Effect of fructans, prebiotics and fibres on the human gut microbiome assessed by 16S rRNA-based approaches: a review.

The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.

Comparison of Multiple Sclerosis Cortical Lesion Types Detected by Multicontrast 3T and 7T MRI.

BACKGROUND AND PURPOSE: Our aims were the following: 1) to compare multicontrast cortical lesion detection using 3T and 7T MR imaging, 2) to compare cortical lesion type frequency in relapsing-remitting and secondary-progressive MS, and 3) to assess whether detectability is related to the magnetization transfer ratio, an imaging marker sensitive to myelin content. MATERIALS AND METHODS: Multicontrast 3T and 7T MR images from 10 participants with relapsing-remitting MS and 10 with secondary-progressive MS. We used the following 3T contrast sequences: 3D-T1-weighted, quantitative T1, FLAIR, magnetization-transfer, and 2D proton-density- and T2-weighted. We used the following 7T contrast sequences: 3D-T1-weighted, quantitative T1, and 2D-T2*-weighted. RESULTS: Cortical lesion counts at 7T were the following: 720 total cortical lesions, 420 leukocortical lesions (58%), 27 intracortical lesions (4%), and 273 subpial lesions (38%). Cortical lesion counts at 3T were the following: 424 total cortical, 393 leukocortical (93%), zero intracortical, and 31 subpial (7%) lesions. Total, intracortical, and subpial 3T lesion counts were significantly lower than the 7T counts (P < .002). Leukocortical lesion counts were not significantly different between scanners. Total and leukocortical lesion counts were significantly higher in secondary-progressive MS, at 3T and 7T (P ≤ .02). Subpial lesions were significantly higher in secondary-progressive MS at 7T (P = .006). The magnetization transfer ratio values of leukocortical lesions visible on both scanners were significantly lower than the magnetization transfer ratio values of leukocortical lesions visible only at 3T. No significant difference was found in magnetization transfer ratio values between subpial lesions visible only at 7T and subpial lesions visible on both 3T and 7T. CONCLUSIONS: Detection of leukocortical lesions at 3T is comparable with that at 7T MR imaging. Imaging at 3T is less sensitive to intracortical and subpial lesions. Leukocortical lesions not visible on 7T T2*-weighted MRI may be associated with less demyelination than those that are visible. Detectability of subpial lesions does not appear to be related to the degree of demyelination.

Morphology-Specific Discrimination between MS White Matter Lesions and Benign White Matter Hyperintensities Using Ultra-High-Field MRI.

BACKGROUND AND PURPOSE: Recently published North American Imaging in Multiple Sclerosis guidelines call for derivation of a specific radiologic definition of MS WM lesions and mimics. The purpose of this study was to use SWI and magnetization-prepared FLAIR images for sensitive differentiation of MS from benign WM lesions using the morphologic characteristics of WM lesions. MATERIALS AND METHODS: Seventeen patients with relapsing-remitting MS and 18 healthy control subjects were enrolled retrospectively. For each subject, FLAIR and multiecho gradient-echo images were acquired using 7T MR imaging. Optimized postprocessing was used to generate single-slice SWI of cerebral veins. SWI/FLAIR images were registered, and 3 trained readers performed lesion assessment. Morphology, location of lesions, and the time required for assessment were recorded. Analyses were performed on 3 different pools: 1) lesions of >3 mm, 2) nonconfluent lesions of >3 mm, and 3) nonconfluent lesions of >3 mm with no or a single central vein. RESULTS: The SWI/FLAIR acquisition and processing protocol enabled effective assessment of central veins and hypointense rims in WM lesions. Assessment of nonconfluent lesions with ≥1 central vein enabled the most specific and sensitive differentiation of patients with MS from controls. A threshold of 67% perivenous WM lesions separated patients with MS from controls with a sensitivity of 94% and specificity of 100%. Lesion assessment took an average of 12 minutes 10 seconds and 4 minutes 33 seconds for patients with MS and control subjects, respectively. CONCLUSIONS: Nonconfluent lesions of >3 mm with ≥1 central vein were the most sensitive and specific differentiators between patients with MS and control subjects.

Proliferative leukoplakia: Proposed new clinical diagnostic criteria.

OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathological standpoint and suggest an updated classification. SUBJECTS AND METHODS: Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathological features and malignant transformation (MT). RESULTS: There were 42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous and multisite and non-contiguous lesions comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathological diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range: 1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

Initial Investigation into Microbleeds and White Matter Signal Changes following Radiotherapy for Low-Grade and Benign Brain Tumors Using Ultra-High-Field MRI Techniques.

BACKGROUND AND PURPOSE: External beam radiation therapy is a common treatment for many brain neoplasms. While external beam radiation therapy adheres to dose limits to protect the uninvolved brain, areas of high dose to normal tissue still occur. Patients treated with chemoradiotherapy can have adverse effects such as microbleeds and radiation necrosis, but few studies exist of patients treated without chemotherapy. MATERIALS AND METHODS: Ten patients were treated for low-grade or benign neoplasms with external beam radiation therapy only and scanned within 12-36 months following treatment with a 7T MR imaging scanner. A multiecho gradient-echo sequence was acquired and postprocessed into SWI, quantitative susceptibility mapping, and apparent transverse relaxation maps. Six patients returned for follow-up imaging approximately 18 months following their first research scan and were imaged with the same techniques. RESULTS: At the first visit, 7/10 patients had microbleeds evident on SWI, quantitative susceptibility mapping, and apparent transverse relaxation. All microbleeds were within a dose region of >45 Gy. Additionally, 4/10 patients had asymptomatic WM signal changes evident on standard imaging. Further analysis with our technique revealed that these lesions were venocentric, suggestive of a neuroinflammatory process. CONCLUSIONS: There exists a potential for microbleeds in patients treated with external beam radiation therapy without chemotherapy. This finding is of clinical relevance because it could be a precursor of future neurovascular disease and indicates that additional care should be taken when using therapies such as anticoagulants. Additionally, the appearance of venocentric WM lesions could be suggestive of a neuroinflammatory mechanism that has been suggested in diseases such as MS. Both findings merit further investigation in a larger population set.

Highcor: a novel data-driven regressor identification method for BOLD fMRI.

A data-driven regressor selection technique for reducing physiological noise in BOLD fMRI is presented that capitalizes on additional information contained in the phase of the signal time-course. This method, termed highcor, identifies a set of suspect voxels by selecting based on high temporal correlation between the magnitude and phase components of the time-course. Temporal regressors are generated from principal component analysis of this voxel set. Regressor spectral content is investigated with high temporal resolution datasets, and filtering performance is demonstrated. The technique is benchmarked against compcor, an increasingly popular data driven technique. Highcor was found to select a unique set of physiological noise source voxels, and identification of confound and physiologically related signals was robust even at slow temporal sampling rates. Filtering using regressors derived from compcor and highcor voxels resulted in reductions in overall temporal standard deviation in cortical areas of 16.1%±3.1%, and 18.1%±3.8%, (mean±sd.) as measured over 36 BOLD fMRI datasets that featured an anti-saccade task. An approach combining both methods resulted in further reductions of temporal standard deviations by 31.4%±3.8%. In these regions, mean temporal SNR values were improved from 38.7±3.4 to 47.7±3.7 (cc), 49.2±2.2 (hc), and 57.8±2.3 (hc+cc). tSNR increases from data-driven filtering translated into some associated improvements in overall detection of task in the sample datasets.

Comparison of multiecho postprocessing schemes for SWI with use of linear and nonlinear mask functions.

BACKGROUND AND PURPOSE: SWI is an MR technique conventionally implemented with single-echo gradient-echo data. The purpose of this study was to compare single-echo SWI processing and 2 multiecho SWI processing schemes: postaverage, where an SWI image is created for each echo and then averaged to create a single volume; and frequency-based, where a SWI image is generated from an average frequency image. Linear and nonlinear mask functions were investigated for all 3 processing schemes. MATERIALS AND METHODS: Comprehensive optimizations were performed. Single and multigradient-echo data were acquired at 3T in 10 volunteers. Contrast-to-noise ratio was measured in various structures. Visibilities of the same structures were ranked in different SWI images by trained raters. RESULTS: When image evaluation was based on measurements of contrast-to-noise ratio, the nonlinear mask and frequency-based scheme were superior. However, when image evaluation was based on ranks of qualitative visibility, the linear mask and postaverage scheme were superior. Although the nonlinear mask and frequency-based scheme allow increased contrast of paramagnetic perturbers such as the globus pallidus, periventricular veins, red nucleus, and subthalamic nucleus, they do not necessarily increase the information content of the image; rather, they result in a harsh contrast that is visually unpleasing to radiologists and wherein more subtle structure is relatively less apparent. CONCLUSIONS: Linearly masked postaverage SWI is the recommended implementation of multiecho SWI for radiologic use; however, nonlinearly masked frequency-based SWI may have use in computer-based segmentation or registration.

Poster - Thur Eve - 13: Quantifying specific absorption rate of shielded RF coils through electromagnetic simulations for 7-T MRI.

Ultra-high field MRI has many advantages such as increasing spatial resolution and exploiting contrast never before seen in-vivo. This contrast has been shown to be beneficial for many applications such as monitoring early and late effect to radiation therapy and transient changes during disease to name a few. However, at higher field strengths the RF wave, needed to for transmitting and receiving signal, approaches that of the head. This leads to constructive and deconstructive interference and a non -uniform flip angle over the volume being imaged. A transmit or transceive RF surface coil arrays is currently a method of choice to overcome this problem; however, mutual inductance between elements poses a significant challenge for the designer. A method to decouple elements in such an array is by using circumferential shielding; however, the potential benefits and/or disadvantages have not been investigated. This abstract primarily focuses on understanding power deposition - measured through Specific Absorption Rate - in the sample using circumferentially shielded RF coils. Various geometries of circumferentially shielded coils are explored to determine the behaviour of shield width and its effect on required transmit power and power deposition to the sample. Our results indicate that there is an optimization on shield width depending on the imaging depth. Additionally, the circumferential shield focuses the field more than unshielded coils, meaning that slight SAR may even be lower for circumferential shielded RF coils in array.

A cradle-shaped gradient coil to expand the clear-bore width of an animal MRI scanner.

The never ending quest for higher magnetic field strengths in MRI and MRS has led to small and medium bore scanners at 9.4 T and above for both human and animal use; however, these bore diameters restrict the size of object that can be accommodated when using a conventional gradient coil. By replacing a cylindrical gradient-coil insert with a single-sided gradient coil, the scanner's functionality can be extended to include localized imaging of wider samples. As a prototype, a three-axis, cradle-shaped gradient coil was designed, fabricated and implemented in a 9.4 T animal MRI scanner. Since gradient fields are required only to be monotonic over the desired field of view, the cradle gradient coil was designed to produce high gradient efficiencies (up to 2.25 mT m(-1) A(-1) over a 5 cm imaging region) at the expense of gradient linearity. A dedicated three-dimensional algorithm was developed to correct the resultant image distortion. Preliminary images of a grid phantom and a mouse demonstrated the fidelity of the algorithm in correcting image distortion of greater than 200%. Eddy currents were measured along each gradient axis. A large 65.2 (Hz mT(-1) m) B(0) eddy current was produced by the y-axis, suggesting potential limitations of single-sided gradient coils.

Functional MRI of oropharyngeal air-pulse stimulation.

Although the posterior oral cavity and oropharynx play a major role in swallowing, their central representation is poorly understood. High-field functional magnetic resonance imaging of the brain was used to study the central processing of brief air-pulses, delivered to the peritonsillar region of the lateral oropharynx, in six healthy adults. Bilateral air-pulse stimulation was associated with the activation of a bilateral network including the primary somatosensory cortex and the thalamus, classic motor areas (primary motor cortex, supplementary motor area, cingulate motor areas), and polymodal areas (including the insula and frontal cortex). These results suggest that oropharyngeal stimulation can activate a bilaterally distributed cortical network that overlaps cortical regions previously implicated in oral and pharyngeal sensorimotor functions such as tongue movement, mastication, and swallowing. The present study also demonstrates the utility of air-pulse stimulation in investigating oropharyngeal sensorimotor processing in functional brain imaging experiments.

Perirhinal and hippocampal contributions to visual recognition memory can be distinguished from those of occipito-temporal structures based on conscious awareness of prior occurrence.

The ability of humans to distinguish consciously between new and previously encountered objects can be probed with visual recognition memory tasks that require explicit old-new discriminations. Medial temporal-lobe (MTL) lesions impair performance on such tasks. Within the MTL, both perirhinal cortex and the hippocampus have been implicated. Cognitive processes can also be affected by past object encounters in the absence of conscious recognition, as in repetition priming tasks. Past functional neuroimaging findings in healthy individuals suggest that even in tasks that require conscious recognition decisions for visual stimuli, posterior cortical structures in the ventral visual pathway distinguish between old and new objects at a nonconscious level. Conclusive evidence that differentiates the neural underpinnings of conscious from nonconscious processes in recognition memory, however, is still missing. In particular, functional magnetic resonance imaging (fMRI) findings for the MTL have been inconsistent towards this end. In the present fMRI study, we tested whether perirhinal and hippocampal contributions to recognition memory can be distinguished from those of occipito-temporal structures in the ventral visual pathway based on the participants' reported conscious awareness of prior occurrence. Images of objects with a large degree of feature overlap served as stimuli; they were selected to ensure an involvement of perirhinal cortex in the present recognition task, based on evidence from past lesion-based research. We found that both perirhinal cortex and occipito-temporal cortex showed a differential old-new response that reflected a repetition-related decrease in activity (i.e., new > old). Whereas in perirhinal cortex this decrease was observed with respect to whether subjects reported objects to be old or new, irrespective of the true item status, in occipito-temporal cortex it occurred in relation to whether objects were truly old or new, irrespective of the participants' conscious reports. Hippocampal responses differed in their exact pattern from those of perirhinal cortex, but were also related to the conscious recognition reports. These results indicate that both perirhinal and hippocampal contributions can be distinguished from those of occipito-temporal structures in the ventral visual pathway based on the participants' reported conscious awareness of prior occurrence.

Comparison of memory- and visually guided saccades using event-related fMRI.

Previous functional imaging studies have shown an increased hemodynamic signal in several cortical areas when subjects perform memory-guided saccades than that when they perform visually guided saccades using blocked trial designs. It is unknown, however, whether this difference results from sensory processes associated with stimulus presentation, from processes occurring during the delay period before saccade generation, or from an increased motor signal for memory-guided saccades. We conducted fMRI using an event-related paradigm that separated stimulus-related, delay-related, and saccade-related activity. Subjects initially fixated a central cross, whose color indicated whether the trial was a memory- or a visually guided trial. A peripheral stimulus was then flashed at one of 4 possible locations. On memory-guided trials, subjects had to remember this location for the subsequent saccade, whereas the stimulus was a distractor on visually guided trials. Fixation cross disappearance after a delay period was the signal either to generate a memory-guided saccade or to look at a visual stimulus that was flashed on visually guided trials. We found slightly greater stimulus-related activation for visually guided trials in 3 right prefrontal regions and right rostral intraparietal sulcus (IPS). Memory-guided trials evoked greater delay-related activity in right posterior inferior frontal gyrus, right medial frontal eye field, bilateral supplementary eye field, right rostral IPS, and right ventral IPS but not in middle frontal gyrus. Right precentral gyrus and right rostral IPS exhibited greater saccade-related activation on memory-guided trials. We conclude that activation differences revealed by previous blocked experiments have different sources in different areas and that cortical saccade regions exhibit delay-related activation differences.

Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation.

OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Distinguishing subregions of the human MT+ complex using visual fields and pursuit eye movements.

In humans, functional imaging studies have demonstrated a homologue of the macaque motion complex, MT+ [suggested to contain both middle temporal (MT) and medial superior temporal (MST)], in the ascending limb of the inferior temporal sulcus. In the macaque monkey, motion-sensitive areas MT and MST are adjacent in the superior temporal sulcus. Electrophysiological research has demonstrated that while MT receptive fields primarily encode the contralateral visual field, MST dorsal (MSTd) receptive fields extend well into the ipsilateral visual field. Additionally, macaque MST has been shown to receive extraretinal smooth-pursuit eye-movement signals, whereas MT does not. We used functional magnetic resonance imaging (fMRI) and the neural properties that had been observed in monkeys to distinguish putative human areas MT from MST. Optic flow stimuli placed in the full field, or contralateral field only, produced a large cluster of functional activation in our subjects consistent with previous reports of human area MT+. Ipsilateral optic flow stimuli limited to the peripheral retina produced activation only in an anterior subsection of the MT+ complex, likely corresponding to putative MSTd. During visual pursuit of a single target, a large portion of the MT+ complex was activated. However, during nonvisual pursuit, only the anterolateral portion of the MT+ complex was activated. This subsection of the MT+ cluster could correspond to putative MSTl (lateral). In summary, we observed three distinct subregions of the human MT+ complex that were arranged in a manner similar to that seen in the monkey.

Imaging function in the working brain with fMRI.

The intrinsic flexibility of functional magnetic resonance imaging has allowed ever more innovative neuroscience applications. New acquisition and analysis techniques have contributed to improvements in detection sensitivity, as well as spatial and temporal resolution. Furthermore, by considering the dynamic evolution of the active brain areas in a network, computational models are making the first steps towards linking brain and mind.

Brief visual stimulation allows mapping of ocular dominance in visual cortex using fMRI.

We have used high spatial resolution (0.55 mm x 0.55 mm) functional magnetic resonance imaging (fMRI) to show that when stimulus duration is brief (<6 sec), the hyperoxic hemodynamic response to neural activity can resolve the columnar architecture of ocular dominance within the primary visual cortex of humans. Our fMRI maps of ocular dominance columns are strikingly similar in appearance, size, and orientation to those reported in the literature using optical imaging of intrinsic signals (OIS) in animal cortex and histology of post-mortem human specimens. We also demonstrate that under brief visual stimulation conditions, our results are consistent over repeated experiments. This is not the case for long duration stimuli (> or = 10 sec). A simulated random data set exhibited the same response properties as maps obtained when using these prolonged visual stimuli. Our results suggest that brief visual stimulation is essential for fMRI to successfully resolve ocular dominance columns using the hyperoxic phase of the hemodynamic response to neural activity at our prescribed spatial resolution.

Cerebral cortical representation of automatic and volitional swallowing in humans.

Although the cerebral cortex has been implicated in the control of swallowing, the functional organization of the human cortical swallowing representation has not been fully documented. Therefore, the present study determined the cortical representation of swallowing in fourteen healthy right-handed female subjects using single-event-related functional magnetic resonance imaging (fMRI). Subjects were scanned during three swallowing activation tasks: a naïve saliva swallow, a voluntary saliva swallow, and a water bolus swallow. Swallow-related laryngeal movement was recorded simultaneously from the output of a bellows positioned over the thyroid cartilage. Statistical maps were generated by computing the difference between the magnitude of the voxel time course during 1) a single swallowing trial and 2) the corresponding control period. Automatic and volitional swallowing produced activation within several common cortical regions, the most prominent and consistent being located within the lateral precentral gyrus, lateral postcentral gyrus, and right insula. Activation foci within the superior temporal gyrus, middle and inferior frontal gyri, and frontal operculum also were identified for all swallowing tasks. In contrast, activation of the caudal anterior cingulate cortex was significantly more likely in association with the voluntary saliva swallow and water bolus swallow than the naïve swallow. These findings support the view that, in addition to known brain stem areas, human swallowing is represented within a number of spatially and functionally distinct cortical loci which may participate differentially in the regulation of swallowing. Activation of the insula was significantly lateralized to the right hemisphere for the voluntary saliva swallow, suggesting a functional hemispheric dominance of the insula for the processing of swallowing.

An fMRI study of the selective activation of human extrastriate form vision areas by radial and concentric gratings.

The ventral form vision pathway of the primate brain comprises a sequence of areas that include V1, V2, V4 and the inferior temporal cortex (IT) [1]. Although contour extraction in the V1 area and responses to complex images, such as faces, in the IT have been studied extensively, much less is known about shape extraction at intermediate cortical levels such as V4. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that the human V4 is more strongly activated by concentric and radial patterns than by conventional sinusoidal gratings. This is consistent with global pooling of local V1 orientations to extract concentric and radial shape information in V4. Furthermore, concentric patterns were found to be effective in activating the fusiform face area. These findings support recent psychophysical [2,3] and physiological [4,5] data indicating that analysis of concentric and radial structure represents an important aspect of processing at intermediate levels of form vision.

Spectroscopic lineshape correction by QUECC: combined QUALITY deconvolution and eddy current correction.

Lineshape distortion due to residual eddy currents and magnetic field inhomogeneities are often present in short echo time (1)H spectroscopic data. Lineshape correction methods such as QUALITY deconvolution and eddy current correction (ECC), which use a separate reference spectrum for lineshape correction, have shortcomings when unsuppressed water is chosen as the reference. This paper outlines a method of integrating both techniques to overcome these limitations while still using unsuppressed water as the reference signal. This hybrid lineshape correction technique (QUECC) is demonstrated in vivo using stimulated echo acquisition mode (STEAM) localized 4.0 Tesla data. Metabolite quantification precision increased by an average of 7%-46% compared to QUALITY deconvolution (depending on filtering) and by an average of 6% compared to ECC.

BOLD fMRI response of early visual areas to perceived contrast in human amblyopia.

In this study, we used a temporal two-alternative forced choice psychophysical procedure to measure the observer's perception of a 22% physical contrast grating for each eye as a function of spatial frequency in four subjects with unilateral amblyopia and in six subjects with normal vision. Contrast thresholds were also measured using a standard staircase method. Additionally, blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure the neuronal response within early visual cortical areas to monocular presentations of the same 22% physical contrast gratings as a function of spatial frequency. For all six subjects with normal vision and for three subjects with amblyopia, the psychophysically measured perception of 22% contrast as a function of spatial frequency was the same for both eyes. Threshold contrast, however, was elevated for the amblyopic eye for all subjects, as expected. The magnitude of the fMRI response to 22% physical contrast within "activated" voxels was the same for each eye as a function of spatial frequency, regardless of the presence of amblyopia. However, there were always fewer "activated" fMRI voxels during amblyopic stimulation than during normal eye stimulation. These results are consistent with the hypotheses that contrast thresholds are elevated in amblyopia because fewer neurons are responsive during amblyopic stimulation, and that the average firing rate of the responsive neurons, which reflects the perception of contrast, is unaffected in amblyopia.