fMRI evidence of improved visual function in patients with progressive retinitis pigmentosa by eye-movement training

Abstract

To evaluate changes in the visual processing of patients with progressive retinitis pigmentosa (RP) who acquired improved reading capability by eye-movement training (EMT), we performed functional magnetic resonance imaging (fMRI) before and after EMT. Six patients with bilateral concentric contraction caused by pigmentary degeneration of the retina and 6 normal volunteers were recruited. Patients were given EMT for 5 min every day for 8-10 months. fMRI data were acquired on a 3.0-Tesla scanner while subjects were performing reading tasks. In separate experiments (before fMRI scanning), visual performances for readings were measured by the number of letters read correctly in 5 min. Before EMT, activation areas of the primary visual cortex of patients were 48.8% of those of the controls. The number of letters read correctly in 5 min was 36.6% of those by the normal volunteers. After EMT, the activation areas of patients were not changed or slightly decreased; however, reading performance increased in 5 of 6 patients, which was 46.6% of that of the normal volunteers (p< 0.05). After EMT, increased activity was observed in the frontal eye fields (FEFs) of all patients; however, increases in the activity of the parietal eye fields (PEFs) were observed only in patients who showed greater improvement in reading capability. The improvement in reading ability of the patients after EMT is regarded as an effect of the increased activity of FEF and PEF, which play important roles in attention and working memory as well as the regulation of eye movements.

Keywords: Eye-movement training; Frontal eye fields; Functional magnetic resonance imaging; Parietal eye fields; Reading capability; Retinitis pigmentosa.

Fig. 1

A: Effect of eye-movement training (EMT) on reading task performance. Sta- tistical analyses were performed on data from 6 normal volunteers (Normal) vs. 6 patients with concentric contraction where P (pre) and P (post) denote before and after EMT, respectively. Data are shown as mean ± standard error (SE). Normal vs. patients, unpaired Welch’s t -test ( +, p < 0.05; + +, p < 0.01). P (pre) vs. P (post), paired t-test. Statistical analysis of P (pre) vs. P (post) without patient 6 (see Tables 1 and 2) yielded p < 0.05 (n = 5). B: Effect of EMT on fMRI task performance. Data are shown as mean ± SE. Normal vs. patients, unpaired Welch’s t-test ( +, p < 0.05; + +, p < 0.01). P (pre) vs. P (post), paired t -test. NS denotes no significance. Statistical analysis of P (pre) vs. P (post) without patient 6 (see Tables 1 and 2) yielded p = 0.057 (n = 5).

Fig. 2

A: Examples of activation maps during the fMRI task (TANKA tasks) of a normal volunteer (left) and a patient with concentric contraction before (middle) and after (right) eye-movement training (EMT). Top, sagittal slice at x = 10 (MNI). Bottom, axial slice at z = – 8 (MNI). B: Number of activation voxels in the primary visual cortex along the calcarine sulcus. Data are shown as mean ± SE. Normal volunteers (Normal) (n = 6) vs. patients (n = 6), unpaired Welch’s t-test ( + +, p < 0.01). P (pre) vs. P (post), paired t -test. NS denotes no significance..

Fig. 3

Activation maps during the fMRI task (TANKA tasks) of a normal volunteer (N) (top: typical example) and individual patients (only the number is shown) before eye- movement training (EMT). Axial slice at z = + 55 is focusing on the superior parietal lobule (SPL), inferior parietal lobule (IPL), supplementary motor area (SMA), supple- mentary eye fields (SEFs), FEF, dorsolateral prefrontal cortex (DLPFC), and primary motor area (M1). Axial slice at z = + 35 is focusing on those areas except for SMA and SEFs. Activations of the V3 and those of V1/V2 and medial temporal lobule (V5 / MT) can be observed in the slice at z = + 25 and z = + 5 and − 15, respectively.

Fig. 4

Subtraction of neural activity during the fMRI task (TANKA tasks) before and after eye-movement training (EMT). Axial slices at z = – 15, + 5, + 25, + 35, and + 55 are shown.

Fig. 5

Number of activation voxels in the frontal eye fields (FEFs) and parietal eye fields (PEFs). P (pre) and P (post) denote before and after eye-movement training of patients, respectively. [F] and [P] denote the FEFs and PEFs, respectively. Data are shown as mean ± SE. Normal volunteers (Normal) (n = 6) vs. patients (n = 6) at FEFs (Normal [F] vs. P (pre) [F] or Normal [F] vs. P (post) [F]), unpaired Student’s t -test (^*, p < 0.05; ^**, p < 0.01). Normal volunteers (Normal) (n = 6) vs. patients (n = 6) at PEFs (Normal [P] vs. P (pre) [P] or Normal [P] vs. P (post) [P]), unpaired Welch’s t -test ( +, p < 0.05; + +, p < 0.01). P (pre) vs. P (post), paired t -test. NS denotes no significance. Statistical analysis of P (pre) [F] vs. P (post) [F] without patient 6 (see Tables 1 and 2 ) yielded p < 0.01 (n = 5).