Biomedical subjects

Anders H Andersen

Publications and source records attributed to Anders H Andersen.

14 recordsLinked to original sources

PubMed2006

Assessing nigrostriatal dysfunctions by pharmacological MRI in parkinsonian rhesus macaques.

New imaging techniques are needed to longitudinally monitor the development, progression and treatment of Parkinson's disease. The present study was designed to test whether the blood oxygenation level-dependent (BOLD) response to dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated to specific histological and behavioral features of the parkinsonian state. Nine adult rhesus monkeys were rendered hemiparkinsonian by intracarotid administration of MPTP. Three months after MPTP treatment, the trained, MRI-adapted awake animals were scanned with a phMRI technique while being administered a presynaptic (D-amphetamine) or postsynaptic (apomorphine) dopamine stimulating agents. The primary findings were (1) the putamen and substantia nigra (SN) but not the caudate nucleus displayed significant BOLD responses to these dopaminergic drugs; (2) a significant relationship was found between amphetamine-evoked activation and the number of surviving dopamine neurons in the SN, which was also correlated with bradykinesia; and (3) inverse relationships were seen in response to apomorphine and amphetamine stimulation between the MPTP-lesioned and unlesioned putamen and SN. The results suggest that phMRI may prove useful for longitudinally monitoring the progression and treatment of PD.

Animals↗

PubMed2006

Brain activity during stimulation of the trigeminal nerve with noxious heat.

OBJECTIVE: The aim of this study was to observe areas of brain activation with painful hot stimulation to the trigeminal nerve. STUDY DESIGN: Nine healthy pain-free women (mean age 26.2 +/- 6.9 yrs) with a natural, regular menstrual cycle participated in the study. Whole-brain functional magnetic resonance imaging (fMRI) data were acquired for each participant on day 2 or 3 after the onset of menses using echo-planar imaging at 1.5T with near-isotropic spatial resolution and a temporal resolution of 4 s. RESULTS: Whole-brain fMRI with a Peltier thermode inside the head coil yielded a feasible imaging protocol with little disturbance from the thermode. Painful thermal stimulation of the left trigeminal system activated discrete brain regions within the insula, cingulate gyrus, thalamus, inferior parietal lobe/postcentral gyrus, right middle and inferior frontal gyri, cuneus, precuneus, and precentral gyrus. CONCLUSION: Painful stimulation of the trigeminal nerve resulted in activation of similar brain areas generally known for pain processing of painful peripheral stimulation.

Adult↗

PubMed2006

Dissociation of automatic and strategic lexical-semantics: functional magnetic resonance imaging evidence for differing roles of multiple frontotemporal regions.

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and target being manipulated. Study 1 demonstrated automatic semantic priming in the left mid-fusiform gyrus (mid-FFG) and strategic semantic priming in five regions: left middle temporal gyrus (MTG), bilateral anterior cingulate, anterior left inferior prefrontal cortex (aLIPC), and posterior LIPC (pLIPC). These priming effects were explored in more detail in two subsequent studies. Study 2 replicated the automatic priming effect in mid-FFG and demonstrated that automatic priming in this region is preferential for the semantic domain. Study 3 demonstrated a neural dissociation in regions contributing to the strategic semantic priming effect. Strategic semantic facilitation was observed in the aLIPC and MTG, whereas strategic semantic inhibition was observed in the pLIPC and anterior cingulate. These studies provide reproducible evidence for a neural dissociation between three well established components of the lexical-semantic processing system.

Adolescent↗

PubMed2006

Multivariate analysis of fMRI data by oriented partial least squares.

Partial least squares (PLS) has been used in multivariate analysis of functional magnetic resonance imaging (fMRI) data as a way of incorporating information about the underlying experimental paradigm. In comparison, principal component analysis (PCA) extracts structure merely by summarizing variance and with no assurance that individual component structures are directly interpretable or that they represent salient and useful features. Oriented partial least squares (OrPLS) is a new PLS-like analysis paradigm in which extracted components can be oriented away from undesirable noise or confounds in the data and toward a desired targeted structure reflecting the fMRI experiment.

Algorithms↗

PubMed2006

fMRI in alert, behaving monkeys: an adaptation of the human infant familiarization novelty preference procedure.

Functional magnetic resonance imaging (fMRI) is increasingly used in non-human primate research. In the present study, we adapt the familiarization-novelty preference (FNP) procedure used in human infant research to examine visual behavior in alert, unanaesthetized rhesus monkeys that were acclimated to the fMRI environment, but did not undergo behavioral training. In keeping with the typical FNP paradigm, we recorded eye movements (looking time and number of fixations) while monkeys viewed a series of four identical pictures (familiarization phase) followed by two different pictures (novelty phase). Number of fixations and looking time both increased during the novelty phase, thereby demonstrating visual discrimination of the new from the old picture. Importantly, discrimination did not occur on catch trials in which six identical pictures were presented. Moreover, brain activation in the amygdala was more strongly associated with the novelty phase than with the familiarization phase. In addition, magnitude of brain activation in the amygdala was correlated with the behavioral effect of visual discrimination. These findings demonstrate the feasibility of using eye movements as an index of visual discrimination in untrained monkeys during fMRI scanning. This methodological approach helps to extend the repertoire of research tools for fMRI in non-human primates.

Adaptation, Physiological↗

PubMed2006

Cerebral activation during thermal stimulation of patients who have burning mouth disorder: an fMRI study.

The pathophysiology of burning mouth disorder (BMD) is not clearly understood, but central neuropathic mechanisms are thought to be involved. The aim of this study was to gain insight into the pathophysiology associated with BMD by using functional magnetic resonance imaging (fMRI). Areas of brain activation following thermal stimulation of the trigeminal nerve of eight female patients with BMD (mean age 49.1+/-10.1) were mapped using fMRI and compared with those of eight matched pain-free volunteers (mean age 50.3+/-12.3). Qualitative and quantitative differences in brain activation patterns between the two study groups were demonstrated. BMD patients displayed greater fractional signal changes in the right anterior cingulate cortex (BA 32/24) and bilateral precuneus than did controls (p<0.005). The control group showed larger fractional signal changes in the bilateral thalamus, right middle frontal gyrus, right pre-central gyrus, left lingual gyrus, and cerebellum than did the BMD patients (p<0.005). In addition, BMD patients had less volumetric activation throughout the entire brain compared to the control group. Overall, BMD patients displayed brain activation patterns similar to those of patients with other neuropathic pain conditions and appear to process thermal painful stimulation to the trigeminal nerve qualitatively and quantitatively different than pain-free individuals. These findings suggest that brain hypoactivity may be an important feature in the pathophysiology of BMD.

Adult↗

PubMed2006

Iron accumulation in the striatum predicts aging-related decline in motor function in rhesus monkeys.

Changes in the nigrostriatal system may be involved with the motor abnormalities seen in aging. These perturbations include alterations in dopamine (DA) release, regulation and transport in the striatum and substantia nigra, striatal atrophy and elevated iron levels in the basal ganglia. However, the relative contribution of these changes to the motor deficits seen in aging is unclear. Thus, using the rhesus monkey as a model, the present study was designed to examine several of these key alterations in the basal ganglia in order to help elucidate the mechanisms contributing to age-related motor decline. First, 32 female rhesus monkeys ranging from 4 to 32 years old were evaluated for their motor capabilities using an automated hand-retrieval task. Second, non-invasive MRI methods were used to estimate brain composition and to indirectly measure relative iron content in the striatum and substantia nigra. Third, in vivo microdialysis was used to evaluate basal and stimulus-evoked levels of DA and its metabolites in the striatum and substantia nigra of the same monkeys. Our results demonstrated significant decreases in motor performance, decreases in striatal DA release, and increases in striatal iron levels in rhesus monkeys as they age from young adulthood. A comprehensive statistical analysis relating age, motor performance, DA release, and iron content indicated that the best predictor of decreases in motor ability, above and beyond levels of performance that could be explained by age alone, was iron accumulation in the striatum. This suggests that striatal iron levels may be a biomarker of motor dysfunction in aging; and as such, can be monitored non-invasively by longitudinal brain MRI scans. The results also suggest that treatments aimed at reducing accumulation of excess iron in the striatum during normal aging may have beneficial effects on age-related deterioration of motor performance.

Aging↗

PubMed2006

Influence of estrogen on brain activation during stimulation with painful heat.

PURPOSE: Several studies have shown that women express higher pain sensitivity during periods of low estrogen than during periods of high estrogen. The aim of this study was to show whether the difference in pain sensitivity could be visualized as a function of brain activity by means of functional magnetic resonance imaging (fMRI). METHODS: Nine healthy, pain-free women (mean age, 26.2 +/- 6.9 years) with a natural, regular menstrual cycle participated in the study. Whole-brain fMRI data were acquired during a period of high and during a period of low estrogen at 1.5 T using echo-planar imaging with near-isotropic spatial resolution and a temporal resolution of 4 seconds. Heat pain thresholds were obtained before the scans, and pain ratings were obtained before and after each scan. Blood samples were taken after each scan to verify the appropriate level of estrogen. RESULTS: The heat pain thresholds during the low (46.4 degrees +/- 3.5 degrees C) and high (46.4 degrees +/- 3.8 degrees C) estrogen conditions were not significantly different. The pain ratings before (4.6 +/- 2.2 low versus 3.6 +/- 2.1 high) and during the scans (4.4 +/- 2.4 low versus 4.7 +/- 2.3 high) also did not differ between the 2 conditions. Generally, similar patterns of activation were observed for both estrogen conditions. However, significant differences were found in the magnitude of activation of the anterior part of the anterior cingulate (BA 24/32), the cerebellum, and the precuneus. Furthermore, activations in the anterior part of the anterior cingulate, left cerebellum, and precuneus were unique to the low-estrogen phase. These regions have been linked with attention to or anticipation of pain. CONCLUSIONS: The results of this study suggest that the affective component of pain may be enhanced during the low-estrogen phase of the menstrual cycle in healthy women.

Adult↗

PubMed2004

Regional brain response to faces of humans and dogs.

The extent to which the brain regions associated with face processing are selective for that specific function remains controversial. In addition, little is known regarding the extent to which face-responsive brain regions are selective for human faces. To study regional selectivity of face processing, we used functional magnetic resonance imaging to examine whole brain activation in response to human faces, dog faces, and houses. Fourteen healthy right-handed volunteers participated in a passive viewing, blocked experiment. Results indicate that the lateral fusiform gyrus (Brodmann's area 37) responds maximally to both dog and human faces when compared with other sites, followed by the middle/inferior occipital gyrus (BA 18/19). Sites that were activated by houses versus dog and human faces included the medial fusiform gyrus (BA 19/37), the posterior cingulate (BA 30), and the superior occipital gyrus (BA 19). The only site that displayed significant differences in activation between dog and human faces was the lingual/medial fusiform gyrus. In this site, houses elicited the strongest activation, followed by dog faces, while the response to human faces was negligible and did not differ from fixation. The parahippocampal gyrus/amygdala was the sole site that displayed significant activation to human faces, but not to dog faces or houses.

Adolescent↗

PubMed2004

Structure-seeking multilinear methods for the analysis of fMRI data.

In comprehensive fMRI studies of brain function, the data structures often contain higher-order ways such as trial, task condition, subject, and group in addition to the intrinsic dimensions of time and space. While multivariate bilinear methods such as principal component analysis (PCA) have been used successfully for extracting information about spatial and temporal features in data from a single fMRI run, the need to unfold higher-order data sets into bilinear arrays has led to decompositions that are nonunique and to the loss of multiway linkages and interactions present in the data. These additional dimensions or ways can be retained in multilinear models to produce structures that are unique and which admit interpretations that are neurophysiologically meaningful. Multiway analysis of fMRI data from multiple runs of a bilateral finger-tapping paradigm was performed using the parallel factor (PARAFAC) model. A trilinear model was fitted to a data cube of dimensions voxels by time by run. Similarly, a quadrilinear model was fitted to a higher-way structure of dimensions voxels by time by trial by run. The spatial and temporal response components were extracted and validated by comparison to results from traditional SVD/PCA analyses based on scenarios of unfolding into lower-order bilinear structures.

Analysis of Variance↗

PubMed2003

A functional magnetic resonance imaging study in patients with benign essential blepharospasm.

OBJECTIVE To identify blinking-induced functional magnetic resonance imaging (fMRI) activation patterns in five benign essential blepharospasm (BEB) patients and five age-matched control subjects. METHODS fMRI brain activation maps were obtained during repeated conditions of spontaneous and voluntary blinking in BEB and control groups. Blood oxygen level-dependent intensity images were collected from two separate runs as 16 axial and 16 coronal, 8 mm thick slices using a T2-star weighted gradient echo EPI sequence, coregistered with anatomic images. Spatially normalized and isotropically blurred activation maps for each subject were combined within groups of BEB patients and control subjects to generate maps of the intersubject mean fractional signal change.RESULTS Substantially greater activation during spontaneous and voluntary blinking was seen in BEB patients compared with control subjects in the anterior visual cortex, anterior cingulate cortex, primary motor cortex, central region of the thalamus, and superior cerebellum. In both groups, activations were generally greater for voluntary than for spontaneous blinking. CONCLUSIONS The activations observed might represent a hyperactive cortical circuit linking visual cortex, limbic system, supplementary motor cortex, cerebellum, and supranuclear motor pathways innervating the periorbital muscles.

Blepharospasm↗

PubMed2002

Automated segmentation of multispectral brain MR images.

This work presents a robust and comprehensive approach for the in vivo automated segmentation and quantitative tissue volume measurement of normal brain composition from multispectral magnetic resonance imaging (MRI) data. Statistical pattern recognition methods based on a finite mixture model are used to partition the intracranial volume into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) spaces. A masking algorithm initially extracts the brain volume from surrounding extrameningeal tissue. Radio frequency (RF) field inhomogeneity effects in the images are then removed using a recursive method that adapts to the intrinsic local tissue contrast. Our technique supports heterogeneous data with multispectral MR images of different contrast and intensity weighting acquired at varying spatial resolution and orientation. The proposed image segmentation methods have been tested using multispectral T1-, proton density-, and T2-weighted MRI data from young and aged non-human primates as well as from human subjects.

Algorithms↗

PubMed2002

Functional MRI studies in awake rhesus monkeys: methodological and analytical strategies.

Functional imaging of the non-human primate brain in awake animals is now feasible because of recent methodological advances. Here we detail our procedures for conducting functional MRI (fMRI) studies in rhesus monkeys. Our emphasis has been on analyzing drug-evoked responses within and across test groups, meaning that techniques have had to be developed for training and testing relatively large groups of animals. Group size is important as unbiased estimates are best derived from analyzing responses in multiple animals with replicate scans per animal due to partial volume errors in evaluating small brain regions and motion artifacts during scanning. While the procedures presented here were developed for mapping responses obtained from stimulating dopaminergic systems, much of the methodology is generally applicable for non-human primate fMRI studies and addresses specific problems encountered in imaging awake animals. These are (1) adapting animals to an MRI environment, (2) minimizing head movements, (3) reducing ambient scanning noise levels, and (4) developing multivariate methods of image data analysis suitable for eliciting the dynamic brain response while (5) detecting and deleting outlying observations due to motion artifacts. Procedures are demonstrated for first pre-processing and analyzing responses in a voxel-based approach in a single animal and then proceeding to analyze responses across animals and replicate scans for regions of interest. Collectively, the procedures described provide an approach for fMRI mapping of elicited responses using conventional 1.5T MR scanners.

Animals↗

PubMed2002

Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys.

The powerful trophic effects that glial cell line-derived neurotrophic factor (GDNF) exerts on midbrain dopamine neurones suggest its use in treating Parkinson's disease. However, some important questions remain about the possible therapeutic applications of GDNF. Here we demonstrate that the chronic infusion of 5 or 15 micro g/day GDNF into the lateral ventricle or the striatum, using programmable pumps, promotes restoration of the nigrostriatal dopaminergic system and significantly improves motor functions in rhesus monkeys with neural deficits modelling the terminal stages of Parkinson's disease. The functional improvements were associated with pronounced upregulation and regeneration of nigral dopamine neurones and their processes innervating the striatum. When compared with vehicle recipients, these functional improvements were associated with (i) >30% bilateral increase in nigral dopamine neurone cell size; (ii) >20% bilateral increase in the number of nigral cells expressing the dopamine marker tyrosine hydroxylase; (iii) >70 and >50% bilateral increase in dopamine metabolite levels in the striatum and the pallidum, respectively; (iv) 233 and 155% increase in dopamine levels in the periventricular striatal region and the globus pallidus, respectively, on the lesioned side; and (v) a five-fold increase in tyrosine hydroxylase-positive fibre density in the periventricular striatal region on the lesioned side. In addition, chronic GDNF treatment did not induce the side-effects generally associated with chronic administration of levodopa, the most widely used treatment for Parkinson's disease. Thus, the results suggest that the prolonged and controlled delivery of GDNF into the brain could be used to intervene in long-term neurodegenerative disease processes like Parkinson's disease. Additional studies are required to determine the potential differences between chronic, intraventricular and intraputamenal (or intranigral) delivery of GDNF to maximize the efficacy of infusion treatments.

3,4-Dihydroxyphenylacetic Acid↗