M. Wahl

The human thalamus processes syntactic and semantic language violations

Numerous linguistic operations have been assigned to cortical brain areas, but the contributions of subcortical structures to human language processing are still being discussed. Using simultaneous EEG recordings directly from deep brain structures and the scalp, we show that the human thalamus systematically reacts to syntactic and semantic parameters of auditorily presented language in a temporally interleaved manner in coordination with cortical regions. In contrast, two key structures of the basal ganglia, the globus pallidus internus and the subthalamic nucleus, were not found to be engaged in these processes. We therefore propose that syntactic and semantic language analysis is primarily realized within cortico-thalamic networks, whereas a cohesive basal ganglia network is not involved in these essential operations of language analysis.

Task-related differential dynamics of EEG alpha- and beta-band synchronization in cortico-basal motor structures

Movement‐related processing results in the modulation of neuronal synchronization over several electroencephalography (EEG) frequency ranges, including alpha‐ (8–12 Hz) and beta‐band (14–30 Hz). Whether modulation patterns differ across sites within the motor system remains unclear, but could denote how information is conveyed across the cortico‐basal network. We therefore compared the event‐related synchronization/desynchronization (ERS/ERD) in recordings from the scalp, basal ganglia and thalamic structures during a motor task.

Differential influence of levodopa on reward-based learning in Parkinson's disease

The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinsons disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the “overdose hypothesis” which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patients’ actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks.

The human thalamus is crucially involved in executive control operations

The processing of executive control is thought to involve cortical as well as thalamic brain areas. However, the questions of how thalamic structures contribute to the control of behavior and how cortical versus thalamic processing is coordinated remain to be settled. We therefore aimed at specifying respective activations during the performance of a go/no-go task. To this end, an electroencephalogram was recorded simultaneously from scalp and thalamic electrodes in seven patients undergoing deep brain stimulation. Meanwhile, left- or right-directed precues were presented indicating with which index finger a button press should be putatively executed. Thereafter, 2 sec elapsed until a go or no-go stimulus determined if the prepared movement had to be performed or withheld. In fronto-central scalp as well as in thalamic recordings, event-related potentials upon go versus no-go instructions were expressed differentially. This task effect was unrelated to motor processes and emerged significantly prior at thalamic than at scalp level. Amplitude fluctuations of depth and scalp responses showed site- and task-dependent correlations, particularly between thalamic and no-go-related activities at frontal recording sites. We conclude that an early classification of go and no-go instructions is performed already thalamically. It further appears that this information is subsequently utilized by cortical areas engaged in the definite inhibition of the prepared action.

Evaluation of a telemedical care programme for patients with Parkinson's disease.

We reviewed a telemedicine-based care model for drug optimization in Parkinsons disease. In this model patients send video recordings made in the home to the treating team via the Internet. These serve as the basis for making therapeutic decisions, in particular drug adjustments. Data from 78 patients were analysed with respect to outcome, method acceptance and management of the procedure. During the 30-day telemedicine programme, the patients recorded an average of 3.2 videos per day. The patients’ motor score on the Unified Parkinsons Disease Rating Scale (UPDRS) was 31 points at enrolment and three months after ICP termination it was significantly lower at 24 points (P < 0.01), i.e. there was less impairment. The patients rated their condition better at the end than at the beginning of the programme: on a 6-point scale, the mean rating at the beginning was 3.2 and the mean rating at the end was 2.8 (P < 0.001). A blinded investigator rated the patients’ videos on the same scale: at the beginning the mean score was 3.0 and at the end it was 2.8 (P < 0.05). The information from the questionnaire showed overall acceptance and practicability of the method. Both patients’ and neurologists’ use of the method was high. The method seems to be feasible for therapy optimization in Parkinsons disease, and of particular interest for patients with complex conditions who do not necessarily have to undergo hospital treatment.

Anticipatory activity in the human thalamus is predictive of reaction times.

Responding to environmental stimuli in a fast manner is a fundamental behavioral capacity. The pace at which one responds is known to be predetermined by cortical areas, but it remains to be shown if subcortical structures also take part in defining motor swiftness. As the thalamus has previously been implicated in behavioral control, we tested if neuronal activity at this level could also predict the reaction time of upcoming movements. To this end we simultaneously recorded electrical brain activity from the scalp and the ventral intermediate nucleus (VIM) of the thalamus in patients undergoing thalamic deep brain stimulation. Based on trial-to-trial analysis of a Go/NoGo task, we demonstrate that both cortical and thalamic neuronal activity prior to the delivery of upcoming Go stimulus correlates with the reaction time. This result goes beyond the demonstration of thalamic activity being associated with but potentially staying invariant to motor performance. In contrast, it indicates that the latencies at which we respond to environmental stimuli are not exclusively related to cortical pre-movement states but are also correlated with anticipatory thalamic activity.

Abnormal distracter processing in adults with attention-deficit-hyperactivity disorder.

Background Subjects with Attention-Deficit Hyperactivity Disorder (ADHD) are overdistractible by stimuli out of the intended focus of attention. This control deficit could be due to primarily reduced attentional capacities or, e. g., to overshooting orienting to unexpected events. Here, we aimed at identifying disease-related abnormalities of novelty processing and, therefore, studied event-related potentials (ERP) to respective stimuli in adult ADHD patients compared to healthy subjects. Methods Fifteen unmedicated subjects with ADHD and fifteen matched controls engaged in a visual oddball task (OT) under simultaneous EEG recordings. A target stimulus, upon which a motor response was required, and non-target stimuli, which did not demand a specific reaction, were presented in random order. Target and most non-target stimuli were presented repeatedly, but some non-target stimuli occurred only once (‘novels’). These unique stimuli were either ‘relative novels’ with which a meaning could be associated, or ‘complete novels’, if no association was available. Results In frontal recordings, a positive component with a peak latency of some 400 ms became maximal after novels. In healthy subjects, this novelty-P3 (or ‘orienting response’) was of higher magnitude after complete than after relative novels, in contrast to the patients with an undifferentially high frontal responsivity. Instead, ADHD patients tended to smaller centro-parietal P3 responses after target signals and, on a behavioural level, responded slower than controls. Conclusion The results demonstrate abnormal novelty processing in adult subjects with ADHD. In controls, the ERP pattern indicates that allocation of meaning modulates the processing of new stimuli. However, in ADHD such a modulation was not prevalent. Instead, also familiar, only context-wise new stimuli were treated as complete novels. We propose that disturbed semantic processing of new stimuli resembles a mechanism for excessive orienting to commonly negligible stimuli in ADHD.

Speed effects of deep brain stimulation for Parkinson's disease†

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) accelerates reaction time (RT) in patients with Parkinsons disease (PD), particularly in tasks in which decisions on the response side have to be made. This might indicate that DBS speeds up both motor and nonmotor operations. Therefore, we studied the extent to which modifications of different processing streams could explain changes of RT under subthalamic DBS. Ten PD patients on‐DBS and off‐DBS and 10 healthy subjects performed a choice‐response task (CRT), requiring either right or left finger button presses. At the same time, EEG recordings were performed, so that RTs could be assessed together with lateralized readiness potentials (LRP), indicative of movement preparation. Additionally, an oddball task (OT) was run, in which right finger responses to target stimuli were recorded along with cognitive P300 responses. Generally, PD patients off‐DBS had longer RTs than controls. Subthalamic DBS accelerated RT only in CRT. This could largely be explained by analog shortenings of LRP. No DBS‐dependent changes were identified in OT, neither on the level of RT nor on the level of P300 latencies. It follows that RT accelerations under DBS of the STN are predominantly due to effects on the timing of motor instead of nonmotor processes. This starting point explains why DBS gains of response speed are low in tasks in which reactions are initiated from an advanced level of movement preparation (as in OT), and high whenever motor responses have to be raised from scratch (as in CRT).

Thalamo-cortical processing of near-threshold somatosensory stimuli in humans

Somatosensory stimuli elicit complex cortical responses that are discernible as somatosensory evoked potentials (SEPs) in scalp electroencephalographic recordings. Whereas earlier SEP components, occurring up to 100 ms after stimulus delivery, have been labeled ‘preconscious’, later responses have been associated with stimulus awareness. To date, how far these processes are primarily cortical or comprise additional subcortical operations remains open. Therefore, we recorded thalamic and scalp SEPs evoked by perceived as well as unperceived median nerve stimulation in neurosurgical patients with electrodes implanted into the ventral intermediate nucleus of the thalamus for deep brain stimulation. At stimulation intensities below perceptual threshold, only thalamic SEP components appeared consistently during the first 75 ms after stimulus delivery. Stimulation that was perceived by the patients elicited cortical as well as thalamic SEPs that lasted longer than 75 ms. These results indicate that the thalamus remains active after the primary propagation of a sensory signal to the cortex, and suggest that the transition from elementary to higher‐order somatosensory processing is based on thalamo‐cortical interactions.

Modulation of Habit Formation by Levodopa in Parkinson's Disease

Dopamine promotes the execution of positively reinforced actions, but its role for the formation of behaviour when feedback is unavailable remains open. To study this issue, the performance of treated/untreated patients with Parkinsons disease and controls was analysed in an implicit learning task, hypothesising dopamine-dependent adherence to hidden task rules. Sixteen patients on/off levodopa and fourteen healthy subjects engaged in a Go/NoGo paradigm comprising four equiprobable stimuli. One of the stimuli was defined as target which was first consistently preceded by one of the three non-target stimuli (conditioning), whereas this coupling was dissolved thereafter (deconditioning). Two task versions were presented: in a ‘Go version’, only the target cue required the execution of a button press, whereas non-target stimuli were not instructive of a response; in a ‘NoGo version’, only the target cue demanded the inhibition of the button press which was demanded upon any non-target stimulus. Levodopa influenced in which task version errors grew from conditioning to deconditioning: in unmedicated patients just as controls errors only rose in the NoGo version with an increase of incorrect responses to target cues. Contrarily, in medicated patients errors went up only in the Go version with an increase of response omissions to target cues. The error increases during deconditioning can be understood as a perpetuation of reaction tendencies acquired during conditioning. The levodopa-mediated modulation of this carry-over effect suggests that dopamine supports habit conditioning under the task demand of response execution, but dampens it when inhibition is required. However, other than in reinforcement learning, supporting dopaminergic actions referred to the most frequent, i. e., non-target behaviour. Since this is passive whenever selective actions are executed against an inactive background, dopaminergic treatment could in according scenarios contribute to passive behaviour in patients with Parkinsons disease.