Stéphane Thobois

Word processing in Parkinson's disease is impaired for action verbs but not for concrete nouns.

Recent studies have demonstrated that processing of action words recruits cortical motor regions that are also involved in the planning and execution of the actions words refer to. The functional role of these regions in word understanding remains, however, to be clarified. The present study investigates this issue by examining the impact of Parkinsons disease (PD) on lexical decision performance for action words, relative to concrete nouns, in a masked priming paradigm. Priming effects for the two word categories were measured in non-demented PD patients off and on dopaminergic treatment, and in healthy participants. Our results revealed that although overall performances did not differ between verbs and nouns, priming effects showed a clear dissociation between word categories. While priming for concrete nouns was not affected by Levodopa intake, it dissociated as a function of treatment for action verbs. No priming was actually obtained for action verbs in PD patients off dopaminergic treatment. Following Levodopa intake, this deficit recovered, however, because priming effects for verbs became comparable to those for concrete nouns and similar to performance of healthy participants. Overall, this study thus brings compelling evidence that processing lexico-semantic information about action words depends on the integrity of the motor system.

Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys

The cardinal symptoms of Parkinsons disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine (DA) is decreased by 60-80%. It is likely that compensatory mechanisms during the early phase of DA depletion delay the appearance of motor symptoms. In a previous study, we proposed a new PD monkey model with progressive MPTP intoxication. Monkeys developed all of the motor symptoms and then fully recovered despite a large DA cell loss in the substantia nigra (SN). Compensatory mechanisms certainly help to offset the dysfunction induced by the DA lesion, facilitating motor recovery in this model. Neurotransmitter measurements in the striatal sensorimotor and associative/limbic territories of these monkeys subsequently revealed that DA and serotonin (5-HT) could play a role in recovery mechanisms. To try to determine the involvement of these neurotransmitters in compensatory mechanisms, we performed local injections of DA and 5-HT antagonists (cis-flupenthixol and mianserin, respectively) into these two striatal territories and into the external segment of the globus pallidus (GPe). Injections were performed on monkeys that were in an asymptomatic state after motor recovery. Most parkinsonian motor symptoms reappeared in animals with DA antagonist injections either in sensorimotor, associative/limbic striatal territories or in the GPe. In contrast to the effects with DA antagonist, there were mild parkinsonian effects with 5-HT antagonist, especially after injections in sensorimotor territories of the striatum and the GPe. These results support a possible, but slight, involvement of 5-HT in compensatory mechanisms and highlight the possible participation of 5-HT in some behavioural disorders. Furthermore, these results support the notion that the residual DA in the different striatal territories and the GPe could be involved in important mechanisms of compensation in PD.

Parkinson's Disease Revealed by a Resting Tongue Tremor

A 63-year-old patient, without any family medical history, was referred for permanent and disabling abnormal movements of the tongue, which represented his only complaint. This abnormal movement lasted for 1 year and started after a transient ischemic attack characterized by dysarthria and ataxia. Since then, this abnormal movement has persisted, and a mild, intermittent right-hand tremor accompanied by micrographia then appeared a few months later. The patient was first treated by his general practitioner with gabapentine (800 mg/day) and piribedil (150 mg/day) without any improvement, but with side effects such as nausea and vomiting. The patient was then referred to our neurological department. Neurological examination showed a mild, slow, pill-rolling resting tremor of the right hand’s thumb, an intermittent tremor of the mandible, and a severe rest tremor of the tongue. Tongue tremor disappeared when the tongue was protracted and then reappeared after a few seconds, suggesting a re-emergence phenomenon (see Video 1). A mild rigidity (1/4 on item 3.3 of the International Parkinson and Movement Disorder Society UPDRS part III score) and bradykinesia of the right arm, as well as a loss of right-arm swing when walking, were also noted (see Video 1). The rest of the neurological examination was normal. Brain MRI was normal. Tremor recording was performed, with a SYNERGY-MEDELEC device. EMG (electromyography) signals were obtained from pairs of silver/silver chloride electrodes placed over the arms’ muscle bellies. As regards the tongue, EMG signal was obtained from adhesive electrodes placed after drying the surface of the tongue. Bandpass was filtered at 20 to 500 Hz. Frequency of tremor and burst duration were measured by manual analysis of EMG. The recording confirmed a 5-Hz rest tremor of the tongue and right hand (Fig. 1B). I-FP-CIT single-photon emission CT (SPECT) demonstrated a marked reduction of tracer uptake in the left striatum (Fig. 1A). Thus, a diagnosis of probable PD, revealed by predominant tongue tremor, was suspected and pramipexole was prescribed at 1.05 mg/day. After 2 months, this treatment led to a clear improvement of body bradykinesia, but not of tongue tremor. Thus, the dose was further increased to 2.1 mg/day.

Rapid eye movement sleep behaviour disorder symptomatic of a brain stem cavernoma.

A 75‐year‐old man complained of excessive daytime sleepiness (EDS), difficulty falling asleep and nocturnal agitation during sleep. Restless legs syndrome (RLS) was diagnosed and treated. Because of persistent EDS, snoring and nycturia, a nocturnal polysomnography (PSG) was performed. PSG showed high sleep fragmentation related to a moderate to severe obstructive sleep apnea syndrome. Continuous positive airway pressure treatment (CPAP) was proposed. Because of the persistence of abnormal nocturnal behaviours, characterized by screaming, punching and falling out of bed, a video‐PSG with CPAP treatment was performed. The recording showed typical chin electromyography (EMG) activity increase associated with violent movements during rapid eye movement (REM) sleep, suggesting REM sleep behaviour disorders (RBD). Clinical neurological examination found no parkinsonian syndrome, no dysautonomic sign and no neurological focal sign. Dopamine transporter imaging [123I‐FP‐CIT single photon emission computed tomography (SPECT)] did not find any presynaptic dopaminergic pathways degeneration. Brain magnetic resonance imaging showed a vascular lesion suggestive of cavernoma located in the pons. The present case illustrates the complexity of sleep disturbance diagnosis with a possible entanglement of aetiologies responsible for nocturnal agitation, and confirms that an isolated pons cavernoma should be considered among the rare causes of RBD.

Molecular Imaging of Opioid System in Idiopathic Parkinson's Disease

Opioid receptors are localized throughout peripheral and central nervous system and interact with endogenous opioid peptides and drugs including heroin, synthetic opioids, and pain relievers (codeine, morphine). If several opioid PET tracers exist for preclinical studies, only a few have been used in human. Some tracers are selective for one subtype of opioid receptors (e.g., [11C]CAF (carfentanil) for μ receptor) while others are not ([11C]DPN (diprenorphine)). As shown by imaging studies, the opioid system is involved in pain processing, but also in addiction, neuropsychiatric manifestations (harm avoidance, sadness, novelty seeking behavior), feeding and food disorders and, finally, movement disorders and levodopa-induced dyskinesias. However, no imaging study has analyzed the potential dysfunction of opioid system in pain manifestations in Parkinsons disease. In addition, the involvement of opioid system in impulse control disorders and neuropsychiatric manifestations has never been studied in Parkinsons disease. Thus, there is an urgent need to understand the impact of opioid system dysfunctions in Parkinsons disease.

Modulation of Brain Functioning by Deep Brain Stimulation: Contributions from PET Functional Imaging

Deep brain stimulation (DBS) represents a major advance in the treatment of various severe movement disorders as well as more recently psychiatric disorders. However, despite its large clinical application, our understanding about the consequences of DBS is still unclear. Nevertheless, positron emission tomography (PET) technique provides a direct in vivo insight into the neural changes induced by DBS. Accordingly, this chapter aims to provide an up-to-date review of the most important findings obtained by PET functional neuroimaging studies in DBS implanted patients for movement and affective disorders.