The effective connectivity of brain networks can be assessed using functional magnetic resonance imaging (fMRI) to quantify the effects of local electrical microstimulation (EM) on distributed neuronal activity. The delivery of EM to specific brain regions, particularly with layer specificity, requires MRI compatible equipment that provides fine control of a stimulating electrode’s position within the brain while minimizing imaging artifacts. To this end, we developed a microdrive made entirely of MRI compatible materials. The microdrive uses an integrated penetration grid to guide electrodes and relies on a micro-drilling technique to eliminate the need for large craniotomies, further reducing implant maintenance and image distortions. The penetration grid additionally serves as a built-in MRI marker, providing a visible fiducial reference for estimating probe trajectories. Following the initial implant procedure, these features allow for multiple electrodes to be inserted, removed, and repositioned with ...

MR Imaging techniques (volumetric MRI and MRSI) are a non-invasive way to assess neuroanatomy and neurochemistry in humans by measuring brain volumes and CNS levels of certain neurochemicals, esp. the neuron-specific N-acetyl-aspartate (NAA). The present study sought to quantify the absolute value of [NAA] and volume of the dorsolateral prefrontal cortex in children diagnosed with FAS (n=5; 7 to 10 yrs; 1 boy/4 girls) as compared to historical controls (n=5; 9 to 12 yrs; 1 boy/4 girls), using a 1.5-T General Electric Signa scanner (Horizon hardware, 5.7 software). Gray matter volumes in both left and right dorsolateral prefrontal neocortex were significantly decreased in the FAS subjects compared to controls (p's<0.02). In the FAS subjects, the absolute values of [NAA] in left and right dorsolateral prefrontal neocortex were decreased 20% (left) and 16% (right) from controls. The results of the present study demonstrate significant decreases in the size and decreased neuronal functioning (i.e., reduced [NA...

Neurological disease drives symptoms through pathological changes to circuit functions. Therefore, understanding circuit mechanisms that drive behavioral dysfunction is of critical importance for quantitative diagnosis and systematic treatment of neurological disease. Here, we describe key technologies that enable measurement and manipulation of neural activity and neural circuits. Applying these approaches led to the discovery of circuit mechanisms underlying pathological motor behavior, arousal regulation, and protein accumulation. Finally, we discuss how optogenetic functional magnetic resonance imaging reveals global scale circuit mechanisms, and how circuit manipulations could lead to new treatments of neurological diseases.

Rivka Ravid, W.Kamphorst, L. Boe, P.Van der Valk, C.Polman, F. Barkhof, J. Guerts, H. Vrenken, J. Bot The Netherlands Brain Bank, Pathological Institue , MS Centrum , Amsterdam, The Netherlands. Brain Banks for research on Multiple Sclerosis (MS) are an essential repository for post-mortem specimens obtained at autopsy.The rapidly growing number of sophisticated neurobiological techniques applied on post-mortem brain tissues increases the pressure on brain banks to supply suitable autopsy material to the scientific community. The golden standard protocol of modern models for brain banks should comprise the following 7 basic entities; 1.A well established local donor system in which consent is obtained for the use of tissues for scientific research. 2. Compatibility of protocols for tissue procurement, management, preparation and storage for diagnostics and scientific research. 3. Rapid autopsies with a very short post-mortem delay and a fresh dissection; these are a prerequisite for an increasing range of ...

Magnetic resonance imaging of rats and mice provides detailed information in animal models of a variety of diseases: heart disease (Franco et al., 1999), prostate cancer (Hsu et al., 1998), osteoarthritis (Munasinghe et al., 1996), and in C57/Bl/6 and ApoE-deficient mice following cerebral ischemia (McDaniel et al, 2001). As part of ongoing research, the Mouse Atlas Project, we have used image analysis software developed for human brain imaging to create a multi-subject brain atlas of normal, adult male, C57Bl/6 mice. T2-weighted MRM images were acquired (RARE 3D imaging protocol (8 echoes), matrix dimensions = 256 x 256 x 512; FOV = 1.5 cm x 1.5 cm x 3.0 cm; repetition time = 1500 ms; effective time = 10 ms; number of averages = 4). Following manual skull stripping of the images, we created a linearly aligned common brain from the extracted brains using two stages of registration and then using a non-linear 168 parameter model registered each of the brains to this standard using AIR 5.2.5 (Woods et. al., ...

The FIRST (Functional Imaging Research Schizophrenia Testbed) Biomedical Informatics Research Network (fBIRN) program is the first-ever large scale, multi-center fMRI study of schizophrenia (http://www.nbirn.net). To accurately pool fMRI scan data across sites of different field strengths, scanner manufactures and pulse sequence types, a calibration protocol was implemented in which 5 normal volunteers were scanned at each of the 11 participating fBIRN sites. We present the initial results of a subset of this data and compare activation results from a sensorimotor (SM) and hypoxic challenge or breath-hold (BH) task (which putatively measures vascular responsivity devoid of cognition). Because cerbral perfusion is a filter through which neural events are interpreted in fMRI, measures of BOLD signal taken from BH scans were used to normalize activation data from cognitive SM tasks between subjects and sites. Subject dependent ROIs in visual, auditory and motor cortices were defined using activation maps from...

The entorhinal cortex (EC) and hippocampal formation (HF) are pathologically affected very early in Alzheimer’s disease (AD). Therefore, the in vivo quantitation of changes in these regions is of great interest for identifying those at risk for developing AD. In the present study we used proportional odds models to assess the relationship between EC and HF size and risk of incident AD among 58 non-demented elderly people. All participants were followed with yearly clinical evaluations and high resolution MRI scans for up to 6 years. 23/58 people received a diagnosis of amnestic mild cognitive impairment (MCI) during the baseline evaluation and 35/58 had no cognitive impairment (NCI). EC and HF volumes were derived from 1.6 mm gapless T1 weighted coronal images reformatted to be perpendicular to the long axis of the HF. The Analyze software was used for volumetric determinations and the coregistration of sequential scans. Of the 58 non-demented subjects, 14 developed AD during the follow-up period. Results ...

Prion diseases are a group of invariably fatal neurodegenerative diseases associated with the conformational transformation of prion protein PrPC (C-cellular) into a toxic and infectious conformer PrPSc (Sc-scrapie). PrPSc accumulates in organs which express PrPC, using PrPC as a template for its own replication. Carriers of prion infections harbor PrPSc in the lymphatic organs for months and years before the disease involves their brains and first neurological symptoms occur. Asymptomatic carriers constitute a reservoir for further spread of infection to other humans through organ transplantation and blood transfusion. Currently, no test which identifies asymptomatic carries of prion infection exists. Therefore, we have developed a novel MRI approach to visualize the presence of PrPSc in lymphatic organs. Several synthetic, non-toxic peptides that have high binding affinity to PrPSc were developed using a pepscan approach. PrP145-174 which had the highest binding affinity was synthesized with DTPA on its ...

Introduction: One of the most important unsolved problems in neuroscience is the wiring diagram of the human brain. Different approaches have been used in an attempt to elucidate the connections in the cerebrum in terms of their topographic arrangement [1] as well as in the forms of matrices [2]. Our group has formulated an MRI-based topographic system of human cerebral connectivity [1]. In the present study a list of the connections of each cerebral parcellation unit (PU) has been compiled in matrix form. This connectivity matrix reflects the current body of experimental animal and human data. Methods: To map the cerebral corticocortical, corticothalamic, corticostriatal, corticopontine, hippocampal-cortical and amygdala-cortical connectivity, a meta-analysis of relevant human and non-human primate literature was conducted. Coding of connections was as follows: “1” was assigned to U-fibers and short intragyral and juxtagyral (both intralobar and juxtalobar) connections, “2” was assigned to medium-range in...

Introduction: Currently, detecting neurogenesis in the dentate gyrus can only be accomplished in post-mortem tissue. Imaging neurogenesis in living subjects is needed in order to establish its functional significance. Neurogenesis is coupled to angiogenesis, which in turn is coupled to cerebral blood volume (CBV), a variable that can be measured with MRI. In principle, dentate gyrus CBV measured with MRI is expected to be sensitive to neurogenesis. Nevertheless, any manipulation that induces neurogenesis will also cause non-neurogenesis effects, which may also affect CBV. Thus, dentate gyrus CBV is sensitive but not specific to neurogenesis. We hypothesized that we could impose specificity by adjusting dentate gyrus CBV with CBV measured from the CA1 subfield, a neighboring hippocampal subregion that reflects non-neurogenesis factors. Here, we test this hypothesis by determining whether adjusted dentate gyrus CBV, as measured in vivo with MRI, is correlated with neurogenesis. Methods: We used MRI to measur...