Magnocellular pathway impairment in schizophrenia: evidence from functional magnetic resonance imaging

Abstract

Sensory processing deficits in schizophrenia have been documented for several decades, but their underlying neurophysiological substrates are still poorly understood. In the visual system, the pattern of pathophysiology reported in several studies is suggestive of dysfunction within the magnocellular visual pathway beginning in early sensory cortex or even subcortically. The present study used functional magnetic resonance imaging to investigate further the neurophysiological bases of visual processing deficits in schizophrenia and in particular the potential role of magnocellular stream dysfunction. Sinusoidal gratings systematically varying in spatial frequency content were presented to subjects at low and high levels of contrast to differentially bias activity in magnocellular and parvocellular pathways based on well established differences in neuronal response profiles. Hemodynamic responses elicited by different spatial frequencies were mapped over the occipital lobe and then over the entire brain. Retinotopic mapping was used to localize the occipital activations with respect to the boundaries of visual areas V1 and V2, which were demarcated in each subject. Relative to control subjects, schizophrenia patients showed markedly reduced activations to low, but not high, spatial frequencies in multiple regions of the occipital, parietal, and temporal lobes. These findings support the hypothesis that schizophrenia is associated with impaired functioning of the magnocellular visual pathway and further suggest that these sensory processing deficits may contribute to higher-order cognitive deficits in working memory, executive functioning, and attention.

Figures

Figure 1.

Stimuli and paradigm. Right, Continuously counterphase-reversing sinusoidal gratings were presented at fixation. In one cycle lasting 64 s, the gratings monotonically increased SF content from 0.2 to 4.9 cpd. Left, Analyses of SF selectivity were based on the BOLD signal response latency. Cortical regions with short response latencies were maximally sensitive to low SFs. Peak response latencies during the middle of the stimulation cycle correspond to preferred sensitivity to a mid-range SFs, and areas with long response latencies were maximally sensitive to high SFs.

Figure 2.

Differences between patients and controls in cortical areas activated by stimuli varying in SF. A, Group-averaged response latency maps mapped onto a template of the occipital ROI (within dashed yellow lines) in Talairach coordinates. Color scale represents latency values corresponding to stimuli at different SFs (ranging from 0.2 to 4.9 cpd; see color scale below). Separate maps are shown for left (LH) and right (RH) hemisphere activations for control and patient groups in response to stimuli at 100% contrast. B, Same as A for stimuli at low (12%) contrast. C, Number of voxels within the occipital ROI (averaged across hemispheres and individuals in each group) with preferential responses at 100% contrast stimuli at different SFs. Corresponding ranges of SFs (LSF, MLSF, MHSF, and HSF) used in subsequent analyses are depicted in dashed white lines. D, Same as C for the low (12%)-contrast stimuli.

Figure 3.

Mean number of voxels in retinotopically mapped areas V1 and V2 activated by LSF, MLSF, MHSF, and HSF stimuli at high contrast (left column) and low contrast (right column). Significant differences between controls (solid color) and patients (hatch pattern) are indicated by asterisks: *p < 0.010; **p < 0.005; ***p < 0.001. Error bars represent SEM.

Figure 4.

Cortical areas within the occipital ROI with significant group differences in SF selectivity. Maps of p values (see scales on right) are displayed on the left (LH) and right (RH) hemispheres of a template brain in Talairach coordinates for high (100%; top) and low (12%; bottom) contrast. The mean number of voxels showing peak responses at each SF within regions with a significant group difference is plotted for control subjects (black traces) and patients (gray traces).

Figure 5.

Whole-brain analysis of group differences in SF selectivity. Statistical significance maps resulting from the comparison of response latency maps for patients versus controls (p values; see scale on right) are displayed on the inflated left (LH) and right (RH) hemispheres of a template brain in Talairach coordinates for high- (100%; top) and low- (12%; bottom) contrast stimuli. For each hemisphere, the lateral (left column) and medial (right column) views are shown. FG, Fusiform gyrus; Inf. Par., inferior parietal lobe; STG, superior temporal gyrus.

Figure 6.

Scatterplots of correlation between CS and fMRI measures of SF selectivity. Linear correlations between the number of voxels with phase values corresponding to preferential responses to the LSF stimuli used in fMRI and individual CS values at 0.5 cpd (top), 1.0 cpd (middle), and 2.0 cpd (bottom) for patient (gray dots) and control (black dots) subjects.