The dopaminergic mechanisms that control reward-motivated behavior are the subject of intense study, but it is yet unclear how, in humans, neural activity in mesolimbic reward-circuitry and its functional neuroimaging correlates are related to dopamine release. To address this question, we obtained functional magnetic resonance imaging (fMRI) measures of reward-related neural activity and [11C]raclopride positron emission tomography measures of dopamine release in the same human participants, while they performed a delayed monetary incentive task. Across the cohort, a positive correlation emerged between neural activity of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic neurotransmission, during reward anticipation and reward-related [11C]raclopride displacement as an index of dopamine release in the ventral striatum, major target of SN/VTA dopamine neurons. Neural activity in the ventral striatum/nucleus accumbens itself also correlated with ventral striatal dopamine ...

Cerebral cortical development involves complex changes in cellular architecture and connectivity that occur at regionally varying rates. Using diffusion tensor magnetic resonance imaging (DTI) to analyze cortical microstructure, previous studies have shown that cortical maturation is associated with a progressive decline in water diffusion anisotropy. We applied high-resolution DTI to fixed postmortem fetal baboon brains and characterized regional changes in diffusion anisotropy using surface-based visualization methods. Anisotropy values vary within the thickness of the cortical sheet, being higher in superficial layers. At a regional level, anisotropy at embryonic day 90 (E90; 0.5 term; gestation lasts 185 d in this species) is low in allocortical and periallocortical regions near the frontotemporal junction and is uniformly high throughout isocortex. At E125 (0.66 term), regions having relatively low anisotropy (greater maturity) include cortex in and near the Sylvian fissure and the precentral gyrus. B...

We used the combination of functional magnetic resonance imaging and event-related potentials to decompose the processing stages (mental chronometry) of working memory retrieval. Our results reveal an early transient activation of inferotemporal cortex, which was accompanied by the onset of a sustained activation of posterior parietal cortex. We furthermore observed late transient responses in ventrolateral prefrontal cortex and late sustained activity in medial frontal and premotor areas. We propose that these neural signatures reflect the cognitive stages of task processing, perceptual evaluation (inferotemporal cortex), storage buffer operations (posterior parietal cortex), active retrieval (ventrolateral prefrontal cortex), and action selection (medial frontal and premotor cortex). This is also supported by their differential temporal contribution to specific subcomponents of the P300 cognitive potential.

Disrupted-in-schizophrenia-1 (DISC1), identified at the breakpoint of a chromosome (1;11)(q42.1; q14.3) translocation co-segregating with schizophrenia in a large Scottish family, is now a most promising candidate gene for schizophrenia. The translocation could lead to occurrence of the C-terminal truncated mutant DISC1 protein (mutDISC1). Our previous cellular and biochemical studies suggest that mutDISC1 acts in a dominant-negative fashion by directly associating with wild-type DISC1. Thus, overexpression of mutDISC1 can also provide a model of an overall loss of endogenous DISC1 function. To address function of DISC1 in vivo, especially its possible role in the pathophysiology of schizophrenia, we generated transgenic mice expressing mutDISC1 under the CaMKII promoter. Here we report the production of the mice and its characterization in vivo, such as neuroanatomical assessment with MRI and behavioral assays. Notably, we observed in the DISC1 transgenic mice enlargement of lateral ventricles that resemb...

In rats, cyclically fluctuating levels of gonadal hormones have been shown to modulate dendritic spine and synaptic density (Cooke & Woolley 2005; Woolley 2000). Furthermore, primate data point to an effect of estrogen on spine and synaptic density in the prefrontal cortex (Tang et al. 2004). While similar studies cannot readily be carried out in the living human brain, neuroimaging offers a means of investigating the effects of changing hormonal environments upon human neuroanatomy. In the current study, seven pre-menopausal woman between the ages of 22 and 40 were scanned once during the follicular phase (days 4-8 after menses) and once during the luteal phase (days 6-10 after the luteinizing hormone surge) of their menstrual cycles. High resolution (0.94 x 0.94 x 1.2mm) structural MRI scans were acquired on a 3-Tesla GE Scanner using an MP-RAGE sequence with 124 sagittal slices. Optimized voxel-based morphometry analysis (Good et al. 2001) revealed increased grey matter volume in an area of subgenual ci...

Magnetic resonance imaging and computer image analysis in human clinical studies effectively identify abnormal neuroanatomy in disease populations. As more mouse models of neurological disorders are discovered, such an approach may prove useful for translational studies. Here, we demonstrate the effectiveness of a similar strategy for mouse neuroscience studies by phenotyping mice with the cerebellar deficient folia ( cdf ) mutation. Using in vivo multiple-mouse magnetic resonance imaging for increased throughput, we imaged groups of cdf mutant, heterozygous, and wild-type mice and made an atlas-based segmentation of the structures in 15 individual brains. We then performed computer automated volume measurements on the structures. We found a reduced cerebellar volume in the cdf mutants, which was expected, but we also found a new phenotype in the inferior colliculus and the olfactory bulbs. Subsequent local histology revealed additional cytoarchitectural abnormalities in the olfactory bulbs. This demonstra...

Repeated stimulus presentation (priming) is generally associated with a reduction in neuronal firing, macroscopically mirrored by a decrease in oscillatory electrophysiological markers as well as reduced hemodynamic responses. However, these repetition effects seem to be dependent on stimulus familiarity. We investigate the spatiotemporal correlates of repetition priming in cortical word-recognition networks and their modulation by stimulus familiarity (i.e., words vs pseudowords). Event-related functional magnetic resonance imaging results show reduced activation for repeated words in occipitotemporal cortical regions. Electroencephalogram recordings reveal a significant reduction of induced gamma-band responses (GBRs) between 200 and 350 ms after stimulus onset, accompanied by a decrease in phase synchrony between electrode positions. Pseudoword repetition, in contrast, leads to an activation increase in the same areas, to increased GBRs, and to an increased phase coupling. This spatiotemporal repetition...

The brightness and color of a surface depends on its contrast with nearby surfaces. For example, a gray surface can appear very light when surrounded by a black surface or dark when surrounded by a white surface. Some theories suggest that perceived surface brightness and color is represented explicitly by neural signals in cortical visual field maps; these neural signals are not initiated by the stimulus itself but rather by the contrast signals at the borders. Here, we use functional magnetic resonance imaging (fMRI) to search for such neural “filling-in” signals. Although we find the usual strong relationship between local contrast and fMRI response, when perceived brightness or color changes are induced by modulating a surrounding field, rather than the surface itself, we find there is no corresponding local modulation in primary visual cortex or other nearby retinotopic maps. Moreover, when we model the obtained fMRI responses, we find strong evidence for contributions of both local and long-range edg...

Over 1.5 million cases of TBI are reported annually in the U.S., yet reliable tools for prognosis of persistent symptoms following mild TBI are elusive. Diffuse Axonal Injury (DAI) is the most common form of damage, yet current MRI techniques cannot quantify DAI, limiting prognosis and treatment. We present a method to quantitatively evaluate the integrity of white matter tracks reproducibly. The Reproducible Objective Quantification Scheme (ROQS) presents guidelines for selection of 15 reproducible Regions of Interest (ROI) based on anatomically identifiable structures. These ROI are applied to Diffusion Tensor Imaging (DTI) to provide estimates of anisotropy indices and diffusion coefficients. This same method is also applied to Magnetization Transfer Imaging (MTI), which provides a normalized measure (MT Ratio) of the amount of signal suppression that correlates to the type of matter being imaged. Normal volunteers (n=25) were imaged using DTI and MTI to establish population parameters for each ROI. Int...

Introduction: Rapid progress in the development of real time MRI imaging of specific nerve projections in the CNS has been made in the last few years. Of particular interest has been the demonstration of MnCl2 as an MRI contrast agent enabling visualisation of specific axonal pathways in the nervous system. We report here for the first time in vivo transynaptic transport of MnCL2 in the visual system of rats demonstrated with MRI. Materials and Methods: Adult inbred Fisher rats (n=4) were subjected to unilateral intravitreal injection of 2 ul of 100 mM MnCl2 with all procedures in accordance to national local authority regulations. MRI was performed at 2.35 T using a Bruker Biospec Avance DBX-100 (Bruker AG, Germany), with a 72 mm volume coil for transmission and an actively decoupled quadrature rat head surface coil for receive-only. Water-cooled BGA-12 (200 mT/m) gradients were used. The MRI protocol was according to Brekken et al. 2003. Results: MRI performed 36 hours post-injection demonstrated specifi...