Biomedical subjects

D C Noll

Publications and source records attributed to D C Noll.

At least 19 recordsLinked to original sources

PubMed2006

Bilateral basal ganglia activation associated with sensorimotor adaptation.

Sensorimotor adaptation tasks can be classified into two types. When subjects adapt movements to visual feedback perturbations such as in prism lens adaptation, they perform kinematic adaptations. When subjects adapt movements to force field perturbations such as with robotic manipulanda, they perform kinetic adaptations. Neuroimaging studies have shown basal ganglia involvement in kinetic adaptations, but have found little evidence of basal ganglia involvement in kinematic adaptations, despite reports of deficits in patients with diseases of the basal ganglia, such as Parkinson's and Huntington's disease, in these. In an effort to resolve such apparent discrepancy, we used FMRI to focus on the first few minutes of practice during kinematic adaptation. Human subjects adapted to visuomotor rotations in the context of a joystick aiming task while lying supine in a 3.0 T MRI scanner. As demonstrated previously, early adaptive processes were associated with BOLD activation in the cerebellum and the sensory and motor cortical regions. A novel finding of this study was bilateral basal ganglia activation. This suggests that, at least for early learning, the neural correlates of kinematic adaptation parallel those of other types of skill learning. We observed activation in the right globus pallidus and putamen, along with the right prefrontal, premotor and parietal cortex, which may support spatial cognitive processes of adaptation. We also observed activation in the left globus pallidus and caudate nucleus, along with the left premotor and supplementary motor cortex, which may support the sensorimotor processes of adaptation. These results are the first to demonstrate a clear involvement of basal ganglia activation in this type of kinematic motor adaptation.

Adaptation, Physiological↗

PubMed2006

Working memory for order and the parietal cortex: an event-related functional magnetic resonance imaging study.

Memory for order information has been tied to the frontal lobes, however, parietal activation is observed in many functional neuroimaging studies. Here we report functional magnetic resonance findings from an event-related experiment involving working memory for order. Five letters were presented for storage, followed after a delay by two probe items. Probe items could be separated by zero to three positions in the memory set and subjects had to indicate whether the items were in the correct order. Analyses indicate that activation in left parietal cortex shows a systematic decrease in activation with increasing probe distance. This finding is consistent with an earlier study in which we suggested that parietal cortical regions mediate the representation of order information via magnitude codes.

Adult↗

PubMed2004

Feedforward and feedback processes in motor control.

In this study, we utilized functional magnetic resonance imaging (fMRI) to examine which brain regions contribute to feedback and feedforward motor control processes. Several studies have investigated the contributions of cortical and subcortical brain regions to motor performance by independently varying factors such as movement rate, force, and speed, and observing the neural responses. Such studies have contributed greatly to our understanding of neural coding of movement variables. Under natural movement conditions, however, these factors interact in a complex manner to produce differing performance levels. In the current investigation, we induced performance changes in a less constrained way, by having subjects move a joystick to hit targets of differing sizes on an LCD screen. These parametric changes in target size resulted in the well-known speed-accuracy tradeoff effect, allowing us to examine the brain regions responsive to global shifts in motor performance levels. That is, movements made to larger targets relied more on feedforward control whereas movements made to smaller targets relied more on feedback control. Using functional MRI, we identified two sets of brain regions in which activation was modulated with task difficulty. Areas exhibiting activation that was positively correlated with increasing target size included primary motor cortex, premotor cortex, and the basal ganglia, regions that are typically classified as playing a role in force control and movement planning. Brain regions whose activation was negatively correlated with increasing target size included the ipsilateral sensorimotor cortex, multiple cerebellar regions, and the thalamus. These areas contributed to motor performance under higher levels of task difficulty. The results elucidate cortical and subcortical brain regions that are responsive to global shifts in motor performance, reflecting changes along the continuum of feedforward and feedback motor control.

Adult↗

PubMed2002

T(2)(*) dependence of low frequency functional connectivity.

Resting state low frequency (<0.08 Hz) fluctuations in MR timecourses that are temporally correlated between functionally related areas have been observed in recent studies. These fluctuations have been assumed to arise from spontaneous blood oxygenation level-dependent (BOLD) oscillations. This work examines the T(2)(*) characteristics of the low frequency fluctuations (functional connectivity) and compares them to those of task activation induced signal changes. Multi-echo spiral data were fit using a mono-exponential decay model to generate T(2)(*) and intensity (I(0)) parameter timecourses. Resultant correlation maps show that both functional connectivity and BOLD activation modulate T(2)(*), not I(0). Regression analysis also finds that both have a linear dependence on echo time. Thus, functional connectivity and task activation MR signal changes appear to arise from the same BOLD-related origins.

Brain Mapping↗

PubMed2002

Cerebellar hemispheric activation ipsilateral to the paretic hand correlates with functional recovery after stroke.

An experimental lesion in the primary motor or sensory cortices in monkeys leads to functional reorganization in areas surrounding the lesion or in contralateral homologous regions. In humans, task-dependent brain activation after motor stroke seems to be multifocal and bilateral. Although many active structures are seen after stroke, their roles are unclear. For instance, the uninjured primary motor cortex may play a significant role in recovery or may be associated with mirror movements. Other motor areas, particularly those outside the affected middle cerebral artery distribution, have also been thought to play such a role, including the medial pre-motor areas and both cerebellar hemispheres. The lateral pre-motor areas might also contribute but the demarcation of primary motor and pre-motor cortices is not trivial. It is not known from existing studies how brain activation relates to behavioural change over the time course of recovery. We used functional MRI (fMRI) to study 12 patients longitudinally over the first 6 months of stroke recovery. All subjects had acute stroke causing unilateral arm weakness and had some ability to move the impaired hand within 1 month. Each patient had both motor testing and fMRI during finger and wrist movements at four points during the observed period. Six of these patients showed good motor recovery, whereas the other six did not. The imaging results support a role for the cerebellum in mediating functional recovery from stroke. The data suggest that patients with good recovery have clear changes in the activation of the cerebellar hemisphere opposite the injured corticospinal tract. Patients with poor recovery do not show such changes in cerebellar activation. No other brain region had a significant correlation with recovery. Interestingly, activation in the cerebellum ipsilateral to the injury increases transiently after stroke, independently of the success of recovery. The present work suggests a possible link between cerebellar activation and behavioural recovery from hand weakness from stroke. The underlying mechanism is not known, but it could relate to haemodynamic changes such as diaschisis or to the postulated role of the cerebellum in motor skill learning.

Acute Disease↗

PubMed2001

Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia.

BACKGROUND: Previously we proposed that dorsolateral prefrontal cortex (PFC) supports a specific working memory (WM) subcomponent: the ability to represent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented in such a form that it supports selection of the appropriate behavioral response. Furthermore, we hypothesized that WM deficits in schizophrenia reflect impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medication-naive, first-episode patients with schizophrenia during a WM, task-isolating context processing. METHODS: Fourteen first-episode, medication-naive patients with schizophrenia and 12 controls similar in age, sex, and parental education underwent functional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test. RESULTS: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed intact activation of posterior and inferior PFC. In addition, patients demonstrated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands. CONCLUSIONS: These results demonstrate selectivity in dorsolateral PFC dysfunction among medication-naive first-episode patients with schizophrenia, suggesting that a specific deficit in PFC function is present at illness onset, prior to the administration of medication or the most confounding effects of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impairment in context processing due to a disturbance in dorsolateral PFC function.

Adult↗

PubMed2001

Sensitivity of prefrontal cortex to changes in target probability: a functional MRI study.

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right-handed adults were scanned using a gradient-echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but "X". The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability.

Adolescent↗

PubMed2001

The anatomy of auditory word processing: individual variability.

This study used functional magnetic resonance imaging (fMRI) to investigate the neural substrate underlying the processing of single words, comparing activation patterns across subjects and within individuals. In a word repetition task, subjects repeated single words aloud with instructions not to move their jaws. In a control condition involving reverse speech, subjects heard a digitally reversed speech token and said aloud the word "crime." The averaged fMRI results showed activation in the left posterior temporal and inferior frontal regions and in the supplementary motor area, similar to previous PET studies. However, the individual subject data revealed variability in the location of the temporal and frontal activation. Although these results support previous imaging studies, demonstrating an averaged localization of auditory word processing in the posterior superior temporal gyrus (STG), they are more consistent with traditional neuropsychological data, which suggest both a typical posterior STG localization and substantial individual variability. By using careful head restraint and movement analysis and correction methods, the present study further demonstrates the feasibility of using overt articulation in fMRI experiments.

Adult↗

PubMed2001

Lateralization of motor circuits and handedness during finger movements.

Although functional lateralization in the human brain has been studied intensively, there remains significant controversy over the brain mechanisms that instantiate it. The main objective of the present study is to characterize the regions associated with the generation of different movements by the fingers of both hands by right- and left-handed people. Thirteen right- and left-handers were studied using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during performance of single and sequential finger movement tasks. We used single-shot whole-brain spiral fMRI to map the functional components of the motor system during these tasks. Regions of interest included the primary motor and sensory cortices, the pre-motor cortices and the cerebellum. Sequential movements were associated with intense brain activation in several bilateral regions, whereas single movements were associated with less activation in fewer regions, but with greater laterality. Right- and left-handers differed in their pattern of activation, sharing a pattern of activation on simple movements but responding differently to sequential movements. On simple movements, the brain activation patterns of left- and right-handers were similar in volume, number of areas and laterality. By contrast, on sequential movement, left-handers activated larger volumes and a larger number of brain areas than right-handers, and showed significantly less brain lateralization. These results highlight differences in the functional organization of motor areas in right- and left-handed people. The discrepancies that might reflect differences in the network features of motor systems in these two groups, could also determine differences in motor activity that occur during recovery from injury (e.g. after stroke).

Adult↗

PubMed2001

Somatotopy in human primary motor and somatosensory hand representations revisited.

High-resolution functional magnetic resonance imaging of healthy volunteers was used to study the functional anatomy of the human primary motor (M1) and somatosensory (S1) cortical hand representations during simple movements of thumb, little finger and wrist and a sequential movement of the middle three fingers. Rest served as a control state. The results demonstrated an orderly somatotopy in both M1 and S1, even though the cortical areas active with individual movements significantly overlapped. Moreover, the activation patterns in M1 and S1 differed in three aspects: (i) S1 activation was distributed into significantly more clusters than M1 and the primary cluster was smaller; (ii) the overlaps of areas active with different movements were significantly larger in M1 than in S1; (iii) the difference between the three-finger sequential movement and the single-finger movements was more pronounced in S1 than in M1. The sequence-activated S1 cortex was distributed into significantly more clusters. There was also a trend for a bigger volume difference between sequence and the single finger movements in S1 than M1. These data suggest that while the distributed character dominates in M1 and S1, a somatotopic arrangement exists for both M1 and S1 hand representations, with the S1 somatotopy being more discrete and segregated, in contrast to the more integrated and overlapping somatotopy in M1.

Adult↗

PubMed2001

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.

Adult↗

PubMed2000

Three-dimensional tailored RF pulses for the reduction of susceptibility artifacts in T(*)(2)-weighted functional MRI.

A three-dimensional tailored RF pulse method for reducing intravoxel dephasing artifacts in T *(2)-weighted functional MRI is presented. A stack of spirals k-space trajectory is employed to excite a disk of magnetization for small tip angles. Smaller disks with a linear through-plane phase are inserted into the disk to locally refocus regions which are normally dephased due to susceptibility variations. Numerical simulations and imaging experiments which use the tailored RF pulses are presented. Limitations of the method and improvements are also discussed.

Artifacts↗

PubMed2000

Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex.

Investigations of working memory (WM) systems in the frontal cortex have revealed two stimulus dimensions along which frontal cortical representations may be functionally organized. One hypothesized dimension dissociates verbal from nonverbal WM processes, dividing left from right frontal regions. The second hypothesized dimension dissociates spatial from nonspatial WM, dividing dorsal from ventral frontal regions. Here we used functional magnetic resonance imaging to probe WM processes associated with three different types of stimuli: letters (verbal and nonspatial), abstract shapes (nonverbal and nonspatial), and locations (nonverbal and spatial). In a series of three experiments using the "n-back" WM paradigm, direct statistical comparisons were made between activation patterns in each pairwise combination of the three stimulus types. Across the experiments, no regions that demonstrated responses to WM manipulations were discovered to be unique to any of the three stimulus types. Therefore, no evidence was found to support either a left/right verbal/nonverbal dissociation or a dorsal/ventral spatial/nonspatial dissociation. While this could reflect a limitation of the present behavioral and imaging techniques, other factors that could account for the data are considered, including subjects' strategy selection, encoding of information into WM, and the nature of representational schemes in prefrontal cortex.

Adolescent↗

PubMed2000

Tracking the hemodynamic responses to reward and punishment in the striatum.

Research suggests that the basal ganglia complex is a major component of the neural circuitry that mediates reward-related processing. However, human studies have not yet characterized the response of the basal ganglia to an isolated reward, as has been done in animals. We developed an event-related functional magnetic resonance imaging paradigm to identify brain areas that are activated after presentation of a reward. Subjects guessed whether the value of a card was higher or lower than the number 5, with monetary rewards as an incentive for correct guesses. They received reward, punishment, or neutral feedback on different trials. Regions in the dorsal and ventral striatum were activated by the paradigm, showing differential responses to reward and punishment. Activation was sustained following a reward feedback, but decreased below baseline following a punishment feedback.

Adult↗

PubMed2000

Anterior cingulate and the monitoriing of response conflict: evidence from an fMRI study of overt verb generation.

Studies of a range of higher cognitive functions consistently activate a region of anterior cingulate cortex (ACC), typically posterior to the genu and superior to the corpus collosum. In particular, this ACC region appears to be active in task situations where there is a need to override a prepotent response tendency, when responding is underdetermined, and when errors are made. We have hypothesized that the function of this ACC region is to monitor for the presence of "crosstalk" or competition between incompatible responses. In prior work, we provided initial support for this hypothesis, demonstrating ACC activity in the same region both during error trials and during correct trials in task conditions designed to elicit greater response competition. In the present study, we extend our testing of this hypothesis to task situations involving underdetermined responding. Specifically, 14 healthy control subjects performed a verb-generation task during event-related functional magnetic resonance imaging (fMRI), with the on-line acquisition of overt verbal responses. The results demonstrated that the ACC, and only the ACC, was more active in a series of task conditions that elicited competition among alternative responses. These conditions included a greater ACC response to: (1) Nouns categorized as low vs. high constraint (i.e., during a norming study, multiple verbs were produced with equal frequency vs. a single verb that produced much more frequently than any other); (2) the production of verbs that were weak associates, rather than, strong associates of particular nouns; and (3) the production of verbs that were weak associates for nouns categorized as high constraint. We discuss the implication of these results for understanding the role that the ACC plays in human cognition.

Adolescent↗

PubMed1999

Systematic noise compensation for simultaneous multislice acquisition using rosette trajectories (SMART).

Simultaneous multislice acquisition using rosette trajectories (SMART) is a recently introduced functional magnetic resonance imaging pulse sequence that offers high-speed data acquisition by simultaneously exciting several slices. A drawback to its benefit of rapid acquisition is the cumulative effect of the systematic noise present in the off-resonant slices. In this work, a systematic noise compensation method is implemented to gauge the performance of the multislice SMART method versus a single-slice rosette method in a motor activation study. The normalized standard deviation of the noise-compensated image timecourse is reduced by 25% (single-slice rosette) and 62% (SMART), and the normalized volume of motor activation is increased by 25% (single-slice rosette) and 44% (SMART). The noise-compensated SMART method has an average timecourse standard deviation only 9% higher than the noise-compensated single-slice rosette method, while increasing the acquisition rate threefold.

Artifacts↗

PubMed1999

3D spiral cardiac/respiratory ordered fMRI data acquisition at 3 Tesla.

Three-dimensional (3D), multi-shot functional magnetic resonance imaging (fMRI) data acquisitions are desirable because of higher resolution and reduced susceptibility artifacts, due to shorter readouts and thinner slices. However, 3D multi-shot techniques are more susceptible to physiological noise, which can increase inter-image variance and lead to inaccurate assessment of activation. This work presents a 3D spiral fMRI data acquisition method at 3 T in which the acquisition of views was ordered to match the phase of either the respiratory or the cardiac cycle. For the acquisition timing parameters used in this work, cardiac ordering was found to reduce inter-image variance by 19%. Cardiac ordered data acquisitions showed the same reduction in variance as sequentially ordered data with cardiac contributions estimated and removed using an externally acquired reference prior to reconstruction. Respiratory ordering showed no reduction in fluctuation noise due to poor alignment of views to the respiratory phase.

Algorithms↗

PubMed1999

A direct comparison between whole-brain PET and BOLD fMRI measurements of single-subject activation response.

We present the results of a direct comparison of single-subject activation using identical tasks for both functional PET and fMRI whole-brain studies. We examined the most commonly employed methods for each modality. For fMRI this is the blood oxygenation level-dependent (BOLD) contrast method with echo-planar imaging. In PET single-subject activation studies are based on the development of high sensitivity 3D imaging of regional cerebral blood flow from multiple [15O]water injections. The identical activation paradigm of a visually cued sequential finger opposition was used for PET and fMRI. For both modalities the entire brain volume difference images were smoothed to the same final resolution and the peak t value within the primary sensory/motor (PSM) area was then identified. All contiguous voxels in the PSM above a predetermined threshold of statistical significance were determined. Finally, the difference-weighted centroid location was calculated for the PSM region for each modality. These studies showed a very similar pattern of activation, with the volume of activation greater in fMRI and higher levels of statistical significance. The centroids of activation, however, differed by 9 +/- 3 mm between the modalities, with the fMRI centroid location dorsal to that for PET. These results were stable across all processing options including differing levels of image smoothing and thresholds of statistical significance. These results are consistent with the hypothesis that draining veins contribute a substantial signal for fMRI activation studies and indicate caution for the interpretation of BOLD fMRI images with activation sites near draining veins.

Adult↗