. Of other SCA types saccadic slow velocity and dysmetria are less evaluated in SCA2(2).
Methods:
SCA2 patients (n=40, M/F: 26/14, mean age 52.67±8.94 years) were recruited after genetic confirmation (Table 1). Healthy control participants (HC, n=25, M/F: 13/12, mean age 49.36±8.16 years) without neurological or psychiatric symptoms were recruited.
Patients underwent the ICARS assessment, Mini-Mental Status Exam (MMSE), and Standard Progressive Matrices, on the day of MR investigations. MRI data were acquired on a 3T MR scanner (Ingenia 3.0 T, Philips Healthcare, The Netherlands) with a 32-channel head coil. A 3D T1-weighted Turbo Field Echo (TFE) sequence was used with the following parameters: TR = 8.1 ms, TE = 3.7 ms, FOV = 250 mm, 1 mm isovoxel, 350 slices (thickness = 0.5 mm), flip angle = 10°. Task-based functional MRI (fMRI) data included 180 dynamics across 35 contiguous axial slices with parameters TR = 2000 ms and TE = 40 ms. MRI images were analyzed using Statistical Parametric Mapping (SPM) and CONN software with default parameters.
Simultaneous task-based fMRI paradigm and eye-tracking data acquisition were implemented using SuperLab software (v5.0, Cedrus Corporation, USA) and MR-compatible binocular LCD goggles (Nordic Neuro Lab, Norway) with an eye tracker (Arrington Research Inc., USA).
A saccadic paradigm (Figure 1), comprising rest and active blocks was presented to elicit horizontal, vertical, and circular saccades around a central fixation point. The active block included three types of blocks: circular saccades (clockwise for 16 seconds, counter clockwise for 16 seconds), horizontal saccades (left to right for 10 seconds, right to left for 10 seconds), and vertical saccades (up to down for 10 seconds, down to up for 10 seconds).
Patients underwent the ICARS assessment, Mini-Mental Status Exam (MMSE), and Standard Progressive Matrices, on the day of MR investigations. MRI data were acquired on a 3T MR scanner (Ingenia 3.0 T, Philips Healthcare, The Netherlands) with a 32-channel head coil. A 3D T1-weighted Turbo Field Echo (TFE) sequence was used with the following parameters: TR = 8.1 ms, TE = 3.7 ms, FOV = 250 mm, 1 mm isovoxel, 350 slices (thickness = 0.5 mm), flip angle = 10°. Task-based functional MRI (fMRI) data included 180 dynamics across 35 contiguous axial slices with parameters TR = 2000 ms and TE = 40 ms. MRI images were analyzed using Statistical Parametric Mapping (SPM) and CONN software with default parameters.
Simultaneous task-based fMRI paradigm and eye-tracking data acquisition were implemented using SuperLab software (v5.0, Cedrus Corporation, USA) and MR-compatible binocular LCD goggles (Nordic Neuro Lab, Norway) with an eye tracker (Arrington Research Inc., USA).
A saccadic paradigm (Figure 1), comprising rest and active blocks was presented to elicit horizontal, vertical, and circular saccades around a central fixation point. The active block included three types of blocks: circular saccades (clockwise for 16 seconds, counter clockwise for 16 seconds), horizontal saccades (left to right for 10 seconds, right to left for 10 seconds), and vertical saccades (up to down for 10 seconds, down to up for 10 seconds).
·Schematic overview of the three different eye movement tasks used in one paradigm. Paradigm started and ended with a fixation target presented for 10s at the center of the screen.
Results:
Patients with SCA2 exhibited alterations in eye movement patterns, with irregular ocular drift, reduced pupil reflex, slower saccades, lower MMSE scores and reduced IQ scores compared to HC (Figure 4).
During circular movement task, SCA2 displayed inhibitory connectivity from cerebellar regions to dorsal mode attention networks (F(3,69) = 8.79) along with superior and left lateral sensorimotor networks (F(3,69) = 7.79). HC also had a faciliatory connectivity from cerebellar regions to default mode regions (MPFC, PCC; F(3,69) = 4.43); salience (bilateral RPFC) and language network (left IFG- F(3,69) = 4.14) which was not present in SCA2.
In right-left task, SCA2 showed more inhibitory connectivity from posterior cerebellum to right IPS (intraparital sulcus- F(3,69) = 6.57). The inhibitory connectivty from bilateral cerebellum to medial prefrontal cortex (MPFC F(3,69) = 14.60) was not seen in SCA2, but intra-cerebellar connectivity was increased. In SCA2, facilitatory connectivity from bilateral cerebellum to visual nodes of dorsal attention network (F(3,69) = 16.85) were seen.
In up-down task, inhibitory connectivity was seen between posterior cerebellum and left IPS (F(3,69) = 13.88) in SCA2. HC showed Facilitatory connectivity between bilateral cerebellum with fronto parietal regions (F(3,69) = 8.74) and language network nodes (F(3,69) = 4.36), but not in SCA2.
During circular movement task, SCA2 displayed inhibitory connectivity from cerebellar regions to dorsal mode attention networks (F(3,69) = 8.79) along with superior and left lateral sensorimotor networks (F(3,69) = 7.79). HC also had a faciliatory connectivity from cerebellar regions to default mode regions (MPFC, PCC; F(3,69) = 4.43); salience (bilateral RPFC) and language network (left IFG- F(3,69) = 4.14) which was not present in SCA2.
In right-left task, SCA2 showed more inhibitory connectivity from posterior cerebellum to right IPS (intraparital sulcus- F(3,69) = 6.57). The inhibitory connectivty from bilateral cerebellum to medial prefrontal cortex (MPFC F(3,69) = 14.60) was not seen in SCA2, but intra-cerebellar connectivity was increased. In SCA2, facilitatory connectivity from bilateral cerebellum to visual nodes of dorsal attention network (F(3,69) = 16.85) were seen.
In up-down task, inhibitory connectivity was seen between posterior cerebellum and left IPS (F(3,69) = 13.88) in SCA2. HC showed Facilitatory connectivity between bilateral cerebellum with fronto parietal regions (F(3,69) = 8.74) and language network nodes (F(3,69) = 4.36), but not in SCA2.
·Eye-tracking data collected using MR-compatible binocular LCD goggles, showing analyses of ocular drift, pupil size, and eye movement patterns across four quadrants for both SCA2 patients and healthy
Conclusions:
In SCA2, abnormal oculomotor movements, particularly saccadic irregularities, are predominantly associated with cerebellar impairment, and more pronounced as cerebellar atrophy progresses.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Perception, Attention and Motor Behavior:
Attention: Visual
Physiology, Metabolism and Neurotransmission:
Neurophysiology of Imaging Signals
Keywords:
FUNCTIONAL MRI
1|2Indicates the priority used for review
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