V1 projection zone signals in human macular degeneration depend on task, not stimulus

Abstract

We used functional magnetic resonance imaging to assess abnormal cortical signals in humans with juvenile macular degeneration (JMD). These signals have been interpreted as indicating large-scale cortical reorganization. Subjects viewed a stimulus passively or performed a task; the task was either related or unrelated to the stimulus. During passive viewing, or while performing tasks unrelated to the stimulus, there were large unresponsive V1 regions. These regions included the foveal projection zone, and we refer to them as the lesion projection zone (LPZ). In 3 JMD subjects, we observed highly significant responses in the LPZ while they performed stimulus-related judgments. In control subjects, where we presented the stimulus only within the peripheral visual field, there was no V1 response in the foveal projection zone in any condition. The difference between JMD and control responses can be explained by hypotheses that have very different implications for V1 reorganization. In controls retinal afferents carry signals indicating the presence of a uniform (zero-contrast) region of the visual field. Deletion of retinal input may 1) spur the formation of new cortical pathways that carry task-dependent signals (reorganization), or 2) unmask preexisting task-dependent cortical signals that ordinarily are suppressed by the deleted signals (no reorganization).

Figure 1.

A schematic diagram of the subjects’ visual fields and stimulus position. (A–D) The visual field and stimulus position is shown for the measured eye in JMD1–JMD4, respectively. Dark gray regions represent absolute scotomas; the transparent light gray regions show the visual field location of the stimulus. The star indicates the subjects’ PRL. In JMD1, 3 (A, C) the foveal position was estimated by monitoring the visual axis during visual field measurement, and in JMD2, 4 (B, D), the foveal position was estimated by the location of the physiological blind spots. Note that relative scotomas usually exist between the PRL and the absolute scotoma region. Units are degrees of visual angle.

Figure 2.

Passive viewing stimuli elicit stimulus-synchronized response in the PRL-PZ but not the LPZ. The response elicited during the passive viewing of scrambled faces is shown on an inflated cortical surface of the right hemisphere. The black box shows the position of the expanded region showing the phase-specified coherence map in JMD1 and C1. All data overlaid on the inflated brain exceed an absolute phase-specified coherence level of 0.30. The graphs show the average response during 1 stimulus cycle in a set of ROIs. The ROI positions (3-mm-radius circles) are shown on the cortical surface, spanning the shortest line connecting the PRL-PZ to the occipital pole. In JMD1, no stimulus-synchronized response is observed in the LPZ; in some regions near the occipital pole the response to the mean luminance exceeds the response to the stimulus (negative BOLD; left bottom graphs). In C1, the response patterns qualitatively resemble those of JMD1. The average single time curves show no stimulus-synchronized activity in the sLPZ.

Figure 3.

During the OBT, stimulus-synchronized responses are present in the LPZ of JMD1 but not in C1. The data are shown in an identical format as figure 2. The left panel shows stimulus-synchronized responses that extended beyond the PRL-PZ into the LPZ of JMD1. Note the occipital pole that previously responded preferentially to the mean-luminance presentations (Fig. 2, left bottom graphs), now responds in phase with the stimulus (Fig. 3, left bottom panels). In C1 this response was not observed, although some regions responded stronger to the mean-luminance presentations. In both subjects, increased responses in ventral cortex can be observed.

Figure 4.

Viewing the stimuli while performing the OBT elicits a stimulus-synchronized response in the LPZ in JMD2, 3 but not in JMD4. We compare the activation pattern elicited by passive viewing (JMD2, 3) or stimulus unrelated judgments (JMD4) (left panels) and OBT (right panels) of the drifting contrast pattern (insets). The panels from the 3 rows are JMD2, 3, 4, respectively. (A–C) The phase-specified coherence map. (D–F) The average time course during 1 stimulus cycle in the PRL-PZ (top) and the LPZ (bottom). Stimulus-synchronized responses are present in the PRL-PZ and negative or weak responses are present in the occipital pole. (G–L) Stimulus-synchronized responses while performing the OBT, are shown in an identical format to figure (A–F). In JMD2 and 3, a stimulus-synchronized response is elicited in the PRL-PZ and the LPZ, even though there should not be any input from the lesioned retina. In JMD4, a stimulus-synchronized response in the LPZ is not observed, although some regions responded stronger to the mean-luminance presentations (L). Ventral, dorsal, and lateral occipital responses increase during the OBT condition.

Figure 5.

The spatial profile of phase-specified coherence in controls (C1–3) and JMD1. The spatial profile of phase-specified coherence is plotted as a function of distance from the PRL-PZ to occipital pole (A) in 3 controls, and (B) the comparison of JMD1 and controls (gray shadow). The 3-mm-radius circle ROIs are selected on the cortical surface from the PRL-PZ to the occipital pole chosen along the shortest line connecting the 2 locations. The distance between the ROIs is 5 mm. The distance between the PRL-PZ and the occipital pole is different among the subjects, therefore we show the normalized distance. A solid line indicates the phase-specified coherence from viewing stimuli with the OBT, whereas dotted lines indicate the phase-specified coherence elicited by passive viewing of the stimuli (no task; NT) or viewing the stimuli with the fixation task (fixation task; FT in Fig. 6). In the control subjects, the phase-specified coherence decreases with increasing distance from the simulated PRL-PZ. This decrease of the phase-specified coherence is similar for all viewing conditions (A). For JMD1 (B), when passively viewing the stimuli, at increasing distance from the PRL-PZ into the occipital pole (LPZ) the coherence levels decrease to negative or close to negative values (B, dotted lines). The OBT elicits strong positive coherence levels around the occipital pole (LPZ) (B, solid line) as compared with passive viewing (B, dotted lines) and the control subject (B, gray shadow). Almost all error bars are hidden within symbols.

Figure 6.

The spatial profile of phase-specified coherence in JMD2–4. The spatial profile of phase-specified coherence as a function of distance from the PRL-PZ to the occipital pole in 3 JMD subjects (A–C). The data are shown in an identical format as Figure 5. The insets in the graphs show the corresponding cortical surface and the shortest line from the PRL-PZ to the occipital pole (dotted line). The PRL-PZ always yields a positive phase-specified coherence level. When passively viewing the stimuli or performing stimulus unrelated judgments, at increasing distance from the PRL-PZ into the occipital pole the coherence levels decrease to negative or close to negative values. The OBT elicits strong positive coherence levels around the occipital pole except for JMD4 as compared with passive viewing or stimulus unrelated judgments and the control subjects (Fig. 5A). In JMD4, the decrease from the PRL-PZ of the phase-specified coherence is similar for all viewing conditions (C).

Figure 7.

Responses in the LPZ may result from an imbalance in geniculo-cortical and cortico-cortical projections. (A) Control subjects, passive viewing: the contrast pattern in the periphery elicits a V1 and extrastriate response. The zero-contrast signal from the foveal region elicits no response. (B) Control subjects, OBT: The OBT elicits a task-dependent V1 cortico-cortical feed-back signal (dashed arrows). There is also a zero-contrast geniculo-cortical signal in the sLPZ. The combination of these 2 signals produces no activation in the LPZ. (C, D) In JMD subjects, there is no feed-forward signal from damaged retina. In passive viewing, no V1 signal is expected. But during the OBT cortico-cortical signals are not met by a corresponding zero-contrast geniculo-cortical signal. Consequently, feed-back signals are unmasked in V1 (and elsewhere), producing a stimulus-synchronized activation in the LPZ.