Shifted inferior frontal laterality in women with major depressive disorder is related to emotion-processing deficits.

BACKGROUND: Facial emotion perception (FEP) is a critical human skill for successful social interaction, and a substantial body of literature suggests that explicit FEP is disrupted in major depressive disorder (MDD). Prior research suggests that weakness in FEP may be an important phenomenon underlying patterns of emotion-processing challenges in MDD and the disproportionate frequency of MDD in women. Method Women with (n = 24) and without (n = 22) MDD, equivalent in age and education, completed a FEP task during functional magnetic resonance imaging. RESULTS: The MDD group exhibited greater extents of frontal, parietal and subcortical activation compared with the control group during FEP. Activation in the inferior frontal gyrus (IFG) appeared shifted from a left >right pattern observed in healthy women to a bilateral pattern in MDD women. The ratio of left to right suprathreshold IFG voxels in healthy controls was nearly 3:1, whereas in the MDD group, there was a greater percentage of suprathreshold IFG voxels bilaterally, with no leftward bias. In MDD, relatively greater activation in right IFG compared with left IFG (ratio score) was present and predicted FEP accuracy (r = 0.56, p < 0.004), with an inverse relationship observed between FEP and subgenual cingulate activation (r = - 0.46, p = 0.02). CONCLUSIONS: This study links, for the first time, disrupted IFG activation laterality and increased subgenual cingulate activation with deficient FEP in women with MDD, providing an avenue for imaging-to-assessment translational applications in MDD.

Symbolic representations in motor sequence learning.

It has been shown that varying the spatial versus symbolic nature of stimulus presentation and response production, which affects stimulus-response (S-R) mapping requirements, influences the magnitude of implicit sequence learning (Koch and Hoffman, 2000). Here, we evaluated how spatial and symbolic stimuli and responses affect the neural bases of sequence learning. We selectively eliminated the spatial component of stimulus presentation (spatial vs. symbolic), response execution (manual vs. vocal), or both. Fourteen participants performed the alternating serial reaction time task under these conditions in an MRI scanner, with interleaved acquisition to allow for recording of vocal response reaction times. Nine regions of interest (ROIs) were selected to test the hypothesis that the dorsolateral prefrontal cortex (DLPFC) was preferentially engaged for spatially cued conditions and cerebellum lobule HVI, crus I and II were associated with symbolically cued learning. We found that the left cerebellum lobule HVI was selectively recruited for symbolic learning and the percent signal change in this region was correlated with learning magnitude under the symbolic conditions. In contrast, the DLPFC did not exhibit selective activation for learning under spatial conditions. The inferior parietal lobule exhibited increased activation during learning regardless of the condition, supporting its role in forming an abstract representation of learned sequences. These findings reveal different brain networks that are flexibly engaged depending on the conditions of sequence learning.

Working memory for order and the parietal cortex: an event-related functional magnetic resonance imaging study.

Memory for order information has been tied to the frontal lobes, however, parietal activation is observed in many functional neuroimaging studies. Here we report functional magnetic resonance findings from an event-related experiment involving working memory for order. Five letters were presented for storage, followed after a delay by two probe items. Probe items could be separated by zero to three positions in the memory set and subjects had to indicate whether the items were in the correct order. Analyses indicate that activation in left parietal cortex shows a systematic decrease in activation with increasing probe distance. This finding is consistent with an earlier study in which we suggested that parietal cortical regions mediate the representation of order information via magnitude codes.

Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia.

BACKGROUND: Previously we proposed that dorsolateral prefrontal cortex (PFC) supports a specific working memory (WM) subcomponent: the ability to represent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented in such a form that it supports selection of the appropriate behavioral response. Furthermore, we hypothesized that WM deficits in schizophrenia reflect impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medication-naive, first-episode patients with schizophrenia during a WM, task-isolating context processing. METHODS: Fourteen first-episode, medication-naive patients with schizophrenia and 12 controls similar in age, sex, and parental education underwent functional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test. RESULTS: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed intact activation of posterior and inferior PFC. In addition, patients demonstrated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands. CONCLUSIONS: These results demonstrate selectivity in dorsolateral PFC dysfunction among medication-naive first-episode patients with schizophrenia, suggesting that a specific deficit in PFC function is present at illness onset, prior to the administration of medication or the most confounding effects of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impairment in context processing due to a disturbance in dorsolateral PFC function.

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.

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.

Localizing the lexicon for reading aloud:replication of a PET study using fMRI.

Functional magnetic resonance imaging (fMRI) was used to investigate the neural basis of written word recognition in two normal subjects. With a 1.5T scanner and temporal surface coil, T2 gradient echo images were obtained while subjects read words aloud. As a control condition, subjects visualized false font strings and said the word "range' each time such a string appeared. These two conditions were presented in an oscillatory pattern, alternating 30 s of each condition for a total of 4 min. Comparison of the two conditions using cross-correlation demonstrated strong activation in both subjects in the left posterior superior temporal gyrus, near the site predicted for the visual input lexicon by Déjerine and recently demonstrated by positron emission tomography.

A modified electrode cap for EEG recordings in MRI scanners.

A stretchable electrode cap containing 64 electrodes was modified to make it compatible for functional magnetic resonance imaging (fMRI). Metallic components were individually tested for magnetic susceptibility, and those that perturbed a free-swinging magnet or moved in a strong magnetic field were replaced with non-ferromagnetic components. Studies with a phantom indicate that placement of the cables carrying signals from the cap to the amplifiers can significantly affect MR image quality. Anatomical and functional images obtained with the modified electrode cap show modest signal loss, but not enough to substantially interfere with the low-noise images required for fMRI. The cap enables faster application of large arrays of electrodes in conjunction with MRI studies, and thus makes combined EEG/fMRI studies more practical, especially those with EEG source localization as one of the goals.

Multishot rosette trajectories for spectrally selective MR imaging.

In nuclear magnetic resonance, different spectral components often correspond to different chemical species and as such, spectral selectivity can be a valuable tool for diagnostic imaging. In the work presented here, a multishot image acquisition method based upon rosette K-space trajectories has been developed and implemented for spectrally selective magnetic resonance imaging (MRI). Parametric forms for the gradient waveforms and design constraints are derived, and an example multishot gradient design is presented. The spectral behavior for this imaging method is analyzed in a simulation model. For frequencies that are near to the resonant frequency, this method results in a lower intensity, but undistorted image, while for frequencies that are off-resonance by a large amount, the object is incoherently dephased into noise. A method by which acquisitions are delayed by small amounts is introduced to further reduce the residual intensity for off-resonant signals. An image reconstruction method based on convolution gridding, including a correction method for small amounts of magnetic field inhomogeneity, is implemented. Finally, the spectral selectivity is demonstrated in vivo in a study in which both water and lipid images are generated from a single imaging data set.

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.

Parallel data resampling and Fourier inversion by the scan-line method.

Fourier inversion is an efficient method for image reconstruction in a variety of applications, for example, in computed tomography and magnetic resonance imaging. Fourier inversion normally consists of two steps, interpolation of data onto a rectilinear grid, if necessary, and inverse Fourier transformation. Here, the authors present interpolation by the scan-line method, in which the interpolation algorithm is implemented in a form consisting only of row operations and data transposes. The two-dimensional inverse Fourier transformation can also be implemented with only row operations and data transposes. Accordingly, Fourier inversion can easily be implemented on a parallel computer that supports row operations and data transposes on row distributed data. The conditions under which the scan-line implementations are algorithmically equivalent to the original serial computer implementation are described and methods for improving accuracy outside of those conditions are presented. The scan-line algorithm is implemented on the iWarp parallel computer using the Adapt language for parallel image processing. This implementation is applied to magnetic resonance data acquired along radial-lines and spiral trajectories through Fourier transform space.

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.

The anatomy of auditory word processing: individual variability.

This study used functional magnetic resonance imaging (fMRI) to investigate the neural substrate underlying the processing of single words, comparing activation patterns across subjects and within individuals. In a word repetition task, subjects repeated single words aloud with instructions not to move their jaws. In a control condition involving reverse speech, subjects heard a digitally reversed speech token and said aloud the word "crime." The averaged fMRI results showed activation in the left posterior temporal and inferior frontal regions and in the supplementary motor area, similar to previous PET studies. However, the individual subject data revealed variability in the location of the temporal and frontal activation. Although these results support previous imaging studies, demonstrating an averaged localization of auditory word processing in the posterior superior temporal gyrus (STG), they are more consistent with traditional neuropsychological data, which suggest both a typical posterior STG localization and substantial individual variability. By using careful head restraint and movement analysis and correction methods, the present study further demonstrates the feasibility of using overt articulation in fMRI experiments.

Different neural circuits subserve reading before and after therapy for acquired dyslexia.

Rehabilitative measures for stroke are not generally based on basic neurobiological principles, despite evidence from animal models that certain anatomical and pharmacological changes correlate with recovery. In this report, we use functional magnetic resonance imaging (fMRI) to study in vivo human brain reorganization in a right handed patient with an acquired reading disorder from stroke. With phonological dyslexia, her whole-word (lexical) reading approach included inability to read nonwords and poor reading of function words. Following therapy, she was able to read nonwords and function words, and preferred a decompositional (sub-lexical) strategy in general. fMRI was performed during a reading task before and after treatment. Prior to therapy, her main focus of brain activation was in the left angular gyrus (area 39). After therapy, it was instead in the left lingual gyrus (area 18). This result suggests first that it is possible to alter brain physiology with therapy for acquired language disorders, and second, that two reading strategies commonly used in normal reading use distinct neural circuits, possibly reconciling several conflicting neuroimaging studies of reading.

Age differences in symbolic representations of motor sequence learning.

We recently reported that young adults (YA) preferentially recruit cerebellar lobule HVI for symbolic motor sequence learning [3]. Learning magnitude in the symbolic condition was correlated with activation level in lobule HVI. Here, we evaluated age differences in the symbolic representation of motor sequence learning. Fourteen YA and 14 older adults (OA) performed the alternating serial reaction time task (ASRT) under conditions in which the spatial processing component was selectively eliminated from stimulus presentation (spatial versus symbolic), response execution (manual versus vocal), or both. Results showed that OA had reduced learning magnitudes relative to YA. Using the cerebellum lobule HVI as a region-of-interest, we found that OA had significantly lower activation in this region than YA during the symbolic learning conditions (FWE, P<0.05). Similar to YA, OA also showed a significant correlation between learning magnitude and cerebellar activation in the symbolic conditions. These results suggest that although YA and OA recruit similar neural networks during implicit learning, OA under-recruit relevant brain areas which may partially explain their implicit sequence learning deficits.

Magnetic Resonance Imaging Estimation of Longitudinal Relaxation Rate Change (ΔR1) in Dual Gradient Echo Sequences Using an Adaptive Model.

Magnetic Resonance Imaging (MRI) estimation of contrast agent concentration in fast pulse sequences such as Dual Gradient Echo (DGE) imaging is challenging. An Adaptive Neural Network (ANN) was trained with a map of contrast agent concentration estimated by Look-Locker (LL) technique (modified version of inversion recovery imaging) as a gold standard. Using a set of features extracted from DGE MRI data, an ANN was trained to create a voxel based estimator of the time trace of CA concentration. The ANN was trained and tested with the DGE and LL information of six Fisher rats using a K-Fold Cross-Validation (KFCV) method with 60 folds and 10500 samples. The Area Under the Receiver Operator Characteristic Curve (AUROC) for 60 folds was used for training, testing and optimization of the ANN. After training and optimization, the optimal ANN (4:7:5:1) produced maps of CA concentration which were highly correlated (r =0.89, P < 0.0001) with the CA concentration estimated by the LL technique. The estimation made by the ANN had an excellent overall performance (AUROC = 0.870).

Neuroanatomical correlates of motor acquisition and motor transfer.

The acquisition of new motor skills is dependent on task practice. In the case of motor transfer, learning can be facilitated by prior practice of a similar skill. Although a multitude of studies have investigated the brain regions contributing to skill acquisition, the neural bases associated with the savings seen at transfer have yet to be determined. In the current study, we used functional MRI to examine how brain activation differs during acquisition and transfer of a visuomotor adaptation task. Two groups of participants adapted manual aiming movements to three different rotations of the feedback display in a sequential fashion, with a return to baseline display conditions between each rotation. Subjects showed a savings in the rate of adaptation when they had prior adaptive experiences (i.e., positive transfer of learning). This savings was associated with a reduction in activity of brain regions typically recruited early in the adaptation process, including the right inferior frontal gyrus, primary motor cortex, inferior temporal gyrus, and the cerebellum (medial HIII). Moreover, although these regions exhibit activation that is correlated across subjects with the rate of acquisition, the degree of savings at transfer was correlated with activity in the right cingulate gyrus, left superior parietal lobule, right inferior parietal lobule, left middle occipital gyrus, and bilaterally in the cerebellum (HV/VI). The cerebellar activation was in the regions surrounding the posterior superior fissure, which is thought to be the site of storage for acquired internal models. Thus we found that motor transfer is associated with brain activation that typically characterizes late learning and storage. Transfer seems to involve retrieval of a previously formed motor memory, allowing the learner to move more quickly through the early stage of learning.

Bilateral basal ganglia activation associated with sensorimotor adaptation.

Sensorimotor adaptation tasks can be classified into two types. When subjects adapt movements to visual feedback perturbations such as in prism lens adaptation, they perform kinematic adaptations. When subjects adapt movements to force field perturbations such as with robotic manipulanda, they perform kinetic adaptations. Neuroimaging studies have shown basal ganglia involvement in kinetic adaptations, but have found little evidence of basal ganglia involvement in kinematic adaptations, despite reports of deficits in patients with diseases of the basal ganglia, such as Parkinson's and Huntington's disease, in these. In an effort to resolve such apparent discrepancy, we used FMRI to focus on the first few minutes of practice during kinematic adaptation. Human subjects adapted to visuomotor rotations in the context of a joystick aiming task while lying supine in a 3.0 T MRI scanner. As demonstrated previously, early adaptive processes were associated with BOLD activation in the cerebellum and the sensory and motor cortical regions. A novel finding of this study was bilateral basal ganglia activation. This suggests that, at least for early learning, the neural correlates of kinematic adaptation parallel those of other types of skill learning. We observed activation in the right globus pallidus and putamen, along with the right prefrontal, premotor and parietal cortex, which may support spatial cognitive processes of adaptation. We also observed activation in the left globus pallidus and caudate nucleus, along with the left premotor and supplementary motor cortex, which may support the sensorimotor processes of adaptation. These results are the first to demonstrate a clear involvement of basal ganglia activation in this type of kinematic motor adaptation.

Variable-averaging RARE.

The RARE method and its variants have become popular, rapid-imaging alternatives to conventional spin-echo imaging, particularly for long repetition time proton density and T2-weighted imaging. One variant is to generate both early and late echo images using the same pulse sequence, which has the added benefit of reduced edge artifacts and blurring. Described in this paper is variable-averaging RARE (VA-RARE), a method by which independent amounts of averaging can be set for the early and late echo images generated by a single scanning sequence. Through the use of this method, the signal-to-noise ratio (SNR) of late echo images can be improved without unnecessarily increasing the number of averages for the early echo image, thus saving scanning time. Comparisons to various alternatives are made with respect to scanning time and image quality. Phantom measurements and in vivo images are given to demonstrate the effectiveness of VA-RARE as an efficient method for improving SNR of late echo time images in RARE imaging.

Deming, quality and the small medical group administrator.

As administrators, writes Douglas Noll, we can coordinate and implement quality measures affecting our practices and which impact the patient's total medical experience. Unfortunately, many smaller groups cannot hire an outside consultant or single employee whose sole purpose would be to monitor quality. Noll offers several simple practices that administrators can use to improve the quality of service in their groups.