Uni-manual sensorimotor coordination performed at low movement rates is bi-stable, displaying a tendency towards either synchronization or syncopation. Under parametric increases in movement rate the syncopated pattern becomes unstable until at some critical frequency the system passes into a monostable regime and spontaneous switches to synchronized coordination ensue. Functional imaging studies have demonstrated robust differences in neural activity underlying these two coordination patterns when performed at movement rates well within the bistable regime. Such data suggest that neural networks distinguishing between coordination modes may be related to the relative differences in stability and contribute to the generation of behavioral transitions. Here we use blood oxygen level dependent (BOLD) functional magnetic resonance imaging to measure neural activity of the brain for the purpose of establishing a relationship between brain areas that distinguish between the two stable coordination patterns and ...

The present study evaluates the contribution of the thalamus to cognition using structural MRI-based volumetry in combination with neurocognitive testing of healthy subjects, Korsakoff's (KS) and Alzheimer's (AD) patients. Fifty-seven healthy subjects ranging from 21 to 82 years old were included. It could be shown that a highly significant decrease in thalamic volume occurred with higher age, stronger than and independent of total brain volume (r=-0.599, p=0.000). In young, but not in middle-aged or old subjects, thalamic volume was related to speeded information processing. This was evident from performance on the Stroop test, a memory scanning task and a variant of the trail making task. No relationship was found with higher cognitive functions such as semantic or episodic memory. Thalamic volumes of KS patients were smaller than those of healthy controls and non-KS alcoholics. Similarly, AD patients showed reductions in thalamic volume as compared to both healthy subjects and age-associated cognitive d...

Transient fetal subplate zone (SP) consists of loosely arranged axons, postmigratory and migratory neurons, growth cones, synapses and glia (Kostovic & Rakic, J Comp Neurol 297:441, 1990). The developmental peak of SP occurs during the sequential ingrowth of major cortical afferent fibre systems when SP serves as a waiting compartment. To explore the potential of MRI technique for in vivo imaging of the SP, we correlated MR images of postmortem fetal brains with variously stained histological sections of age-matched brains. On Tlw MR images (2T Prestige), the SP is clearly delineated as a zone of low signal intensity, situated between the cortical plate and external axonal stratum. This low intensity probably reflects special biochemical and cytological features of the SP, i.e., its high water content, large extracellular space, and fibrillar structure. The SP appears around 15 weeks of gestation (WG), becomes extensive at 22 WG and expands further until 30 WG, when its resolution begins in depth of cortic...

Our functional MRI studies of complex finger movements in normal subjects have demonstrated two distinct loci of activity on the anterior bank of the central sulcus in primary motor cortex (M1). The first site is located on the knob formed by the inter-digitation of M1 and primary sensory cortex (S1), and the second is found lateral to this knob. The question then arises as to whether these functionally distinct areas share the same neuroanatomical features and whether or not both are part of M1. In order to relate our functional observations to the cyto- and chemoarchitecture of these areas, we imaged (T1-weighted MRI) post-mortem tissue and then performed basic neuroanatomy with Nissl histochemistry and immunohistochemistry for calcium binding proteins (calbindinD28 and parvalbumin) and a non-phosphorylated neurofilament protein (SMI-32). While brain activation in the medial location was clearly embedded in M1, the lateral site was difficult to assess cyto- and chemoarchitectonically. This was due to a d...

In addition to CO2 insensitivity and reduced drive to breathe during sleep, CCHS patients often show impaired responses to transient blood pressure elevation. In adult man, fMRI studies indicate that the brain regions recruited for blood pressure regulation are extensive. We examined fMRI signal changes to a cold pressor challenge in selected brain sites of 7 CCHS children (3 male pairs, 8-15 yrs), ventilator-dependent only during sleep, no Hirschsprung's Disease) and in 7 age- and gender-matched controls. A series of 20 image slices (25 repetitions, Echo Planar technique) through the entire brain was collected during baseline and during application of a cold bag of deuterium oxide to the forehead. Baseline images were subtracted from experimental conditions, and the resultant difference images were subjected to multiple paired t-tests with Bonferroni correction (p<0.01) using MedX software. Brain areas responsive to the cold pressor challenge in controls included sites within the cerebellum, frontal corte...

Explicit and implicit sequence learning has been extensively studied, but explicit and implicit learning of visuo-motor transformations is less well understood. Gradual, implicit, rotation of visual feedback in a tracking task leads to greater learning than a sudden, explicit, rotation and may involve different neural circuits. We studied this task with whole brain fMRI at 3T. 5 right handed subjects (4 female, 1 male) followed alternating motion of a visual target with a cursor controlled by a joystick. In experiment 1, we used 5 conditions in a 30s block design: rest (eye movement only), normal tracking, adaptation to step (30° in 1 trial) or ramp rotation (1° per trial ramping to 30°) and re-adaptation to normal tracking. Comparison of adaptation vs. normal movement highlighted the main motor areas but also bilateral posterior parietal cortex BA39. Contrasting step and ramp adaptation showed activation of extrastiate visual areas and BA39. In experiment 2, we tested cued and uncued ramp rotation, with s...

Afferent activation of the olfactory bulbs is important in maternal recognition of pups. This processing of olfactory information occurs early after parturition and contributes to mother-pup bonding. The present studies use functional magnetic resonance imaging (fMRI) to follow lactation-induced changes in neuronal activity in the olfactory system and somatosensory cortex. Prior to imaging, animals were acclimated to a head and body holder and the imaging protocol. Mothers were imaged on postnatal day 4. Animals were initially anesthetized with 4% isoflurane, secured in the holder and allowed to awaken. A cradle containing six pups was positioned under the mother in the magnet. A thin shield separated the pups from the mother. When the shield was slid away the pups would be exposed to the six hind-limb teats and begin suckling. When slid back, the shield dislodged the pups from the teats. A boxcar design of 5 min off/5 min on for three consecutive repetitions was used. Functional images were acquired using...

Corticotropin-releasing factor (CRF) is a neuromodulator of brain functions such as learning and anxiety, and is involved in several psychiatric disorders. Targeting CRF binding sites with spatial and temporal resolution by using magnetic resonance imaging (MRI) would greatly facilitate research on the CRF system. Therefore, we synthesized and pharmacologically characterized a CRF analog labeled with gadolinium, the contrast agent most commonly used in MRI. The chelator DOTA was coupled to the N-terminus of human/rat CRF (h/rCRF) under standard solid phase peptide synthesis conditions. The obtained DOTA-h/rCRF was purified and loaded with gadolinium (Gd) in a reaction monitored with mass spectrometry. After purification, Gd-DOTA-h/rCRF was tested for its pharmacological properties using transfected human embryonic kidney (HEK) 293 cells producing either rat CRF receptor (CRFR) 1, mouse CRFR2β or rat CRF binding protein (CRFBP). The affinities of Gd-DOTA-h/rCRF to rat CRFR1 (IC50 = 4.5 nM) and mouse CRFR2β ...

Hypoxia and edema are frequent and serious complications of traumatic brain injury (TBI). Therefore, we examined the effects of hypoxia on edema formation after moderate lateral fluid percussion (LFP) injury using NMR diffusion weighted imaging (DWI). Adult Sprague-Dawley rats were separated into 4 groups: sham uninjured (S), hypoxia alone (H), trauma alone (T), trauma and hypoxia (TH). Rats in Groups T and TH received LFP brain injury, with Groups H and TH undergoing 30 min of severe hypoxia (FiO2 = 0.11) immediately after surgery or TBI (respectively). DWIs were obtained at 2, 4, 24 hours and 1 week postinjury and apparent diffusion coefficient (ADC) maps were constructed. Rats in Groups T and TH showed an early decrease (p<0.001) in ADC values in the ipsilateral cortex 4 hr postinjury, followed one week later by elevated ADCs (p<0.05). No significant differences were seen between T and TH groups in cortex. In contrast, the ipsilateral hippocampus for Group TH showed only increasing ADC values. This hype...

The good coverage and high resolution afforded by functional magnetic resonance imaging (fMRI) make it an excellent tool for the noninvasive imaging of the human brain. Equally interesting, however, is the use of this technique in animal studies using high magnetic fields. In the latter case, highly