Reading and controlling human brain activation using real-time functional magnetic resonance imaging

Understanding how to control how the brain's functioning mediates mental experience and the brain's processing to alter cognition or disease are central projects of cognitive and neural science. The advent of real-time functional magnetic resonance imaging (rtfMRI) now makes it possible to observe the biology of one's own brain while thinking, feeling and acting. Recent evidence suggests that people can learn to control brain activation in localized regions, with corresponding changes in their mental operations, by observing information from their brain while inside an MRI scanner. For example, subjects can learn to deliberately control activation in brain regions involved in pain processing with corresponding changes in experienced pain. This may provide a novel, non-invasive means of observing and controlling brain function, potentially altering cognitive processes or disease.     

Amygdala activation to sad pictures during high-field (4 tesla) functional magnetic resonance imaging

Fear-related processing in the amygdala has been well documented, but its role in signaling other emotions remains controversial. The authors recovered signal loss in the amygdala at high-field strength using an inward spiral pulse sequence and probed its response to pictures varying in their degree of portrayed sadness. These pictures were presented as intermittent task-irrelevant distractors during a concurrent visual oddball task. Relative to neutral distractors, sad distractors elicited greater activation along ventral brain regions, including the amygdala, fusiform gyrus, and inferior frontal gyrus. In contrast, oddball targets engaged dorsal sectors of frontal, parietal, and cingulate cortices. The amygdala's role in emotional evaluation thus extends to images of grief and despair as well as to those depicting violence and threat.     

Using proton magnetic resonance imaging and spectroscopy to understand brain "activation"

Upon stimulation, areas of the brain associated with specific cognitive processing tasks may undergo observable physiological changes, and measures of such changes have been used to create brain maps for visualization of stimulated areas in task-related brain "activation" studies. These perturbations usually continue throughout the period of the stimulating event, and then subside when the event is terminated. In this communication, we consider the nature and meaning of these task-related brain activations. Since stimulation usually results in an increase in the frequency of neuron depolarizations or "spikes", an energy expensive activity that requires ATP for restoration of ionic gradients, additional energy supplies must be rapidly deployed to the stimulated areas or rates of re-polarization could be decreased, and refractory periods between spikes increased. As a result, maximum spiking rates may be decreased and some frequency-encoded information lost. The energy available to brain cells to re-synthesize ATP from ADP is a function of levels of glucose and oxygen in blood, and their availability to stimulated neurons is a function of the rate at which focal blood supplies can be increased (hyperemia). In this review we explore how neurons transmit meaningful encoded information; how the integrity of that information is dependent on a continuous supply of energy, and how proton magnetic imaging and spectroscopy may aid in understanding the process. Finally, evidence is presented that the neuropeptide, N-acetylaspartylglutamate, is a neuronal astrocyte-vascular feedback signal that regulates activation induced focal hyperemic responses.     

Articulatory/phonetic sequencing at the level of the anterior perisylvian cortex: a functional magnetic resonance imaging (fMRI) study

Damage to the anterior peri-intrasylvian cortex of the dominant hemisphere may give rise to a fairly consistent syndrome of articulatory deficits in the absence of relevant paresis of orofacial or laryngeal muscles (apraxia of speech, aphemia, or phonetic disintegration). The available clinical data are ambiguous with respect to the relevant lesion site, indicating either dysfunction of the premotor aspect of the lower precentral gyrus or the anterior insula in the depth of the Sylvian fissure. In order to further specify the functional anatomic substratum of this syndrome, functional magnetic resonance imaging (fMRI) was performed during reiteration of syllables differing in their demands on articulatory/phonetic sequencing (CV versus CCCV versus CVCVCV). Horizontal tongue movements and a polysyllabic lexical item served as control conditions. Repetition of the CV and CCCV monosyllables elicited a rather bilateral symmetric hemodynamic response at the level of the anterior and posterior bank of the central sulcus (primary sensorimotor cortex), whereas a more limited area of neural activity arose within this domain during production of lexical and nonlexical polysyllables, significantly or exclusively lateralized toward the left hemisphere. There is neurophysiological evidence that primary sensorimotor cortex mediates the "fractionation" of movements. Assuming that the polysyllables considered are organized as coarticulated higher-order units, the observed restricted and lateralized cortical activation pattern, most presumably, reflects a mode of "nonindividualized" motor control posing fewer demands on "movement fractionation." These findings may explain the clinical observation of disproportionately worse repetition of trisyllabic items as compared to monosyllables in apraxia of speech. The various test materials failed to elicit significant activation of the anterior insula. If at all, only horizontal tongue movements yielded a hemodynamic reaction extending beyond the sensorimotor cortex to premotor areas. Since limbic projections target the inferior dorsolateral frontal lobe, the enlarged region of activation during horizontal tongue movements might reflect increased attentional requirements of this task.     

Multivariate strategies in functional magnetic resonance imaging

We discuss aspects of multivariate fMRI modeling, including the statistical evaluation of multivariate models and means for dimensional reduction. In a case study we analyze linear and non-linear dimensional reduction tools in the context of a 'mind reading' predictive multivariate fMRI model.     

Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging

Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in the controls produced robust activation in Broca's area (left inferior frontal gyrus) and in superior medial frontal gyrus and right cerebellum. The ASD group had substantially reduced Broca's activation, but increased left temporal (Wernicke's) activation. Furthermore, the ASD group showed diminished activation differences between concrete and abstract words, consistent with behavioral studies. The current study suggests Broca's area is a region of abnormal neurodevelopment in ASD, which may be linked with semantic and related language deficits frequently observed in ASD.     

Fiber tracking using magnetic resonance diffusion tensor imaging and its applications to human brain development

Diffusion tensor imaging is unique in its ability to noninvasively visualize white matter fiber tracts in the human brain in vivo. Diffusion is the incoherent motion of water molecules on a microscopic scale. This motion is itself dependent on the micro-structural environment that restricts the movement of the water molecules. In white matter fibers there is a pronounced directional dependence on diffusion. With white matter fiber tracking or tractography, projections among brain regions can be detected in the three-dimensional diffusion tensor dataset according to the directionality of the fibers. Examples of developmental changes in diffusion, tracking of major fiber tracts, and examples of how diffusion tensor tractography and functional magnetic resonance imaging can be combined are provided. These techniques are complimentary and allow both the identification of the eloquent areas of the brain involved in specific functional tasks, and the connections between them. The noninvasive nature of magnetic resonance imaging will allow these techniques to be used in both longitudinal developmental and diagnostic studies. An overview of the technique and preliminary applications are presented, along with its current limitations.     

Functional magnetic resonance imaging activation in response to prompts of romantically disillusioning events

To differentiate romantic disillusionment from similar constructs of dissatisfaction and regret, functional Magnetic Resonance Imaging (fMRI) data obtained when romantically involved individuals (N = 39) were reminded of relationship events representing these emotions were analyzed. Whole‐brain activations suggested disillusionment‐linked processes not observed for dissatisfaction or regret. Compared to dissatisfying events, disillusioning ones showed greater activity in regions pertaining to evaluation, reflection, and reconciling conflicting information (e.g., anterior cingulate cortex). No regions showed significantly more activation for dissatisfying than disillusioning events. Compared to regret‐inducing events, disillusioning events showed greater activation in areas thought pertinent to detail processing and decision making (occipital fusiform and lingual gyrus). Regret‐inducing events activated regions suggesting the planning and thoughts of how one could have acted differently (e.g., prefrontal cortex).     

Operant-contingency-based preparation of children for functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is used to study brain function during behavioral tasks. The participation of pediatric subjects is problematic because reliable task performance and control of head movement are simultaneously required. Differential reinforcement decreased head motion and improved vigilance task performance in 4 children (2 with behavioral disorders) undergoing simulated fMRI scans. Results show that behavior analysis techniques can improve child cooperation during fMRI procedures.     

Using the memory activation capture (MAC) procedure to investigate the temporal dynamics of hypothesis generation

Research investigating top-down capture has demonstrated a coupling of working memory content with attention and eye movements. By capitalizing on this relationship, we have developed a novel methodology, called the memory activation capture (MAC) procedure, for measuring the dynamics of working memory content supporting complex cognitive tasks (e.g., decision making, problem solving). The MAC procedure employs briefly presented visual arrays containing task-relevant information at critical points in a task. By observing which items are preferentially fixated, we gain a measure of working memory content as the task evolves through time. The efficacy of the MAC procedure was demonstrated in a dynamic hypothesis generation task in which some of its advantages over existing methods for measuring changes in the contents of working memory over time are highlighted. In two experiments, the MAC procedure was able to detect the hypothesis that was retrieved and placed into working memory. Moreover, the results from Experiment 2 suggest a two-stage process following hypothesis retrieval, whereby the hypothesis undergoes a brief period of heightened activation before entering a lower activation state in which it is maintained for output. The results of both experiments are of additional general interest, as they represent the first demonstrations of top-down capture driven by participant-established WM content retrieved from long-term memory.     

Ethical and practical considerations in managing incidental findings in functional magnetic resonance imaging

Functional magnetic resonance imaging has emerged as a powerful tool for mapping the neurologic underpinnings of sensory, motor and cognitive function. Much of this evolution carries assumptions about the subject population under study and, in particular, the neurologic status of subjects entered into studies either as healthy controls or as belonging to a specific disease group. Recent reports of incidental MRI abnormalities in normal volunteers for fMRI studies have brought to attention a variety of practical challenges and ethical dilemmas for researchers, many of whom are not physicians and most of whom have no formal radiological training. We propose a minimum standard for consenting subjects in fMRI protocols, and consider strategies over the longer term that call for expert physician participation, archiving of incidental findings including false positives, and the adoption of guidelines for handling variation in neural activations or performance that appear outside expected norms.     

Overactive action monitoring in obsessive-compulsive disorder: evidence from functional magnetic resonance imaging

The anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been found to be hyperactive at rest, during symptom provocation, and after commission of errors in cognitive tasks. This hyperactivity might reflect an abnormality in conflict detection, a hypothesized basic mechanism for the action-monitoring function of the ACC. This hypothesis was tested using functional magnetic resonance imaging, by scanning 11 OCD patients and 13 matched control subjects while they performed a version of the continuous-performance task with four trial types that induced graded levels of response conflict. Although a behavioral index of conflict (i.e., accuracy) was similar for patients and control subjects, the ACC activation was increased in patients during high-conflict trials. The error-related activity in the same brain region was also higher in patients, consistent with previous electrophysiological findings. Both conflict- and error-related activity showed trends for positive correlations with severity of OCD symptoms, but not with anxiety. These findings suggest that as part of an overactive action-monitoring system, the ACC is more directly involved in the pathophysiology of OCD than previously thought.     

Decreased functional brain activation in Friedreich ataxia using the Simon effect task

The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression.     

Comparison of brain activation during word retrieval done silently and aloud using fMRI

Using functional MRI we compared the patterns of activation in an effortful word retrieval task (stem completion) performed both silently and aloud. The silent and overt conditions showed expected differences in activation magnitude in regions such as primary motor cortex. Some regions, such as frontal operculum and dorsolateral frontal cortex, showed similar activation magnitude across conditions. Thalamus was more active on the left in both conditions and showed a symmetric drop in activity in the silent compared with the overt condition. Putamen was also more active in the overt condition and showed a larger decrease in activity on the right than on the left in the silent compared with the overt condition. Thus it appears that silent and overt performance of this task engage the thalamus and putamen in different ways.     

Some problems for representations of brain organization based on activation in functional imaging

Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of brain damage. However, the enthusiastic onslaught of brain images, frequently presented as veridical representations of mental function, has sometimes overwhelmed some basic facts about brain organization repeatedly observed over more than a century. In particular, the lateralization of speech and language to the left cerebral hemisphere in over 90% of the right-handed population does not appear to have been taken as a serious constraint in the interpretation of imaging results in studies of these functions. This paper reviews a number of areas in which standard activation assumptions yield results that are at odds with clinical experience. The activation approach will be contrasted with a performance-based analysis of functional image data, which, at least in the case of speech production, yields results in better agreement with lesion data. Functional imaging represents enormous opportunities for understanding brain-behavior relationships, but at the present level of understanding of what is being represented in such images, it is premature to adhere to a single approach based on the strong but questionable assumptions inherent in most activation studies.     

The neural reality of syntactic transformations: evidence from functional magnetic resonance imaging

The functional anatomy of syntactic transformations, a major computational operation invoked in sentence processing, was identified through a functional magnetic resonance imaging investigation. A grammaticality judgment task was used, presented through a novel hidden-blocks design. Subjects listened to transformational and nontransformational sentences in which a host of other complexity generators (number of words, prepositions, embeddings, etc.) were kept constant. A series of analyses revealed that the neural processing of transformations is localizable, evoking a highly lateralized and localized activation in the left inferior frontal gyrus (Broca's region) and bilateral activation in the posterior superior temporal sulcus. The pattern of activation associated with transformational analysis was distinct from the one observed in neighboring regions, and anatomically separable from the effects of verb complexity, which yielded significant activation in the left posterior superior temporal sulcus. Taken together with neuropsychological evidence, these results uncover the neural reality of syntactic transformations.