Goal-directed Task Research Articles

Differences in Default Mode Network Connectivity in Meditators and Non-meditators During an Attention Task

Activity in the default mode network (DMN) is reduced during non-self-referential goal-directed tasks in healthy individuals. In this study, we investigated differences in DMN functional connectivity between regular meditators and non-meditators during an attention paradigm. Non-meditators and regular meditators, matched by age, years of education, and gender were instructed to name the color of single words visually presented in a Stroop Word-Color Task (SWCT) adapted for functional magnetic resonance imaging (fMRI). The task was performed when the participants were not formally meditating. Logistic analysis based on imaging data indicated that the connectivity between the PCC (precuneus/posterior cingulate cortex) and the right and left parietal lobules helps differentiating regular meditators from non-meditators. Granger causality results showed that the activity in the PCC contains information to predict the activity in the right lateral parietal cortex and that the accuracy in this prediction is higher in regular meditators when compared to non-meditators. This suggests a stronger link between these two regions in regular meditators. In contrast to regular meditators, the PCC is more influenced by the left parietal region (related to the process of reading—which is the interference in the SWCT), and this region is more influenced by the PCC in non-meditators. These functional connectivity differences in the DMN between groups possibly reflect a higher degree of interference and probably more distraction during the SWCT in non-meditators compared with meditators.

Sex differences in spatial accuracy relate to the neural activation of antagonistic muscles in young adults.

Sex is an important physiological variable of behavior, but its effect on motor control remains poorly understood. Some evidence suggests that women exhibit greater variability during constant contractions and poorer accuracy during goal-directed tasks. However, it remains unclear whether motor output variability or altered muscle activation impairs accuracy in women. Here, we examine sex differences in endpoint accuracy during ankle goal-directed movements and the activity of the antagonistic muscles. Ten women (23.1±5.1years) and 10 men (23±3.7years) aimed to match a target (9° in 180ms) with ankle dorsiflexion. Participants performed 50 trials and we recorded the endpoint accuracy and the electromyographic (EMG) activity of the primary agonist (Tibialis Anterior; TA) and antagonist (Soleus; SOL) muscles. Women exhibited greater spatial inaccuracy (Position error: t=-2.65, P=0.016) but not temporal inaccuracy relative to men. The motor output variability was similar for the two sexes (P>0.2). The spatial inaccuracy in women was related to greater variability in the coordination of the antagonistic muscles (R 2 0.19, P=0.03). These findings suggest that women are spatially less accurate than men during fast goal-directed movements likely due to an altered activation of the antagonistic muscles.

An Interactive Simulator for Imposing Virtual Musculoskeletal Dynamics

disease processes are often marked by both neural and muscular changes that alter movement control and execution, but these adaptations are difficult to tease apart because they occur simultaneously. This is addressed by swapping an individual's limb dynamics with a neurally controlled facsimile using an interactive musculoskeletal simulator (IMS) that allows controlled modifications of musculoskeletal dynamics. This paper details the design and operation of the IMS, quantifies and describes human adaptation to the IMS, and determines whether the IMS allows users to move naturally, a prerequisite for manipulation experiments. healthy volunteers (n = 4) practiced a swift goal-directed task (back-and-forth elbow flexion/extension) for 90 trials with the IMS off (normal dynamics) and 240 trials with the IMS on, i.e., the actions of a user's personalized electromyography-driven musculoskeletal model are robotically imposed back onto the user. after practicing with the IMS on, subjects could complete the task with end-point errors of 1.56°, close to the speed-matched IMS-off error of 0.57°. Muscle activity, joint torque, and arm kinematics for IMS-on and -off conditions were well matched for three subjects (root-mean-squared error [RMSE] = 0.16N·m), but the error was higher for one subject with a small stature (RMSE = 0.25N·m). a well-matched musculoskeletal model allowed IMS users to perform a goal-directed task nearly as well as when the IMS was not active. this advancement permits real-time manipulations of musculoskeletal dynamics, which could increase our understanding of muscular and neural co-adaptations to injury, disease, disuse, and aging.

Impaired Activation of Visual Attention Network for Motion Salience Is Accompanied by Reduced Functional Connectivity between Frontal Eye Fields and Visual Cortex in Strabismic Amblyopia.

Strabismic amblyopia is now acknowledged to be more than a simple loss of acuity and to involve alterations in visually driven attention, though whether this applies to both stimulus-driven and goal-directed attention has not been explored. Hence we investigated monocular threshold performance during a motion salience-driven attention task involving detection of a coherent dot motion target in one of four quadrants in adult controls and those with strabismic amblyopia. Psychophysical motion thresholds were impaired for the strabismic amblyopic eye, requiring longer inspection time and consequently slower target speed for detection compared to the fellow eye or control eyes. We compared fMRI activation and functional connectivity between four ROIs of the occipital-parieto-frontal visual attention network [primary visual cortex (V1), motion sensitive area V5, intraparietal sulcus (IPS) and frontal eye fields (FEF)], during a suprathreshold version of the motion-driven attention task, and also a simple goal-directed task, requiring voluntary saccades to targets randomly appearing along a horizontal line. Activation was compared when viewed monocularly by controls and the amblyopic and its fellow eye in strabismics. BOLD activation was weaker in IPS, FEF and V5 for both tasks when viewing through the amblyopic eye compared to viewing through the fellow eye or control participants' non-dominant eye. No difference in V1 activation was seen between the amblyopic and fellow eye, nor between the two eyes of control participants during the motion salience task, though V1 activation was significantly less through the amblyopic eye than through the fellow eye and control group non-dominant eye viewing during the voluntary saccade task. Functional correlations of ROIs within the attention network were impaired through the amblyopic eye during the motion salience task, whereas this was not the case during the voluntary saccade task. Specifically, FEF showed reduced functional connectivity with visual cortical nodes during the motion salience task through the amblyopic eye, despite suprathreshold detection performance. This suggests that the reduced ability of the amblyopic eye to activate the frontal components of the attention networks may help explain the aberrant control of visual attention and eye movements in amblyopes.

Age-associated differences in motor output variability and coordination during the simultaneous dorsiflexion of both feet

Older adults are more variable than young adults on tasks that demand the simultaneous control of more than one effector, and the difference between age groups may be related to their different capacity of coordinating the force output of the involved effectors. The goal of this study was to determine whether age-associated differences in motor output variability during tasks involving the simultaneous dorsiflexion of two feet can be partially explained by differences in coordination and possibly attenuated by physical training. Ten young and 22 old adults (10 trained and 12 untrained old adults) volunteered to participate in the study. Trained older adults had experience in a high-intensity mixed modality training (MMT) regime for a minimum of 1 year. Volunteers performed successive trials of a constant force task and a goal-directed task, with and without visual feedback. Within- and between-trial variability were calculated and coordination was quantified using the uncontrolled manifold (UCM) approach (i.e., co-variation of the force outputs of both feet were used to quantify a motor synergy index). Older adults exhibited greater variability and lower synergy (p < .05), independently of physical training status, than young adults. Removal of visual feedback caused greater variability and lower synergy for all groups (p < .05). Our results suggest that older adults exhibit greater motor output variability in tasks involving the simultaneous dorsiflexion of both feet possibly due to a lack of coordination between the feet.

A biologically inspired model based on a multi-scale spatial representation for goal-directed navigation

Inspired by the multi-scale nature of hippocampal place cells, a biologically inspired model based on a multi-scale spatial representation for goal-directed navigation is proposed in order to achieve robotic spatial cognition and autonomous navigation. First, a map of the place cells is constructed in different scales, which is used for encoding the spatial environment. Then, the firing rate of the place cells in each layer is calculated by the Gaussian function as the input of the Q-learning process. The robot decides on its next direction for movement through several candidate actions according to the rules of action selection. After several training trials, the robot can accumulate experiential knowledge and thus learn an appropriate navigation policy to find its goal. The results in simulation show that, in contrast to the other two methods(G-Q, S-Q), the multi-scale model presented in this paper is not only in line with the multi-scale nature of place cells, but also has a faster learning potential to find the optimized path to the goal. Additionally, this method also has a good ability to complete the goal-directed navigation task in large space and in the environments with obstacles.

Interactions between the anterior cingulate-insula network and the fronto-parietal network during perceptual decision-making

Information processing in the human brain during cognitively demanding goal-directed tasks is thought to involve several large-scale brain networks, including the anterior cingulate-insula network (aCIN) and the fronto-parietal network (FPN). Recent functional MRI (fMRI) studies have provided clues that the aCIN initiates activity changes in the FPN. However, when and how often these networks interact remains largely unknown to date. Here, we systematically examined the oscillatory interactions between the aCIN and the FPN by using the spectral Granger causality analysis of reconstructed brain source signals from the scalp electroencephalography (EEG) recorded from human participants performing a face-house perceptual categorization task. We investigated how the aCIN and the FPN interact, what the temporal sequence of events in these nodes is, and what frequency bands of information flow bind these nodes in networks. We found that beta band (13–30Hz) and gamma (30–100Hz) bands of interactions are involved between the aCIN and the FPN during decision-making tasks. In gamma band, the aCIN initiated the Granger causal control over the FPN in 25–225 ms timeframe. In beta band, the FPN achieved a control over the aCIN in 225–425 ms timeframe. These band-specific time-dependent Granger causal controls of the aCIN and the FPN were retained for behaviorally harder decision-making tasks. These findings of times and frequencies of oscillatory interactions in the aCIN and FPN provide us new insights into the general neural mechanisms for sensory information-guided, goal-directed behaviors, including perceptual decision-making processes.

Dissociated patterns of anti-correlations with dorsal and ventral default-mode networks at rest.

Previous studies of resting state functional connectivity have demonstrated that the default-mode network (DMN) is negatively correlated with a set of brain regions commonly activated during goal-directed tasks. However, the location and extent of anti-correlations are inconsistent across different studies, which has been posited to result largely from differences in whether or not global signal regression (GSR) was applied as a pre-processing step. Notably, coordinates of seed regions-of-interest defined within the posterior cingulate cortex (PCC)/precuneus, an area often employed to study functional connectivity of the DMN, have been inconsistent across studies. Taken together with recent observations that the DMN contains functionally heterogeneous subdivisions, it is presently unclear whether these seeds map to different DMN subnetworks, whose patterns of anti-correlation may differ. If so, then seed location may be a non-negligible factor that, in addition to differences in preprocessing steps, contributes to the inconsistencies reported among published studies regarding DMN correlations/anti-correlations. In this study, they examined anti-correlations of different subnetworks within the DMN during rest using both seed-based and point process analyses, and discovered that: (1) the ventral branch of the DMN (vDMN) yielded significantly weaker anti-correlations than that associated with the dorsal branch of the DMN (dDMN); (2) vDMN anti-correlations introduced by GSR were distinct from dDMN anti-correlations; (3) PCC/precuneus seeds employed by earlier studies mapped to different DMN subnetworks, which may explain some of the inconsistency (in addition to preprocessing steps) in the reported DMN anti-correlations. Hum Brain Mapp 38:2454-2465, 2017. © 2017 Wiley Periodicals, Inc.

To Do or Not to Do? Task Control Deficit in Obsessive-Compulsive Disorder

Task control is an executive control mechanism that facilitates goal-directed task selection by suppressing irrelevant automatic “stimulus-driven” behaviors. In the current study, we test the hypothesis that less efficient task control in individuals diagnosed with obsessive-compulsive disorder (OCD) is associated with OCD symptoms, and specifically, with the inability to inhibit unwanted behaviors in OCD. Thirty-five healthy controls, 30 participants with OCD, and 26 participants with generalized anxiety disorder (GAD) completed the object-interference (OI) task to measure task control, the stop-signal task to measure response inhibition, and the arrow-flanker task to evaluate executive abilities not contingent upon task control. OCD patients, but not GAD patients or healthy controls, exhibited impaired performance on the OI task. The deficit in task control, but not in response inhibition, correlated with OCD symptom severity. We suggest that reduced task control may be one of the neurocognitive processes that underlie the inability to inhibit unwanted behaviors in OCD.

Using Optimal Control to Disambiguate the Effect of Depression on Sensorimotor, Motivational and Goal-Setting Functions.

Differentiating the ability from the motivation to act is of central importance to psychiatric disorders in general and depression in particular. However, it has been difficult to develop quantitative approaches to relate depression to poor motor performance in goal-directed tasks. Here, we use an inverse optimal control approach to provide a computational framework that can be used to infer and factorize performance deficits into three components: sensorimotor speed, goal setting and motivation. Using a novel computer-simulated driving experiment, we found that (1) severity of depression is associated with both altered sensorimotor speed and motivational function; (2) moderately to severely depressed individuals show an increased distance from the stop sign indicating aversive learning affecting goal setting functions. Taken together, the inverse optimal control framework can disambiguate on an individual basis the sensorimotor from the motivational dysfunctions in depression, which may help to develop more precisely targeted interventions.

Altered dynamics of brain connectivity in major depressive disorder at-rest and during task performance

Major depressive disorder (MDD) has been associated with alterations in several functional brain networks. Previous studies investigating brain networks in MDD during the performance of a task have yielded inconsistent results with the function of the brain at rest. In this study, we used functional magnetic resonance imaging at rest and during a goal-directed task to investigate dynamics of functional connectivity in 19 unmedicated patients with MDD and 19 healthy controls across both experimental paradigms. Patients had spatial differences in the default mode network (DMN), in the executive network (EN), and in the dorsal attention network (DAN) compared to controls at rest and during task performance. In patients the amplitude of the low frequency (LFO) oscillations was reduced in the motor and in the DAN networks during both paradigms. There was a diagnosis by paradigm interaction on the LFOs amplitude of the salience network, with increased amplitude change between task and rest in patients relative to controls. Our findings suggest that the function of several networks could be intrinsically affected in MDD and this could be viable phenotype for the investigation on the neurobiological mechanisms of this disorder and its treatment.

Whole-body multi-contact motion in humans and humanoids: Advances of the CoDyCo European project

Traditional industrial applications involve robots with limited mobility. Consequently, interaction (e.g. manipulation) was treated separately from whole-body posture (e.g. balancing), assuming the robot firmly connected to the ground. Foreseen applications involve robots with augmented autonomy and physical mobility. Within this novel context, physical interaction influences stability and balance. To allow robots to surpass barriers between interaction and posture control, forthcoming robotic research needs to investigate the principles governing whole-body motion and coordination with contact dynamics. There is a need to investigate the principles of motion and coordination of physical interaction, including the aspects related to unpredictability. Recent developments in compliant actuation and touch sensing allow safe and robust physical interaction from unexpected contact including humans. The next advancement for cognitive robots, however, is the ability not only to cope with unpredictable contact, but also to exploit predictable contact in ways that will assist in goal achievement. Last but not least, theoretical results needs to be validated in real-world scenarios with humanoid robots engaged in whole-body goal-directed tasks. Robots should be capable of exploiting rigid supportive contacts, learning to compensate for compliant contacts, and utilizing assistive physical interaction from humans. The work presented in this paper presents state-of-the-art in these domains as well as some recent advances made within the framework of the CoDyCo European project.

Effect of nucleus accumbens lesions on socially motivated behaviour of young domestic chicks

Behaviour of young domestic chicks when isolated from conspecifics is influenced by two conflicting drives: fear of potential predator and craving for company. The nucleus accumbens (Ac) has been suggested to influence social behaviour, as well as motivation in goal-directed tasks. In this study, the Ac of 1-day-old domestic chicks was lesioned bilaterally, using radiofrequency method. Open field behaviour before and after presenting a silhouette of a bird of prey was recorded, followed by a behavioural test to measure group size preference and social motivation of chicks. Ac-lesioned individuals emitted more distress calls and ambulated more in the open field test, however, they reacted to the predatory stimulus very similarly to control chicks: their vocalization was reduced and the intergroup difference in motor activity also disappeared. There was no difference between the lesioned and control chicks in the latency to approach their conspecifics in the social motivation test, and both groups chose the larger flock (eight) of conspecifics over the smaller one (three). Concerning the role of Ac in social behaviour, a difference between lesioned and sham birds was evident here only in the absence of detectable stimulus (predator or conspecifics). These findings may reflect either decreased fear of exposure to predators or increased craving for conspecifics suggesting that the likely function of Ac is to modulate goal-driven, including socially driven, behaviours, especially when the direct stimulus representing the goal is absent. This is in harmony with the known promotion of impulsiveness by Ac lesions.

Value of pre-cue information for motor tasks performed by children with developmental coordination disorder (DCD)

People commonly use pre-cue information to advance and reduce the information processing time required for a motor task (e.g., motor planning). However, children with developmental coordination disorder (DCD) exhibit difficulties performing pre-cued goal-directed tasks. The purpose of the present study was to investigate the use of valid, neutral, and invalid pre-cue information for a goal-directed task. The participants were 11 children with DCD (mean age = 7.94 yrs.) and 11 typically developed (TD) age- and gender-matched children. The children with DCD exhibited delayed motor planning (e.g., reaction time) under the invalid condition compared to that of the TD children. The children with DCD used atypical strategies for motor execution and depended more on online corrections (e.g., increased deceleration time and movement units) to reach the target. These results suggest that children with DCD have difficulties handling unpredictable situations and that the use of atypical motor execution strategies did not affect movement time.

Extending Energy Optimization in Goal-Directed Aiming from Movement Kinematics to Joint Angles

ABSTRACTEnergy optimization in goal-directed aiming has been demonstrated as an undershoot bias in primary movement endpoint locations, especially in conditions where corrections to target overshoots must be made against gravity. Two-component models of upper limb movement have not yet considered how joint angles are organized to deal with the energy constraints associated with moving the upper limb in goal-directed aiming tasks. To address this limitation, participants performed aiming movements to targets in the up and down directions with the index finger and two types of rod extensions attached to the index finger. The rod extensions were expected to invoke different energy optimizing strategies in the up and down directions by allowing the distal joints the opportunity to contribute to end effector displacement. Primary movements undershot the farthest target to a greater extent in the downward direction compared to the upward direction, showing that movement kinematics optimize energy expenditure in consideration of the effects of gravity. As rod length increased, shoulder elevation was optimized in movements to the far-up target and elbow flexion was optimally minimized in movements to the far-down target. The results suggest energy optimization in the control of joint angles independent of the force of gravity.

EP 84. Motor control and learning strategy for efficient neurorehabilitation

Introduction Parkinson’s, stroke, and other neurological diseases may significantly affect the control of voluntary, ballistic-like movements that normally are performed automatically and optimally as regards position accuracy, energy expenditure and movement execution time. The control functions (neural signals to muscles) are to be re-learnt and re-optimised with respect to these performance indices. In our study, a natural approach for efficient motor learning in goal-directed motion tasks, incl. walking is proposed. It is based on novel concepts and underlying principles of neurophysiology, natural dynamics, and biological cybernetics. We believe that such a motor control and learning strategy may be very useful to achieve efficiency in neurorehabilitation. Method Test control functions that could sensibly optimize motor performance have a triphasic (burst-pause-burst) shape. Their parameters are intrinsic ones that human has to (re-) learn in dynamic point-to-point motion tasks, ( Karniel and Inbar, 1997 ). The control learning scheme has the following main steps, ( Kiryazov and Kiriazov, 2010 ): (1) parameterise test control functions; (2) select most appropriate pairs of control parameters and controlled outputs; (3) make corrections in the control parameters until reach the target, applying simple, natural learning algorithm, within a very low number of trials. Results Using realistic mathematical models, our motor learning approach was applied to motion tasks like reaching movements, Fig. 1 , and performing steps. In the latter case, we decomposed the task to perform a step into two point-to-point leg movements, Fig. 2 . In the computer simulations we verified our control concepts and the fact that the learning control process is fast converging. In addition, we did some real (able-bodied) experiments with rapid aiming movements of the arm and they confirm the feasibility and efficacy of the proposed approach. Discussion Based on the conceptual framework above proposed it is possible to design reliable control strategies in neurorehabilitation, ( Despotova and Kiriazov, 2015 ). The neural structures that compute the required control forces are the so-called internal models, and we believe that the proposed approach can be used to rebuild such models (cortical reorganization) by proper training procedures. Recent research has shown that voluntary exercises can increase levels of brain-derived neurotrophic factor and other growth factors, stimulate neurogenesis, and improve brain plasticity and motor learning performance. Conclusion Our approach can also be used for the purposes of neuro-muscular rehabilitation, with assistive robotic devices applied or in functional electrical stimulation. In the latter case, optimising the timing sequence for stimulating muscles may produce smoother and more accurate movements. Another interesting problem is the design of brain-computer interfaces for direct control of human/robot motion and this is a subject of ongoing research.

Primate superior colliculus neurons activated by unexpected sensation.

Midbrain superior colliculus (SC) contains a variety of neuronal types, influencing a rich spectrum of functions beyond gaze orienting. Here, we report on a novel class of SC neurons in the rhesus monkey (Macaca mulatta) that are activated by an unexpected perturbation in a goal-directed arm-movement task. One monkey subject reached for and pressed an illuminated target on a working panel upon a visual go-signal, while maintaining visual fixation elsewhere. On 50% of trials, a task perturbation occurred-the working panel abruptly and unexpectedly moved against the subject's hand after he pressed the target. During the performance, we recorded single SC neurons and found neurons activated exclusively for the task perturbation. These perturbation neurons were localized in the deep lateral zone of the SC, were silent during non-perturbed trials, did not appear to respond to task-irrelevant stimuli, and they had intriguingly long neuronal latencies. If the perturbation neurons' activity relates to the hand-target contact, it may reflect the saliency of an unexpected sensation, i.e. a sensation that is not self-induced and thus cannot be predicted on a basis of the monkey's motor program.

Unwanted reminders: The effects of emotional memory suppression on subsequent neuro-cognitive processing.

The neural basis of voluntarily suppressing conscious access to one's own memories (retrieval suppression [RS]) has recently received considerable attention. However, to date there has been limited research examining the effects of RS on subsequent processing of associated retrieval cues. In this study 47 healthy participants completed a Think/No Think task for memories of emotionally unpleasant visual scenes. While undergoing functional magnetic resonance imaging (fMRI), participants were then presented with cues associated with both suppressed ("no-think-cues") and non-suppressed ("think-cues") memories, and then asked to perform simple arithmetic problems. We observed that, compared to think-cues, no-think-cues were associated with greater left mid/anterior insula activation and with greater insula-anterior cingulate functional connectivity; left insula activation also predicted worse arithmetic performance. These results suggest that cues associated with suppressed negative memories may lead to greater activation of the brain's "salience" network, and reduced available cognitive resources for completion of an ongoing goal-directed task.

Resting-state functional connectivity differentiates anxious apprehension and anxious arousal.

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self-referential processing than during goal-directed tasks. The present study assessed resting-state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole-brain, seed-based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner-focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations.

Transient Distraction and Attentional Control during a Sustained Selective Attention Task.

Distracting stimuli in the environment can pull our attention away from our goal-directed tasks. fMRI studies have implicated regions in right frontal cortex as being particularly important for processing distractors [e.g., de Fockert, J. W., & Theeuwes, J. Role of frontal cortex in attentional capture by singleton distractors. Brain and Cognition, 80, 367-373, 2012; Demeter, E., Hernandez-Garcia, L., Sarter, M., & Lustig, C. Challenges to attention: A continuous arterial spin labeling (ASL) study of the effects of distraction on sustained attention. Neuroimage, 54, 1518-1529, 2011]. Less is known, however, about the timing and sequence of how right frontal or other brain regions respond selectively to distractors and how distractors impinge upon the cascade of processes related to detecting and processing behaviorally relevant target stimuli. Here we used EEG and ERPs to investigate the neural consequences of a perceptually salient but task-irrelevant distractor on the detection of rare target stimuli embedded in a rapid, serial visual presentation (RSVP) stream. We found that distractors that occur during the presentation of a target interfere behaviorally with detection of those targets, reflected by reduced detection rates, and that these missed targets show a reduced amplitude of the long-latency, detection-related P3 component. We also found that distractors elicited a right-lateralized frontal negativity beginning at 100 msec, whose amplitude negatively correlated across participants with their distraction-related behavioral impairment. Finally, we also quantified the instantaneous amplitude of the steady-state visual evoked potentials elicited by the RSVP stream and found that the occurrence of a distractor resulted in a transient amplitude decrement of the steady-state visual evoked potential, presumably reflecting the pull of attention away from the RSVP stream when distracting stimuli occur in the environment.