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Biomedical subjects

Scott T Grafton

Publications and source records attributed to Scott T Grafton.

16 recordsLinked to original sources

A distributed left hemisphere network active during planning of everyday tool use skills.

Determining the relationship between mechanisms involved in action planning and/or execution is critical to understanding the neural bases of skilled behaviors, including tool use. Here we report findings from two fMRI studies of healthy, right-handed adults in which an event-related design was used to distinguish regions involved in planning (i.e. identifying, retrieving and preparing actions associated with a familiar tools' uses) versus executing tool use gestures with the dominant right (experiment 1) and non-dominant left (experiment 2) hands. For either limb, planning tool use actions activates a distributed network in the left cerebral hemisphere consisting of: (i) posterior superior temporal sulcus, along with proximal regions of the middle and superior temporal gyri; (ii) inferior frontal and ventral premotor cortices; (iii) two distinct parietal areas, one located in the anterior supramarginal gyrus (SMG) and another in posterior SMG and angular gyrus; and (iv) dorsolateral prefrontal cortex (DLFPC). With the exception of left DLFPC, adjacent and partially overlapping sub-regions of left parietal, frontal and temporal cortex are also engaged during action execution. We suggest that this left lateralized network constitutes a neural substrate for the interaction of semantic and motoric representations upon which meaningful skills depend.

Adult↗

Functional imaging of face and hand imitation: towards a motor theory of empathy.

Empathy requires the ability to map the feelings of others onto our own nervous system. Until recently, there was no plausible mechanism to explain how such a mapping might occur. The discovery of mirror neurons, however, suggests that the nervous system is capable of mapping the observed actions of others onto the premotor cortex of the self, at least for reaching and grasping movements. Is there a mirroring system for emotive actions, such as facial expression? Subjects (N = 15; all right-handed; eight men, seven women) watched movies of facial expressions (smile or frown) and hand movements (move index or middle finger) while brain activity was imaged using functional magnetic resonance imaging (fMRI). Subjects watched the movies under three different conditions: passive viewing, active imitation, and an active motor control. Subjects also performed a verb generation task to functionally identify language-processing areas. We found evidence for a common cortical imitation circuit for both face and hand imitation, consisting of Broca's area, bilateral dorsal and ventral premotor areas, right superior temporal gyrus (STG), supplementary motor area, posterior temporo-occipital cortex, and cerebellar areas. For faces, passive viewing led to significant activation in the right ventral premotor area, whereas imitation produced bilateral activation. This result is consistent with evidence for right hemisphere (RH) dominance for emotional processing, and suggests that there may be a right hemisphere mirroring system that could provide a neural substrate for empathy.

Adult↗

From facial cue to dinner for two: the neural substrates of personal choice.

The current experiment examined the neural substrates of response selection, comparing conditions that required participants to make criterion-free selections from sets of same-sex faces (i.e., inconsequential decision) to choosing a dinner date from opposite-sex faces (i.e., consequential decision). In each of these tasks, either a single face (i.e., no choice) or two or three faces (i.e., free choice) appeared for selection. The results revealed that regions of dorsal premotor cortex (PMd) and parietal cortex bilaterally, as well as an area along the medial surface of the superior frontal gyrus, were activated by both consequential and inconsequential decisions, thereby providing evidence for a common selection network. Consequential decisions were further indexed by activation of the insula/ventrolateral prefrontal cortex (BA 47) and the paracingulate gyrus (BA 32). The implications of these findings for current accounts of response selection and social-cognitive functioning are considered.

Adult↗

Sharing neuroimaging studies of human cognition.

After more than a decade of collecting large neuroimaging datasets, neuroscientists are now working to archive these studies in publicly accessible databases. In particular, the fMRI Data Center (fMRIDC), a high-performance computing center managed by computer and brain scientists, seeks to catalogue and openly disseminate the data from published fMRI studies to the community. This repository enables experimental validation and allows researchers to combine and examine patterns of brain activity beyond that of any single study. As with some biological databases, early scientific, technical and sociological concerns hindered initial acceptance of the fMRIDC. However, with the continued growth of this and other neuroscience archives, researchers are recognizing the potential of such resources for identifying new knowledge about cognitive and neural activity. Thus, the field of neuroimaging is following the lead of biology and chemistry, mining its accumulating body of knowledge and moving toward a 'discovery science' of brain function.

Brain↗

Actions or hand-object interactions? Human inferior frontal cortex and action observation.

Cells in macaque ventral premotor cortex (area F5c) respond to observation or production of specific hand-object interactions. Studies in humans associate the left inferior frontal gyrus, including putative F5 homolog pars opercularis, with observing hand actions. Are these responses related to the realized goal of a prehensile action or to the observation of dynamic hand movements? Rapid, event-related fMRI was used to address this question. Subjects watched static pictures of the same objects being grasped or touched while performing a 1-back orienting task. In all 17 subjects, bilateral inferior frontal cortex was differentially activated in response to realized goals of observed prehensile actions. Bilaterally, precentral gyrus was most frequently activated (82%) followed by pars triangularis (73%) and pars opercularis (65%).

Brain Mapping↗

Motor subcircuits mediating the control of movement extent and speed.

The functional correlates of movement extent, speed, and covariates were investigated using PET mapping of regional cerebral blood flow (rCBF) in 13 healthy right-handed adults. A whole-arm smooth pursuit tracking task was used to strictly control potential confounds such as movement duration, error, and feedback control. During each of four scans, images of relative rCBF were obtained while subjects matched the constant velocity movements of a target using a joystick-controlled cursor. Between scans, subjects were completely adapted to one of four joystick-to-cursor gains, thereby allowing constant visual stimulation and eye movements across arm movements that ranged in extent from 6 to 24 cm. Subjects were unaware of the changes in visuomotor gain. Analyses of arm and eye movements indicated that the only significant difference in behavior across the four gain conditions was the extent and velocity of arm movements, which were closely correlated with each other. Parametric statistical methods identified brain areas where rCBF covaried with the mean movement extent of individual subjects during individual scans. Increasing movement extent was associated with parallel increases of rCBF in bilateral basal ganglia (BG; putamen and globus pallidus) and ipsilateral cerebellum. Modest extent effects were detected also in the sensorimotor cortices bilaterally. No significant inverse relations were found. We conclude that a small subcircuit within the motor control system contributes to the control of movement extent and covariates and that the BG and cerebellum play central roles in the operation of that circuit.

Adult↗

A positron emission tomography study of methylphenidate in adults with ADHD: alterations in resting blood flow and predicting treatment response.

A hallmark symptom of attention-deficit hyperactivity disorder (ADHD) is an excess of motoric behavior or hyperactivity. Methylphenidate (MPH) is known to reduce hyperactivity in individuals with ADHD. Yet little is known about how it alters neural activity and how this relates to its clinical effects. The goal of this study is to examine MPH-induced changes during resting brain metabolism, and to examine how these changes correlate with measures of behavioral response to the drug. Measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) were acquired at rest for ten adult subjects with ADHD during both an unmedicated state and after a 3-week period of chronic dosing with a clinically optimal dose of MPH. Compared with the on-MPH condition, the off-MPH condition was associated with relative increases in rCBF bilaterally in the precentral gyri, left caudate nucleus, and right claustrum. The on-MPH condition was associated with relative increases in rCBF in the cerebellar vermis. A correlational analysis measured the relation between rCBF in the off-medication condition to change in ADHD ratings between the off- and on-MPH condition to identify brain regions associated with treatment response. The degree of change in the ratings was negatively correlated with rCBF increases in the midbrain, cerebellar vermis, and the precentral and middle frontal gyri in the off-MPH condition. The majority of these brain regions are involved in the planning and execution of motor behavior. These data suggest that MPH modulates brain regions associated with motor function to achieve a reduction in ADHD symptoms.

Adult↗

From 'acting on' to 'acting with': the functional anatomy of object-oriented action schemata.

In this chapter it is proposed that object-based actions can be broadly classified into types. In the first, objects are 'acted on' without a specific purpose. In the second, objects are 'acted with'. In the latter case the grasp reflects the subsequent goal of the subject. Recent evidence from human functional imaging suggests different neural substrates for acting on an object (dorsal parietal cortex) and for acting with an object. Specifically, it is argued that conceptual knowledge of tool use and the pragmatics of action rely on an inferior parieto-medial frontal network in the left hemisphere.

Animals↗

The functional anatomy of parkinsonian bradykinesia.

To investigate the difficulty that patients with Parkinson's disease (PD) have in performing fast movements, we used H(2)(15)O PET to study regional cerebral blood flow (rCBF) associated with performance of a simple predictive visuomanual tracking task at three different velocities. Tracking movements in PD patients (versus tracking with the eyes alone) were associated with a general underactivation of the areas normally activated by the task (sensorimotor cortex contralateral to the moving arm, bilateral dorsal premotor cortices, and ipsilateral cerebellum). Presupplementary motor cortex (pre-SMA) ipsilateral to the moving arm had greater than normal movement-related activations. Increasing movement velocity led to increased rCBF in multiple premotor and parietal cortical areas and basal ganglia in the patients as opposed to the few cerebral locations that are normally velocity-related. The functional correlates of PD bradykinesia are: (1) impaired recruitment of cortical and subcortical systems that normally regulate kinematic parameters of movement such as velocity; and (2) increased recruitment of multiple premotor areas including both regions specialized for visuomotor control (ventral premotor and parietal cortices) and some that are not (pre-SMA). The overactivation of cortical regions observed in patients may be functional correlates of compensatory mechanisms and/or impaired suppression as a facet of the primary pathophysiology of PD.

Brain↗

Graspable objects grab attention when the potential for action is recognized.

Visually guided grasping movements require a rapid transformation of visual representations into object-specific motor programs. Here we report that graspable objects may facilitate these visuomotor transformations by automatically grabbing visual spatial attention. Human subjects viewed two task-irrelevant objects--one was a 'tool', the other a 'non-tool'--while waiting for a target to be presented in one of the two object locations. Using event-related potentials (ERPs), we found that spatial attention was systematically drawn to tools in the right and lower visual fields, the hemifields that are dominant for visuomotor processing. Using event-related fMRI, we confirmed that tools grabbed spatial attention only when they also activated dorsal regions of premotor and prefrontal cortices, regions associated with visually guided actions and their planning. Although it is widely accepted that visual sensory gain aids perception, our results suggest that it may also have consequences for object-directed actions.

Attention↗

Swinging in the brain: shared neural substrates for behaviors related to sequencing and music.

Music consists of precisely patterned sequences of both movement and sound that engage the mind in a multitude of experiences. We move in response to music and we move in order to make music. Because of the intimate coupling between perception and action, music provides a panoramic window through which we can examine the neural organization of complex behaviors that are at the core of human nature. Although the cognitive neuroscience of music is still in its infancy, a considerable behavioral and neuroimaging literature has amassed that pertains to neural mechanisms that underlie musical experience. Here we review neuroimaging studies of explicit sequence learning and temporal production--findings that ultimately lay the groundwork for understanding how more complex musical sequences are represented and produced by the brain. These studies are also brought into an existing framework concerning the interaction of attention and time-keeping mechanisms in perceiving complex patterns of information that are distributed in time, such as those that occur in music.

Animals↗

Initial human PET imaging studies with the dopamine transporter ligand 18F-FECNT.

UNLABELLED: The aim of this study was to do an initial assessment of the usefulness of 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-(18)F-fluoroethyl)nortropane ((18)F-FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT) density in healthy humans and subjects with Parkinson's disease (PD). METHODS: We investigated 6 neurologically healthy subjects and 5 PD patients: 2 with mild unilateral disease, 1 with mild-to-moderate bilateral disease, and 2 with moderately severe bilateral disease. The healthy subjects underwent a 3-h PET scan (26 frames) and the PD subjects underwent a 2-h PET scan (23 frames) while (18)F-FECNT was being injected over the first 5 min of the scan. Arterial blood samples were taken throughout scanning for well-counter and metabolite analysis to determine the presence of possible active metabolites. The scans were reconstructed; then we placed spheric regions of interest in the caudate nuclei, putamena, thalami, brain stem, cerebellum, and occipital cortex of each subject. The radioactivity level in each region was calculated for each frame of a subject's PET scan. Then we calculated target tissue-to-cerebellum ratios for each time frame. RESULTS: The analysis of arterial blood samples revealed that metabolism of the tracer was rapid. The ether-extractable component of the arterial input was >98% pure (18)F-FECNT. The caudate nucleus and putamen exhibited the highest uptake and prolonged retention of the radioligand. They both attained maximum uptake at approximately 90 min, with the healthy subjects' average caudate- and putamen-to-cerebellum ratios (+/-SD) at that time being 9.0 +/- 1.2 and 7.8 +/- 0.7, respectively. The maximal caudate-to-cerebellum ratios for the healthy subjects ranged from 7.6 to 10.5 and their maximal putamen-to-cerebellum ratios ranged from 7.1 to 9.3. The 2 early-stage, unilateral PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 5.3 +/- 1.1 and a left ratio of 5.9 +/- 0.7 and an average right putamen-to cerebellum ratio of 2.8 +/- 0.1 and a left ratio of 3.0 +/- 0.6. The late-stage PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 3.7 +/- 0.4 and a left ratio of 3.9 +/- 0 and an average right putamen-to cerebellum ratio of 1.8 +/- 0.1 and a left ratio of 1.8 +/- 0. CONCLUSION: These results indicate that (18)F-FECNT is an excellent candidate radioligand for in vivo imaging of the DAT system in humans. It has a much higher affinity for DAT than for the serotonin transporter and yields the highest peak striatum-to-cerebellum ratios and has among the most favorable kinetics of (18)F-radiolabeled DAT ligands. Having picked up presymptomatic changes in the hemisphere opposite the unaffected side of the body in our early-stage (unilateral) PD patients, it appears that, like other DAT radioligands, it may be able to identify presymptomatic PD.

Adult↗

Motor sequence learning with the nondominant left hand. A PET functional imaging study.

Whereas the human right hemisphere is active during execution of contralateral hand movements, the left hemisphere is engaged for both contra- and ipsilateral movements, at least for right-handed subjects. Whether this asymmetry is also found during motor learning remains unknown. Implicit sequence learning by the nondominant left hand was examined with the serial reaction time (SRT) task during functional brain imaging. As learning progressed, increases in brain activity were observed in left lateral premotor cortex (PMC) and bilaterally in supplementary motor areas (SMA), with the increase significantly greater in the left hemisphere. The left SMA site was similar to one previously identified with right-hand learning, suggesting that this region is critical for representing a sequence independent of effector. Learning with the left hand also recruited a widespread set of temporal and frontal regions, suggesting that motor skill learning with the nondominant hand develops within both cognitive and motor-related functional networks. After skill acquisition, subjects performed the SRT task with their right hands, and sequence transfer was tested with the original and a mirror-ordered sequence. With the original sequence, the stimulus sequence and series of response locations remained unchanged, but the finger movements were different. With the mirror-ordered sequence, the response sequence involved finger movements homologous to those used during training. Performance of the original and mirror sequence by the right hand was significantly better than with random stimuli. Mirror transformation of the sequence by the right hand was associated with a marked increase in regional activity in the left motor cortex, consistent with a role for sequential transformation at this level of the motor output pathway.

Adult↗

Cerebellar involvement in response reassignment rather than attention.

A number of functional hypotheses have recently been advanced to account for how the cerebellum may contribute to cognition. Neuropsychological studies suggest the cerebellum is involved in switching attentional set. We present evidence that fails to support this hypothesis. Rather, we propose that in such tasks, the cerebellum is involved with the remapping of response alternatives to different types of stimuli. In our experiment, participants fixated on the center of a screen onto which a random presentation of four visual stimuli was presented. The stimuli were grouped along two dimensions (color: red square or blue square; shape: white circle or white triangle). Participants were instructed to respond with a button press only to presented stimuli for a particular dimension (e.g., red squares), to switch between two dimensions (where the target on the attended dimension served both as a signal for a response and as an indicator to shift attention to the other dimension), or to switch attention between two dimensions but make an overt response only to targets on one of the dimensions. Using functional imaging, we identify areas of lateral cerebellar cortex that are recruited when subjects must reassign motor responses to different stimuli. Furthermore, we demonstrate that switching of attention between dimensions without a motor response does not produce stronger activation within the cerebellum compared with conditions involving response and attention to a single dimension. These results suggest the cerebellum is involved in response reassignment.

Adult↗

Neural substrates of response-based sequence learning using fMRI.

Representation of sequential structure can occur with respect to the order of perceptual events or the order in which actions are linked. Neural correlates of sequence retrieval associated with the order of motor responses were identified in a variant of the serial reaction time task in which training occurred with a spatially incompatible mapping between stimuli and finger responses. After transfer to a spatially compatible version of the task, performance enhancements indicative of learning were only present in subjects required to make finger movements in the same order used during training. In contrast, a second group of subjects performed the compatible task using an identical sequence of stimuli (and different order of finger movements) as in training. They demonstrated no performance benefit, indicating that learning was response based. Analysis was restricted to subjects demonstrating low recall of the sequence structure to rule out effects of explicit awareness. The interaction of group (motor vs. perceptual transfer) with sequence retrieval (sequencing vs. rest) revealed significantly greater activation in the bilateral supplementary motor area, cingulate motor area, ventral premotor cortex, left caudate, and inferior parietal lobule for subjects in the motor group (illustrating successful sequence retrieval at the response level). Retrieval of sequential responses occurs within mesial motor areas and related motor planning areas.

Adolescent↗