Ravi S. Menon

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model.

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R2*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

Visually guided grasping produces fMRI activation in dorsal but not ventral stream brain areas

Although both reaching and grasping require transporting the hand to the object location, only grasping also requires processing of object shape, size and orientation to preshape the hand. Behavioural and neuropsychological evidence suggests that the object processing required for grasping relies on different neural substrates from those mediating object recognition. Specifically, whereas object recognition is believed to rely on structures in the ventral (occipitotemporal) stream, object grasping appears to rely on structures in the dorsal (occipitoparietal) stream. We used functional magnetic resonance imaging (fMRI) to determine whether grasping (compared to reaching) produced activation in dorsal areas, ventral areas, or both. We found greater activity for grasping than reaching in several regions, including anterior intraparietal (AIP) cortex. We also performed a standard object perception localizer (comparing intact vs. scrambled 2D object images) in the same subjects to identify the lateral occipital complex (LOC), a ventral stream area believed to play a critical role in object recognition. Although LOC was activated by the objects presented on both grasping and reaching trials, there was no greater activity for grasping compared to reaching. These results suggest that dorsal areas, including AIP, but not ventral areas such as LOC, play a fundamental role in computing object properties during grasping.

Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation

BACKGROUND The goal of this study was to examine the neuronal circuitry underlying dissociative responses to traumatic script-driven imagery in sexual-abuse-related posttraumatic stress disorder (PTSD). Pilot studies in our laboratory have shown that PTSD patients had very different responses to traumatic script-driven imagery. Approximately 70% of patients relived their traumatic experience and showed an increase in heart rate while recalling the traumatic memory. The other 30% of patients had a dissociative response with no concomitant increase in heart rate. This article focuses on the latter group. METHODS The neuronal circuitry underlying dissociative responses in PTSD was studied using the traumatic script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength in 7 subjects with sexual-abuse-related PTSD and 10 control subjects. RESULTS Compared with control subjects, PTSD patients in a dissociative state showed more activation in the superior and middle temporal gyri (BA 38), the inferior frontal gyrus (BA 47), the occipital lobe (BA 19), the parietal lobe (BA 7), the medial frontal gyrus (BA 10), the medial cortex (BA 9), and the anterior cingulate gyrus (BA 24 and 32). CONCLUSIONS These findings suggest that prefrontal and limbic structures underlie dissociative responses in PTSD. Differences observed clinically, psychophysiologically, and neurobiologically between patients who respond to traumatic script-driven imagery with dissociative versus nondissociative responses may suggest different neuronal mechanisms underlying these two distinct reactions.

Resting-State Networks Show Dynamic Functional Connectivity in Awake Humans and Anesthetized Macaques

Characterization of large‐scale brain networks using blood‐oxygenation‐level‐dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within‐network functional connectivity fluctuates on the order of seconds to minutes. Time‐varying profiles of resting‐state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the “oculomotor (OCM) network” strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time‐dependent analysis reliably revealed transient states of large‐scale synchronization that spanned all seeds. The results illustrate that resting‐state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure. Hum Brain Mapp 34:2154–2177, 2013.

Human fMRI evidence for the neural correlates of preparatory set

We used functional magnetic resonance imaging (fMRI) to study readiness and intention signals in frontal and parietal areas that have been implicated in planning saccadic eye movements—the frontal eye fields (FEF) and intraparietal sulcus (IPS). To track fMRI signal changes correlated with readiness to act, we used an event-related design with variable gap periods between disappearance of the fixation point and appearance of the target. To track changes associated with intention, subjects were instructed before the gap period to make either a pro-saccade (look at target) or an anti-saccade (look away from target). FEF activation increased during the gap period and was higher for anti- than for pro-saccade trials. No signal increases were observed during the gap period in the IPS. Our findings suggest that within the frontoparietal networks that control saccade generation, the human FEF, but not the IPS, is critically involved in preparatory set, coding both the readiness and intention to perform a particular movement.

Motor Area Activity During Mental Rotation Studied by Time-Resolved Single-Trial fMRI

The functional equivalence of overt movements and dynamic imagery is of fundamental importance in neuroscience. Here, we investigated the participation of the neocortical motor areas in a classic task of dynamic imagery, Shepard and Metzlers mental rotation task, by time-resolved single-trial functional Magnetic Resonance Imaging (fMRI). The subjects performed the mental-rotation task 16 times, each time with different object pairs. Functional images were acquired for each pair separately, and the onset times and widths of the activation peaks in each area of interest were compared to the response times. We found a bilateral involvement of the superior parietal lobule, lateral premotor area, and supplementary motor area in all subjects; we found, furthermore, that those areas likely participate in the very act of mental rotation. We also found an activation in the left primary motor cortex, which seemed to be associated with the right-hand button press at the end of the task period.

An fMRI study of the selective activation of human extrastriate form vision areas by radial and concentric gratings

The ventral form vision pathway of the primate brain comprises a sequence of areas that include V1, V2, V4 and the inferior temporal cortex (IT) [1]. Although contour extraction in the V1 area and responses to complex images, such as faces, in the IT have been studied extensively, much less is known about shape extraction at intermediate cortical levels such as V4. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that the human V4 is more strongly activated by concentric and radial patterns than by conventional sinusoidal gratings. This is consistent with global pooling of local V1 orientations to extract concentric and radial shape information in V4. Furthermore, concentric patterns were found to be effective in activating the fusiform face area. These findings support recent psychophysical [2,3] and physiological [4,5] data indicating that analysis of concentric and radial structure represents an important aspect of processing at intermediate levels of form vision.

Recall of emotional states in posttraumatic stress disorder: an fMRI investigation

BACKGROUND The goal of this study was to examine the neuronal circuitry underlying different emotional states (neutral, sad, anxious, and traumatic) in posttraumatic stress disorder (PTSD) in traumatized subjects versus traumatized subjects without PTSD. METHODS Traumatized subjects with (n = 10) and without (n = 10) PTSD were studied using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength. RESULTS Compared to the trauma-exposed comparison group, PTSD subjects showed significantly less activation of the thalamus and the anterior cingulate gyrus (area 32) in all three emotional states (sad, anxious, and traumatic). CONCLUSION These findings suggest thalamic and anterior cingulate dysfunction in the recollection of traumatic as well as other negative events. Thalamic and anterior cingulate dysfunction may underlie emotion dysregulation often observed clinically in PTSD.

Differential effects of viewpoint on object-driven activation in dorsal and ventral streams

Using fMRI, we showed that an area in the ventral temporo-occipital cortex (area vTO), which is part of the human homolog of the ventral stream of visual processing, exhibited priming for both identical and depth-rotated images of objects. This pattern of activation in area vTO corresponded to performance in a behavioral matching task. An area in the caudal part of the intraparietal sulcus (area cIPS) also showed priming, but only with identical images of objects. This dorsal-stream area treated rotated images as new objects. The difference in the pattern of priming-related activation in the two areas may reflect the respective roles of the ventral and dorsal streams in object recognition and object-directed action.

A prospective study of cognitive impairment in ALS.

Objective: To characterize prospectively the cognitive profile in ALS. Methods: Clinically definite ALS patients (11 men, 2 women), age 39.9 to 74.0 years (mean age, 54.2 ± 9.6 years; mean disease duration, 21.1 ± 10.5 months) underwent neuropsychologic, language, and speech testing followed by MR 1H spectroscopy (4 T). Five spousal control subjects completed an identical protocol. Eight ALS patients participated in follow-up studies at a 6-month interval. Results: Relative to control subjects, ALS patients showed mild impairment in word generation, recognition memory (faces), and motor-free visual perception. Bulbar-onset patients showed greater impairment in a number of measures (working memory, problem solving/cognitive flexibility, visual perception, and recognition memory for words and faces), and cognitive impairment appeared more progressive over time. ALS patients demonstrated anomia on a confrontation naming test, with no significant problems following commands or repeating. Speech motor performance scores and intelligibility scores were not significantly different. No significant declines in forced vital capacity, forced expiratory volume, or peak expiratory flow rates were observed. Although normal at initial testing (T1), MR 1H spectroscopy demonstrated a reduction of the N-acetylaspartate/creatine (NAA/Cr) ratio in the nondominant precentral motor strip across the two testing intervals. In contrast, the NAA/Cr ratio obtained from the anterior cingulate gyrus at T1 was already reduced in bulbar-onset patients (p < 0.001), whereas no deficits were observed in limb-onset individuals in the same region. Conclusions: Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound neuropsychological dysfunction whereas both language and speech capabilities remained relatively preserved. Of note, the absence of bulbar signs did not predict an absence of cognitive decline.