The orbitofrontal cortex has been cytoarchitectonically and connectionally subdivided into a medial and a lateral part which are assumed to subserve distinct functions in emotional processing. However the exact spatiotemporal mechanisms of negative and positive emotional processing in medial and lateral orbitofrontal cortex remain unclear. We therefore investigated spatiotemporal orbitofrontal and prefrontal cortical activation patterns during emotional stimulation in a combined fMRI/MEG study. We investigated 10 healthy subjects, 5 women and 5 men. Positive and negative pictures from the International Affective Picture system (IAPS) were used for emotional stimulation, whereas neutral and gray pictures were taken as control conditions. fMRI/MEG measurements covered the whole frontal lobe and a time window between -2000 and +200 ms around motor responses (right index finger extension) associated with each picture. Positively and negatively correlated activities were determined in various prefrontal/frontal cortical regions in fMRI. Isocontour maps and single dipoles in MEG were analyzed in 50 ms time windows ranging from -2000 to +200 ms. Dipoles and fMR images were mapped on three-dimensional anatomical MRI so that anatomical localization of single dipoles and regional fMRI activity could be compared. Both negative and positive emotional conditions differed from non-emotional control conditions by strong orbitofrontal and lateral prefrontal activation as well as by the presence of early magnetic fields (-1700 to +1100 ms). Negative emotional processing was characterized by strong medial orbitofrontal activation and earlier (-1700 ms), stronger and more medially oriented orbitofrontal dipoles. In contrast positive emotional processing showed a rather strong activation in lateral prefrontal cortex with later (-1500 ms), weaker and more laterally oriented orbito and prefrontal dipoles. Negative emotional processing can be characterized by strong and early medial orbitofrontal cortical activation, whereas positive emotional processing showed rather later and weaker activation in lateral orbitofrontal/prefrontal cortex. Such a functional dissociation between medial and lateral orbito-frontal/prefrontal cortex during negative and positive emotional processing lends further support to the assumption of a functional subdivision in the orbitofrontal cortex.

Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI). We investigated 10 akinetic catatonic patients in a postacute state and compared them with 10 noncatatonic postacute psychiatric controls (age-, sex-, diagnosis-, and medication-matched) and 10 healthy controls. Positive and negative pictures from the International Affective Picture System were used for emotional stimulation. FMRI measurements covered the whole frontal lobe, activation signals in various frontal cortical regions were obtained, and functional connectivity between the different prefrontal cortical regions was investigated using structural equation modeling. Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls. Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity. It is concluded that catatonic symptoms may be closely related to dysfunction in the orbitofrontal cortex and consequent alteration in the prefrontal cortical network during emotional processing. Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome in schizophrenic or affective psychosis.

Fast, low-angle shoot functional magnetic resonance imaging (fMRI), based on the blood oxygenation level-dependent (BOLD) effect, was combined with optical recording of intrinsic signals (ORIS) and 2-deoxyglucose labeling in gerbil barrel cortex. We observed over the activated barrel a positive BOLD signal and increased levels of deoxyhemoglobin and total hemoglobin during each period of prolonged (30 sec) D2 vibrissal stimulation. These data show that the hemodynamic basis of this fMRI signal is not necessarily a washout of deoxyhemoglobin, as generally assumed. Instead, they suggest that a positive BOLD signal can also be caused by a local increase of blood volume, even if deoxyhemoglobin levels are persistently elevated. We also show that this alternative interpretation is consistent with theoretical models of the BOLD signal. The changes in BOLD signal and blood volume, which are most tightly correlated with the periodic stimulation, peak at the site of neuronal activation. These results contribute to the understanding of the hemodynamic mechanisms underlying the BOLD signal and also suggest analysis methods, which improve the spatial localization of neuronal activation with both fMRI and ORIS.

Electrodynamic speakers compatible with (functional) magnetic resonance imaging (MRI) are described. The speakers magnets are removed, their function is replaced by the scanner's magnetic field, resulting in an uncommon but efficient operation. The method can be used with headphones as well as woofers. Functional MRI is not associated with any known biological risks, but as a method for visualization of task-specific activation of brain regions it is undesirably noisy. Thus, it requires both noise protection and efficient sound transmission systems for delivering acoustic stimuli to subjects. Woofers could possibly be used in active noise-control systems. The speakers described in this paper can be used for either task.

Working memory (WM) tasks involve several interrelated processes during which past information must be transiently maintained, recalled, and compared with test items according to previously instructed rules. It is not clear whether the rule-specific comparisons of perceptual with memorized items are only performed in previously identified frontal and parietal WM areas or whether these areas orchestrate such comparisons by feedback to sensory cortex. We tested the latter hypothesis by focusing on auditory cortex (AC) areas with low-noise functional magnetic resonance imaging in a 2-back WM task involving frequency-modulated (FM) tones. The control condition was a 0-back task on the same stimuli. Analysis of the group data identified an area on right planum temporale equally activated by both tasks and an area on the left planum temporale specifically involved in the 2-back task. A region of interest analysis in each individual revealed that activation on the left planum temporale in the 2-back task positively correlated with the task performance of the subjects. This strongly suggests a prominent role of the AC in 2-back WM tasks. In conjunction with previous findings on FM processing, the left lateralized effect presumably reflects the complex sequential processing demand of the 2-back matching to sample task.

The molecular motor dynein and its associated regulatory subunit dynactin have been implicated in several neurodegenerative conditions of the basal ganglia, such as Huntington's disease (HD) and Perry syndrome, an atypical Parkinson-like disease. This pathogenic role has been largely postulated from the existence of mutations in the dynactin subunit p150(Glued). However, dynactin is also able to act independently of dynein, and there is currently no direct evidence linking dynein to basal ganglia degeneration. To provide such evidence, we used here a mouse strain carrying a point mutation in the dynein heavy chain gene that impairs retrograde axonal transport. These mice exhibited motor and behavioural abnormalities including hindlimb clasping, early muscle weakness, incoordination and hyperactivity. In vivo brain imaging using magnetic resonance imaging showed striatal atrophy and lateral ventricle enlargement. In the striatum, altered dopamine signalling, decreased dopamine D1 and D2 receptor binding in positron emission tomography SCAN and prominent astrocytosis were observed, although there was no neuronal loss either in the striatum or substantia nigra. In vitro, dynein mutant striatal neurons displayed strongly impaired neuritic morphology. Altogether, these findings provide a direct genetic evidence for the requirement of dynein for the morphology and function of striatal neurons. Our study supports a role for dynein dysfunction in the pathogenesis of neurodegenerative disorders of the basal ganglia, such as Perry syndrome and HD.

Various prefrontal cortical regions have been shown to be activated during emotional stimulation, whereas neurochemical mechanisms underlying emotional processing in the prefrontal cortex remain unclear. We therefore investigated the influence of the GABA-A potentiator lorazepam on prefrontal cortical emotional-motor spatio-temporal activation pattern in a combined functional magnetic resonance imaging/magnetoencephalography study. Lorazepam led to the reversal in orbito-frontal activation pattern, a shift of the early magnetic field dipole from the orbito-frontal to medial prefrontal cortex, and alterations in premotor/motor cortical function during negative and positive emotional stimulation. It is concluded that negative emotional processing in the orbito-frontal cortex may be modulated either directly or indirectly by GABA-A receptors. Such a modulation of orbito-frontal cortical emotional function by lorazepam has to be distinguished from its effects on cortical motor function as being independent from the kind of processing either emotional or nonemotional.

In recent years, magnetic resonance imaging (MRI) has emerged as a preferred tool for the diagnosis of amyotrophic lateral sclerosis (ALS) in humans. A widely used animal model for human ALS is the G93A-superoxide dismutase 1 (G93A-SOD1) transgenic mouse model. However, the mechanisms for the selective degeneration of motor neurons in the brainstem and spinal cord are still uncertain. In our study, we applied MRI at 4.7 Tesla to non-invasively evaluate pathological alterations in the brainstem of this animal model and to follow the progression of the disease. Extending previous investigation, we used the relaxation parameter T(2) as a suitable measure for the progression of ALS, and evaluated the potential agreement with histological evaluation and behavioural data of open-field tests. In the brainstem of G93A-SOD1 mice, T(2) values were significantly increased in the motor nuclei Nc. V, Nc. VII and Nc. XII, as early as Day 80, i.e. before the average disease onset at about Day 90. Moreover, this increase is associated with a progressive development of vacuoles in the brainstem motor nuclei and a significantly decreased performance in behavioural tests. Overall, MRI is a very sensitive tool to obtain correlates for neuronal degeneration in vivo. Furthermore, MRI enables us to investigate a follow up at different time points of the disease. These advantages are especially useful for therapeutic studies with respect to survival rates of motor neurons using mouse models. Finally, our data suggest that MRI does not only resemble the findings of behavioural tests, but is potentially superior to behavioural studies.