optic radiation is separated from the lateral ventricle by the structure known as the tapetum. The average distance between the temporal pole and the loop of Meyer measured by these authors (2773.5 mm) (Yamamoto et al., 2005) is also in line with classical anatomical descriptions (Ebeling and Reulen, 1988).

Functional MR imaging

fMRI involves the application of MR techniques for high-resolution (spatial and temporal) investigations of brain physiology. Local changes in cerebral hemodynamics are closely linked to local cerebral activity, and they can be assessed with the technique known as blood oxygen level–dependent (BOLD) fMRI. The BOLD contrast effect depends on changes in the deoxyhemoglobin content of blood during states of increased neuronal activity (Ogawa et al., 1990). Many studies have been performed to assess BOLD signal changes in normal humans under different conditions, e.g., during sensory stimulation or

motor and cognitive activities (Bandettini et al., 1992).

fMRI has now become the technology of choice for many functional activation studies in humans. Its advantages include the possibility to collect anatomic and functional data in a single session, noninvasiveness and lack of exposure to ionizing radiation (which make it suitable for repeated assessments of both patients and volunteers), and high availability (in most medical centers with clinical MR imaging services) (Kollias, 2004). Because visual stimulation is associated with robust changes in signal intensity, fMRI is particularly useful for studying visual function under physiological and pathological conditions.

Activation of the primary visual cortex can be easily demonstrated with BOLD fMRI during experiments involving the delivery of various visual stimuli (Fig. 10). The signals obtained are related to actual changes in visual neuronal activity, as demonstrated by Logothetis et al. (2001). These authors analyzed fMRI signals in light of simultaneously recorded electrical activity in the neurons of the primary visual cortex of

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Fig. 10. Functional magnetic resonance imaging (fMRI) results of a single subject following visual task performance.

monkeys exposed to visual stimulation. In accordance with the results of previous studies (Bandettini et al., 1992; Kollias et al., 2000), their findings confirmed that localized increases in BOLD contrast reflect stimulus-evoked increases in neural activity. The response to a visual stimulus begins within a few hundred milliseconds of neuronal stimulation. The decrease in signal intensity observed 0.5–2.0 s after stimulus onset has been attributed to an early focal deoxygenation phase, which precedes increases in oxygenated hemoglobin caused by local enhancement of blood flow (Ernst and Hennig, 1994).

Direct relations between stimulus intensity and occipital responses have also been reported. Alvarez-Linera Prado et al. (2007) demonstrated correlation between the BOLD response and visual-stimulus intensity and found that cortical reactivity to these stimuli (especially those within the low-to-medium-intensity range) is higher in patients with photophobia than normal controls.

fMRI was first employed to establish the extent of striate and extrastriate cortical areas and to map the retinotopic borders of the visual cortex (Courtney and Ungerleider, 1997; Engel et al., 1997). Precise retinotopic mapping was impossible prior to the mid 1990s, when Engel et al. (1997) developed the technique of phase-encoded retinal stimulation. They used a contrast-reversing

checkerboard (contrast reversal rate, 8 Hz) presented at the center of gaze to create a strong neural response within area V1 of the human visual cortex. Subjects were exposed to expandingring and contracting-ring stimuli, which generated a traveling wave of neural activity within visual cortex. With this new approach, the investigators were able to distinguish the cortical representation of the fovea in the posterior cortex from that of the peripheral retina.

Many efforts were made to correlate neurological deficits with damage to specific brain areas. The first attempts to identify the anatomic sources of specific cerebral functions were based on the study of correlations between loss of function and brain lesion location. The early studies of visual impairments produced by focal lesions suggested that the human visual cortex is organized into two anatomically and functionally distinct units, the ventral and the dorsal pathways. Symptoms like visual object agnosia, prosopagnosia, and achromatopsia are produced by occipitotemporal lesions involving the ventral pathway, whereas optic ataxia, visual neglect, constructional apraxia, gaze apraxia, akinotopsia, and disorders of spatial cognition are the result of occipitoparietal lesions within the dorsal pathway (Boller and Grafman, 1989; Laskowitz et al., 1998).

Anatomical neuroimaging may not be sufficient to determine the extent of brain damage caused by cerebrovascular lesions, neoplasms, inflammatory states, or congenital disease. Many studies have demonstrated good agreement between fMRI findings and the results of traditional visual examinations. Patients with congruous homonymous hemianopia caused by retrochiasmatic lesions (Miki et al., 1996a) and those with visual field defects caused by prechiasmatic and chiasmatic lesions (Miki et al., 1996b) showed abnormal cortical activation that was concordant with the visual defect. fMRI thus appears to be a potentially valuable tool for assessing local brain function in patients with visual deficits.

In patients with space-occupying lesions involving the optic radiation, fMRI examinations revealed activation patterns in the visual cortex that were consistent with the patients’ visual field deficits and with traditional retinotopic representations.

Optic neuritis is a common manifestation of multiple sclerosis, a disease characterized by the development of multifocal, inflammatory, demyelinating lesions of the white matter. In patients with unilateral optic neuritis, fMRI has revealed that the response to visual stimuli of the affected eye is characterized by reductions in the area of activation in the primary visual cortex and by significant increases in the latency of the major positive component of the visual-evoked potential (VEP). fMRI can thus be considered a reliable method for obtaining detailed topographic information related to functional deficits in multiple sclerosis (Gareau et al., 1999).

fMRI can also be used to identify epileptogenic foci in patients with epilepsy based on the demonstration of abnormal activation patterns that are concordant with seizure onset and interictal epileptiform discharges; these studies showed agreement between fMRI data and EEG (Lengler et al., 2007).

Dyslexia is a developmental disorder characterized by low reading achievement in individuals whose cognitive abilities, motivation, and education are adequate for accurate, fluent reading. fMRI studies of subjects with dyslexia frequently exhibit hypoactivation in the left parietotemporal cortex together with hyperactivation in the left inferior frontal cortex. Hoeft et al. (2007) recently reported that the areas of hyperactivation reflected processes related to the subject’s current level of reading ability, independent of the dyslexia, whereas the areas of hypoactivation seen in the left parietotemporal and occipitotemporal lobes represent functional atypicalities related to the dyslexia itself.

In schizophrenics who experience visual hallucinations, fMRI has revealed increased cerebral activity in the ventral extrastriate visual cortex and in the hippocampus (Oertel et al., 2007).

Miki et al. (1996b) performed fMRI during monocular visual stimulation in patients with visual field losses caused by lesions of the optic nerve and chiasm, and the results showed agreement with the pattern of visual field defects. In patients with unilateral optic neuropathy, like that frequently seen in glaucoma, stimulation of the affected eye failed to activate the portion of the

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primary visual cortex corresponding to the central visual field defects and reduced activity in the associated visual cortex. Patients with chiasmal compression, monocular stimulation caused markedly asymmetrical activation of the primary visual cortex, which corresponded to the visual field abnormality.

Recently, Duncan et al. (2007) demonstrated correlation between functional organization of the visual cortex (V1) and visual field deficits in patients with primary open-angle glaucoma (POAG). A retinotopic map of visual space was obtained for visual areas in occipital cortex. Templates were used to project regions within the visual field onto a flattened representation of cortex. The resulting BOLD fMRI response was compared to interocular differences in thresholds for corresponding regions of the visual field. The spatial pattern of activity observed in the flattened representation was consistent with the pattern of visual field loss. In patients withPOAG, the BOLD signal in human visual cortex is altered in a manner that is consistent with the loss of visual function, suggesting that fMRI can be used to quantify functional changes in glaucoma.

Proton MR spectroscopy

MR spectroscopy is a noninvasive tool for investigating the chemical environment of the brain. The proton MR spectrum is characterized by at least three peaks, which represent (1) the compounds creatine and phosphocreatine (Cr), which are generally associated with cellular energy metabolism; (2) choline (Cho), which is associated with cell membrane synthesis; and (3) N-acetyl aspartate (NAA), a marker of neuronal integrity. Several studies have demonstrated the usefulness of MR spectroscopy in clinical settings, for the study of seizure foci and neoplasms and for distinguishing recurrent tumor from radiation necrosis, metabolic diseases, and white-matter disease (Branda˜o and Domingues, 2004).

In a recent study, Boucard et al. (2007) performed proton MR spectroscopy with a singlevoxel technique in patients with glaucoma. They found that absolute levels of NAA in the occipital

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brain of subjects with progressive visual field defects caused by age-related macular degeneration or glaucoma were not significantly different from those found in a group of control subjects. Visual field degeneration in both these diseases progresses slowly, and the authors hypothesized the rate of progression might not be high enough to provoke a decrease in NAA concentration. An alternative explanation is that the cortical area corresponding to the affected retinal region is too small to provoke changes in the NAA concentration that are detectable with proton MR spectroscopy (Boucard et al., 2007).

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