It is believed that the olfactory bulb (OB) codes the olfactory information from the periphery into a spatial activity pattern in the glomerular layer. Here we used high-resolution fMRI to examine how the structural features of odorants are represented spatially in the entire rat OB. The whole OB mapping results showed that the areas activated by the three structurally related odorants, iso-amyl acetate, ethyl acetate, and benzyl acetate distributed broadly across the entire OB. Many of the activated regions are shared by all three odorants. The patterns are more similar between the two aliphatic acetates than between the aliphatic and aromatic acetates. Statistical analysis showed that the similarity between the patterns of iso-amyl acetate in different exposures is significantly higher than between the patterns of iso-amyl acetate and ethyl acetate. One major cluster, covering nearly 60 glomeruli (thresholded at p < 0.01) at the latero-ventral region in the anterior end of the OB, was activated by the al...

Functional MRI in conscious animals provides a new opportunity in drug discovery to identify patterns of brain activity characteristic of different classes of psychotropic molecules. To this end, rats were tested with functionally different classes of drugs used to treat schizophrenia - atypical (clozapine, respiridone) and typical (chlorpromazine, haloperidol) antipsychotics. Rats showed a dose-dependent (change in brain activity dominated by negative BOLD signal) within 10-15 min of iv injection of drug. Since the efficacy of these drugs is related, in part, to their affinity for dopamine receptors, animals were challenged with an ICV injection of apomorphine following neuroleptic treatment. While several areas of the brain were activated by apomorphine administration alone, the most robust increase in BOLD signal intensity occurred in the prefrontal cortex. The typical antipsychotics, haloperidol and chlorpromazine blocked the action of apomorphine in the prefrontal cortex, while respiradol and clozapin...

Objectives: The purpose of the present study is to investigate the cortical changes in pain perception when applying different kind of conditioning sensory stimuli, namely acupuncture (Meridian) and acupuncture-like (Sham) stimuli and to show that these stimuli are essentially those of the stress-inducing stimuli and the results are the consequence of the HPA axis reflexes. Methods: Brain activation was observed with functional magnetic resonance imaging (fMRI) using a set of thermal stimuli as pain stimulus which induced by immersing the index finger into a hot water bath, approximately 51~52°C for 30 seconds. The experiment is performed by applying the pain following Meridian acupuncture and Sham acupuncture which applying needling to the traditionally known acupuncture points and points nearby but not those. These stimuli were manually twirling or rotating of a needle with approximately 1 Hz for a period of 30 seconds and rest period of 30 seconds with repetition of 5 times. Results: The results were co...

Pups reinforcing properties are so robust that they compete with self-administration of cocaine (Hecht et al., Dev Psychobiol 35:136,1999). Indeed, postpartum dams bar press for pups in an operant response paradigm (Lee et al., Behav Brain Res 108:215, 2000). The present studies use fMRI and 3D computational analyses to compare pup-induced vs cocaine-induced changes in brain activity in lactating dams. Mothers were imaged for postnatal days 4 – 8 in response to pups (n=6) or ICV cocaine (20ug/10 ul) (n=6). A third group (n=6), imaged virgin females in response to ICV cocaine. A multi-slice fast spin echo sequence acquired twelve 1.2mm slices in 6s. All imaging consisted of 3 min (30 rep.) of control followed by 5 min (50 rep.) of stimulus. A 4.7T/40cm horiz. magnet was used. The results for n subjects in each group were presented individually and as group composites. The analysis involved three major steps registration, segmentation and statistical analysis. Subjects were registered to a fully segmented 3D...

It has been shown that the blood oxygenation level dependent (BOLD) functional MRI signal at magnetic field strengths of ≤ 1.5T arises predominantly from large vessels, which can be quite distant from the sites of neuronal activity. To improve the spatial localization to the active tissues/capillaries, the use of high field magnets has been proposed. To test this hypothesis, we evaluated the microvascular versus the macrovascular contribution to the BOLD response at high fields (4 and 7T) following visual stimulation in humans. Diffusion-weighted BOLD fMRI was used to selectively attenuate the fast-moving (large-vessel) fMRI signals. Two acquisition schemes were used: a gradient-echo scheme which is sensitive to both large- and small-vessel BOLD effects and a spin-echo scheme which should mitigate large-vessel BOLD effects. A comparison was made between the two sets of results. Diffusion-weighted BOLD fMRI was performed on 24 normal humans with graded flow-crushing gradients (4-7 b values). The visual stim...

Postmortem studies indicate a temporal sequence of primary allocortical and secondary neocortical degeneration during Alzheimer disease (AD) progression. Hippocampus (HC) atrophy correlates with allocortical neuronal degeneration and atrophy of the corpus callosum (CC) reflects loss of intracortical projecting pyramidal neurons in neocortex. First, we wanted to determine the temporal sequence and rate of degeneration of HC and CC in AD. Second, to answer the question, whether rates of atrophy were correlated with rates of cognitive decline and third, whether both markers could be proposed as potential morphological parameters for mapping drug effects on brain structure in longitudinally studied AD patients and healthy control subjects. MRI-derived measures of CC and HC were compared between 27 clinically diagnosed AD patients and 28 age- and gender-matched healthy control subjects. Rates of CC and HC atrophy were determined in 21 AD patients and 10 control subjects studied longitudinally. We found mean rel...

Stereotactic placement of deep brain stimulation (DBS) leads for the treatment of movement disorders has traditionally been guided by microrecording and macrostimulation in awake patients, with subsequent confirmation by MRI after the lead’s stylet has been removed. When placement errors occur, the surgery must be repeated and the lead replaced. Visual guidance by concurrent MRI would improve placement accuracy and reduce the need for repeated surgeries. An MRI-compatible trajectory guidance system (IGN) has been developed to fix DBS leads in place without removing the stylet, and allow remote adjustment of the lead position as needed. In preparation for clinical applications, we performed safety tests of this device in a 1.5-Tesla Siemens Sonata MR system. We evaluated local temperature changes using clinically relevant and ¨worst-case¨ MRI sequences in a semi-solid, gel-filled phantom. The lead tip (Medtronic), with stylet in place, was immersed into the phantom using the trajectory guide and remote intr...

Previously, we have demonstrated that fMRI can be used to map age-associated changes in nigrostriatal system with dopaminergic stimulation in normal rhesus monkeys (NeuroImage 14: 1159-1167, 2001). In the present study, fMRI was used to map dopamine (DA) receptor-mediated blood oxygen level dependent (BOLD) changes indicative of neuronal activity in the basal ganglia of hemiparkinsonian rhesus monkeys. Unilateral infusion of MPTP via the right carotid artery was used to induce unilateral parkinsonian features in 12 monkeys; 3 age-matched normal monkeys served as controls. Apomorphine (APO, 0.1mg/kg s.c.), a mixed dopamine D1/D2 receptor agonist, evoked strong activation in the MPTP-lesioned caudate nucleus, putamen, globus pallidus (GP) and substantia nigra (SN) with little change detected on the intact side of these structures. The activation on the lesioned side persisted in the GP until administration 15 min later of the D1 receptor antagonist (SCH-23390, 0.1mg/kg i.m.). APO-induced activation was rever...

Deep brain stimulation (DBS) is used increasingly in the field of movement disorders. The implanted electrodes create not only a priori risk to patient safety during MR imaging, but also a unique opportunity in the collection of functional MRI (fMRI) data conditioned by direct neural stimulation. We performed safety tests of commercially available bilateral neurostimulation systems (Soletra® 7482, Medtronic), extensions, and leads in a clinical 1.5 T MR system (Siemens, Germany) across a range of MR acquisitions of typical and worst case scenarios. The primary safety risk arises from RF induction of current through the electrode leads. It depends on the RF energy deposited during specific imaging sequences, on physical properties of the electrodes, and on the low impedance and/or resonant paths within the lead geometry. In vitro testing was performed using a phantom filled with a semisolid gel simulating the thermal convection and dielectric properties of human tissues. Each DBS electrode was positioned wi...

The pons is one of the brain areas demonstrating selective degeneration in Machado-Joseph disease (MJD), which is caused by the expansion of a polyglutamine stretch in the protein called ataxin-3. Although the resultant pontine atrophy is readily recognized by magnetic resonance imaging (MRI), the features and natural process of atrophy is not fully understood. To characterize these, we analyzed the midsagittal images of pons obtained by MRI. We found a difference in atrophy between the pontine base and tegmentum. The reduced size of the pontine tegmentum was prominent early after the onset of clinical symptoms. No overlap was seen in the range of the area of pontine tegmentum between MJD and controls. The quotient of atrophy of the pontine tegmentum divided by age correlated well with the CAG repeat number. In contrast, the area of the pontine base correlated negatively with disease duration. Particularly, the size of pontine base appeared to remain in the range of controls for a relatively long time afte...