Beta burst coupling across the motor circuit in Parkinson's disease.

Exaggerated activity in the beta band (13-35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation within the subthalamic nucleus (STN) increases, which is posited to limit the information coding capacity of local circuits. Accordingly, a higher incidence of longer bursts correlates positively with clinical impairment, while the opposite is true for short, more physiological bursts. Here, we test the hypothesis that beta bursts not only indicate local synchronisation within the STN, but also phasic coupling across the motor network and hence entail an even greater restriction of information coding capacity in patients with PD. Local field potentials from the subthalamic nucleus and EEG over the motor cortex area were recorded in nine PD patients after temporary lead externalization after surgery for deep brain stimulation and overnight withdrawal of levodopa. Beta bursts were defined as periods exceeding the 75th percentile of signal amplitude and the coupling between bursts was considered using two distinct measurements, first the % overlapping (%OVL) as a feature of the amplitude coupling and secondly the phase synchrony index (PSI) to measure the phase coupling between regions. %OVL between STN and cortex and between the left and the right STN was higher than expected between the regions than if they had been independent. Similarly, PSI was higher during bursts as opposed to non-bursts periods. In addition, %OVL was greater for long compared to short bursts. Our results support the hypothesis that beta bursts involve long-range coupling between structures in the basal ganglia-cortical network. The impact of this is greater during long as opposed to short duration beta bursts. Accordingly, we posit that episodes of simultaneously elevated coupling across multiple structures in the basal ganglia-cortical circuit further limit information coding capacity and may have further impact upon motor impairment.

The human subthalamic nucleus encodes the subjective value of reward and the cost of effort during decision-making.

Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost.

Proximal conduction block in the pharyngeal-cervical-brachial variant of Guillain-Barré syndrome.

INTRODUCTION: Conduction block (CB) has been included in the Rajabally criteria for axonal Guillain-Barré syndrome (GBS). Because the nerve roots may be affected early in GBS, detection of proximal CB by the triple stimulation technique (TST) can be useful. METHODS: We describe TST findings in 2 patients who presented with the pharyngeal-cervical-brachial (PCB) variant of axonal GBS. RESULTS: In the first patient, although conventional nerve conduction studies (NCS) did not fit electrodiagnostic criteria for axonal GBS, the TST detected proximal CB in the median and ulnar nerves. In the second patient, NCS fulfilled criteria for axonal GBS, and the TST detected proximal CB in the median nerve. After plasmapheresis, NCS and TST findings were normalized, suggesting reversible conduction failure rather than demyelinating CB. CONCLUSION: The TST may be useful for diagnosis of PCB when NCS remain inconclusive. The technique provides additional clues for classifying PCB into the acute nodo-paranodopathies.

Triple-stimulation technique improves the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: A difficult clinical situation occurs when a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patient does not fulfill any of the diagnostic criteria. Moreover, nerve conduction studies (NCS) can be consistent with axonal neuropathy and lead to misdiagnosis. METHODS: We aimed to assess the usefulness of the triple-stimulation technique (TST) for detection of proximal conduction blocks (CBs) in patients with axonal-like CIDP. Four patients with axonal-like CIDP were studied and compared with 10 typical CIDP patients. In the axonal-like group, NCS showed a decrease in compound muscle action potential amplitude without features of demyelination, but nerve biopsy showed features of demyelination in all 4. RESULTS: Twelve nerves were tested with TST, and 8 CBs were detected between the root emergence and the Erb point in the 4 patients, all of whom improved after treatment with intravenous immunoglobulin. CONCLUSION: TST can identify very proximal CBs in CIDP. The sensitivity of nerve conduction studies may be improved by TST in CIDP.

Association between structural and functional corticospinal involvement in amyotrophic lateral sclerosis assessed by diffusion tensor MRI and triple stimulation technique.

INTRODUCTION: We investigated the functional and structural integrity of the corticospinal tract (CST) using diffusion tensor imaging (DTI) and the triple stimulation technique (TST) in patients with amyotrophic lateral sclerosis (ALS). METHODS: Fourteen patients with ALS, 13 healthy controls (HCs), and 6 patients with lower motor neuron (LMN) syndrome underwent DTI and TST. RESULTS: The mean diffusivity was higher in ALS patients than HCs (P < 0.01). The TST ratio was lower in ALS patients compared with HCs (P < 0.001) and in LMN patients compared with HCs (P < 0.05). The increase in the mean diffusivity was correlated with the decrease in the TST ratio (P < 0.01). CONCLUSIONS: Significant correlations exist between the DTI and TST results, indicating both structural and functional involvement of the CST in patients with ALS.

Modulation of human motoneuron activity by a mental arithmetic task.

This study aimed to determine whether the performance of a mental task affects motoneuron activity. To this end, the tonic discharge pattern of wrist extensor motor units was analyzed in healthy subjects while they were required to maintain a steady wrist extension force and to concurrently perform a mental arithmetic (MA) task. A shortening of the mean inter-spike interval (ISI) and a decrease in ISI variability occurred when MA task was superimposed to the motor task. Aloud and silent MA affected equally the rate and variability of motoneuron discharge. Increases in surface EMG activity and force level were consistent with the modulation of the motor unit discharge rate. Trial-by-trial analysis of the characteristics of motor unit firing revealed that performing MA increases activation of wrist extensor SMU. It is suggested that increase in muscle spindle afferent activity, resulting from fusimotor drive activation by MA, may have contributed to the increase in synaptic inputs to motoneurons during the mental task performance, likely together with enhancement in the descending drive. The finding that a mental task affects motoneuron activity could have consequences in assessment of motor disabilities and in rehabilitation in motor pathologies.

Disrupting the right prefrontal cortex alters moral judgement.

Humans daily face social situations involving conflicts between competing moral decision. Despite a substantial amount of studies published over the past 10 years, the respective role of emotions and reason, their possible interaction, and their behavioural expression during moral evaluation remains an unresolved issue. A dualistic approach to moral evaluation proposes that the right dorsolateral prefrontal cortex (rDLPFc) controls emotional impulses. However, recent findings raise the possibility that the right DLPFc processes emotional information during moral decision making. We used repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt rDLPFc activity before measuring decision making in the context of moral dilemmas. Results reveal an increase of the probability of utilitarian responses during objective evaluation of moral dilemmas in the rTMS group (compared to a SHAM one). This suggests that the right DLPFc function not only participates to a rational cognitive control process, but also integrates emotions generated by contextual information appraisal, which are decisive for response selection in moral judgements.

Approximate entropy of motoneuron firing patterns during a motor preparation task.

The aim of this study was to test whether approximate entropy (ApEn) analysis provides a suitable method of detecting differences induced by a motor preparation task in time-ordered inter-spike intervals (ISIs) recorded in tonically firing motoneurons. Unlike classical methods of analyzing neuronal discharge variability, in which serial order is no taken into account, the approximate entropy (ApEn) was proposed by Pincus [Pincus SM. Approximate entropy as a measure of system complexity. Proc Natl Acad Sci USA 1991;88:2297-301] to analyze ordered series. ApEn statistic is a number assigned to an ordered series, where higher values correspond to greater serial irregularity. In the present study, the activity of 31 single motor units (SMUs) was recorded in human extensor carpi radialis muscles and the ISI durations were analyzed during the performance of a pre-cueing reaction time motor task involving a 3-s preparatory period. ApEn values were computed for each SMU during three steps of the preparatory period and during the preceding control period. Lower ApEn values, were found during preparatory period. The decrease in ApEn values, i.e., the increase in serial regularity, was monotonic from the control to the end of the preparatory period. These results show that ApEn model-independent statistics are a relevant means of detecting changes related to motor preparation in the regularity of time-ordered inter-spike intervals (ISIs).

Anticipatory changes in human motoneuron discharge patterns during motor preparation.

The influence of motor preparation on human motoneuron activity was studied by combining single motor unit recording techniques with reaction-time (RT) methods. The tonic activity of wrist extensor motor units associated with voluntary isometric contractions was analysed during preparation for a ballistic wrist extensor muscle contraction, using a time preparation procedure. Two durations of the preparatory period elapsing between the warning signal and the response signal were used in separate blocks of trials: a short preparatory period (1 s) allowing optimum time preparation, and a longer, non-optimum one (3 s). Changes in motoneuron tonic discharge patterns not associated with any changes in the force output were observed during the preparatory period, which suggests that these changes were subtle enough to prevent any changes in muscle contraction from occurring before the forthcoming movement. The changes observed were a lengthening of the mean interspike interval (ISI) and a decrease in the ISI variability. These data confirm that inhibitory mechanisms are activated during motor preparation and suggest that spinal inhibitory mechanisms are involved in the preparatory processes. The mechanisms possibly involved, such as presynaptic inhibition, disfacilitation processes or AHP conductance changes, are discussed. The fact that the preparation-induced effects on motoneuron activity were particularly prominent during the last part of the 3 s preparatory period suggests that they were probably related to the neural processes underlying temporal estimation. The anticipatory changes in motoneuron activity observed here during preparation for action provide evidence that central influences act on spinal motoneurons well before it is time to act.