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Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.

The dorsal premotor cortex (PMd) is abnormally active in patients with idiopathic Parkinson's disease. This has been interpreted as a functional correlate of adaptive plasticity within the motor system to compensate for deficient activation of striato-mesial–frontal projections in these patients. Whether abnormal PMd activity influences excitability in the primary motor cortex (M1) in untreated Parkinson's disease patients and how this premotor–motor interaction might be altered by l-dopa is unclear. To this end, we studied the effects of 1 Hz premotor repetitive transcranial magnetic stimulation (rTMS) on M1 excitability in 10 previously untreated non-tremulous Parkinson's disease patients before (day 1) and after (day 8) their first ever l-dopa treatment and compared the results with those of a group of nine age- and sex-matched healthy controls. In each rTMS session, 1200 pulses of 1 Hz rTMS were applied at an intensity of 80% active motor threshold (AMT) to the PMd contralateral to the clinically more affected side in Parkinson's disease patients and to the left PMd in healthy controls. Intracortical paired pulse excitability of ipsilateral M1 was probed using a TMS paired pulse paradigm where subthreshold conditioning pulses (80% of AMT) were given 2–15 ms prior to a suprathreshold test pulse. In Parkinson's disease patients, abnormal baseline intracortical excitability at an interstimulus interval (ISI) of 5 ms was normalized by premotor rTMS. In contrast, rTMS led to an increased excitability at an ISI of 5 ms in healthy controls. Premotor rTMS effects lasted longer (for at least a week) in patients. These results show that the modifiability of premotor–motor connections is abnormal in untreated Parkinson's disease. A single dose of l-dopa reversed, i.e. normalized, the direction of excitability changes in M1 following premotor rTMS in Parkinson's disease patients, suggesting that dopamine depletion directly or indirectly influences premotor–motor interactions in Parkinson's disease. The rTMS conditioning approach described here provides a promising tool to delineate further the excitability changes in frontal motor areas in response to progressive degeneration of nigrostriatal dopaminergic neurons and also to chronic l-dopa treatment in Parkinson's disease.

According to the basal ganglia-thalamocortical circuit model, dopamine depletion in the nigrostriatal system leads to hypoactivation in the supplementary motor area (SMA) and the primary motor cortex (M1) in Parkinson's disease. This functional cortical deafferentation and its reversibility by levodopa (L-dopa) treatment has been established in previous studies for SMA but remains controversial for M1. We used functional MRI (fMRI) and a simple finger opposition task to correlate blood oxygenation level-dependent (BOLD) signal changes with motor performance, assessed separately for each hand between fMRI scanning sessions. Eight drug-naive patients with an akinetic idiopathic hemiparkinsonian syndrome (Hoehn and Yahr stage 1-1.5) and 10 healthy controls were studied. Patients performed a simple, auditory-paced random finger- opposition task every 3 s before and repeatedly every 20 min after intake of 300 mg of fast-release L-dopa. M1 contralateral to the affected hand and SMA, predominantly of the contralateral side, showed a BOLD signal increase after L-dopa intake. Furthermore, comparing BOLD responses of M1 and SMA between the patients and controls revealed that these areas were hypoactive before L-dopa treatment. Signal changes in M1 and SMA were highly correlated with motor performance, which increased after L-dopa intake. This result is not confounded by a performance effect because the motor task employed during scanning was identical throughout all sessions. In contrast to previous imaging studies in which cortical reorganization in Parkinson's disease was thought to have caused M1 hyperactivation, our data are in accordance with the hypothesis that, in de novo idiopathic hemiparkinsonian syndrome, motor cortex hypoactivation in contralateral M1 and bilateral SMA is caused by a decreased input from the subcortical motor loop, which is reversible by L-dopa.

According to the basal ganglia–thalamocortical circuit model, dopamine depletion in the nigrostriatal system leads to hypoactivation in the supplementary motor area (SMA) and the primary motor cortex (M1) in Parkinson’s disease. This functional cortical deafferentation and its reversibility by levodopa (l‐dopa) treatment has been established in previous studies for SMA but remains controversial for M1. We used functional MRI (fMRI) and a simple finger opposition task to correlate blood oxygenation level‐dependent (BOLD) signal changes with motor performance, assessed separately for each hand between fMRI scanning sessions. Eight drug‐naive patients with an akinetic idiopathic hemiparkinsonian syndrome (Hoehn and Yahr stage 1–1.5) and 10 healthy controls were studied. Patients performed a simple, auditory‐paced random finger‐ opposition task every 3 s before and repeatedly every 20 min after intake of 300 mg of fast‐release l‐dopa. M1 contralateral to the affected hand and SMA, predominantly of the contralateral side, showed a BOLD signal increase after l‐dopa intake. Furthermore, comparing BOLD responses of M1 and SMA between the patients and controls revealed that these areas were hypoactive before l‐dopa treatment. Signal changes in M1 and SMA were highly correlated with motor performance, which increased after l‐dopa intake. This result is not confounded by a performance effect because the motor task employed during scanning was identical throughout all sessions. In contrast to previous imaging studies in which cortical reorganization in Parkinson’s disease was thought to have caused M1 hyperactivation, our data are in accordance with the hypothesis that, in de novo idiopathic hemiparkinsonian syndrome, motor cortex hypoactivation in contralateral M1 and bilateral SMA is caused by a decreased input from the subcortical motor loop, which is reversible by l‐dopa.

Lipoprotein metabolism in brain has not yet been fully elucidated, although there are a few reports concerning lipids in the brain and lipoproteins and apolipoproteins in the cerebrospinal fluid (CSF). To establish normal levels of lipoproteins in human CSF, total cholesterol, phospholipids, and fatty acids as well as apolipoprotein E (apoE) and apoA-I levels were determined in CSF samples from 216 individuals. For particle characterization, lipoproteins from human CSF were isolated by affinity chromatography and analyzed for size, lipid and apolipoprotein composition. Two consecutive immunoaffinity columns with antibodies, first against apoE and subsequently against apoA-I, were used to define four distinct lipoprotein classes. The major lipoprotein fraction consisted of particles of 13;-20 nm containing apoE and apoA-I as well as apoA-IV, apoD, apoH, and apoJ. In the second particle class (13;-18 nm) mainly apoA-I and apoA-II but no apoE was detected. Third, there was a small number of large particles (18;-22 nm) containing no apoA-I but apoE associated with apoA-IV, apoD, and apoJ. In the unbound fraction we detected small particles (10;-12 nm) with low lipid content containing apoA-IV, apoD, apoH, and apoJ. In summary, we established lipid and apolipoprotein levels in CSF in a large group of individuals and described four distinct lipoprotein classes in human CSF, differing in their apolipoprotein pattern, lipid composition, and size. On the basis of our own data and previous findings from other groups, we propose a classification of CSF lipoproteins.

Abstract: We present a three-dimensional (3D) anatomical computer-graphics model of the corticospinal system acquired from equidistant serial anatomical slices of six intracranially-fixed human brains. This model is part of a neuroanatomical reference system (NeuRef) which enables 3D visualization of the brain and shows the relationship of its components such as anatomical structures, functional fibre tracts and arteries. Sections through the models can be matched with corresponding CT or MR images. This allows the probable localisation of corticospinal fibres on CT or MRI.

Conflicting information is available on the propensity different soil clays exhibit to dispersion. We therefore assessed the relative stability of the clay components of 12 soil samples, from various parts of South Africa, to predominantly physical disruption by a mild disruptive treatment [mechanical shaking for 5 min in distilled water (DW), and after the addition of phosphogypsum (PG; 2% by weight) and polyacrylamide (PAM; 0.04% by weight)]. The soils differed markedly in their physical and chemical properties. Clay fractions were of mixed mineralogy and dominated by kaolinite, illite, or smectite. Comparison of the clay mineral composition of the disaggregated clay with that of the original <2 m fraction indicated that the disaggregated clay composition depended on the amendment. In DW, clay-sized quartz and feldspar were disaggregated preferentially over layer silicates. Within the phyllosilicate fraction, the 2:1 clay minerals (mica, smectite) were on average slightly more easily disaggregated than kaolinite. Goethite was the least easily detached clay component in DW. The increase in quartz and feldspar proportions relative to the other components of the clay fraction was dramatically more pronounced when the soils were mixed with PG. With PAM, however, differences in the nature of the clay fraction between original and disaggregated clay were only marginal. Disruption was not particle-size related, as the minerals of the fine-clay fraction showed no selective increase in any of the treatments. These findings indicate that the most inert members of the clay fraction are most actively involved in the process of disaggregation. PG influenced disaggregation in a manner markedly different from that of PAM. Gypsum preferentially stabilised components with a net negative charge over uncharged species. PAM, in contrast, seemed to affect all clay components equally, independent of charge characteristics.

Soil dispersivity tests strongly disturb soils and therefore only remotely reproduce conditions in the field. A quick and inexpensive laboratory method for the assessment of clay dispersivity of soils is proposed that involves a much milder soil treatment. The method is based on the observation that, during the separation of the soil solution from soil pastes, the separated soil solution in some soils contains suspended fine matter. The method involves the consecutive extraction of wetted and only mildly disturbed soil packed in a Buchner funnel, under standardized conditions. The time needed for the completion of the extraction of 20 mL of solution, and the extracted mineral load, are monitored. After drying, the micromorphology of the soil cake can be observed by scanning electron microscopy. By this method, the results obtained from six South African soils compared well with spontaneous dispersion test data (after Rengasamy et al., Aust. J. Soil Res., 1984, 22, 413-31) obtained independently.

Background. Stress reduction and relaxation exercises are therapeutically suggested to patients with Parkinson’s disease (PD) and tremor, but data regarding efficacy or preferential methods are missing. Objective. To investigate the effect of a standardized stress management training (SMT) according to Kaluza on coping with tremor-boosting psychosocial stress factors. Methods. 8-week SMT was applied to 82 PD patients with tremor and 30 controls. Changes in stress-associated factors were measured applying four scales: Kaluza’s “warning signs for stress” and “stress-amplifying thoughts” and Beck Depression Inventory (BDI) and quality of life (PDQ-8). Short-term outcome (8 weeks) was evaluated in both groups, and long-term outcome (3–6 months) was evaluated only in PD patients. Results. At baseline, PDQ-8 was worse in PD patients compared to controls. PD patients improved significantly regarding short- and long-term outcome scores of “warning signs for stress,” “stress-amplifying thoughts,” and BDI scores, independently of disease severity or duration. Younger and male PD patients showed the best benefit. Controls improved comparably to PD patients but significantly only with respect to “stress-amplifying thoughts.” Retrospectively, 88% (29/33) of PD patients were rated SMT as helpful 12–18 months later. Self-practicing SMT exercises correlated significantly with subjectively better coping with tremor-related daily impairment and subjective short-term and long-term tremor reduction. Conclusion. SMT should be a part of therapy of PD patients with tremor.

The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN) and combined subthalamic nucleus and substantia nigra (STN+SNr) high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson’s disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson’s disease (1 female; age: 61.3±7.3 years; disease duration: 12.3±5.4 years; Hoehn and Yahr stage: 2.2±0.39) were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS), Modified Fatigue Impact Scale (MFIS), Becks Depression Inventory (BDI-I), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-RS), and Parkinson’s Disease Questionnaire (PDQ-39). Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.