John M. Ollinger

A Common Network of Functional Areas for Attention and Eye Movements

Functional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level.

Positron-emission tomography

We review positron-emission tomography (PET), which has inherent advantages that avoid the shortcomings of other nuclear medicine imaging methods. PET image reconstruction methods with origins in signal and image processing are discussed, including the potential problems of these methods. A summary of statistical image reconstruction methods, which can yield improved image quality, is also presented.

Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study.

BACKGROUND The amygdala has a central role in processing emotions, particularly fear. During functional magnetic resonance imaging (fMRI) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces. METHODS We applied the masked faces paradigm to patients with major depression (n = 11) and matched control subjects (n = 11) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment. Data were analyzed using left and right amygdala a priori regions of interest, in an analysis of variance block analysis and random effects model. RESULTS Depressed patients had exaggerated left amygdala activation to all faces, greater for fearful faces. Right amygdala did not differ from control subjects. Following treatment, patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces. Control subjects had no differences between the two scanning sessions. CONCLUSIONS Depressed patients have left amygdala hyperarousal, even when processing stimuli outside conscious awareness. Increased amygdala activation normalizes with antidepressant treatment.

Characterizing the Hemodynamic Response: Effects of Presentation Rate, Sampling Procedure, and the Possibility of Ordering Brain Activity Based on Relative Timing

Rapid-presentation event-related functional MRI (ER-fMRI) allows neuroimaging methods based on hemodynamics to employ behavioral task paradigms typical of cognitive settings. However, the sluggishness of the hemodynamic response and its variance provide constraints on how ER-fMRI can be applied. In a series of two studies, estimates of the hemodynamic response in or near the primary visual and motor cortices were compared across various paradigms and sampling procedures to determine the limits of ER-fMRI procedures and, more generally, to describe the behavior of the hemodynamic response. The temporal profile of the hemodynamic response was estimated across overlapping events by solving a set of linear equations within the general linear model. No assumptions about the shape were made in solving the equations. Following estimation of the temporal profile, the amplitude and timing were modeled using a gamma function. Results indicated that (1) within a region, for a given subject, estimation of the hemodynamic response is extremely stable for both amplitude (r(2) = 0.98) and time to peak (r(2) = 0.95), from one series of measurements to the next, and slightly less stable for estimation of time to onset (r(2) = 0.60). (2) As the trial presentation rate changed (from those spaced 20 s apart to temporally overlapping trials), the hemodynamic response amplitude showed a small, but significant, decrease. Trial onsets spaced (on average) 5 s apart showed a 17-25% reduction in amplitude compared to those spaced 20 s apart. Power analysis indicated that the increased number of trials at fast rates outweighs this decrease in amplitude if statistically reliable response detection is the goal. (3) Knowledge of the amplitude and timing of the hemodynamic response in one region failed to predict those properties in another region, even for within-subject comparisons. (4) Across subjects, the amplitude of the response showed no significant correlation with timing of the response, for either time-to-onset or time-to-peak estimates. (5) The within-region stability of the response was sufficient to allow offsets in the timing of the response to be detected that were under a second, placing event-related fMRI methods in a position to answer questions about the change in relative timing between regions.

Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding

The involvement of dorsal frontal and medial temporal regions during the encoding of words, namable line-drawn objects, and unfamiliar faces was examined using functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations were observed in each instance, but lateralization was strongly dependent on the materials being encoded. Encoding of words produced left-lateralized dorsal frontal activation, whereas encoding of unfamiliar faces produced homologous right-lateralized activation. Encoding of namable objects, which are amenable to both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation. A similar pattern of results was observed in the medial temporal lobe. These results indicate that regions in both hemispheres underlie human long-term memory encoding, and these regions can be engaged differentially according to the nature of the material being encoded.

Separating Processes within a Trial in Event-Related Functional MRI

Many cognitive processes occur on time scales that can significantly affect the shape of the blood oxygenation level-dependent (BOLD) response in event-related functional MRI. This shape can be estimated from event related designs, even if these processes occur in a fixed temporal sequence (J. M. Ollinger, G. L. Shulman, and M. Corbetta. 2001. NeuroImage 13: 210-217). Several important considerations come into play when interpreting these time courses. First, in single subjects, correlations among neighboring time points give the noise a smooth appearance that can be confused with changes in the BOLD response. Second, the variance and degree of correlation among estimated time courses are strongly influenced by the timing of the experimental design. Simulations show that optimal results are obtained if the intertrial intervals are as short as possible, if they follow an exponential distribution with at least three distinct values, and if 40% of the trials are partial trials. These results are not particularly sensitive to the fraction of partial trials, so accurate estimation of time courses can be obtained with lower percentages of partial trials (20-25%). Third, statistical maps can be formed from F statistics computed with the extra sum of square principle or by t statistics computed from the cross-correlation of the time courses with a model for the hemodynamic response. The latter method relies on an accurate model for the hemodynamic response. The most robust model among those tested was a single gamma function. Finally, the power spectrum of the measured BOLD signal in rapid event-related paradigms is similar to that of the noise. Nevertheless, high-pass filtering is desirable if the appropriate model for the hemodynamic response is used.

Separating processes within a trial in event-related functional MRI I. The Method.

Many behavioral paradigms involve temporally overlapping sensory, cognitive, and motor components within a single trial. The complex interplay among these factors makes it desirable to separate the components of the total response without assumptions about shape of the underlying hemodynamic response. We present a method that does this. Four conditions were studied in four subjects to validate the method. Two conditions involved rapid event-related studies, one with a low-contrast (5%) flickering checkerboard and another with a high-contrast (95%) checkerboard. In the third condition, the same high-contrast checkerboard was presented with widely spaced trials. Finally, multicomponent trials were formed from temporally adjacent low-contrast and high-contrast stimuli. These trials were presented as a rapid event-related study. Low-contrast stimuli presented in isolation (partial trials) made it possible to uniquely estimate both the low-contrast and high-contrast responses. These estimated responses matched those measured in the first three conditions, thereby validating the method. Nonlinear interactions between adjacent low-contrast and high-contrast responses were shown to be significant but weak in two of the four subjects.

Human brain activity time-locked to perceptual event boundaries

Temporal structure has a major role in human understanding of everyday events. Observers are able to segment ongoing activity into temporal parts and sub-parts that are reliable, meaningful and correlated with ecologically relevant features of the action. Here we present evidence that a network of brain regions is tuned to perceptually salient event boundaries, both during intentional event segmentation and during naive passive viewing of events. Activity within this network may provide a basis for parsing the temporally evolving environment into meaningful units.

Direct Comparison of Prefrontal Cortex Regions Engaged by Working and Long-Term Memory Tasks

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

The Emotional Modulation of Cognitive Processing: An fMRI Study

The functional neuroanatomy of visual processing of surface features of emotionally valenced pictorial stimuli was examined in normal human subjects using functional magnetic resonance imaging (fMRI). Pictorial stimuli were of two types: emotionally negative and neutral pictures. Task performance was slower for the negatively valenced than for the neutral pictures. Significant blood oxygen level dependent (BOLD) increases occurred in the medial and dorsolateral prefrontal cortex, midbrain, substantia innominata, and/or amygdala, and in the posterior cortical visual areas for both stimulus types. Increases were greater for the negatively valenced stimuli. While there was a small but significant BOLD decrease in the subgenual prefrontal cortex, which was larger in response to the negatively valenced pictures, there was an almost complete absence of other decreases prominently seen during the performance of demanding cognitive tasks [Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. Journal of Cognitive Neuroscience, 9, 648-663]. These results provide evidence that the emotional valence and arousing nature of stimuli used during the performance of an attention-demanding cognitive task are reflected in discernable, quantitative changes in the functional anatomy associated with task performance.