Volume and neuron number of the lateral geniculate nucleus in schizophrenia and mood disorders

Abstract

Subjects with schizophrenia show deficits in visual perception that suggest changes predominantly in the magnocellular pathway and/or the dorsal visual stream important for visiospatial perception. We previously found a substantial 25% reduction in neuron number of the primary visual cortex (Brodmann's area 17, BA17) in postmortem tissue from subjects with schizophrenia. Also, many studies have found reduced volume and neuron number of the pulvinar--the large thalamic association nucleus involved in higher-order visual processing. Here, we investigate if the lateral geniculate nucleus (LGN), the visual relay nucleus of the thalamus, has structural changes in schizophrenia. We used stereological methods based on unbiased principles of sampling (Cavalieri's principle and the optical fractionator) to estimate the total volume and neuron number of the magno- and parovocellular parts of the left LGN in postmortem brains from nine subjects with schizophrenia, seven matched normal comparison subjects and 13 subjects with mood disorders. No significant schizophrenia-related structural differences in volume or neuron number of the left LGN or its major subregions were found, but we did observe a significantly increased total volume of the LGN, and of the parvocellular lamina and interlaminar regions, in the mood group. These findings do not support the hypothesis that subjects with schizophrenia have structural changes in the LGN. Therefore, our previous observation of a schizophrenia-related reduction of the primary visual cortex is probably not secondary to a reduction in the LGN.

Fig. 1

a Coronal section approximately at the middle rostral–caudal level of the LGN. The six laminae are indicated. b For volume estimation, the LGN from each subject was subdivided into magnocellular laminae (black), parvocellular laminae (gray), and interlaminar regions (white). c For estimation of neuron numbers, the LGN from each subject was split into a magnocellular part (black) and a parvocellular part (gray)

Fig. 2

a Micrograph showing six typical magnocellular neurons. An unbiased counting frame is shown with the red unbroken exclusion line and a dotted green inclusion line. A neuron was counted if its nucleolus was in focus within the height of the disector and fully or partially inside the counting frame without touching the exclusion line. As shown here, the two neurons in the middle were counted while the neurons just below and above the middle were excluded. b Six representative parvocellular neurons

Fig. 3

The point grid used for volume estimation. A point is infinitesimal and is defined as the intersection of the upper edge and the right edge of the lines in the upper right corner of each cross. The two magnocellular laminae are seen at the lower left. The counts for this field of view are: total LGN: five encircled points; parvocellular laminae: three encircled points; magnocellular laminae: 12 points; interlaminar regions: 19 points. Using the stereological software, the user indicates which region a point hits while the computer keeps track of the tallies

Fig. 4

Top row calibration study of left LGN in one subject that involved counting all neurons in the full section thickness. Section thickness was measured a total of 1,258 times and 1,869 neurons were counted across the magno- and parvocellular parts combined. Bottom row full study of the left LGN in all 29 subjects counting neurons in 8 μm high optical disectors with a top guard zone of 4.4 μm. A total of 11,256 section thicknesses were measured and 14,108 neurons counted across the magno- and parvocellular parts combined. Left distribution of individual section thickness measurements. Middle position of neuronal nucleoli in the z-axis (i.e., distance from the top of section). Right z-positions of neurons corrected for local shrinkage in the z-axis. Section thickness was measured in the center of each counting frame which also defined the local top and bottom of the section. Unevenness in the surfaces of the sections caused a few neurons to appear outside this range as seen in top mid and left plots

Fig. 5

Estimated total volume (left) and neuron number (right) of the left LGN for the comparison (C), schizophrenia (S), and mood disorders (M) groups of subjects. The horizontal bars indicate group means. Lettering at the top indicates significance. Groups not sharing the same letter are significantly different at P<0.05

Fig. 6

Estimated volumes of the three compartments of the left LGN for the comparison (filled circles), schizophrenia (thin circles), and mood disorders (bold circles) groups of subjects. The horizontal bars indicate group means. Lettering at the top indicates significance. Groups not sharing the same letter are significantly different at P<0.05

Fig. 7

Estimated neuron numbers of the two parts of the left LGN for the comparison (filled circles), schizophrenia (thin circles), and mood disorders (bold circles) groups of subjects. The horizontal bars indicate group means

Fig. 8

Scatterplot demonstrating the positive correlation (r = 0.64, P = 0.0002) between total neuron number and volume of LGN. Filled circles indicate subjects from the comparison group, thin circles represent subjects from the schizophrenia group, and bold circles symbolize subjects from the mood disorder group. Line is the regression line

Fig. 9

Total volumes of the left LGN estimated by Cavalieri’s principle from point counts (by RS) or tracing (by DC) for each subject from the comparison (filled circles), schizophrenia (thin circles), and mood disorders (bold circles) groups. Line is the identity line

Fig. 10

Correlation plots for volume and total neuron number of the left LGN versus the left BA17 for the eight subjects included in both this study and our previous study of BA17 [30]. Filled circles indicate comparison subjects and open circles indicate subjects with schizophrenia. Lines are correlation lines for the schizophrenia group (r = 0.982, P = 0.0005, and r = 0.891, P = 0.017, left and right plot, respectively). The broken correlation line at right indicates that the correlation should be interpreted with care as it is predominantly due to the single subject in the lower left of the plot