Faculty Bibliography

OBJECTIVE: Clinical studies suggest resting thermoregulatory cutaneous vasomotor tone could be increased in schizophrenia, resulting in reduced hand blood flow. In animal models, atypical antipsychotics including clozapine potently inhibit sympathetic neural outflow to the thermoregulatory cutaneous vascular beds. We have now determined whether antipsychotic medication administration is associated with an acute increase in hand blood flow in patients with schizophrenia and schizoaffective disorder, and whether this increase correlates with clinical status. METHOD: Hand temperature was measured with an infrared camera in 12 patients with chronic schizophrenia or schizoaffective disorder 30 min prior to, then 30 and 60 min following medication. Clinical status was assessed via the Brief Psychiatric Rating Scale (BPRS). Results were compared using regression and repeated measures analysis of variance. RESULTS: A robust and significant increase in hand temperature (p < 0.001) was observed following antipsychotic administration. The mean increase after 60 min was 4.1 +/- 2.4 degrees C. This increase was significantly associated with colder hand temperature prior to medication (p < 0.05; suggestive of increased resting vasoconstriction) and with more severe psychiatric symptoms (p < 0.05). CONCLUSIONS: Atypical antipsychotics were associated with increased hand blood flow, consistent with inhibition of thermoregulatory sympathetic outflow to the cutaneous vascular bed in patients with schizophrenia and schizoaffective disorder. This increase correlated with symptom severity. Hand temperature increase following antipsychotic medication may therefore be a simple and informative physiological marker of disease activity and potential response in patients with schizophreniform disorders. Given that antipsychotics also inhibit sympathetic outflow to brown adipose tissue, which normally converts energy to heat, future studies should examine whether antipsychotic-induced hand temperature increase is associated with antipsychotic-induced weight gain.

The red-green axis of colour vision evolved recently in primate evolutionary history. Signals serving red-green colour vision travel together with signals serving spatial vision, in the parvocellular (PC) division of the subcortical visual pathway. However, the question of whether receptive fields of PC pathway cells are specialized to transmit red-green colour signals remains unresolved. We addressed this question in single-cell recordings from the lateral geniculate nucleus of anaesthetized marmosets. Marmosets show a high proportion of dichromatic (red-green colour-blind) individuals, allowing spatial and colour tuning properties of PC cells to be directly compared in dichromatic and trichromatic visual systems. We measured spatial frequency tuning for sine gratings that provided selective stimulation of individual photoreceptor types. We found that in trichromatic marmosets, the foveal visual field representation is dominated by red-green colour-selective PC cells. Colour selectivity of PC cells is reduced at greater eccentricities, but cone inputs to centre and surround are biased to create more selectivity than predicted by a purely 'random wiring' model. Thus, one-to-one connections in the fovea are sufficient, but not necessary, to create colour-selective responses. The distribution of spatial tuning properties for achromatic stimuli shows almost complete overlap between PC cells recorded in dichromatic and trichromatic marmosets. These data indicate that transmission of red-green colour signals has been enabled by centre-surround receptive fields of PC cells, and has not altered the capacity of PC cells to serve high-acuity vision at high stimulus contrast.

We measured functional input from short-wavelength selective (S) cones to neurons in the dorsal lateral geniculate nucleus (LGN) and striate cortex (area V1) in anaesthetized marmosets. We found that most magnocellular (MC) and parvocellular (PC) cells receive very little (<5%) functional input from S cones, whereas blue-on cells of the koniocellular (KC) pathway receive dominant input from S cones. Cells dominated by S cone input were not encountered in V1, but V1 cells received more S cone input than PC or MC cells. This suggests that S cone inputs are distributed broadly among neurons in V1. No differences in strength of S cone inputs were seen on comparing dichromatic and trichromatic marmosets, suggesting that the addition of a medium-long wavelength selective cone-opponent ("red-green") channel to a dichromatic visual system does not detectably affect the chromatic properties of the S cone pathways.

Many of the parvocellular pathway (PC) cells in primates show red-green spectral selectivity (cone opponency), but PC ganglion cells in the retina show no anatomical signs of cone selectivity. Here we asked whether responses of PC cells are compatible with "random wiring" of cone inputs. We measured long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cone inputs to PC receptive fields in the dorsal lateral geniculate of marmosets, using discrete stimuli (apertures and annuli) to achieve functional segregation of center and surround. Receptive fields between the fovea and 30 degrees eccentricity were measured. We show that, in opponent PC cells, the center is dominated by one (L or M) cone type, with normally <20% contribution from the other cone type (high "cone purity"), whereas non-opponent cells have mixed L and M cone inputs to the receptive field center. Furthermore, opponent response strength depends on the overall segregation of L and M cone inputs to center and surround rather than exclusive input from one cone type to either region. These data are consistent with random wiring. The majority of PC cells in both foveal (<8 degrees) and peripheral retina nevertheless show opponent responses. This arises because cone purity in the receptive field surround is at least as high as in the center, and the surround in nearly all opponent PC cells is dominated by the opposite cone type to that which dominates the center. These functional biases increase the proportion of opponent PC cells, but their anatomical basis is unclear.

We measured responses to red-green color variation in parvocellular (PC) neurons in the lateral geniculate nucleus of dichromatic ("red-green color blind") marmoset monkeys. Although these animals lack distinct visual pigments to distinguish between wavelengths in this range, many of the colored stimuli nevertheless produced robust responses in PC cells. We show that these responses, which are restricted to high stimulus spatial frequencies (fine image details), arise from chromatic aberrations in the eye. The neural signals produced by chromatic aberrations are of comparable magnitude to signals produced by high-frequency luminance (LUM) modulation and thus could influence cortical pathways for processing of color and object recognition. The fact that genetically "color-blind" primates are not necessarily blind to wavelength-dependent contours in the visual world may have enabled red-green color vision to become linked with high-acuity spatial vision during primate evolution.

The parvocellular (PC) division of the afferent visual pathway is considered to carry neuronal signals which underlie the red-green dimension of colour vision as well as high-resolution spatial vision. In order to understand the origin of these signals, and the way in which they are combined, the responses of PC cells in dichromatic ('red-green colour-blind') and trichromatic marmosets were compared. Visual stimuli included coloured and achromatic gratings, and spatially uniform red and green lights presented at varying temporal phases and frequencies.The sensitivity of PC cells to red-green chromatic modulation was found to depend primarily on the spectral separation between the medium- and long-wavelength-sensitive cone pigments (20 or 7 nm) in the two trichromatic marmoset phenotypes studied. The temporal frequency dependence of chromatic sensitivity was consistent with centre-surround interactions. Some evidence for chromatic selectivity was seen in peripheral PC cells. The receptive field dimensions of parvocellular cells were similar in dichromatic and trichromatic animals, but the achromatic contrast sensitivity of cells was slightly higher (by about 30%) in dichromats than in trichromats. These data support the hypothesis that the primary role of the PC is to transmit high-acuity spatial signals, with red-green opponent signals appearing as an additional response dimension in trichromatic animals.