Seth E. Bouvier

Treatment of multiple sclerosis with the pregnancy hormone estriol.

Multiple sclerosis patients who become pregnant experience a significant decrease in relapses that may be mediated by a shift in immune responses from T helper 1 to T helper 2. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift. We treated nonpregnant female multiple sclerosis patients with the pregnancy hormone estriol in an attempt to recapitulate the beneficial effect of pregnancy. As compared with pretreatment baseline, relapsing remitting patients treated with oral estriol (8mg/day) demonstrated significant decreases in delayed type hypersensitivity responses to tetanus, interferon‐γ levels in peripheral blood mononuclear cells, and gadolinium enhancing lesion numbers and volumes on monthly cerebral magnetic resonance images. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Based on these results, a larger, placebo‐controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis. This novel treatment strategy of using pregnancy doses of estriol in multiple sclerosis has relevance to other autoimmune diseases that also improve during pregnancy.

Comparison of Multiple Sclerosis Lesions at 1.5 and 3.0 Tesla

ObjectiveTo evaluate the relative sensitivity of MR scanning for multiple sclerosis (MS) at 1.5 Tesla (T) and 3.0 T using identical acquisition conditions, as is typical of multicenter clinical trials. MethodsTwenty-five subjects with MS were scanned at 1.5 T and 3.0 T using fast spin echo, and T1-weighted SPGR with and without gadolinium contrast injections. Image data, blinded to field strength, were analyzed using automated segmentation and lesion counting. ResultsRelative to scanning at 1.5 T, the 3.0 T scans showed a 21% increase in the number of detected contrast enhancing lesions, a 30% increase in enhancing lesion volume and a 10% increase in total lesion volume. DiscussionThe improved detection ability using high-field MR imaging is prominent even when sequence parameters are optimized around the midfield units. Multicenter trials using both 1.5 T and 3.0 T instruments may be affected by these sensitivity differences.

Visual Feature Binding Requires Reentry

Reentrant processing has been proposed as a critical mechanism in feature binding. To test this claim, participants were shown arrays of six pairs of crossed vertical and horizontal bars. In each pair, one bar was white; one was red, green, or blue. Identifying the orientation, but not the color, of the nonwhite bar in the target item required correct binding. Four dots appeared around one of the items (the target) and either disappeared with it or persisted for 300 ms after the array disappeared. This type of trailing mask is thought to interfere with target processing by disrupting reentry. Consistent with the hypothesis that binding requires reentrant processing, the trailing mask significantly reduced the accuracy of orientation but not color judgments. In a control condition, when the white bar was omitted, binding was no longer required, and both color and orientation were accurately reported.

Nonlinearities in rapid event-related fMRI explained by stimulus scaling

Because of well-known nonlinearities in fMRI, responses measured with rapid event-related designs are smaller than responses measured with spaced designs. Surprisingly, no study to date has tested whether rapid designs also change the pattern of responses across different stimulus conditions. Here we report the results of such a test. We measured cortical responses to a flickering checkerboard at different contrasts using rapid and spaced event-related fMRI. The relative magnitude of responses across contrast conditions differed between rapid and spaced designs. Modeling the effect of the rapid design as a scaling of stimulus strength provided a good account of the data. The data were less well fit by a model that scaled the strength of responses. A similar stimulus scaling model has explained effects of neural adaptation, which suggests that adaptation may account for the observed difference between rapid and spaced designs. In a second experiment, we changed the stimulus in ways known to reduce neural adaptation and found much smaller differences between the two designs. Stimulus scaling provides a simple way to account for nonlinearities in event-related fMRI and relate data from rapid designs to data gathered using slower presentation rates.

Temporal components in the parahippocampal place area revealed by human intracerebral recordings.

Many high-level visual regions exhibit complex patterns of stimulus selectivity that make their responses difficult to explain in terms of a single cognitive mechanism. For example, the parahippocampal place area (PPA) responds maximally to environmental scenes during fMRI studies but also responds strongly to nonscene landmark objects, such as buildings, which have a quite different geometric structure. We hypothesized that PPA responses to scenes and buildings might be driven by different underlying mechanisms with different temporal profiles. To test this, we examined broadband γ (50–150 Hz) responses from human intracerebral electroencephalography recordings, a measure that is closely related to population spiking activity. We found that the PPA distinguished scene from nonscene stimuli in ∼80 ms, suggesting the operation of a bottom-up process that encodes scene-specific visual or geometric features. In contrast, the differential PPA response to buildings versus nonbuildings occurred later (∼170 ms) and may reflect a delayed processing of spatial or semantic features definable for both scenes and objects, perhaps incorporating signals from other cortical regions. Although the response preferences of high-level visual regions are usually interpreted in terms of the operation of a single cognitive mechanism, these results suggest that a more complex picture emerges when the dynamics of recognition are considered.

Activity in visual area V4 correlates with surface perception

The neural mechanisms responsible for unifying noncontiguous regions of a visual image into a percept of a single surface remain largely unknown. To investigate these mechanisms, we used a novel stimulus in which local luminance was the only cue for surface segmentation. Subjects viewed an array of small adjoining elements that were randomly assigned as either surface or noise every 100 ms. On each trial, the luminance of surface elements was fixed to a single value and the luminance of noise elements was randomly assigned. As the ratio of surface to noise elements changed, subjects perceived either a surface embedded in noise or noise alone. In three functional magnetic resonance imaging (fMRI) experiments, early visual area V1 responded most strongly during trials with a low surface-to-noise ratio while later areas responded most strongly during trials with a high ratio. Furthermore, even at identical surface-to-noise ratios, responses in area V4 were higher during trials in which the subject perceived a surface than during trials in which the subject did not. Early visual areas did not show this pattern. These results suggest that visual area V4 contains neurons critical for the representation of surfaces.

Delayed effects of attention in visual cortex as measured with fMRI

To what extent does attention modulate neural activity in early visual areas? fMRI measurements of attentional modulation in primary visual cortex (V1) show large effects, while single unit recordings show much smaller ones. This discrepancy suggests that fMRI measures of attention may be inflated, perhaps by activity related to other processes. To test whether effects measured with fMRI actually reflect attentional enhancement, we used a rapid acquisition protocol to determine their timing. Subjects were presented with two stimuli on either side of fixation and were cued to attend one and ignore the other. Attended stimuli showed a greater magnitude of response in V1, but this increase was delayed, by roughly one second in time, relative to both unattended responses and response increases due to boosting stimulus contrast. These results suggest that fMRI measurements of attention may primarily depend upon other processes that take a relatively long time to feed back to V1. Our results demonstrate the importance of using the fine timing information available in the fMRI response.

Top-down influences of spatial attention in visual cortex.

It has been known for decades that neurons in visual cortex respond more vigorously when attention is directed to their receptive field. In recent years, substantial progress has been made toward understanding the neural mechanisms involved in controlling spatial attention. Many studies have shown