Search PubMed⌕ Search

Biomedical subjects

James B Rowe

Publications and source records attributed to James B Rowe.

13 recordsLinked to original sources
PubMed2025

Proteomic analysis reveals distinct cerebrospinal fluid signatures across genetic frontotemporal dementia subtypes.

We used an untargeted mass spectrometric approach, tandem mass tag proteomics, for the identification of proteomic signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the Genetic FTD Initiative were analyzed, including samples from 107 presymptomatic (44 C9orf72, 38 GRN, and 25 MAPT) and 55 symptomatic (27 C9orf72, 17 GRN, and 11 MAPT) mutation carriers as well as 76 mutation-negative controls ("noncarriers"). We found shared and distinct proteomic alterations in each genetic form of FTD. Among the proteins significantly altered in symptomatic mutation carriers compared with noncarriers, we found that a set of proteins including neuronal pentraxin 2 and fatty acid binding protein 3 changed across all three genetic forms of FTD and patients with Alzheimer's disease from previously published datasets. We observed differential changes in lysosomal proteins among symptomatic mutation carriers with marked abundance decreases in MAPT carriers but not other carriers. Further, we identified mutation-associated proteomic changes already evident in presymptomatic mutation carriers. Weighted gene coexpression network analysis combined with gene ontology annotation revealed clusters of proteins enriched in neurodegeneration and glial responses as well as synapse- or lysosome-related proteins indicating that these are the central biological processes affected in genetic FTD. These clusters correlated with measures of disease severity and were associated with cognitive decline. This study revealed distinct proteomic changes in the CSF of patients with genetic FTD, providing insights into the pathological processes involved in the disease. In addition, we identified proteins that warrant further exploration as diagnostic and prognostic biomarker candidates.

Humans↗
PubMed2006

Aging is associated with contrasting changes in local and distant cortical connectivity in the human motor system.

Pathophysiological changes in neurological and neuropsychiatric diseases are increasingly described in terms of abnormal network connectivity. However, the anatomical integrity and efficacy of connections among multiple brain regions change with aging, even in healthy adults. We combined low-frequency transcranial magnetic stimulation and positron emission tomography to study the age-related changes in regional activation and effective connectivity, associated with voluntary action by healthy adults between 22 and 68 years old. Contrasting effects of aging on the motor network were seen using analyses of regional activation, effective connectivity mediating task-related neuronal activation and effective connectivity in response to transcranial magnetic stimulation. Low-frequency rTMS reduced cerebral blood flow during both movement and resting conditions, at the site of stimulation and neighboring frontal cortex. Aging was associated with increased movement-related activation in premotor cortex, bilaterally. Increasing age also increased the susceptibility of the cortex to the inhibitory effects of rTMS, at the site of stimulation and its contralateral homologue. Moreover, older subjects showed enhanced local effective connectivity, centered on the left premotor cortex, but reduced effective connectivity between distant motor-related cortical areas. We discuss these results in relation to the HAROLD model of aging and propose that there are differential effects of aging on local and distributed neuronal subpopulations in the motor network. This differential effect of aging has important implications for the study of neurodegenerative and cerebrovascular diseases that primarily affect older people, as well as our understanding of the normal aging process.

Adult↗
PubMed2006

An fMRI study of the neural correlates of graded visual perception.

The neural correlates of clearly perceived visual stimuli have been reported previously in contrast to unperceived stimuli, but it is uncertain whether intermediate or graded perceptual experiences correlate with different patterns of neural activity. In this study, the subjective appearance of briefly presented visual stimuli was rated individually by subjects with respect to perceptual clarity: clear, vague or no experience of a stimulus. Reports of clear experiences correlated with activation in a widespread network of brain areas, including parietal cortex, prefrontal cortex, premotor cortex, supplementary motor areas, insula and thalamus. The reports of graded perceptual clarity were reflected in graded neural activity in a network comprising the precentral gyrus, intraparietal sulcus, basal ganglia and the insula. In addition, the reports of vague experiences demonstrated unique patterns of activation. Different degrees of perceptual clarity were reflected both in the degree to which activation was found within parts of the network serving a clear conscious percept, and additional unique activation patterns for different degrees of perceptual clarity. Our findings support theories proposing the involvement of a widespread network of brain areas during conscious perception.

Adult↗
PubMed2005

Frequency specific changes in regional cerebral blood flow and motor system connectivity following rTMS to the primary motor cortex.

Repetitive transcranial magnetic stimulation (rTMS) to the human primary motor cortex (M1) causes bidirectional changes in corticospinal excitability depending on the stimulation frequency used. We used functional brain imaging to compare the effects of 5 Hz and 1 Hz-rTMS on local and inter-regional connectivity within the motor system. Regional cerebral blood flow (rCBF) was measured as a marker of synaptic activity at rest and during freely selected finger movements. We hypothesized that increased cortical excitability induced by 5 Hz-rTMS over M1 has an opposite effect on the synaptic activity and the connectivity of the motor network from the decreased cortical excitability induced by 1 Hz-rTMS. rTMS at both frequencies induced similar changes in rCBF at the site of stimulation and within areas of the motor network engaged by the task. The two frequencies showed different effects on movement-related coupling between motor areas. Connectivity analyses also indicated a differential effect of 5 and 1 Hz-rTMS on motor network connectivity, suggesting a role for an inferomedial portion of left M1 and left dorsal premotor cortex in maintaining performance. These results suggest that rapid reorganization of the motor system occurs to maintain task performance during periods of altered cortical excitability. This reorganization differs according to the modulation of excitability which is a function of rTMS frequency. This study extends the work of Lee et al. (Lee, L., Siebner, H.R., Rowe, J.B., Rizzo, V. Rothwell, J.C. Frackowiak, R.S. Friston, K.J., 2003. Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J. Neurosci. 23, 5308-5318.) by providing evidence that the pattern of acute reorganization in the motor network following rTMS depends on the direction of conditioning.

Adult↗
PubMed2005

Motion or activity: their role in intra- and inter-subject variation in fMRI.

Functional MRI (fMRI) carries the potential for non-invasive measurements of brain activity. Typically, what are referred to as activation images are actually thresholded statistical parametric maps. These maps possess large inter-session variability. This is especially problematic when applying fMRI to pre-surgical planning because of a higher requirement for intra-subject precision. The purpose of this study was to investigate the impact of residual movement artefacts on intra-subject and inter-subject variability in the observed fMRI activation. Ten subjects were examined using three different word-generation tasks. Two of the subjects were examined 10 times on 10 different days using the same paradigms. We systematically investigated one approach of correcting for residual movement effects: the inclusion of regressors describing movement-related effects in the design matrix of a General Linear Model (GLM). The data were analysed with and without modeling the residual movement artefacts and the impact on inter-session variance was assessed using F-contrasts. Inclusion of motion parameters in the analysis significantly reduced both the intra-subject as well as the inter-subject-variance.

Adult↗
PubMed2004

The prefrontal cortex shows context-specific changes in effective connectivity to motor or visual cortex during the selection of action or colour.

The role of the prefrontal cortex remains controversial. Neuroimaging studies support modality-specific and process-specific functions related to working memory and attention. Its role may also be defined by changes in its influence over other brain regions including sensory and motor cortex. We used functional magnetic imaging (fMRI) to study the free selection of actions and colours. Control conditions used externally specified actions and colours. The prefrontal cortex was activated during free selection, regardless of modality, in contrast to modality-specific activations outside prefrontal cortex. Structural equation modelling (SEM) of fMRI data was used to test the hypothesis that although the same regions of prefrontal cortex may be active in tasks within different domains, there is task-dependent effective connectivity between prefrontal cortex and non-prefrontal cortex. The SEM included high-order interactions between modality, selection and regional activity. There was greater coupling between prefrontal cortex and motor cortex during free selection and action tasks, and between prefrontal cortex and visual cortex during free selection of colours. The results suggest that the functions of the prefrontal cortex may be defined not only by selection-specific rather than modality-specific processes, but also by changing patterns of effective connectivity from prefrontal cortex to motor and sensory cortices.

Adult↗
PubMed2003

Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex.

We used PET to examine the pattern and time course of changes produced by repetitive transcranial magnetic stimulation (rTMS) over the dorsal premotor cortex (PMd) in healthy subjects and in patients with primary focal dystonia. Subjects received 1800 stimuli of subthreshold 1 Hz rTMS or sham stimulation to the left PMd. Afterwards, we measured regional cerebral blood flow (rCBF) as a marker of synaptic activity at rest and during performance of freely selected random finger movement. In both groups of subjects, real rTMS caused widespread bilateral decreases in neuronal activity in prefrontal, premotor, primary motor cortex, and left putamen. Conversely, rCBF in the cerebellum increased. Effects were equivalent at rest and during movement, indicating that the pattern of movement-related activation did not change. rTMS-induced changes in neuronal activity lasted for at least 1 h except in the medial aspect of the left globus pallidus. Conditioning effects on neuronal activity were larger in the patients than in the healthy subjects: there was a greater decrease of rCBF in lateral and medial premotor areas, putamen, and thalamus, including the stimulated premotor cortex, and a larger increase in cerebellar rCBF. Our findings indicate that, in healthy subjects and patients with dystonia, a single session of rTMS can produce powerful and widespread changes in regional synaptic activity as indexed by rCBF. Since the greater effects of premotor rTMS were not related to any differences in task performance, increased responsiveness of the motor system to rTMS reveals a physiological trait that characterizes patients with focal arm dystonia.

Adult↗
PubMed2003

Lateralized cognitive processes and lateralized task control in the human brain.

The principles underlying human hemispheric specialization are poorly understood. We used functional magnetic resonance imaging of letter and visuospatial decision tasks with identical word stimuli to address two unresolved problems. First, hemispheric specialization depended on the nature of the task rather than on the nature of the stimulus. Second, analysis of frontal candidate regions for cognitive control showed increased coupling between left anterior cingulate cortex (ACC) and left inferior frontal gyrus during letter decisions, whereas right ACC showed enhanced coupling with right parietal areas during visuospatial decisions. Cognitive control is thus localized in the same hemisphere as task execution.

Adult↗
PubMed2003

Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of human primary motor cortex (M1) changes cortical excitability at the site of stimulation and at distant sites without affecting simple motor performance. The aim of this study was to explore how rTMS changes regional excitability and how the motor system compensates for these changes. Using functional brain imaging, activation was mapped at rest and during freely selected finger movements after 30 min of 1 Hz rTMS. rTMS increased synaptic activity in the stimulated left M1 and induced widespread changes in activity throughout areas engaged by the task. In particular, movement-related activity in the premotor cortex of the nonstimulated hemisphere increased after 1 Hz rTMS. Analyses of effective connectivity confirmed that the stimulated part of M1 became less responsive to input from premotor and mesial motor areas. Conversely, after rTMS our results were consistent with increased coupling between an inferomedial portion of left M1 and anterior motor areas. These results are important for three reasons. First, they show changes in motor excitability to central inputs from other cortical areas (as opposed to peripheral or exogenous inputs used in previous studies). Second, they suggest that maintenance of task performance may involve activation of premotor areas contralateral to the site of rTMS, similar to that seen in stroke patients. Third, changes in motor activations at the site of rTMS suggest an rTMS-induced remodeling of motor representations during movement. This remapping may provide a neural substrate for acute compensatory plasticity of the motor system in response to focal lesions such as stroke.

Adult↗
PubMed2002

Parahippocampal reactivation signal at retrieval after interruption of rehearsal.

Verbal information is maintained on-line within working memory by rehearsal. However, we still can recall the verbal information when rehearsal is interrupted. Here we show that this is achieved by reactivation of maintained information. We used event-related functional magnetic resonance imaging to identify brain activation at encoding, during memory delay, and at retrieval, within the same trial of a verbal working memory task. On half of the trials, retrieval was tested after arithmetic distraction to interrupt rehearsal of the remembered verbal items. We found that the parahippocampal cortex (PHC) was highly active at retrieval on trials with distraction compared with trials without distraction. The PHC did not show sustained activation during the memory delay. By contrast, the dorsolateral prefrontal cortex (DLPF), left superior temporal region (ST), and Broca's area showed sustained activation during the memory delay, suggesting their role in maintenance of verbal items. After arithmetic distraction, the DLPF and ST were engaged in arithmetic processing. Thus, these areas could not maintain the verbal items during the distraction. At retrieval of verbal items after the distraction, the DLPF, ST and Broca's area were also active. The activity was taken to reflect reactivated representation of the verbal items. The primary role of the PHC in retrieval may be to trigger the reactivation of these cortical areas that had maintained the remembered items, thereby reactivating the information that is no longer maintained on-line.

Adult↗
PubMed2002

Initial demonstration of in vivo tracing of axonal projections in the macaque brain and comparison with the human brain using diffusion tensor imaging and fast marching tractography.

Diffusion tensor imaging (DTI), a magnetic resonance imaging technique, is used to infer major axonal projections in the macaque and human brain. This study investigates the feasibility of using known macaque anatomical connectivity as a "gold-standard" for the evaluation of DTI tractography methods. Connectivity information is determined from the DTI data using fast marching tractography (FMT), a novel tract-tracing (tractography) method. We show for the first time that it is possible to determine, in an entirely noninvasive manner, anatomical connection pathways and maps of an anatomical connectivity metric in the macaque brain using a standard clinical scanner and that these pathways are consistent with known anatomy. Analogous human anatomical connectivity is also presented for the first time using the FMT method, and the results are compared. The current limitations of the methodology and possibilities available for further studies are discussed.

Animals↗