Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression

BACKGROUND:Mitochondrial dysfunction was reported in schizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics. METHODOLOGY/PRINCIPAL FINDINGS:mRNA and protein levels of complex I subunits NDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients with schizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found. Schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed in schizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group. CONCLUSIONS/SIGNIFICANCE:These results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders

Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits

Background Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation. Objective The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry. Results The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior. Conclusions Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression

Neural processing of natural sounds

Natural sounds include animal vocalizations, environmental sounds such as wind, water and fire noises and non-vocal sounds made by animals and humans for communication. These natural sounds have characteristic statistical properties that make them perceptually salient and that drive auditory neurons in optimal regimes for information transmission.Recent advances in statistics and computer sciences have allowed neuro-physiologists to extract the stimulus-response function of complex auditory neurons from responses to natural sounds. These studies have shown a hierarchical processing that leads to the neural detection of progressively more complex natural sound features and have demonstrated the importance of the acoustical and behavioral contexts for the neural responses.High-level auditory neurons have shown to be exquisitely selective for conspecific calls. This fine selectivity could play an important role for species recognition, for vocal learning in songbirds and, in the case of the bats, for the processing of the sounds used in echolocation. Research that investigates how communication sounds are categorized into behaviorally meaningful groups (e.g. call types in animals, words in human speech) remains in its infancy.Animals and humans also excel at separating communication sounds from each other and from background noise. Neurons that detect communication calls in noise have been found but the neural computations involved in sound source separation and natural auditory scene analysis remain overall poorly understood. Thus, future auditory research will have to focus not only on how natural sounds are processed by the auditory system but also on the computations that allow for this processing to occur in natural listening situations.The complexity of the computations needed in the natural hearing task might require a high-dimensional representation provided by ensemble of neurons and the use of natural sounds might be the best solution for understanding the ensemble neural code

The southeastern border of the Upper Rhine Graben : a 3D geological model and its importance for tectonics and groundwater flow

Hydrogeologie des Oberrheins; Grundwasser A 3D geological model of the area east of Basel on the southeastern border of the Upper Rhine Graben, consisting of 47 faults and six stratigraphic horizons relevant for groundwater flow, was developed using borehole data, geological maps, geological cross sections, and outcrop data. This model provides new insight into the discussions about the kinematics of the area between the southeastern border of the Upper Rhine Graben and the Tabular Jura east of Basel. A 3D analysis showed that both thin-skinned and thick-skinned tectonic elements occur in the modeled area and that the Anticline and a series of narrow graben structures developed simultaneously during an extensional stress-field varying from E-W to SSE-NNW, which lasted from the Middle Eocene to Late Oligocene. In a new approach the faults and horizons of the 3D geological model were transferred into discrete elements with distributed hydrogeological properties in order to simulate the 3D groundwater flow regime within the modeled aquifers. A three-layer approach with a horizontal regularly spaced grid combined with an irregular property distribution of transmissivity in depth permitted the piezometric head of the steady-state model to be automatically calibrated to corresponding measurements using more than 200 piezometers. Groundwater modeling results demonstrated that large-scale industrial pumping affected the groundwater flow field in the Upper Muschelkalk aquifer at distances of up to 2 km to the south. The results of this research will act as the basis for further model developments, including salt dissolution and solute transport in the area, and may ultimately help to provide predictions for widespread land subsidence risks