Using fMRI to investigate

Using fMRI, we investigated the functional organization of prefrontal cortex (PFC) as participants briefly thought of a single just-experienced item (i.e., refreshed an active representation). The results of six studies, and a meta-analysis including previous studies, identified regions in left dorsolateral, anterior, and ventrolateral PFC associated in varying degrees with refreshing different types of information (visual and auditory words, drawings, patterns, people, places, or locations). In addition, activity increased in anterior cingulate with selection demands and in orbitofrontal cortex when a nonselected item was emotionally salient, consistent with a role for these areas in cognitive control (e.g., overcoming “mental rubbernecking”). We also found evidence that presenting emotional information disrupted an anterior component of the refresh circuit. We suggest that refreshing accounts for some neural activity observed in more complex tasks, such as working memory, long-term memory, and problem solving, and that its disruption (e.g., from aging or emotion) could have a broad impact.     

Fitting computational models to fMRI data

Many computational models in psychology predict how neural activation in specific brain regions should change during certain cognitive tasks. The emergence of fMRI as a research tool provides an ideal vehicle totest these predictions. Before such tests are possible, however, significant methodological problems must be solved. These problems include transforming the neural activations predicted by the model into predicted BOLD responses, identifying the voxels within each region of interest against which to test the model, and comparing the observed and predicted BOLD responses in each of these regions. In the present article, methods are described for solving each of these problems.     

Imaging the developing brain with fMRI

Advancements in magnetic imaging techniques have revolutionized our ability to study the developing human brain in vivo. The ability to noninvasively image both anatomy and function in healthy volunteers, including young children, has already enhanced our understanding of brain and behavior relations. The application of these techniques to developmental research offers the opportunity to further explore these relationships and allows us to ask questions about where, when and how cognitive abilities develop in relation to changes in underlying brain systems. It is also possible to explore the contributions of maturation versus learning in the development of these abilities through cross-sectional and longitudinal research involving training and intervention procedures. Current imaging methodologies, in conjunction with new and rapidly evolving techniques, hold the promise of even greater insights into developmental issues in the near future. These methodologies and their application to development and learning are discussed in the current paper.     

Using perfusion fMRI to measure continuous changes in neural activity with learning

In this study, we examine the suitability of a relatively new imaging technique, arterial spin labeled perfusion imaging, for the study of continuous, gradual changes in neural activity. Unlike BOLD imaging, the perfusion signal is stable over long time-scales, allowing for accurate assessment of continuous performance. In addition, perfusion fMRI provides an absolute measure of blood flow so signal changes can be interpreted without reference to a baseline. The task we used was the serial response time task, a sequence learning task. Our results show reliable correlations between performance improvements and decreases in blood flow in premotor cortex and the inferior parietal lobe, supporting the model that learning procedures that increase efficiency of processing will be reflected in lower metabolic needs in tissues that support such processes. More generally, our results show that perfusion fMRI may be applied to the study of mental operations that produce gradual changes in neural activity.     

Using fMRI to study recovery from acquired dysphasia

We have used functional magnetic resonance imaging (fMRI) to characterize brain activations associated with two distinct language tasks performed by a 28-year-old woman after partial recovery from dysphasia due to a left frontal hemispheric ischemic stroke. MRI showed that her ischemic lesion extended posteriorly from the left inferior frontal to the perisylvian cortex. fMRI scans of both language tasks revealed substantial differences in activation pattern relative to controls. The nature of this difference was task-specific. During performance of a verbal semantic decision task, the patient, in contrast to controls, activated a network of brain areas that excluded the inferior frontal gyrus (in either hemisphere). A second task involving rhyme judgment was designed to place a heavier cognitive load on language production processes and activated the left inferior frontal gyrus (Broca's area) strongly in normal controls. During this task, the most prominent frontal activation in the patient occurred in the right homologue of Broca's area. Subsequent analysis of this data by methods able to deal with responses of changing amplitude revealed additional, less sustained recruitment by the patient of cortex adjacent to the infarct in the region inferior to Broca's area during rhyming. These results suggest that in addition to changes in cognitive strategy, recovery from dysphasia could be mediated by both the preservation of neuronal networks in and around the infarct and the use of homologous regions in the contralateral hemisphere.     

Application of pharmacological fMRI to developmental psychiatric disorders

Functional magnetic resonance imaging of neural activity induced by pharmacological stimulation (phMRI) is a promising technique for revealing pathophysiology and etiology of developmental psychiatric disorders. Recent investigations of the dopaminergic system have made possible the use of phMRI as a non‐invasive assay for neurotransmitter function. This paper explores applications of phMRI for identification of neurophysiological trait‐dependent and clinical state‐dependent mechanisms that can define biologically valid diagnostic criteria for developmental psychiatric disorders. Further, applications of phMRI for investigations of neurochemical changes induced by long‐term drug exposure, alternative therapies and normal brain maturation are discussed. The paper ends by highlighting methodological challenges posed by experimental control of pharmacological stimulation that is essential for valid interpretation of phMRI results.     

Applications of ERP and fMRI techniques to developmental science

Event‐related potentials (ERPs) and functional magnetic resonance imaging are both measures of functional brain activation that have been applied to developmental questions. However, the two measures are not identical and reflect different aspects of neuronal function at a physiological level. There is increasing interest in using these methods in combination because of the complementary information they provide about brain activation. ERPs provide more detailed information about the timing of neural activity, while fMRI provides more detailed information about its spatial location. Thus, their combined use may provide more detailed spatio‐temporal information than either method alone. In this paper, we review the basic principles of ERP and fMRI and present selected studies from our own work to illustrate their strengths for studies of development. In addition, we discuss the potential benefits and special challenges of the combined use of electrophysiological and functional MRI techniques.     

Place learning in virtual space III: Investigation of spatial navigation training procedures and their application to fMRI and clinical neuropsychology

This paper describes the utilization of a desktop virtual environment task, the Computer-Generated (C-G) Arena, in the study of human spatial navigation. First, four experiments examined the efficacy of various training procedures in the C-G Arena. In Experiment 1, participants efficiently located a hidden target after only observing the virtual environment from a fixed position (placement learning). In Experiment 2, participants efficiently located a hidden target after only observing an experimenter search the virtual environment (observational learning). In Experiment 3, participants failed to display alatent learning effect in the virtual environment. In Experiment 4, all training procedures effectively taught participants the layout of the virtual environment, but the observational learning procedure most effectivelytaught participants the location of a hidden target within the environment. Finally, two experiments demonstrated the application of C-G Arena procedures to neuroimaging (Experiment 5) and neuropsychological (Experiment 6) investigations of human spatial navigation.     

Spatial and temporal limits in cognitive neuroimaging with fMRI

A large body of research in human perception and cognition has been concerned with the segregation of mental events into their presumed hierarchical processing stages, the temporal aspect of such processing being termed ‘mental chronometry’. Advances in single-event functional magnetic resonance imaging (fMRI) have allowed the extraction of relative timing information between the onset of activity in different neural substrates as well as the duration of cognitive processing during a task, offering new opportunities in the study of human perception and cognition. Single-event fMRI studies have also facilitated increased spatial resolution in fMRI, allowing studies of columnar organization in humans. Important processes such as object recognition, binocular vision and other processes are thought to be organized at the columnar level; thus, these advances in the spatial and temporal capabilities of fMRI allow a new generation of cognitive and basic neuroscience studies to be performed, investigating the temporal and spatial relationships between these cortical sub-units. Such experiments bear a closer resemblance to single-unit or evoked-potential studies than to classical static brain activation maps and might serve as a bridge between primate electrophysiology and human studies. These advances are initially demonstrated only in simple visual and motor system tasks and it is likely to be several years before the techniques we describe are robust enough for general use.     

From retinotopy to recognition: fMRI in human visual cortex

Recent advances in functional magnetic resonance imaging (fMRI) have furnished increasingly informative and accurate maps of the retinotopy and functional organization in human visual cortex. Here we review how information in those sensory-based maps is topographically related to, and influenced by, more cognitive visuo-spatial dimensions, such as mental imagery, spatial attention, repetition effects and size perception.     

An fMRI investigation of a novel analogue to the Trail-Making Test

The Trail-Making Test (TMT) is a widely used neuropsychological measure that assesses visuomotor abilities and cognitive flexibility. For the TMT-A condition participants are required to locate and connect numbers (i.e. 1-2-3…) while in the TMT-B condition participants perform the set-shifting task of locating and connecting numbers and letters (i.e. 1-A-2-B…). The TMT-B condition has shown impairments in many clinical populations, particularly schizophrenia patients, but the neurobiological underpinning of the task can be difficult to discern given pragmatic obstacles in adapting the task for neuroimaging. In a behavioural testing experiment we demonstrated a close correspondence between performance on the standard TMT and a novel, computer programmed adaptation of the TMT (pcTMT). The pcTMT was designed for functional magnetic resonance imaging (fMRI) administration and neuroimaging data for this task were obtained in. A whole brain analysis revealed significantly greater activation during the pcTMT-B relative to the pcTMT-A in right inferior/middle frontal cortices, right precentral gyrus, left angular gyrus/left middle temporal gyrus. These results identify the regions that most likely underlie cognitive flexibility during the TMT and are candidate regions underlying the impairment of groups with poor set-shifting abilities.     

Framing deductive reasoning with emotional content: An fMRI study

In the literature concerning the study of emotional effect on cognition, several researches highlight the mechanisms of reasoning ability and the influence of emotions on this ability. However, up to now, no neuroimaging study was specifically devised to directly compare the influence on reasoning performance of visual task-unrelated with semantic task-related emotional information.In the present functional fMRI study, we devised a novel paradigm in which emotionally negative vs. neutral visual stimuli (context) were used as primes, followed by syllogisms composed of propositions with emotionally negative vs. neutral contents respectively. Participants, in the MR scanner, were asked to assess the logical validity of the syllogisms. We have therefore manipulated the emotional state and arousal induced by the visual prime as well as the emotional interference exerted by the syllogism content.fMRI data indicated a medial prefrontal cortex deactivation and lateral/dorsolateral prefrontal cortex activation in conditions with negative context. Furthermore, a lateral/dorsolateral prefrontal cortex modulation caused by syllogism content was observed. Finally, behavioral data confirmed the influence of emotional task-related stimuli on reasoning ability, since the performance was worse in conditions with syllogisms involving negative emotions. Therefore, on the basis of these data, we conclude that emotional states can impair the performance in reasoning tasks by means of the delayed general reactivity, whereas the emotional content of the target may require a larger amount of top-down resources to be processed.     

Auditory context effects in picture naming investigated with event-related fMRI

Naming an object entails a number of processing stages, including retrieval of a target lexical concept and encoding of its phonological word form. We investigated these stages using the picture-word interference task in an fMRI experiment. Participants named target pictures in the presence of auditorily presented semantically related, phonologically related, or unrelated distractor words or in isolation. We observed BOLD signal changes in left-hemisphere regions associated with lexical-conceptual and phonological processing, including the midto-posterior lateral temporal cortex. However, these BOLD responses manifested as signal reductions for all distractor conditions relative to naming alone. Compared with unrelated words, phonologically related distractors showed further signal reductions, whereas only the pars orbitalis of the left inferior frontal cortex showed a selective reduction in response in the semantic condition. We interpret these findings as indicating that the word forms of lexical competitors are phonologically encoded and that competition during lexical selection is reduced by phonologically related distractors. Since the extended nature of auditory presentation requires a large portion of a word to be presented before its meaning is accessed, we attribute the BOLD signal reductions observed for semantically related and unrelated words to lateral inhibition mechanisms engaged after target name selection has occurred, as has been proposed in some production models.     

Suppression of brain activity related to a car-following task with an auditory task: An fMRI study

Driving a car in daily life involves multiple tasks. One important task for safe driving is car-following, the interference of which causes rear-end collisions: the most common type of car accident. Recent reports have described that car-following is hindered even by hands-free mobile telephones. We conducted functional MRI with 18 normal volunteers to investigate brain activity changes that occur during a car-following task with a concurrent auditory task. Participants performed three tasks: a driving task, an auditory task, and a dual task in an fMRI run. During the driving task, participants use a joystick to control their vehicle speed in a driving simulator to maintain a constant distance from a leading car, which moves at varying speed. Language trials and tone discrimination trials are presented during the auditory task. Car-following performance was worse during the dual task than during the single-driving task, showing positive correlation with brain activity in the bilateral lateral occipital complex and the right inferior parietal lobule. In the medial prefrontal cortex and left superior occipital gyrus, the brain activity of the dual task condition was less than that in the single-driving task condition. These results suggest that the decline of brain activity in these regions may induce car-following performance deterioration.     

Ethical issues in the clinical application of fMRI: factors affecting the validity and interpretation of activations

The ability of functional magnetic resonance imaging (fMRI) to localize activations in a single patient, along with the safety and widespread availability of this methodology, has lead to an increasing use of fMRI for clinical purposes such as pre-surgical planning. As methodology continues to improve and more experience with fMRI in the clinical setting is acquired, clinical functional neuroimaging will likely have an increasing influence over patient care. Therefore, ethical use of fMRI, as with other medical techniques, requires understanding the factors impacting the interpretation of the methodology. Issues affecting the validity and interpretation of clinical functional neuroimaging, including effects of altered hemodynamic response function, head motion, and structural changes in the brain, are reviewed. The distinction between correlated and necessary activation in a clinical context is discussed. Different types of statistical errors in fMRI analysis are described, along with their consequences to the patient. Finally, for the future of clinical fMRI development, the need for normative patient data, as well as standardized tasks, scan protocols, and data analyses, is discussed.