[Ocular movement and nystagmus: basics and clinical diagnosis]. / Augenbewegungen und Nystagmus: Grundlagen und klinische Diagnostik.

BACKGROUND: Eye movements are one of the most complex motor functions of the central nervous system (CNS). Eye movement disorders including nystagmus occur in diseases of the CNS and the vestibular system. A systematic clinical examination often allows a topodiagnostic classification of the lesion. OBJECTIVE: The basics of eye movements, the role of the cerebellum, the clinical examination of the oculomotor system, and the most important forms of nystagmus and their diagnostic implications are described. MATERIALS AND METHODS: A literature analysis assessing eye movements, cerebellar control of eye movements, clinical examination of eye movement, and nystagmus was performed. RESULTS: In disorders of eye movement, diseases of the oculomotor cranial nerves and the central nervous structures are to be distinguished from diseases of the orbit, eye muscles, and motor end plates. The former result in cranial nerve-related paralysis of extraocular muscles, disturbances of saccadic and smooth pursuit eye movements, vertical or horizontal gaze palsy, internuclear ophthalmoplegia, or impaired gaze holding. Nystagmus in combination with other disturbances of ocular movement is highly related to a lesion within the CNS. Intense nystagmus with a rotatory component that decreases during fixation usually has a peripheral vestibular cause. CONCLUSION: Clinical examination of eye movements and nystagmus enables the diagnosis of typical eye movement disorders with a strong relation to distinct lesions of the CNS or the peripheral vestibular pathway.

Distinct resting-state perfusion patterns underlie psychomotor retardation in unipolar vs. bipolar depression.

OBJECTIVE: Psychomotor abnormalities characterize both unipolar (UP) depression and bipolar (BP) depression. We aimed to assess their neurobiological correlates in terms of motor activity (AL) and resting-state cerebral blood flow (rCBF) and investigate their association in BP, UP, and healthy controls (HC). METHOD: We enrolled 42 depressed patients (22 BP, 20 UP) and 19 HC matched for age, gender, education, income. AL and rCBF were objectively assessed with the use of wrist actigraphy and arterial spin labeling. Group differences and the association of AL and rCBF were computed. RESULTS: Activity level was significantly reduced in patients, but no difference was found between BP and UP. Increased perfusion was found in BP compared with UP and HC, in multiple brain areas. We found positive correlations of rCBF and AL in BP and UP, in different parts of the insula and frontal regions. Only BP showed a cluster in the left precentral gyrus. In HC, only inverse correlations of AL and rCBF were found. CONCLUSION: The differences in rCBF and in the localization of the clusters of positive AL/rCBF correlations between BP and UP suggest that different neural impairments may underlie motor symptoms in the two disorders, but finally converge in phenotypically similar manifestations.

EEG marker of inhibitory brain activity correlates with resting-state cerebral blood flow in the reward system in major depression.

Frontal alpha band asymmetry (FAA) is a marker of altered reward processing in major depressive disorder (MDD), associated with reduced approach behavior and withdrawal. However, its association with brain metabolism remains unclear. The aim of this study was to investigate FAA and its correlation with resting-state cerebral blood flow (rCBF). We hypothesized an association of FAA with regional rCBF in brain regions relevant to reward processing and motivated behavior, such as the striatum. We enrolled 20 patients and 19 healthy subjects. FAA scores and rCBF were quantified with the use of EEG and arterial spin labeling. Correlations of the two were evaluated, as well as the association with FAA and psychometric assessments of motivated behavior and anhedonia. Patients showed a left-lateralized pattern of frontal alpha activity and a correlation of FAA lateralization with subscores of Hamilton Depression Rating Scale linked to motivated behavior. An association of rCBF and FAA scores was found in clusters in the dorsolateral prefrontal cortex bilaterally (patients), in the left medial frontal gyrus, in the right caudate head and in the right inferior parietal lobule (whole group). No correlations were found in healthy controls. Higher inhibitory right-lateralized alpha power was associated with lower rCBF values in prefrontal and striatal regions, predominantly in the right hemisphere, which are involved in the processing of motivated behavior and reward. Inhibitory brain activity in the reward system may contribute to some of the motivational problems observed in MDD.

Neutron, fluorescence, and optical imaging: An in situ combination of complementary techniques.

An apparatus which enables the simultaneous combination of three complementary imaging techniques, optical imaging, fluorescence imaging, and neutron radiography, is presented. While each individual technique can provide information on certain aspects of the sample and their time evolution, a combination of the three techniques in one setup provides a more complete and consistent data set. The setup can be used in transmission and reflection modes and thus with optically transparent as well as opaque samples. Its capabilities are illustrated with two examples. A polymer hydrogel represents a transparent sample and the diffusion of fluorescent particles into and through this polymer matrix is followed. In reflection mode, the absorption of solvent by a nile red-functionalized mesoporous silica powder and the corresponding change in fluorescent signal are studied.

Neural correlates of disbalanced motor control in major depression.

BACKGROUND: Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF). METHODS: Nineteen control subjects and 20 MDD patients were investigated using arterial spin labeling (ASL) at 3T in the morning to quantify resting state CBF. Afterwards wrist actigraphy was recorded for 24h. CBF, group and activity level (AL) were entered into a whole brain general linear model. RESULTS: MDD patients had reduced AL. Both groups had linear associations of AL and CBF in bilateral rostral prefrontal cortex. Groups differed in four clusters associated with motor control. In controls a positive association was found in the left caudal cingulate zone (CCZ) and an inverse association in the right external globus pallidus (GPe). MDD patients had positive associations in the right orbitofrontal cortex and inverse associations in the left supplemental motor area. LIMITATIONS: Patients were on antidepressant medication. CONCLUSIONS: The pattern of associations between CBF and AL suggest disbalanced motor control in MDD. Findings are in line with the hypothesis of dopamine deficits contributing to motor retardation in MDD.

Tetra-kis(picolinato-κN,O)zirconium(IV) dihydrate.

In the title compound, [Zr(C(6)H(4)NO(2))(4)]·2H(2)O, the Zr(IV) atom is located on a crystallographic fourfold rotoinversion axis ([Formula: see text]) and is coordinated by four picolinate anions with Zr-O and Zr-N distances of 2.120 (2) and 2.393 (2) Å, respectively. An approximate square-anti-prismatic coordination polyhedron of the N,O-coordination ligand atoms is formed, with a distortion towards dodeca-hedral geometry. The crystal packing is stabilized by inter-molecular π-π inter-actions between adjacent picolinate rings [centroid-centroid distances = 3.271 (1) and 3.640 (2) Å], as well as O-H⋯O hydrogen bonds between the solvent mol-ecules and the coordinated ligands, thereby linking the mol-ecules into a supra-molecular three-dimensional network.

Luminescent, redox-active diphenothiazine dumbbells expanded by conjugated arenes and heteroarenes.

Dumbbell-shaped diphenothiazines bridged by conjugatively linked (hetero)aromatic moieties were synthesized in a modular fashion by Suzuki-Miyaura coupling in good yields. The electronic structure was studied by DFT computations, determining the geometry optimized lowest energy conformers and scrutinizing the Kohn-Sham FMOs. The torsional deviation from coplanarity is predominantly influencing the electronic structure, i.e., by deviation from ideal overlap and maximal electron transmission. The reversible oxidation potentials assigned to the phenothiazinyl electrophores in most cases can thereby be qualitatively rationalized. All dumbbell-shaped diphenothiazines are strongly luminescent, which can be attributed to extended π-electron conjugation with considerable excited state electronic coupling as a consequence of large structural and electronic distributional changes upon photoexcitation.

Carbon-yl(N-nitroso-N-oxido-1-naphtylamine-κO,O')(triphenyl-phosphine-κP)rhodium(I) acetone solvate.

The title compound, [Rh(C(10)H(7)N(2)O(2))(C(18)H(15)P)(CO)]·(CH(3))(2)CO, is the second structural report of a metal complex formed with the O,O'-C(10)H(7)N(2)O(2) (neocupferrate) ligand. In the crystal structure, the metal centre is surrounded by one carbonyl ligand, one triphenyl-phosphine ligand and the bidentate neocupferrate ligand, forming a distorted square-planar RhCO(2)P coordination set which is best illustrated by the small O-Rh-O bite angle of 77.74 (10)°. There are no classical hydrogen-bond inter-actions observed for this complex.

[Possible genetic link between Darier's disease and depression. Review of the literature and case history]. / Morbus Darier und Depression - besteht eine genetische Verbindung? Ubersicht und klinischer Fall.

Darier's disease is a rare, inherited autosomal dominant skin disorder caused by a mutation in the sarcoendoplasmatic reticulum calcium transporter (SERCA)-2-gene. In a number of pedigrees, Darier's disease closely relates with affective disorder. The most likely hypothesis for this is a susceptibility gene for affective disorder near the SERCA-2-gene. A 6.5-megabase region could be identified as a susceptibility locus. This region constitutes a susceptability locus also in affective disorder without Darier's disease. The underlying gene has not yet been identified.

Comparison of spatial and temporal pattern for fMRI obtained with BOLD and arterial spin labeling.

Functional magnetic resonance imaging (fMRI) is presently either performed using blood oxygenation level-dependent (BOLD) contrast or using cerebral blood flow (CBF), measured with arterial spin labeling (ASL) technique. The present fMRI study aimed to provide practical hints to favour one method over the other. It involved three different acquisition methods during visual checkerboard stimulation on nine healthy subjects: 1) CBF contrast obtained from ASL, 2) BOLD contrast extracted from ASL and 3) BOLD contrast from Echo planar imaging. Previous findings were replicated; i) no differences between the three measurements were found in the location of the activated region; ii) differences were found in the temporal characteristics of the signals and iii) BOLD has significantly higher sensitivity than ASL perfusion. ASL fMRI was favoured when the investigation demands for perfusion and task related signal changes. BOLD fMRI is more suitable in conjunction with fast event related design.

A novel one-pot pyrrole synthesis via a coupling-isomerization-Stetter-Paal-Knorr sequence.

[reaction: see text]. 1,2,3,5-tetrasubstituted pyrroles can be synthesized in good yields in a one-pot, three-step, four-component process by a coupling-isomerization-Stetter reaction-Paal-Knorr sequence of an electron-poor (hetero)aryl halide, a terminal propargyl alcohol, an aldehyde, and a primary amine. The structures of the 1,4-diketone 4f and the pyrrole 6b were additionally supported by X-ray structure analyses.

Electrophysiological signs of reduced prefrontal response control in schizophrenic patients.

The prefrontal cortex is considered as a brain region important in the etiopathogenesis of schizophrenic disorders. Based on converging results from different research areas, the prefrontal cortex is regarded as the anatomical and functional representation of response control under physiological conditions. In previous studies, a robust electrophysiological marker for the investigation of response control in healthy control subjects was validated. This parameter was termed NoGo anteriorisation and consists of a more anterior peak of the event-related potentials during the inhibition of a prepared motor response (NoGo condition within the Continuous Performance Test) than during its execution (Go condition). The present study investigated these brain electrical correlates of response control in 19 schizophrenic patients and 19 age- and sex-matched healthy subjects. Compared to control subjects, the event-related potentials in schizophrenic patients were located more anterior in the Go condition and, as a trend, more posterior in the NoGo condition. The NoGo anteriorisation was strongly reduced in the schizophrenic group. On a qualitative level, the NoGo anteriorisation was present in all control subjects, but not in eight of the 19 patients. The results were interpreted as an indication of a disturbed prefrontal response control in schizophrenic patients. Further studies will clarify whether this method may be useful as a global test of hypofrontality in different groups of chronic schizophrenias, or as a quantifiable measure of an affected response control system, especially in catatonic subgroups.

Diastereoselective propargylations with planar chiral chromiumcarbonyl arene complex substituted propargyl cations.

The ionization of planar chiral ortho-substituted (arene)Cr(CO)(3)-substituted alpha-propargylic acetates 3 with Lewis acids results in the formation of stable (arene)Cr(CO)(3)-substituted alpha-propargyl cations 4. Subsequent additions of sulfur, nitrogen, oxygen, and pi-carbon nucleophiles to these organometallic electrophiles give rise to the regio- and highly diastereoselective formation of propargyl derivatives 5 in good yields (44-90%; dr = 70:30 to >99:1). The relative stereochemistry of the propargyl acetates 3 and the trapping products 5 was established by several crystal structure analyses, indicating that the cationic propargylations occurred under retention of configuration at the propargylic center. Most important for the diastereoselectivity of the nucleophilic trapping reaction is the configurational stability of the diastereotopic cation 4 as reflected by substituent effects. In situ ionizations according to an S(N)1-mechanism not only result in a considerable loss but also in an inversion of diastereoselectivity.

The neurophysiological meaning of auditory P300 in subtypes of schizophrenia.

Event-related potentials are a powerful tool to investigate the real-time course of brain electrical mass activation during cognitive processing. In several psychiatric disorders, differences compared to healthy subjects have been reliably described. The specificity and the pathophysiological meaning of the findings were unclear in most studies, however. This review summarizes methodological aspects and findings, in healthy subjects and psychiatric patients, of investigations based on the auditory oddball paradigm, which evokes the P300 component of event-related potentials. Recent convergent results from P300 and brain imaging studies allowed the interpretation of P300 findings in psychotic disorders in terms of different specific and meaningful neurophysiological disturbances. Namely, core schizophrenia is characterized by a left-temporal dysfunction associated with deficits in verbal processing. Acute remitting schizophrenia-like psychoses (cycloid psychosis, ICD-10 F23), on the other hand, show normal hemispheric balance but consistent signs of cerebral hyperarousal. Recent studies further indicate that the drive for action of manic patients does not rely on over-excitation but rather on frontal disinhibition. The findings may help to further advance the understandings and sub-grouping of functional psychoses based on pathophysiological mechanisms.

Cognitive response control in writer's cramp.

Disturbances of the motor and sensory system as well as an alteration of the preparation of movements have been reported to play a role in the pathogenesis of dystonias. However, it is unclear whether higher aspects of cortical - like cognitive - functions are also involved. Recently, the NoGo-anteriorization (NGA) elicited with a visual continuous performance test (CPT) during recording of a 21-channel electroencephalogram has been proposed as an electrophysiological standard-index for cognitive response control. The NGA consists of a more anterior location of the positive area of the brain electrical field associated with the inhibition (NoGo-condition) compared with that of the execution (Go-condition) of a prepared motor response in the CPT. This response control paradigm was applied in 16 patients with writer's cramp (WC) and 14 age matched healthy controls. Topographical analysis of the associated event-related potentials revealed a significant (P < 0.05) NGA effect for both patients and controls. Moreover, patients with WC showed a significantly higher global field power value (P < 0.05) in the Go-condition and a significantly higher difference-amplitude (P < 0.05) in the NoGo-condition. A source location analysis with the low resolution electromagnetic tomography (LORETA) method demonstrated a hypoactivity for the Go-condition in the parietal cortex of the right hemisphere and a hyperactivity in the NoGo-condition in the left parietal cortex in patients with WC compared with healthy controls. These results indicate an altered response control in patients with WC in widespread cortical brain areas and therefore support the hypothesis that the pathogenesis of WC is not restricted to a pure sensory-motor dysfunction.

Synthesis of functionalized ethynylphenothiazine fluorophores.

Alkynylated and butadiynyl-bridged phenothiazines with variable functionalization can be synthesized in good yields by cross-coupling and condensation approaches. In addition, the structure of the diethynylated phenothiazine (7a) has been corroborated by an X-ray structure analysis. These oligofunctional heterocycles are fluorescent with modest quantum yields (Phi(f) = 20-35%) and represent suitable building blocks for novel photoexcitable molecular wires.

The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients.

Despite a considerable number of investigations revealing the prefrontal cortex (PFC) to be a major site of pathological changes in schizophrenia, the neuronal basis of these alterations is still unknown. We used a 3-D image analysis technique to investigate the dendritic arborization of Golgi-impregnated prefrontal pyramidal neurons in schizophrenic patients and controls. While the apical dendrites were found to be unchanged in schizophrenics, the basilar dendritic systems were markedly reduced in the patient group. A segment analysis showed that the observed alterations were mainly confined to distal dendritic segments. The dendritic changes are likely to be associated with specific dysfunctions of prefrontal circuitry and point to the pathogenetical relevance of pre- and perinatal disturbances of PFC maturation in schizophrenic patients.

A novel three-component one-pot pyrimidine synthesis based upon a coupling-isomerization sequence.

[reaction: see text] 2,4,6-Tri(hetero)aryl-substituted pyrimidines can be readily synthesized in a three-component one-pot process based upon a coupling-isomerization sequence of an electron-poor (hetero)aryl halide and a terminal propargyl alcohol subsequently followed by a cyclocondensation with amidinium salts.

EEG signs of vigilance fluctuations preceding perceptual flips in multistable illusionary motion.

This EEG study was performed to clarify the time course of brain electrical events and possible vigilance changes associated with perceptual flips during multistable perception. 13 healthy subjects (28.5 3.8 years) were recorded with a 21-channel digital EEG during a stroboscopic alternative motion paradigm implying illusionary motion with ambiguous direction. Perceptual flips were preceded by a significant decrease of EEG frequencies, and followed by a significant frequency increase with a trend to overshoot. EEG slowing is a reliable sign of vigilance decrease and can be related to thalamic deactivation. This is consistent with a recent fMRI study, which showed thalamic deactivation associated with perceptual flips. The study added important chronological information about this phenomenon and allows the conclusion that reduced vigilance facilitates perceptual discontinuities during multistable perception.

Prefrontal hypooxygenation during language processing assessed with near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive optical method which allows in vivo measurements of relative concentrations of oxygenated (O2Hb) and desoxygenated hemoglobin (HHb). It has been successfully applied to assess the blood oxygenation changes during cerebral ischemia in man. An interesting application of NIRS is the investigation of regional cerebral blood oxygenation during physiological brain functions. In the present study, left and right anterior prefrontal brain areas of 10 healthy subjects were investigated with 2-channel NIRS during language processing (reading aloud). Nonverbal visual perception (picture observation) was performed as a control condition. Compared to the respective baseline conditions, a significant HHb increase and an O2Hb decrease as a trend were found during language processing but not during the nonverbal perceptual task, and no hemispheric differences were found. The metabolic activation patterns differed significantly between the tasks indicating the changes due to the language-related efforts but not to visual perception. Based on previous findings of metabolic brain imaging studies the results are best explained as a complementary phenomenon consisting in relative anterior prefrontal hypoperfusion due to a blood volume redistribution which favors language-related temporal areas.