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In this 2-year trial involving patients with Parkinson's disease and early motor complications, subthalamic stimulation plus medical therapy resulted in better quality of life and motor function than medical therapy alone. Parkinson's disease is a progressive neurodegenerative disease that affects dopaminergic neurotransmission, resulting in bradykinesia, rigidity, and rest tremor. After an initial honeymoon period, during which there is a sustained response to dopaminergic treatment, beneficial effects are hampered by levodopa-induced motor complications, 1 progressively compromising quality of life. 2 – 4 Because levodopa-responsive parkinsonian symptoms are improved by high-frequency stimulation of the subthalamic nucleus, 5 , 6 neurostimulation has become an established treatment for advanced Parkinson's disease with medically intractable fluctuations and dyskinesia 7 – 10 and has shown long-term efficacy. 11 – 13 It is typically used after the disease has been present for 11 to 13 years, 7 – . . .

Human self-consciousness as the metarepresentation of ones own mental states and the so-called theory of mind (TOM) capacity, which requires the ability to model the mental states of others, are closely related higher cognitive functions. We address here the issue of whether taking the self-perspective (SELF) or modeling the mind of someone else (TOM) employ the same or differential neural mechanisms. A TOM paradigm was used and extended to include stimulus material that involved TOM and SELF capacities in a two-way factorial design. A behavioral study in 42 healthy volunteers showed that TOM and SELF induced differential states of mind: subjects assigned correctly first or third person pronouns when providing responses to the stimuli. Following the behavioral study, we used functional magnetic resonance imaging (fMRI) in eight healthy, right-handed males to study the common and differential neural mechanisms underlying TOM and SELF. The main factor TOM led to increased neural activity in the anterior cingulate cortex and left temporopolar cortex. The main factor SELF led to increased neural activity in the right temporoparietal junction and in the anterior cingulate cortex. A significant interaction of both factors TOM and SELF was observed in the right prefrontal cortex. These divergent neural activations in response to TOM and SELF suggest that these important differential mental capacities of human self-consciousness are implemented at least in part in distinct brain regions.

We used functional magnetic resonance imaging to explore the brain mechanisms of changing point of view (PoV) in a visuospatial memory task in 3D space. Eye movements were monitored and BOLD signal changes were measured while subjects were presented with 3D images of a virtual environment. Subjects were required to encode the position of a lamp in the environment and, after changing the PoV (angular difference varied from 0° to 180° in 45° steps), to decide whether the lamp position had been changed too or not. Performance data and a scan-path analysis based on eye movement support the use of landmarks in the environment for coding lamp position and increasing spatial updating costs with increasing changes of PoV indicating allocentric coding strategies during all conditions (0°- to 180°-condition). Subtraction analysis using SPM revealed that a parieto–temporo–frontal network including left medial temporal areas was activated during this 3D visuospatial task, independent of angular difference. The activity of the left parahippocampal area and the left lingual gyrus (but not the hippocampus) correlated with increasing changes of the PoV between encoding and retrieval, emphasizing their specific role in spatial scene memory and allocentric coding. The results suggest that these areas are involved in a continuous matching process between internal representations of the environment and the external status quo. In addition, hippocampal activation correlated with performance was found indicating successful recall of spatial information. Finally, in a prefrontal area comprising, the so-called “deep” frontal eye field, activation was correlated with the amount of saccadic eye movements confirming its role in oculomotor processes.

Using functional MRI, we characterized field sign maps of the occipital cortex and created three-dimensional maps of these areas. By averaging the individual maps into group maps, probability maps of functionally defined V1 or V2 were determined and compared to anatomical probability maps of Brodmann areas BA17 and BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought into stereotaxic space—where and how variable? NeuroImage 11, 66–84). Comparison of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and functional probability maps. Taking into account that our functional stimulation (due to constraints of the visual angle of stimulation achievable in the MR scanner) only identified parts of V1 and V2, for statistical evaluation of the spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori measure κ was calculated testing the hypothesis that a region can only be part of functionally defined V1 or V2 if it is also in anatomically defined BA17 or BA18, respectively. κ = 1 means the hypothesis is fully true, κ = 0 means functionally and anatomically defined visual areas are independent. When applying this measure to the probability maps, κ was equal to 0.84 for both V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and anatomically derived segregations of early visual processing areas and serve as a basis for employing anatomical probability maps of V1 and V2 in group analyses to characterize functional activations of early visual processing areas.

While oversampling of the data poses no problem, decimation by a factor greater than the minimum time lag or one that is not a common divisor of the lag may lead to erroneous inferences. [...]as the true lag structure is usually unknown, it seems advisable to proceed with a higher autoregressive model order rather than to decimate.

Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of “social brain” areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self-initiated JA specifically activated areas related to social cognition, decision-making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self-initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects. •Interactive eye-tracking and fMRI to study the development of joint attention•The general JA network comprised social brain and attention related areas.•Self- and other-initiation modulated the JA network.•The interaction partner's familiarity modulated the JA network.•The precuneus and TPJ play critical roles during the development of JA.

Movements result from a complex interplay of multiple brain regions. These regions are assembled into distinct functional networks depending on the specific properties of the action. However, the nature and details of the dynamics of this complex assembly process are unknown. In this study, we sought to identify key markers of the neural processes underlying the preparation and execution of motor actions that always occur irrespective of differences in movement initiation, hence the specific neural processes and functional networks involved. To this end, EEG activity was continuously recorded from 18 right-handed healthy participants while they performed a simple motor task consisting of button presses with the left or right index finger. The movement was performed either in response to a visual cue or at a self-chosen, i.e., non-cued point in time. Despite these substantial differences in movement initiation, dynamic properties of the EEG signals common to both conditions could be identified using time–frequency and phase locking analysis of the EEG data. In both conditions, a significant phase locking effect was observed that started prior to the movement onset in the δ–θ frequency band (2–7Hz), and that was strongest at the electrodes nearest to the contralateral motor region (M1). This phase locking effect did not have a counterpart in the corresponding power spectra (i.e., amplitudes), or in the event-related potentials. Our finding suggests that phase locking in the δ–θ frequency band is a ubiquitous movement-related signal independent of how the actual movement has been initiated. We therefore suggest that phase-locked neural oscillations in the motor cortex are a prerequisite for the preparation and execution of motor actions. •We found phase locking in the delta–theta frequency band in motor areas prior to movement execution.•Phase locking occurred irrespective of how the action was initiated.•Our results suggest that phase locking constitutes a prerequisite to trigger movement execution.

The dimorphic switch from a single-cell budding yeast to a filamentous form enables Saccharomyces cerevisiae to forage for nutrients and the opportunistic pathogen Candida albicans to invade human tissues and evade the immune system. We constructed a genome-wide set of targeted deletion alleles and introduced them into a filamentous S. cerevisiae strain, Σ1278b. We identified genes involved in morphologically distinct forms of filamentation: haploid invasive growth, biofilm formation, and diploid pseudohyphal growth. Unique genes appear to underlie each program, but we also found core genes with general roles in filamentous growth, including MFG1 (YDL233w), whose product binds two morphogenetic transcription factors, Flo8 and Mss11, and functions as a critical transcriptional regulator of filamentous growth in both S. cerevisiae and C. albicans.

Biofilms are formed by the aggregation of microorganisms into multicellular structures that adhere to surfaces. Here we show that bakers' yeast Saccharomyces cerevisiae can initiate biofilm formation. When grown in low-glucose medium, the yeast cells adhered avidly to a number of plastic surfaces. On semi-solid (0.3% agar) medium they formed \"mats\": complex multicellular structures composed of yeast-form cells. Both attachment to plastic and mat formation require Flo11p, a member of a large family of fungal cell surface glycoproteins involved in adherence. The ability to study biofilm formation in a tractable genetic system may facilitate the identification of new targets for antifungal therapy.

In this functional magnetic resonance imaging study, we explored the effects of both stimulus material and encoding task demands on activation in lateral prefrontal cortex (PFC). Two factors were manipulated: material type and task instructions. Subjects encoded words or abstract figures (factor 1: stimulus type) and were required to make either a meaning-based or a form-based (letter or shape) decision about each stimulus (factor 2: task instructions). Abstract figures engendered significantly higher levels of right PFC activity than did words. This effect was seen for meaning-based and form-based processing tasks and was significantly greater for the former. We did not observe a differential response of left lateral PFC to verbal and pictorial material. A double dissociation, however, was found within left PFC. A ventrolateral region (within left inferior frontal gyrus) showed the highest levels of activity when words were processed according to their meaning whereas activity in a more dorsolateral region (within left middle frontal gyrus) was greatest when words were processed according to their form (constituent letters). We have therefore observed a main effect of material type in producing lateralized activation of frontal lobes, although the strength of this effect is sensitive to the nature of the task that subjects are asked to perform. Left-side lateral PFC activity is also sensitive to task instructions but this effect was specific to verbal material. The complex patterns of frontal effect counsel against any simple dichotomy of frontal function at the level of either material or task type.