Exploration of sensory-motor tradeoff behavior in Parkinson's disease.

While slowness of movement is an obligatory characteristic of Parkinson's disease (PD), there are conditions in which patients move uncharacteristically fast, attributed to deficient motor inhibition. Here we investigate deficient inhibition in an optimal sensory-motor integration framework, using a game in which subjects used a paddle to catch a virtual ball. Display of the ball was extinguished as soon as the catching movement started, segregating the task into a sensing and acting phase. We analyzed the behavior of 9 PD patients (ON medication) and 10 age-matched controls (HC). The switching times (between sensing and acting phase) were compared to the predicted optimal switching time, based on the individual estimates of sensory and motor uncertainties. The comparison showed that deviation from predicted optimal switching times were similar between groups. However, PD patients showed a weaker correlation between variability in switching time and sensory-motor uncertainty, indicating a reduced propensity to generate exploratory behavior for optimizing goal-directed movements. Analysis of the movement kinematics revealed that PD patients, compared to controls, used a lower peak velocity of the paddle and intercepted the ball with greater velocity. Adjusting the trial duration to the time for the paddle to stop moving, we found that PD patients spent a smaller proportion of the trial duration for observing the ball. Altogether, the results do not show the premature movement initiation and truncated sensory processing that we predicted to ensue from deficient inhibition in PD.

The Role of Microelectrode Recording and Stereotactic Computed Tomography in Verifying Lead Placement During Awake MRI-Guided Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) has become a cornerstone in the advanced treatment of Parkinson's disease (PD). Despite its well-established clinical benefit, there is a significant variation in the way surgery is performed. Most centers operate with the patient awake to allow for microelectrode recording (MER) and intraoperative clinical testing. However, technical advances in MR imaging and MRI-guided surgery raise the question whether MER and intraoperative clinical testing still have added value in DBS-surgery. OBJECTIVE: To evaluate the added value of MER and intraoperative clinical testing to determine final lead position in awake MRI-guided and stereotactic CT-verified STN-DBS surgery for PD. METHODS: 29 consecutive patients were analyzed retrospectively. Patients underwent awake bilateral STN-DBS with MER and intraoperative clinical testing. The role of MER and clinical testing in determining final lead position was evaluated. Furthermore, interobserver variability in determining the MRI-defined STN along the planned trajectory was investigated. Clinical improvement was evaluated at 12 months follow-up and adverse events were recorded. RESULTS: 98% of final leads were placed in the central MER-track with an accuracy of 0.88±0.45 mm. Interobserver variability of the MRI-defined STN was 0.84±0.09. Compared to baseline, mean improvement in MDS-UPDRS-III, PDQ-39 and LEDD were 26.7±16.0 points (54%) (p < 0.001), 9.0±20.0 points (19%) (p = 0.025), and 794±434 mg/day (59%) (p < 0.001) respectively. There were 19 adverse events in 11 patients, one of which (lead malposition requiring immediate postoperative revision) was a serious adverse event. CONCLUSION: MER and intraoperative clinical testing had no additional value in determining final lead position. These results changed our daily clinical practice to an asleep MRI-guided and stereotactic CT-verified approach.

A hereditary spastic paraplegia predominant phenotype caused by variants in the NEFL gene.

INTRODUCTION: This study reports a large series of patients with a clinical picture dominated by spastic paraplegia in whom variants in the NEFL gene, a known cause for Charcot-Marie-Tooth disease, were identified. METHODS: Index patients referred for a suspicion of hereditary spastic paraplegia (HSP) were clinically assessed and genetic analysis by next-generation sequencing was undertaken. Additional family members were clinically examined and subjected to targeted testing. RESULTS: We identified two different heterozygous dominant variants in the NEFL gene in 25 patients from 14 families. Most of them (21/25) had a clinical diagnosis of HSP, often with a concomitant clinical diagnosis of polyneuropathy (16/21). Two patients were identified with a polyneuropathy with a pyramidal reflex pattern, but without spasticity. Two patients had isolated polyneuropathy. Out of the 21 patients with a diagnosis of HSP, two had co-occurring cerebellar signs. The c.262A > C p.(Thr88Pro) variant was detected in 13 families. Genealogical analysis showed shared ancestors or a similar geographical origin in 12, suggesting a founder effect. The other variant, c.296A > C p.(Asp99Ala), was found in only one family, in which limited segregation analysis could be performed. DISCUSSION: Variants in the NEFL gene can cause HSP, with or without co-existing polyneuropathy, and should be included in diagnostic testing strategies for HSP patients.

The cerebral tremor circuit in a patient with Holmes tremor.

The cerebral network associated with Holmes tremor has never been determined directly. A previous study reported a brain network that is functionally connected, in healthy individuals, to different lesions that cause Holmes tremor (lesion connectome). We report a 71-year-old man with severe left-sided tremor caused by a microbleed near the right red nucleus. Using accelerometry-fMRI, we show tremor-related activity in contralateral sensorimotor cortex and cerebellar vermis. This network was distinct from, but functionally coupled to, the Holmes lesion connectome. We propose that Holmes tremor involves three distinct cerebral mechanisms: a structural lesion, an intermediate lesion connectome, and symptom-related activity.

Uncertainty modulated exploration in the trade-off between sensing and acting.

Many sensorimotor activities have a time constraint for successful completion. In this case, any time devoted to sensory processing is at the expense of time available for motor execution. Earlier studies have explored how this competition between sensory processing and motor execution is resolved by using experimental designs that segregate the sensing and acting phase of the task. It was found that participants switch from the sensing to the acting stage such that the overall (sensorimotor) uncertainty in the outcome of the task is minimized. An unexplained observation in these studies is the substantial variability in switching times. We investigated the variability in switching time by correlating it with the underlying sensorimotor uncertainty. To this end, we used a modified version of the virtual ball catching paradigm proposed by Faisal & Wolpert (2009). Subjects were instructed to catch a ball, but as soon as they initiated their movement the ball disappeared. We extended the range of horizontal velocities and used two different start positions of the ball to quantify the dependence of sensory uncertainty on ball velocity. Velocity dependence of sensory uncertainty allowed us to manipulate sensory uncertainty and hence the sensorimotor uncertainty. We found that the variability in switching times is correlated with two factors. Firstly, variability in switching times is greater when variation in switching time has only minimal effects on sensorimotor uncertainty. Secondly, variability in switching times is greater when the sensorimotor uncertainty is larger. Our results suggest that the variability in switching time reflects an uncertainty-driven exploratory process.

Entrainment for attentional selection in Parkinson's disease.

Neural entrainment plays a crucial role in perception and action, especially when stimuli possess a certain temporal regularity, and is also suggested to serve as a neural process to select and attend the relevant stream in situations where there are competing stimulus streams. Beneficial effects of entrainment have led to the suggestion that rhythmic stimuli can improve motor function in patients with Parkinson's disease (PD). Behavioural studies support this suggestion, but neurophysiological studies have shown reduced entrainment of motor areas in PD. However, oscillatory entrainment in PD has only been tested in paradigms with a single isochronous stimulus stream, whereas entrainment has an enhanced benefit in situations where one rhythmic stimulus stream has to be segregated from distractor stimuli. Therefore, we here used an intermodal selective attention task with concurrent auditory and visual stimulus streams while recording oscillatory brain activity with Magnetoencephalography (MEG). We aimed to (i) replicate earlier findings of deficient motor entrainment in PD patients in conditions where there is a single stimulus stream, and (ii) to evaluate whether increasing the benefit of entrainment by introducing a distractor stream would lead to entrainment in PD patients not seen otherwise. Contrary to this hypothesis, PD patients showed reduced motor entrainment compared to controls during both conditions, as indexed by beta oscillatory activity. These results suggest that entrainment in PD patients is deficient, even under conditions that encourage entrainment.

Impaired auditory-to-motor entrainment in Parkinson's disease.

Several electrophysiological studies suggest that Parkinson's disease (PD) patients have a reduced tendency to entrain to regular environmental patterns. Here we investigate whether this reduced entrainment concerns a generalized deficit or is confined to movement-related activity, leaving sensory entrainment intact. Magnetoencephalography was recorded during a rhythmic auditory target detection task in 14 PD patients and 14 control subjects. Participants were instructed to press a button when hearing a target tone amid an isochronous sequence of standard tones. The variable pitch of standard tones indicated the probability of the next tone to be a target. In addition, targets were occasionally omitted to evaluate entrainment uncontaminated by stimulus effects. Response times were not significantly different between groups and both groups benefited equally from the predictive value of standard tones. Analyses of oscillatory beta power over auditory cortices showed equal entrainment to the tones in both groups. By contrast, oscillatory beta power and event-related fields demonstrated a reduced engagement of motor cortical areas in PD patients, expressed in the modulation depth of beta power, in the response to omitted stimuli, and in an absent motor area P300 effect. Together, these results show equally strong entrainment of neural activity over sensory areas in controls and patients, but, in patients, a deficient translation of the adjustment to the task rhythm to motor circuits. We suggest that the reduced activation reflects not merely altered resonance to rhythmic external events, but a compromised recruitment of an endogenous response reflecting internal rhythm generation.NEW & NOTEWORTHY Previous studies suggest that motor cortical activity in PD patients has a reduced tendency to entrain to regular environmental patterns. This study demonstrates that the deficient entrainment in PD concerns the motor system only, by showing equally strong entrainment of neural activity over sensory areas in controls and patients but, in patients, a deficient translation of this adjustment to the task rhythm to motor circuits.

Lateralized electrical brain activity reveals covert attention allocation during speaking.

Speakers usually begin to speak while only part of the utterance has been planned. Earlier work has shown that speech planning processes are reflected in speakers' eye movements as they describe visually presented objects. However, to-be-named objects can be processed to some extent before they have been fixated upon, presumably because attention can be allocated to objects covertly, without moving the eyes. The present study investigated whether EEG could track speakers' covert attention allocation as they produced short utterances to describe pairs of objects (e.g., "dog and chair"). The processing difficulty of each object was varied by presenting it in upright orientation (easy) or in upside down orientation (difficult). Background squares flickered at different frequencies in order to elicit steady-state visual evoked potentials (SSVEPs). The N2pc component, associated with the focusing of attention on an item, was detectable not only prior to speech onset, but also during speaking. The time course of the N2pc showed that attention shifted to each object in the order of mention prior to speech onset. Furthermore, greater processing difficulty increased the time speakers spent attending to each object. This demonstrates that the N2pc can track covert attention allocation in a naming task. In addition, an effect of processing difficulty at around 200-350ms after stimulus onset revealed early attention allocation to the second to-be-named object. The flickering backgrounds elicited SSVEPs, but SSVEP amplitude was not influenced by processing difficulty. These results help complete the picture of the coordination of visual information uptake and motor output during speaking.

Timing of beta oscillatory synchronization and temporal prediction of upcoming stimuli.

Modulations of beta oscillatory power serve a predictive role, in preparation of future actions. It is well known that beta amplitude decreases prior to voluntary movements and expected tactile stimuli. Paradoxically, recent studies have reported a beta amplitude increase prior to expected visual and auditory stimuli. Moreover, it has been suggested that, in isochronic stimulus series, the rising beta slope is adjusted to the duration of the interstimulus interval. We investigated the characteristics of such timing related pre-stimulus beta power increases using visual stimulus sequences that were presented at three regular rates (0.61, 0.74 and 0.95Hz). EEG was recorded from twenty participants while they attended the sequences by performing a clock reading task. Time-frequency analyses showed a consistent pattern of beta modulation: the post-stimulus beta power decrease was followed by a steep increase. Contrary to recent views, we found that the peaks of beta power, for the three presentation rates, were reached at a similar latency post-stimulus, instead of a fixed interval preceding the next stimulus. This demonstrates that, at interstimulus intervals between 1-2s, beta synchronization slopes are not modulated by timing mechanisms related to prediction of upcoming stimuli. We reconcile the discrepant results by proposing that when shorter interval durations are used, as in previous studies, beta resynchronization is interrupted by the presentation of a new stimulus, making it seem as if beta power peaks prior to upcoming stimuli. We emphasize caution with respect to the notion that the timing of beta synchronization is an expression of predictive timing.

Separating Visual and Motor Components of Motor Cortex Activation for Multiple Reach Targets: A Visuomotor Adaptation Study.

Ethologically inspired models of movement preparation view the sensorimotor system as sampling information from the environment in a parallel fashion in preparation for multiple potential actions. In support, the configuration of the physical workspace, manipulated by the number or spatial separation of potential targets, has been shown to modulate sensorimotor neural activity. It is unclear, however, whether this modulation is driven by the sensory layout of the workspace or through the associated motor plans. Here, we combine a delayed-movement pre-cuing task with visuomotor adaptation to address this question in human subjects while recording MEG. By dissociating visual and motor coordinates of two targets using visuomotor adaptation, the task was designed to evaluate, in a selective fashion, the effects of visual and movement target separation on movement preparatory activity. The results did not allow the intended comparison due to an unanticipated effect of the direction of visuomotor adaptation on baseline oscillatory power in beta and low-gamma bands. Fortuitously, this effect was dependent on whether the adaptation direction decreased or increased the angular separation between alternative movements. That is, there was a sustained reduction of oscillatory power, which was stronger at small compared with large target separation. These results support a direct influence of movement target separation on motor cortex neural activity, mediated by lateral interactions between simultaneously active motor plans. The results further demonstrate a novel effect of visuomotor adaptation on motor cortex oscillatory activity, with properties that support the local nature of learned changes in visuomotor mapping. SIGNIFICANCE STATEMENT: There is growing evidence that the motor cortex routinely prepares for different movements simultaneously, each suited to a possible course of events in the immediate environment. The preparatory motor cortex activity for different movements can be seen as a competition between groups of neurons. This competition is influenced by how similar the alternative movements are; for example, in terms of direction, determined by the proximity of alternative movement goals. This study investigates whether the proximity of alternative reach goals has a direct influence on motor cortex activity (in the form of brain oscillations) or if it has an effect only through conscious evaluation of the separation between targets. We establish that there is a direct effect, supporting the biased competition model of action selection.

Effects of rhythmic stimulus presentation on oscillatory brain activity: the physiology of cueing in Parkinson's disease.

The basal ganglia play an important role in beat perception and patients with Parkinson's disease (PD) are impaired in perception of beat-based rhythms. Rhythmic cues are nonetheless beneficial in gait rehabilitation, raising the question how rhythm improves movement in PD. We addressed this question with magnetoencephalography recordings during a choice response task with rhythmic and non-rhythmic modes of stimulus presentation. Analyses focused on (i) entrainment of slow oscillations, (ii) the depth of beta power modulation, and (iii) whether a gain in modulation depth of beta power, due to rhythmicity, is of predictive or reactive nature. The results show weaker phase synchronisation of slow oscillations and a relative shift from predictive to reactive movement-related beta suppression in PD. Nonetheless, rhythmic stimulus presentation increased beta modulation depth to the same extent in patients and controls. Critically, this gain selectively increased the predictive and not reactive movement-related beta power suppression. Operation of a predictive mechanism, induced by rhythmic stimulation, was corroborated by a sensory gating effect in the sensorimotor cortex. The predictive mode of cue utilisation points to facilitation of basal ganglia-premotor interactions, contrasting with the popular view that rhythmic stimulation confers a special advantage in PD, based on recruitment of alternative pathways.

De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.

BACKGROUND: Mutations of SCN8A encoding the neuronal voltage-gated sodium channel NaV1.6 are associated with early-infantile epileptic encephalopathy type 13 (EIEE13) and intellectual disability. Using clinical exome sequencing, we have detected three novel de novo SCN8A mutations in patients with intellectual disabilities, and variable clinical features including seizures in two patients. To determine the causality of these SCN8A mutations in the disease of those three patients, we aimed to study the (dys)function of the mutant sodium channels. METHODS: The functional consequences of the three SCN8A mutations were assessed using electrophysiological analyses in transfected cells. Genotype-phenotype correlations of these and other cases were related to the functional analyses. RESULTS: The first mutant displayed a 10 mV hyperpolarising shift in voltage dependence of activation (gain of function), the second did not form functional channels (loss of function), while the third mutation was functionally indistinguishable from the wildtype channel. CONCLUSIONS: Comparison of the clinical features of these patients with those in the literature suggests that gain-of-function mutations are associated with severe EIEE, while heterozygous loss-of-function mutations cause intellectual disability with or without seizures. These data demonstrate that functional analysis of missense mutations detected by clinical exome sequencing, both inherited and de novo, is valuable for clinical interpretation in the age of massive parallel sequencing.

Rhythmic entrainment of slow brain activity preceding leg movements.

OBJECTIVE: The time course of the contingent negative variation (CNV) as well as beta-power are known to entrain to regular task rhythms, revealing implicit anticipatory timing. Thus far, these effects have been established for manual responses only. Here we investigate entrainment preceding leg movements. METHODS: High-density EEG was recorded while participants were standing and responded to series of rhythmically presented arrow stimuli by making brisk leg movements. The standard interval between reaction stimuli differed between series and was either 1500 or 2000 ms. Each series' final interval was 1750 ms, representing a timing perturbation. RESULTS: Entrainment was manifested in the CNV time course, where the maximum amplitude was reached just before the next stimulus was presented. The pattern of beta-(de)synchronization similarly entrained to the task rhythm. CNV scalp topographies suggested effector dependency of the entrainment-induced CNV. CONCLUSION: We demonstrate that lower limb motor control, like upper limb control, readily entrains to a regular task rhythm. SIGNIFICANCE: These findings are relevant to Parkinson's disease (PD), where problems are found in rhythm processing and temporal preparation. Investigation of the neural correlates of leg movement entrainment is important in view of presumed relations between entrainment and cueing of gait in PD.

A shift from prospective to reactive modulation of beta-band oscillations in Parkinson's disease.

Increased beta (13-30 Hz) oscillatory synchrony in basal ganglia-cortical circuits is a physiological characteristic of Parkinson's disease (PD). While the function of the beta rhythm is unknown, there is evidence that its modulation serves a predictive role, in preparation of future actions. We investigate the relation between predictive beta modulation and entrainment of brain oscillations in a task inviting behavioral entrainment by a regular task structure. MEG was recorded during a serial choice response task, in a group of 12 PD patients and 12 control subjects. In one condition, the reaction stimuli allowed for temporal preparation only (random condition), while in a second condition (predictable condition) the reaction stimuli allowed both temporal and effector preparation. Reaction times were identical between groups, and both groups benefited equally from the known effector side in the predictable condition. Analysis of oscillatory activity, by contrast, revealed marked differences between groups. In patients, the proportion of preparatory beta power desynchronization preceding the reaction stimuli was significantly smaller than in controls, while the proportion of beta desynchronization following the events was larger. In addition to this shift from prospective to reactive modulation of beta-band oscillations, patients showed a trend to reduced motor cortical pre-stimulus delta phase synchronization, and later gamma power synchronization than controls. Delta phase synchronization was, furthermore, significantly correlated with predictive beta desynchronization, supporting the relevance of hierarchical coupling between oscillations of different frequencies for the analysis of oscillatory changes in PD. Together, these features of task-related oscillatory activity indicate that entrainment fails to engender the same predictive mode of motor activation in PD patients as in healthy controls.

Competitive interactions in sensorimotor cortex: oscillations express separation between alternative movement targets.

Choice behavior is influenced by factors such as reward and number of alternatives but also by physical context, for instance, the relative position of alternative movement targets. At small separation, speeded eye or hand movements are more likely to land between targets (spatial averaging) than at larger separation. Neurocomputational models explain such behavior in terms of cortical activity being preshaped by the movement environment. Here, we manipulate target separation, as a determinant of motor cortical activity in choice behavior, to address neural mechanisms of response selection. Specifically, we investigate whether context-induced changes in the balance of cooperative and competitive interactions between competing groups of neurons are expressed in the power spectrum of sensorimotor rhythms. We recorded magnetoencephalography while participants were precued to two possible movement target locations at different angles of separation (30, 60, or 90°). After a delay, one of the locations was cued as the target for a joystick pointing movement. We found that late delay-period movement-preparatory activity increased more strongly for alternative targets at 30 than at 60 or 90° of separation. This nonlinear pattern was evident in slow event-related fields as well as in beta- and low-gamma-band suppression. A comparable pattern was found within an earlier window for theta-band synchronization. We interpret the late delay effects in terms of increased movement-preparatory activity when there is greater overlap and hence less competition between groups of neurons encoding two response alternatives. Early delay-period theta-band synchronization may reflect covert response activation relevant to behavioral spatial averaging effects.

Leakage of decision uncertainty into movement execution in Parkinson's disease?

The concept of segregated basal ganglia-cortical loops entails that functional disturbances may result from abnormal processing within loops, but also from abnormal communication between loops. Cognitive and motor processes subserved by different basal ganglia-frontal loops may interfere with one another as a result of such abnormal communication, leakage, between loops. In Parkinson's disease, movement execution has been found susceptible to decision uncertainty, attributed to this mechanism. Here, we evaluate whether this mechanism of abnormal coupling or leakage extends to perceptual decision-making with trial-by-trial control of decision uncertainty. We examined 10 Parkinson's disease (PD) patients and healthy control subjects in a random-dot motion direction discrimination task with concurrent EEG recording. Random-dot motion was manipulated to make direction discrimination easy or difficult. Reaction times (RT) and movement times (MT) were recorded, and EEG was analysed to extract movement-related potentials. Easy versus difficult direction discrimination produced robust, equally large RT differences in patients and controls (>400 ms), along with a marked difference in error rates, confirming the efficacy of the task. Effects of easy versus difficult discrimination on MT were comparatively small (<50 ms) and did not differ between groups, despite robustly slower MT in patients. Lateralised movement-related EEG potentials reproduced the MT difference between patients and controls. Together, the results do not demonstrate an enhanced effect of decision uncertainty onto movement execution in PD. We surmise that leakage of decision uncertainty into movement execution is probably task-dependent, consistent with the view that the degree to which partial information is allowed to influence the motor system is under strategic control.

Oscillatory dynamics of response competition in human sensorimotor cortex.

Neurophysiological studies in non-human primates have provided evidence for simultaneous activation of competing responses in the (pre)motor cortex. Human evidence, however, is limited, partly because experimental approaches have often mapped competing responses to paired effectors represented in opposite hemispheres, which restricts the analysis to between-hemisphere comparisons and allows simultaneous execution. A demonstration of competition between different movement plans in the motor cortex is more compelling when simultaneous execution of the alternative responses is ruled out and they are represented in one motor cortex. Therefore, in the current MEG study we have used a unimanual Eriksen flanker paradigm with alternative responses assigned to flexion and extension of the right index finger, activating different direction-sensitive neurons within the finger representation area of the same motor cortex. Results showed that for stimuli eliciting response competition the pre-response motor cortex beta-band (17-29 Hz) power decreased stronger than for stimuli that did not induce response competition. Furthermore, response competition elicited an additional pre-response mid-frontal high-gamma band (60-90 Hz) power increase. Finally, larger gamma-band effect sizes correlated with greater behavioral response delay induced by response competition. Taken together, our results provide evidence for co-activation of competing responses in the human brain, consistent with evidence from non-human primates.

Theory of mind deficits in Parkinson's disease: a product of executive dysfunction?

OBJECTIVE: Patients with Parkinson's disease (PD) can perform poorly on tasks involving theory of mind (ToM): the ability to reason about mental states. We investigated whether patients' ToM deficits were independent of executive dysfunction. METHOD: Experiment 1 aimed to establish that ToM deficits were present, and 2 following experiments manipulated the working memory (WM) demands of the ToM task. RESULTS: In Experiment 1, 15 patients with PD performed significantly more poorly than controls on a false belief vignette task but not on a faux pas task. Errors were related to poor verbal fluency. In Experiment 2, 24 patients with PD made fewer errors on shorter false belief vignettes than the original FBT, and errors on the latter were related to WM impairment. In Experiment 3, the FBT was presented as a comic strip visible throughout questioning, reducing WM demands. Patients (n = 24) made memory errors but no false belief errors on the comic strip. They exhibited no verbal fluency or WM impairments, but did exhibit deficits on a black-and-white Stroop task. False belief errors were not correlated with executive performance. CONCLUSIONS: PD patients made very few ToM errors that were independent of errors on memory questions, so in this sample, ToM deficits per se appear unlikely. However, patients still made errors on ToM tasks when associated incidental WM demands were considerably reduced, highlighting the need for future investigations of ToM in PD to account for the role of more general cognitive restrictions exhibited by even some medicated, early stage patients.

The contents of predictions in sentence comprehension: activation of the shape of objects before they are referred to.

When comprehending concrete words, listeners and readers can activate specific visual information such as the shape of the words' referents. In two experiments we examined whether such information can be activated in an anticipatory fashion. In Experiment 1, listeners' eye movements were tracked while they were listening to sentences that were predictive of a specific critical word (e.g., "moon" in "In 1969 Neil Armstrong was the first man to set foot on the moon"). 500 ms before the acoustic onset of the critical word, participants were shown four-object displays featuring three unrelated distractor objects and a critical object, which was either the target object (e.g., moon), an object with a similar shape (e.g., tomato), or an unrelated control object (e.g., rice). In a time window before shape information from the spoken target word could be retrieved, participants already tended to fixate both the target and the shape competitors more often than they fixated the control objects, indicating that they had anticipatorily activated the shape of the upcoming word's referent. This was confirmed in Experiment 2, which was an ERP experiment without picture displays. Participants listened to the same lead-in sentences as in Experiment 1. The sentence-final words corresponded to the predictable target, the shape competitor, or the unrelated control object (yielding, for instance, "In 1969 Neil Armstrong was the first man to set foot on the moon/tomato/rice"). N400 amplitude in response to the final words was significantly attenuated in the shape-related compared to the unrelated condition. Taken together, these results suggest that listeners can activate perceptual attributes of objects before they are referred to in an utterance.

Frontoparietal theta activity supports behavioral decisions in movement-target selection.

There is recent EEG evidence describing task-related changes of theta power in spatial attention and reaching/pointing tasks. Here, we aim to better characterize this theta activity and determine whether it is associated with visuospatial memory or with visuospatial selection functions of the frontoparietal cortex. We recorded EEG from 20 participants during a movement precuing task with center-out joystick movements. Precues displayed 1, 2, or 4 potential targets and were followed (stimulus onset asynchrony 1.2 s) by a central response cue indicating the movement-target. Remembering the precued target location(s) was mandatory in one and optional in a second version of the task. Analyses evaluated two slow brain potentials (CNV, contingent negative variation and CDA, contralateral delay activity) and task-related power changes. Results showed a differential modulation of frontal CNV and parietal CDA, consistent with earlier described set-size effects on motor preparation and visual short-term memory. Short-lived phases of theta event-related synchronization (ERS) were found 150-500 ms after precue and response cue presentation, exhibiting parietal and frontal maxima. The increase of frontoparietal theta power following response cue presentation was strongly modulated by target load, i.e., absent for 1-target (when the movement-target could be selected in advance), contrasting with a robust 20-50% ERS response in 2- and 4-target conditions. The scalp distribution, the timing, and the modulation by set-size suggest a role of theta activity in movement-target selection. The results support a recently proposed view of theta as emerging around behavioral decision points, linked to the evaluation of choice-relevant information.