Marked reductions in visual evoked responses but not γ-aminobutyric acid concentrations or γ-band measures in remitted depression.

BACKGROUND: Magnetic resonance spectroscopy (MRS) studies have consistently demonstrated reduced cortical γ-aminobutyric acid (GABA) concentrations in individuals with major depression. However, evidence for a persistent deficit during remission, which would suggest that GABA dysfunction is a possible trait marker of depression, is equivocal. Although MRS measures total concentration of GABA, magneto-encephalography provides direct measures of neural activity, with cortical γ oscillations shaped by the activity of GABAergic inhibitory interneurons. In this study we investigated whether γ oscillations and GABA concentrations would differ in individuals with remitted depression (RD) compared with never depressed control subjects (ND). METHODS: Thirty-seven healthy, unmedicated female volunteers (n = 19 RD, and n = 18 ND) were recruited. The γ oscillation frequencies and amplitudes in the visual cortex, induced by simple grating stimuli, were quantified with time-frequency analyses. Distinct GABA/glutamate + glutamine MRS peaks were resolved from MEGA-PRESS difference spectra in prefrontal, occipital, and subcortical volumes. RESULTS: The RD and ND individuals did not differ in the frequency of subclinical depressive symptoms. The ND were slightly older (mean = 23 years vs. 21 years), but age did not correlate with dependent measures. There were no group differences in GABA levels or induced cortical γ measures, but RD individuals had markedly reduced M80 (C1) components of the pattern-onset evoked response (46% reduction, Cohen's d = 1.01, p = .006). CONCLUSIONS: Both MRS and magneto-encephalography measures of the GABA system are normal in RD. However, the early visual evoked response is a potential trait marker of the disorder.

Decreased gray matter concentration in the lateral geniculate nuclei in human amblyopes.

PURPOSE: In a group of humans with strabismic amblyopia, the relationship was examined between the structure and function of different brain regions. Three question were addressed: (1) Is the lateral geniculate nucleus (LGN) in humans with amblyopia structurally as well as functionally abnormal? (2) Do structural anomalies in the visual cortex correlate with the previously reported cortical functional losses? (3) Is there a link between the functional anomalies in the visual cortex and any structural anomalies in the geniculate? METHODS: The structure was compared by using voxel-based morphometry (VBM) and the function by functional magnetic resonance imaging (fMRI). RESULTS: The results showed that the geniculate is structurally abnormal in humans with strabismic amblyopia. CONCLUSIONS: These findings add further weight to the role of the LGN in the cortical deficits exhibited in human strabismic amblyopes.

A comment on the severity of the effects of non-white noise in fMRI time-series.

Analysis of fMRI time-series data is usually performed within the general linear model (GLM), and conclusions are based on the probability (p) of a false-positive voxel. In its simplest form, this process assumes that temporal noise in the time-series is random (white); if it is not, then an error in the estimation of p will occur. Various methods for correcting the problem have been developed, but they are not always used. Analysis packages vary in their ability to deal with this problem, and there is a lack of consistent advice to non-experts concerning whether this issue is serious or is small enough to be ignored. The variability of expert opinion partly reflects the fact that the magnitude of the error that occurs when estimating p in fMRI data is largely undocumented. In this discussion, aimed more at "neuroscience users" than methods experts, we try to clarify the position by documenting the scale of the error in a simple block-design experiment. Based on a fixed-effects group analysis of null datasets (8 participants scanned while at rest), we show that the magnitude of the problem can be very substantial. Without correction, it was necessary to set a nominal probability threshold of about p=0.000001 in order to achieve an actual probability of a false positive of 0.001. This means that if task-related activations were present in such a dataset, only if they reached the former, very low nominal p value could they be relied upon. With the use of standard correction methods, the error was largely removed. Our results suggest that some form of pre-whitening or correction for effects of non-white noise is essential in single-subject GLM analyses and fixed-effects group analyses of fMRI data. It is less important but probably prudent to apply a correction at the first level of random-effects group analyses. We also evaluate the effect of high-pass filtering. We find that the number of false positives in a fixed-effects analysis increases markedly as the filter cut-off frequency is increased. The sensitivity benefits derived from high-pass filtering may thus be partially offset by a significant increase in the number of false positives.

Negative BOLD in the visual cortex: evidence against blood stealing.

The positive BOLD (blood oxygen level-dependent) response elicited in human visual cortex by a localized visual stimulus is accompanied by a reduction in the BOLD response in regions of the visual cortex that represent unstimulated locations in the visual field. We have suggested previously that this negative BOLD reflects attention-related suppression of neural activity, but it might also be explained in terms of "blood stealing," i.e., hemodynamic changes that have no neural correlate. We distinguish two possible hemodynamic effects of this type: (1). blood flow reduction caused by locally reduced pressure in vessels that share their blood supply with nearby dilated vessels; and (2). blood flow reduction caused by active constriction of vessels under neural control. The first is ruled out as an explanation of negative BOLD by showing that a visual stimulus that stimulates primary visual cortex in one hemisphere can cause extensive suppression in the other hemisphere i.e., it is not a local phenomenon. Negative BOLD most likely reflects suppression of neural activity, but could also reflect an active blood flow control system.

Surround modulation measured with functional MRI in the human visual cortex.

Visual context profoundly influences 1) the responses of mammalian visual neurons and 2) the perceptual sensitivity of human observers to localized visual stimuli. We present data from functional MRI studies demonstrating contextual modulation in the human visual cortex. Subjects viewed a circular grating patch that was continuously present. A surround grating was added in an ON-OFF block design to reveal its effect on the central region. Stimulus-correlated activation was quantified and visualized on a flattened map of the occipital gray matter. Modulation was measured in a region of interest activated by the central grating alone. The observed effects were predominantly suppressive, consistent with the effects typically found in single neurons and perception. Suppression was greatest when the surround and center had the same orientation and was reduced or absent when it was orthogonal. When spatial phase was manipulated, suppression was greatest for in-phase center/surround gratings and much reduced or reversed (facilitation) for opposite-phase stimuli. With eccentric stimulus presentation, suppression was reduced and facilitation became more common. The findings provide a direct demonstration of the existence of powerful and stimulus-specific surround effects in human visual cortex.