Douglas C. Noll

Dissociating working memory from task difficulty in human prefrontal cortex

A functional magnetic resonance imaging (fMRI) study was conducted to determine whether prefrontal cortex (PFC) increases activity in working memory (WM) tasks as a specific result of the demands placed on WM, or to other processes affected by the greater difficulty of such tasks. Increased activity in dorsolateral PFC (DLPFC) was observed during task conditions that placed demands on active maintenance (long retention interval) relative to control conditions matched for difficulty. Furthermore, the activity was sustained over the entire retention interval and did not increase when task difficulty was manipulated independently of WM requirements. This contrasted with the transient increases in activity observed in the anterior cingulate, and other regions of frontal cortex, in response to increased task difficulty but not WM demands. Thus, this study established a double-dissociation between regions responsive to WM versus task difficulty, indicating a specific involvement of DLPFC and related structures in WM function.

Activation of the prefrontal cortex in a nonspatial working memory task with functional MRI

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of the prefrontal cortex during performance of subjects in a nonspatial working memory task. Subjects observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Functional scanning was performed using a newly developed spiral scan image acquisition technique that provides high‐resolution, multislice scanning at approximately five times the rate usually possible on conventional equipment (an average of one image per second). Using these methods, activation of the middle and inferior frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Effect sizes (2–4%) closely approximated those that have been observed within primary sensory and motor cortices using similar fMRI techniques. Furthermore, activation increased and decreased with a time course that was highly consistent with the task manipulations. These findings corroborate the results of positron emission tomography studies, which suggest that the prefrontal cortex is engaged by tasks that rely on working memory. Furthermore, they demonstrate the applicability of newly developed fMRI techniques using conventional scanners to study the associative cortex in individual subjects.

Homodyne detection in magnetic resonance imaging

Magnetic detection of complex images in magnetic resonance imaging (MRI) is immune to the effects of incidental phase variations, although in some applications information is lost or images are degraded. It is suggested that synchronous detection or demodulation can be used in MRI systems in place of magnitude detection to provide complete suppression of undesired quadrature components, to preserve polarity and phase information, and to eliminate the biases and reduction in signal-to-noise ratio (SNR) and contrast in low SNR images. The incidental phase variations in an image are removed through the use of a homodyne demodulation reference, which is derived from the image or the object itself. Synchronous homodyne detection has been applied to the detection of low SNR images, the reconstruction of partial k-space images, the simultaneous detection of water and lipid signals in quadrature, and the preservation of polarity in inversion-recovery images.

Activation of Prefrontal Cortex in Children during a Nonspatial Working Memory Task with Functional MRI

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed.

Nonlinear Aspects of the BOLD Response in Functional MRI

Functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) contrast has progressed rapidly and is commonly used to study function in many regions of the human brain. This paper introduces a method for characterizing the linear and nonlinear properties of the hemodynamic response. Such characterization is essential for accurate prediction of time-course behavior. Linearity of the BOLD response was examined in the primary visual cortex for manipulations of the stimulus amplitude and duration. Stimuli of 1, 2, 4, and 8 s duration (80% contrast) and 10, 20, 40, and 80% contrast (4 s duration) were used to test the hemodynamic response. Superposition of the obtained responses was performed to determine if the BOLD response is nonlinear. The nonlinear characteristics of the BOLD response were assessed using a Laplacian linear system model cascaded with a broadening function. Discrepancies between the model and the observed response provide an indirect measure of the nonlinearity of the response. The Laplacian linear system remained constant within subjects so the broadening function can be used to absorb nonlinearities in the response. The results show that visual stimulation under 4 s in duration and less than 40% contrast yield strong nonlinear responses.

Spatial Domain Method for the Design of RF Pulses in Multicoil Parallel Excitation

Parallel excitation has been introduced as a means of accelerating multidimensional, spatially‐selective excitation using multiple transmit coils, each driven by a unique RF pulse. Previous approaches to RF pulse design in parallel excitation were either formulated in the frequency domain or restricted to echo‐planar trajectories, or both. This paper presents an approach that is formulated as a quadratic optimization problem in the spatial domain and allows the use of arbitrary k‐space trajectories. Compared to frequency domain approaches, the new design method has some important advantages. It allows for the specification of a region of interest (ROI), which improves excitation accuracy at high speedup factors. It allows for magnetic field inhomogeneity compensation during excitation. Regularization may be used to control integrated and peak pulse power. The effects of Bloch equation nonlinearity on the large‐tip‐angle excitation error of RF pulses designed with the method are investigated, and the utility of Tikhonov regularization in mitigating this error is demonstrated. Magn Reson Med, 2006.

A Developmental Functional MRI Study of Spatial Working Memory

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

Fast, iterative image reconstruction for MRI in the presence of field inhomogeneities

In magnetic resonance imaging, magnetic field inhomogeneities cause distortions in images that are reconstructed by conventional fast Fourier transform (FFT) methods. Several noniterative image reconstruction methods are used currently to compensate for field inhomogeneities, but these methods assume that the field map that characterizes the off-resonance frequencies is spatially smooth. Recently, iterative methods have been proposed that can circumvent this assumption and provide improved compensation for off-resonance effects. However, straightforward implementations of such iterative methods suffer from inconveniently long computation times. This paper describes a tool for accelerating iterative reconstruction of field-corrected MR images: a novel time-segmented approximation to the MR signal equation. We use a min-max formulation to derive the temporal interpolator. Speedups of around 60 were achieved by combining this temporal interpolator with a nonuniform fast Fourier transform with normalized root mean squared approximation errors of 0.07%. The proposed method provides fast, accurate, field-corrected image reconstruction even when the field map is not smooth.

Anterior Cingulate and the Monitoring of Response Conflict: Evidence from an fMRI Study of Overt Verb Generation

Studies of a range of higher cognitive functions consistently activate a region of anterior cingulate cortex (ACC), typically posterior to the genu and superior to the corpus collosum. In particular, this ACC region appears to be active in task situations where there is a need to override a prepotent response tendency, when responding is underdetermined, and when errors are made. We have hypothesized that the function of this ACC region is to monitor for the presence of crosstalk or competition between incompatible responses. In prior work, we provided initial support for this hypothesis, demonstrating ACC activity in the same region both during error trials and during correct trials in task conditions designed to elicit greater response competition. In the present study, we extend our testing of this hypothesis to task situations involving underdetermined responding. Specifically, 14 healthy control subjects performed a verb-generation task during event-related functional magnetic resonance imaging (fMRI), with the on-line acquisition of overt verbal responses. The results demonstrated that the ACC, and only the ACC, was more active in a series of task conditions that elicited competition among alternative responses. These conditions included a greater ACC response to: (1) Nouns categorized as low vs. high constraint (i.e., during a norming study, multiple verbs were produced with equal frequency vs. a single verb that produced much more frequently than any other); (2) the production of verbs that were weak associates, rather than, strong associates of particular nouns; and (3) the production of verbs that were weak associates for nouns categorized as high constraint. We discuss the implication of these results for understanding the role that the ACC plays in human cognition.

A homogeneity correction method for magnetic resonance imaging with time-varying gradients

When time-varying gradients are used for imaging, the off-resonance behavior does not just cause geometric distortion as is the case with spin-warp imaging, but changes the shape of the impulse response and causes blurring. This effect is well known for projection reconstruction and spiral k-space scanning sequences. The authors introduce a reconstruction and homogeneity correction method to correct for the zeroth order effects of inhomogeneity using prior knowledge of the inhomogeneity. In this method, the data are segmented according to collection time, reconstructed using some fast, linear algorithm, correlated for inhomogeneity, and then superimposed to yield a homogeneity corrected image. This segmented method is compared to a conjugate phase reconstruction in terms of degree of correction and execution time. The authors apply this method to in vivo images using projection-reconstruction and spiral-scan sequences.