Biomedical subjects

Simon J Graham

Publications and source records attributed to Simon J Graham.

At least 19 recordsLinked to original sources

PubMed2007

Improving functional magnetic resonance imaging motor studies through simultaneous electromyography recordings.

Specially designed optoelectronic and data postprocessing methods are described that permit electromyography (EMG) of muscle activity simultaneous with functional MRI (fMRI). Hardware characterization and validation included simultaneous EMG and event-related fMRI in 17 healthy participants during either ankle (n = 12), index finger (n = 3), or wrist (n = 2) contractions cued by visual stimuli. Principal component analysis (PCA) and independent component analysis (ICA) were evaluated for their ability to remove residual fMRI gradient-induced signal contamination in EMG data. Contractions of ankle tibialis anterior and index finger abductor were clearly distinguishable, although observing contractions from the wrist flexors proved more challenging. To demonstrate the potential utility of simultaneous EMG and fMRI, data from the ankle experiments were analyzed using two approaches: 1) assuming contractions coincided precisely with visual cues, and 2) using EMG to time the onset and offset of muscle contraction precisely for each participant. Both methods produced complementary activation maps, although the EMG-guided approach recovered more active brain voxels and revealed activity better in the basal ganglia and cerebellum. Furthermore, numerical simulations confirmed that precise knowledge of behavioral responses, such as those provided by EMG, are much more important for event-related experimental designs compared to block designs. This simultaneous EMG and fMRI methodology has important applications where the amplitude or timing of motor output is impaired, such as after stroke.

Adult↗

PubMed2006

Clustered functional MRI of overt speech production.

To investigate the neural network of overt speech production, event-related fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speech-related movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the cortical and subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum, reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

Acoustic Stimulation↗

PubMed2006

In vivo characterization of traumatic brain injury neuropathology with structural and functional neuroimaging.

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior.

Brain Injuries↗

PubMed2005

Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Hemiparesis is the commonest disabling deficit caused by stroke. In animals, dextroamphetamine (AMPH) paired with training enhances motor recovery, but its clinical efficacy is uncertain. METHODS: In a randomized, double-blind, placebo-controlled trial, 71 stroke patients were stratified by hemiparesis severity and randomly assigned to 10 sessions of physiotherapy coupled with either 10 mg AMPH or placebo. Study treatments were administered by 1 physiotherapist, beginning 5 to 10 days after stroke and continuing twice per week for 5 weeks. Outcomes were assessed by 1 physiotherapist at baseline, after each treatment session, at 6 weeks, and at 3 months. The primary outcome was motor recovery (impairment level) on the Fugl-Meyer (FM) scale. Secondary outcomes assessed mobility, ambulation, arm/hand function, and independence in activities of daily living. RESULTS: Baseline hemiparesis was severe overall (mean FM score 27.7+/-20.0). Motor scores improved during treatment in both groups (mean change, baseline to 3 months 29.5+/-16.6). Repeated-measures ANOVA revealed no significant differences in recovery between the treatment groups for the entire cohort (n=67) or for subgroups with a severe hemiparesis (n=43), moderate hemiparesis (n=24), or cortically based stroke (n=26). In the moderate subgroup, there was a significant drug x time interaction for upper extremity motor recovery (F=5.14; P<0.001), although there was a significant baseline imbalance in motor scores in this subgroup. CONCLUSIONS: In stroke patients with a severe motor deficit, 10 mg AMPH coupled with physiotherapy twice per week for 5 weeks in the early poststroke period provided no additional benefit in motor or functional recovery compared with physiotherapy alone. Patients with moderate severity hemiparesis deserve further investigation. Increased intensity and longer duration drug/therapy dosing regimens should be explored, targeting the upper and lower limbs separately.

Aged↗

PubMed2005

An fMRI study of the Trail Making Test.

This study investigated the cerebral correlates of the Trail Making Test (TMT), used commonly as a measure of frontal lobe function. Such work sheds additional light on the known shortcomings of the TMT as a localizing instrument, as indicated, for example, by studies of patients with focal brain lesions. Functional magnetic resonance imaging (fMRI) was used to record brain activity while participants performed the TMT using a custom-built, fiber-optic fMRI-compatible writing device, the "virtual stylus". Unlike in a previous fMRI study that used a verbal adaptation of the TMT, the virtual stylus enabled a closer depiction of the brain regions engaged by the actual paper-and-pencil task. Twelve, right-handed healthy young adults participated. In Part A of the task, participants were required to link in ascending order numbers (1-2-3 ...) that were randomly distributed on a computer screen. In Part B, participants were required to link alternately between numbers and letters (1-A-2-B ...). Although behavioral performance was somewhat less than typically obtained with the TMT due to use of the virtual stylus, distinct left-sided dorsolateral and medial frontal activity was revealed when comparing Part B versus Part A. These findings agree with existing literature showing sensitivity of the TMT to frontal regions in the left hemisphere. However, other activity was also observed (left middle and superior temporal gyrus) reinforcing that the brain-behavior correlations for the TMT are multifaceted and not restricted to the frontal lobe.

Adult↗

PubMed2005

Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe.

CONTEXT: The pathophysiology of major depressive disorder (MDD) includes disturbances in several neuroanatomical substrates and neurotransmitter systems. The challenge is to elucidate the brain mechanisms of MDD behavioral symptoms, chiefly those of anhedonia. OBJECTIVES: To visualize the neuroanatomical substrates implicated in altered reward processing in MDD, using functional magnetic resonance imaging in combination with a dopaminergic probe (a 30-mg dose of oral dextroamphetamine sulfate) to stimulate the brain reward system; and to test the hypothesis that a hypersensitive response to dextroamphetamine in MDD involves the prefrontal cortex and the striatum. DESIGN AND INTERVENTIONS: Among subjects with MDD and healthy control subjects, functional magnetic resonance imaging data were collected before and after single-blind administration of dextroamphetamine. SETTING: Subjects were recruited through local newspaper advertisements and by word of mouth. PARTICIPANTS: Twelve depressed subjects (mean age, 34.83 years; male-female ratio, 6:6) met criteria for MDD according to the DSM-IV, were not taking antidepressants, and had no comorbid Axis I disorders. Twelve control subjects (mean age, 29.33 years; male-female ratio, 5:7) were healthy volunteers without a history of Axis I disorders. MAIN OUTCOME MEASURES: Functional magnetic resonance imaging blood oxygen level-dependent activation was measured during a controlled task, and dextroamphetamine-induced subjective effects were assessed using the Addiction Research Center Inventory. RESULTS: Subjects with MDD had a hypersensitive response to the rewarding effects of dextroamphetamine (2-fold increase; t(21) = 2.74, P = .01), with altered brain activation in the ventrolateral prefrontal cortex and the orbitofrontal cortex and the caudate and putamen (F(1,44) = 11.93, P = .001). CONCLUSION: Dopamine-related neuroanatomical substrates are involved in altered reward processing in MDD, shedding light on the neurobiology of the anhedonic symptoms in MDD and suggesting these substrates as future therapeutic targets.

Adult↗

PubMed2005

Retrospective coregistration of functional magnetic resonance imaging data using external monitoring.

Coregistration is essential for correcting head motion artifacts in functional magnetic resonance imaging (fMRI). Coregistration algorithms typically realign images through optimization of a similarity measure based on voxel signal intensities. However, coregistration can also be performed through external monitoring, whereby a tracking device measures head motion directly and independently of the imaging data. This paper describes development of external monitoring using fMRI-compatible infrared cameras. Three subjects participated in block-design fMRI experiments consisting of bilateral finger tapping alone and tapping combined with visuomotor tracking to produce controlled task-correlated head motion. Functional MRI time-series were coregistered using the external monitoring technique and a known image-based algorithm for comparison. Over various performance characteristics, external monitoring and image-based coregistration exhibited good agreement, in particular reducing signals correlated with millimeter task-correlated motions by 50-100%, with a 5% difference between the two techniques. These results promise future applications and refinements of external monitoring in patient populations where head motion is especially problematic. Possibilities include 3D prospective coregistration during real-time fMRI, coregistration of individual slices, and motion correction in anatomic MRI.

Adult↗

PubMed2005

T1, T2 relaxation and magnetization transfer in tissue at 3T.

T1, T2, and magnetization transfer (MT) measurements were performed in vitro at 3 T and 37 degrees C on a variety of tissues: mouse liver, muscle, and heart; rat spinal cord and kidney; bovine optic nerve, cartilage, and white and gray matter; and human blood. The MR parameters were compared to those at 1.5 T. As expected, the T2 relaxation time constants and quantitative MT parameters (MT exchange rate, R, macromolecular pool fraction, M0B, and macromolecular T2 relaxation time, T2B) at 3 T were similar to those at 1.5 T. The T1 relaxation time values, however, for all measured tissues increased significantly with field strength. Consequently, the phenomenological MT parameter, magnetization transfer ratio, MTR, was lower by approximately 2 to 10%. Collectively, these results provide a useful reference for optimization of pulse sequence parameters for MRI at 3 T.

Animals↗

PubMed2005

A functional magnetic resonance imaging (FMRI) study of cue-induced smoking craving in virtual environments.

Smokers who are exposed to smoking-related cues show cardiovascular reactivity and smoking craving compared with their responses to neutral cues, and increased cue reactivity predicts decreased likelihood of successful cessation. Several brain imaging studies suggested four candidate brain regions that might differ in gray matter volumes and densities between smokers and nonsmokers. However, in these studies, smokers were only exposed to smoking-related objects. In our pilot study utilizing a virtual reality (VR) technique, virtual environments (VEs) were more immersive and evoked smoking craving more effectively than traditionally used methods. In this study, we sought to test whether smokers could experience cue-induced smoking craving inside the MRI scanner by using the VR system. The smoking cue reactivity scenario was based in part on our preliminary task and consisted of 2D and 3D (or VE) conditions. The group mean of participants had increased activity in the prefrontal cortex (PFC), left anterior cingulate gyrus (ACC), left supplementary motor area, left uncus, right inferior temporal gyrus, right lingual gyrus, and right precuneus in the 2D condition. Areas of differential activation in the 3D condition were as follows: left superior temporal gyrus, right superior frontal gyrus, and left inferior occipital gyrus in the 3D condition. This finding is consistent with those of previous studies of nicotine craving showing PFC and ACC activation. However, in the 3D condition, the PFC including the superior frontal gyrus as well as the superior temporal gyrus, inferior occipital gyrus, and cerebellum were activated. Therefore, in the 3D condition, participants seemed to have more attention, visual balance, and coordinating movement than in the 2D condition.

Adolescent↗

PubMed2004

Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis.

Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naive, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire profile search and K-mean cluster analysis. Microarray-based data for a subset of genes were validated using real-time PCR TaqMan analysis. Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression. The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling. Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease. The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development. In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat. These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).

Animals↗

PubMed2004

Activation in SI and SII: the influence of vibrotactile amplitude during passive and task-relevant stimulation.

Using functional magnetic resonance imaging (fMRI), responses in human somatosensory cortex were quantified in response to changes in the amplitude of peripheral stimulation during (1) passive vibration and (2) an attention-demanding tactile tracking task whereby changes in vibration amplitude were used to guide motor behaviour. Functional MRI was conducted using a scanner operating at 1.5 T, and vibration was delivered to the volar surface of the right index finger with a custom-built magnetomechanical device. Results showed that primary somatosensory cortex (SI) reliably reflects changes in vibration amplitude applied to the finger during passive vibration and also in the presence of a task that modulates the activity in SI. Secondary somatosensory cortex did not reveal any clear relationship with vibration amplitude but was more often activated during the attention demanding tracking task compared with passive vibration. The present study supports an increasing stimulus-response relationship between vibrotactile stimuli and activity in SI that persists during attentive, active states.

Adult↗

PubMed2004

An integrative MEG-fMRI study of the primary somatosensory cortex using cross-modal correspondence analysis.

We develop a novel approach of cross-modal correspondence analysis (CMCA) to address whether brain activities observed in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) represent a common neuronal subpopulation, and if so, which frequency band obtained by MEG best fits the common brain areas. Fourteen adults were investigated by whole-head MEG using a single equivalent current dipole (ECD) and synthetic aperture magnetometry (SAM) approaches and by fMRI at 1.5 T using linear time-invariant modeling to generate statistical maps. The same somatosensory stimulus sequences consisting of tactile impulses to the right sided: digit 1, digit 4 and lower lip were used in both neuroimaging modalities. To evaluate the reproducibility of MEG and fMRI results, one subject was measured repeatedly. Despite different MEG dipole locations and locations of maximum activation in SAM and fMRI, CMCA revealed a common subpopulation of the primary somatosensory cortex, which displays a clear homuncular organization. MEG activity in the frequency range between 30 and 60 Hz, followed by the ranges of 20-30 and 60-100 Hz, explained best the defined subrepresentation given by both MEG and fMRI. These findings have important implications for improving and understanding of the biophysics underlying both neuroimaging techniques, and for determining the best strategy to combine MEG and fMRI data to study the spatiotemporal nature of brain activity.

Adult↗

PubMed2004

Distributed self in episodic memory: neural correlates of successful retrieval of self-encoded positive and negative personality traits.

Words processed with reference to the self are generally better remembered than words processed in semantic terms. An account of this phenomenon, labeled the Self Reference Effect (SRE), is that the self promotes elaboration and organization of encoded information. Although a few neuroimaging studies associated self-referential encoding with activations of the medial prefrontal cortex, no previous study has investigated the neural correlates of remembering emotional words encoded in an SRE paradigm. The main goal of this study was to define with fMRI the neural correlates of the successful retrieval of negative and positive personality traits encoded in a self-referential mode. Functional MRI scans were acquired for 11 subjects as they recognized positive and negative emotional personality traits adjectives encoded in a self-referential condition, a semantic condition and in a phonemic condition. The correct recognition of self-encoded personality traits engaged dorso-medial prefrontal cortex and lateral prefrontal regions, premotor cortex, parietal and occipital cortex, caudate and cerebellum. The specific recognition of self-encoded negative personality traits involved greater neural activation in the right extra-striate region than the recognition of positive personality traits. Our fMRI findings suggest that specific processes may operate at both encoding and retrieval to subserve the SRE. Unlike self-encoding, the retrieval of personality traits is modulated by the valence of the stimuli with greater activation for negative words. Our results indicate that personally relevant words may signal important emotional clues and support the notion of a widely distributed set of brain regions involved in maintaining the concepts of self.

Adult↗

PubMed2004

Optimizing the experimental design for ankle dorsiflexion fMRI.

Compared to motor studies of the upper limb, few experiments have sought a relationship between blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) sensorimotor signals and the resulting lower limb output. In Experiment 1, using an fMRI simulator system, we determined the optimized experimental protocol based on two design types and four behavioral movement types during ankle dorsiflexion. Experiment 2 involved testing the BOLD sensitivity at 1.5 T during ankle movements. Subjects performed large- and small-amplitude dorsiflexion movement types using an event-related design, with the intent of contrasting spatial and temporal features of the BOLD signal. In both experiments, the subject's behavior was guided by visual biofeedback of their ankle flexion angle, using an MR-compatible fiberoptic tape. From Experiment 1, we found electromyography (EMG) difference voltage ratio of approximately 2:1 for large (40 degrees ) and small (15 degrees ) dorsiflexion, 0.13 mV and 0.07 mV, respectively. In Experimental 2, we found the peak BOLD % signal changes of 1.04% and 0.89%, for large (40 degrees ) and small (15 degrees ) dorsiflexion, respectively. In addition, graded dorsiflexion produced graded BOLD signals in the primary sensorimotor and supplementary motor areas in 10 of 12 healthy young subjects, attesting to the feasibility of lower-limb fMRI at 1.5 T. This study provides insight into the cortical network involved in dorsiflexion using an experimental paradigm that is likely to translate effectively to hemiparetic stroke subjects.

Adult↗

PubMed2004

Nicotine craving and cue exposure therapy by using virtual environments.

Smokers who are exposed to cues associated with smoking show cardiovascular reactivity and an increase in smoking urges as compared to when they are presented with neutral cues. Cue exposure therapy (CET), which refers to the repeated exposure to drug-related cues in order to extinguish this learned association, has increasingly been proposed as a potential treatment of addictive behaviors, including tobacco smoking. The result of our pilot study suggests that a cue elicited using a virtual environment (VE) is more effective than other cue exposure devices. The VE was composed of craving environments (virtual bar) and objects (an alcoholic drink, a packet of cigarettes, a lighter, an ashtray, a glass of beer, and advertising posters) that are likely to trigger craving, a smoking avatar, and an audio environment that included the noisy sound and music of a restaurant. Sixteen late-adolescent males who smoked at least 10 cigarettes a day were recruited to participate in the VE-CET study. The CET virtual bar program consisted of six sessions, and the participants were exposed repeatedly to each session using different questions and procedures. Although the effects of CET did not yield significant reductions in all of the dependent variables, the craving for cigarettes was gradually decreased during the course of the sessions. This tendency was closely related to the reduction in the smoking count between the morning before the experiment and the start of the experiment. Based on these preliminary results, it appears that VE-CET maybe a useful tool to use in treatment programs to help reduce craving in those who are nicotine dependent.

Adolescent↗

PubMed2004

The functional neuroanatomy of episodic and semantic autobiographical remembering: a prospective functional MRI study.

Autobiographical memory comprises episodic and semantic components mediated by dissociable states of consciousness, one promoting the experience of the self at a specific moment in the past, and the other involving self-knowledge that does not require ''mental time travel.'' These components can be difficult to dissociate using retrospective autobiographical stimuli collection. In this study, we manipulated the episodic/semantic distinction within prospectively collected autobiographical stimuli. Over several months, participants made recordings documenting specific episodes, repeated episodes, and world knowledge. These recordings were later played back to participants during scanning with functional MRI. The results indicated overlapping but distinct patterns of brain activity corresponding to episodic and semantic autobiographical memory. Both episodic and semantic autobiographical memory engaged the left anteromedial prefrontal cortex associated with self-reference, but the episodic condition did so to a greater degree. The episodic condition uniquely engaged the medial temporal, posterior cingulate, and diencephalic regions associated with remote memory recovery. Whereas the episodic condition engaged the right temporo-parietal cortex involved in reconstruction of spatial context and attentional orienting, the semantic condition engaged the left temporo-parietal and parieto-frontal systems involved in egocentric spatial processing and top-down attentional control. Episodic recollection was also associated with suppression of emotional paralimbic regions. These findings support a functional neuroanatomical dissociation between episodic and semantic autobiographical memory, providing concordance to amnesic syndromes with disproportionate impairment in one of these two forms of autobiographical memory.

Adult↗

PubMed2003

An fMRI study investigating cognitive modulation of brain regions associated with emotional processing of visual stimuli.

Brain regions modulated by cognitive tasks during emotional processing were investigated using fMRI. Participants performed indirect and direct emotional processing tasks on positive and negative faces and pictures. We used a multivariate technique, partial least squares (PLS) to determine spatially distributed patterns of brain activity associated with different tasks and stimulus conditions, as well as the interaction between the two. The pattern of brain activity accounting for the most task-related covariance represented a task x stimulus interaction and distinguished indirect processing of pictures and direct processing of faces from direct processing of pictures and indirect processing of faces. The latter two conditions were characterised by limbic (e.g. amygdala, insula, thalamus) and temporal lobe activity, in addition to greater activity in the ventral prefrontal cortex. Indirect and direct processing of pictures and faces, respectively, were represented by more dorsal prefrontal and parietal activity. These findings indicate that brain activity during processing of emotional content is critically dependent on both the type of stimulus and processing task. In addition, these results support the idea that the pattern of activity in the emotional network can be influenced in a 'top-down' fashion via cognitive factors such as attentional control, and as such, have important clinical implications for emotional disorders, such as depression and anxiety.

Adult↗

PubMed2003

A meta-analysis of structural and functional brain imaging in dementia of the Alzheimer's type: a neuroimaging profile.

We conducted a quantitative review of the imaging literature using meta-analytic methodology to characterize further the magnitude of hippocampal deficit in probable Alzheimer's disease (AD) and to determine whether other neuroanatomic structures in AD can better discriminate the disease from normal aging. Additionally, we parceled the discriminability of neuroanatomic structures by duration of disease to determine those structures most sensitive to AD in its early and late stages. One hundred twenty-one studies published between 1984 and 2000 met criteria for inclusion in the present analysis. In total, structural (i.e., CT and MRI) and functional (i.e., SPECT and PET) neuroimaging results from 3511 patients with AD, and 1632 normal healthy controls were recorded across meta-analyses. Our results include neuroimaging profiles for both early onset and longer duration patients with AD. In sum, these profiles yield a signature of diagnostic markers in both cortical and subcortical neuroanatomic areas. This signature is consistent with the clinical phenomenology of Alzheimer's dementia and should aid in the positive identification of AD.

Aged↗