Regular articleIncreased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness
Introduction
The neural system shows remarkable plasticity in the early phase of development, which is restricted to a “critical period” (Feldman, 2000). The synaptic density in the visual cortex in the human neonate is comparable to the adult level but increases to a maximum subsequently because of a burst of synaptogenesis during the first postnatal year (Huttenlocher and de Courten, 1987). The density then gradually decreases to reach the adult level at about 11 years of age. This decreasing phase of synaptic density is called “synaptic revision.”
Although the individual variability in synaptic density is relatively small during the initial phase of synaptogenesis, the subsequent reduction of synapses in the visual cortex has been shown to depend on visual experience (Bourgeois et al., 1989). Synaptic elimination is impaired by visual deprivation during visual development Stryker and Harris 1986, Winfield 1983.
Previous studies using positron emission tomography (PET) have demonstrated high cerebral blood flow (CBF) and high glucose metabolism in the visual cortex of subjects with early-onset blindness, that is, loss of vision before completion of visual development De Volder et al 1997, Veraart et al 1990, Wanet-Defalque et al 1988. The authors discussed that these findings indicated high baseline neural activity in the visual cortex of individuals with early-onset blindness during the resting state because of lack of synaptic elimination during the visual development.
PET can obtain in vivo images of regional cerebral functions that include not only blood flow and metabolism but also receptor-binding capacity. Using PET with [11C]flumazenil (FMZ), a highly specific benzodiazepine antagonist, the distribution of central benzodiazepine receptors (BZRs) in the human brain can be shown. These receptors are one of the γ-aminobutyric acid type A (GABAA) receptor complex. Since the receptors are widely distributed in the cerebral cortex, [11C]FMZ PET images are thought to demonstrate the neural density in the cerebral cortex (Malizia and Richardson, 1995). Thus these are used to investigate the densities in various diseases Gilman et al 1995, Gilman et al 1996, Holthoff et al 1993, Ohyama et al 1999, Savic et al 1988. Past studies have shown that GABAergic inhibition plays an important role in neural plasticity in the cerebral cortex Butefisch et al 2000, Fagiolini and Hensch 2000, Gupta et al 2000, Hensch et al 1998, Jones 1993, Sillito et al 1981, Zheng and Knudsen 1999. However, there are few reports documenting the distribution of neurotransmitter receptors in the visual cortex of subjects with early-onset blindness (Sanabria-Bohorquez et al., 2001).
Because the GABAergic system of visual cortex is involved in neural plasticity, we hypothesized that the modification of GABAergic system induced by visual deprivation will be different from that of other neural systems. To investigate this, we studied the CBF and BZR distribution in subjects with early-onset blindness and compared the findings with those from blindfolded, sighted subjects using [15O]water and [11C]FMZ PET.
Section snippets
Subjects
We recruited six blind volunteers who lost their vision early in life as a result of bilateral ocular lesions (24.3 ± 2.4 years; mean ± SD). Table 1 summarizes their clinical profiles. They were thought to be blind since birth except the blind subject No. 3. By 6 years of age, they were reliably diagnosed as loss of light perception by ophthalmologists, but were otherwise neurologically normal. All of the blind subjects could read Braille. The control group consisted of seven sighted male
Results
In all the blind subjects, abnormal MRI findings, such as phthisis bulbi, were found in the eyes. However, no abnormality, such as brain atrophy, was detected within the brain in any of the sighted or blind subjects.
The results of SPM {Z} are summarized in Table 2. The normalized CBF was significantly larger in the left cuneus, lingualis gyrus, inferior occipital gyrus, and right middle occipital gyrus for subjects with early-onset blindness than for sighted control subjects (Table 2, Fig. 2,
CBF in the visual cortex
The increased resting CBF in individuals with early-onset blindness compared with sighted controls suggests a high neural activity in the occipital cortex, confirming the results of past studies using ROI (De Volder et al., 1997). In the visual system, synaptic changes in the visual cortex depend on visual experience (Bourgeois et al., 1989). As the visual input increases during visual development, those synapses with high priority in visual information processing survive, while the other
Acknowledgements
The authors thank Mr. S. Ishii for production of [11C]FMZ and Ms. M. Ando for care of subjects in the PET scanning.
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