During adolescence, the dopaminergic system in the brain is undergoing dramatic processing that includes synaptic pruning and alteration in dopaminergic receptor numbers. We used phMRI to investigate the differences in neuronal responses to acute cocaine challenge in the adolescent and adult brain. Methods – Adolescent (22 days old, P22, n=7) and adult (>60 days old, n=6) Sprague-Dawley rats were used in this study. Rats were scanned in a 9.4T Bruker scanner under 1% halothane anesthesia with an acute cocaine challenge (0.5mg/kg, i.v.). Regional cerebral blood volume (rCBV) changes were assessed by using IRON method with echo planar imaging sequence (TR/TE 10ms/6ms). Dopamine (DA) release by microdialysis was assessed in the caudate/putamen in a separate group of P22 rats. Results – Cocaine challenge on the adult rats induced bi-phasic rCBV changes (negative followed by positive rCBV changes) in the caudate/putamen (CPU), Nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and thalamus. Cocaine chall...

Subjects with chronic alcoholism demonstrate cognitive performance ranging from normal to severely impaired. Some chronic alcoholism subjects have white matter volume reductions in prefrontal, posterior superior temporal, and posterior parietal-occipital regions and less prominent, diffuse grey matter volume reductions. We examined measures of membrane phospholipid and high-energy phosphate metabolism and neuronal integrity [NA(s-τc)] by 31P-1H magnetic resonance spectroscopic imaging in a cohort of chronic alcoholism subjects without cognitive changes (CUCAL) (5M, 48.2±3.7 yrs) and with cognitive impairment (CICAL) (4M, 49.5±4.0 yrs) compared with controls (16M, 40.8±5.9 yrs). Cognitive status was determined by an index from the Halstead-Reitan Battery. CUCAL subjects had increased levels of membrane phospholipid building blocks [PME(s-τc)] in the right (R) occipital cortex compared with controls. Compared with CUCAL subjects, CICAL subjects had: 1) increased measures of PME(s-τc) in R superior temporal a...

The parahippocampal gyrus, located in the medial temporal lobe, is a key brain area in memory processing. Several recent functional studies performed either in humans or in non human primates have revealed the implication of its rostral part, the temporal pole in declarative memory. The temporal pole is located rostral to the entorhinal and piriform cortices. We have analyzed the general organization of the temporal pole in humans from MR images and histological slices, on both, macroscopic and cytoarchitectonic aspects. This work was also performed to provide anatomical landmarks to facilitate and precise the brain structures implicated in memory as revealed by functional MRI and PET activation studies. The basic analysis has been performed from the brain of 9 healthy people. The brains were serially sectioned and stained with thionin to determine cytarchitectonic boundaries. T1-weighted MR images obtained in controls were analyzed in reference to the neighboring anatomical landmarks. The features of the ...

Human studies of cognition have suggested that the frontal cortex may be preferentially affected in healthy aging. Such studies, however, cannot exclude brain changes related to underlying Alzheimer’s disease (AD) pathology. We investigated regional patterns of gray matter using MRI in 7 young (age=10±2 yrs; 2F/5M) and 12 old (age=24±3 yrs; 4F/8M) healthy rhesus macaques (RM) on a voxel basis to evaluate the effects of aging in a non-human primate model in which the pathology of AD does not occur. We hypothesized that older age in the RM would be associated with reductions in gray matter in frontal brain regions thought to decline in healthy aging in humans. Volumetric T1 MRI scans were acquired on a 1.5T scanner. For each scan, the brain was manually segmented from non-brain tissue and SPM2 voxel-based morphometry was used to spatially normalize and segment gray matter with a customized template for the RM. Multivariate network analysis using the scaled subprofile model (SSM) identified a linear combinati...

The modern “obesogenic” environment is characterized by an abundance of readily available hyperpalatable, energy-dense foods. These foods are highly valued and extremely rewarding: exposure to these foods and associated cues activates a diverse brain network underlying reward processing and

Selecting an appropriate response among competing alternatives is fundamental to the successful performance of a variety of everyday tasks. Cognitive neuroscience has begun to investigate the neural mechanisms for this response selection process. Current research suggests a frontal-parietal network of brain regions (including dorsal prefrontal, dorsal premotor, and superior parietal cortices) mediate response selection, at least for spatial material. Most of these studies used blocked experimental designs, comparing blocks of a difficult response-selection task with blocks of an easy one. Thus, the frontal-parietal activity reported may be due either to the activation of the stimulus-response rule sets, or to the application of the stimulus-response rules. Our current event-related fMRI study investigates these response selection sub-processes. In it, participants responded to a visually presented stimulus with either a spatially ordered (easy) or unordered (hard) manual response. On some trials, 4 to 9 se...

Dopamine (DA) receptors play a central role in such diverse pathologies as Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map DA-associated circuitry in nonhuman primates with high sensitivity and spatial resolution. Seven control cynomolgous monkeys and 10 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated parkinsonian primates were studied longitudinally using both positron emission tomography (PET) and phMRI. Amphetamine challenge (2.5 mg/kg, i.v.) in control monkeys increased relative cerebral blood volume (rCBV) in a number of brain regions not described previously, such as parafascicular thalamus, precentral gyrus, and dentate nucleus of the cerebellum. With the high spatial resolution, we were also able to readily identify changes in rCBV in the anterior cingulate, substantia nigra, ventral tegmental area, caudate (tail and head), putamen, and nucleus accumbens. Amphetamine induced decrea...

Intraplantar injection of capsaicin produces primary and secondary hyperalgesia, modelling some of the symptoms associated with persistent pain states. Previous functional magnetic resonance imaging (fMRI) studies of Blood Oxygen Level Dependent (BOLD) haemodynamic responses have demonstrated nociceptive-evoked activation of the brain (Malisza and Docherty, 2001). Here, T2-weighted BOLD-contrast fMRI was used to study the time course of capsaicin-evoked BOLD responses in halothane anaesthetised rats (Shah et al., 2004). Rapid Acquisition Relaxation Enhanced (RARE) sequence data was obtained from a continuous scan comprising of 12 basal volume sets, each collected every 4 min 40sec, followed by intradermal injection of capsaicin (30µg/5µl saline with 7% Tween 80, n=8) and a further collection of 18 volume sets. Data were analysed using SPM99 (random effects analysis, p<0.05). Capsaicin-evoked significant increases in BOLD response in the nucleus accumbens (T=6.81, p<0.05), ventral-medial thalamic nuclei (T=...

We investigated somatosensory cortical activation in squirrel monkeys using high-field imaging (9.4T, Bruker) during vibrotactile and electrocutaneous stimulation of the hand. Accompanying high-resolution T1 anatomical experiments were used to define the laminar organization of SI. Vibrotactile stimulation was administered by piezoelectric elements that drove a circular contact (0.5 mm dia.) onto the surface of a digit segment. Electrocutaneous stimuli were presented via electrodes positioned on the digit volar surfaces and base of the palm. All stimuli were delivered in a blocked design. In T1-images, whole brain coverage was achieved with a 7 cm coil to achieve a 195µm in-plane resolution. For EPI data, a 3 cm coil was positioned over somatosensory cortex for a 625µm in-plane resolution. Isoflurane anesthesia (0.5-0.8%) was maintained by monitoring physiological variables (SpO2, BPM, CO2; see Cheney et al., this meeting). Data was acquired from two monkeys that were scanned over 20 fMRI sessions. Prelimi...

Repeated exposure to amphetamine (AMPH sensitization) causes long-lasting neuronal adaptations even after long periods of drug withdrawal. Such long-term adaptations include augmented dopamine (DA) release in the nucleus accumbens (NAcc) and downstream molecular adaptations. We have used pharmacological MRI (phMRI) to map the neuronal adaptations in chronic AMPH-treated rats and correlated the results to microdialysis measurement of DA release and c-fos expression in the NAcc. Methods - Sprague-Dawley rats were injected with AMPH (n=6, 5-7.5mg/kg/day, i.p.) or saline (n=5) for 5 days. After 14 days of withdrawal, animals were scanned in a 9.4T Bruker scanner with an AMPH challenge (3mg/kg, i.v.). MR images were acquired repeatedly using IRON method with conventional gradient echo sequence (TR/TE 600ms/6ms). rCBV changes were quantified in selected regions. DA release by microdialysis and c-fos expression by immunohistochemistry were assessed in the NAcc. Results - Rats from the chronic AMPH and saline pret...