Tereza Serranová

Deep brain stimulation of the subthalamic nucleus affects resting EEG and visual evoked potentials in Parkinson's disease

OBJECTIVE We studied changes of the EEG spectral power induced by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinsons disease (PD). Also analyzed were changes of visual evoked potentials (VEP) with DBS on and off. METHODS Eleven patients with advanced PD treated with bilateral DBS STN were examined after an overnight withdrawal of L-DOPA and 2 h after switching off the neurostimulators. All underwent clinical examination followed by resting EEG and VEP recordings, a procedure repeated after DBS STN was switched on. RESULTS With DBS switched on, the dominant EEG frequency increased from 9.44+/-1.3 to 9.71+/-1.3 Hz (P<0.01) while its relative spectral power dropped by 11% on average (P<0.05). Switching on the neurostimulators caused a decrease in the N70/P100 amplitude of the VEP (P<0.01), which inversely correlated with the intensity of DBS (black-and-white pattern: P<0.01; color pattern: P<0.05). CONCLUSIONS Despite artifacts generated by neurostimulators, the VEP and resting EEG were suitable for the detection of effects related to DBS STN. The acceleration of dominant frequency in the alpha band may be evidence of DBS STN influence on speeding up of intracortical oscillations. The spectral power decrease, seen mainly in the fronto-central region, might reflect a desynchronization in the premotor and motor circuits, though no movement was executed. Similarly, desynchronization of the cortical activity recorded posteriorly may by responsible for the VEP amplitude decrease implying DBS STN-related influence even on the visual system. SIGNIFICANCE Changes in idling EEG activity observed diffusely over scalp together with involvement of the VEP suggest that the effects of DBS STN reach far beyond the motor system influencing the basic mechanisms of rhythmic cortical oscillations.

Subthalamic Nucleus Stimulation Affects Incentive Salience Attribution in Parkinson's Disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinsons disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty‐four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS–related sensitivity to food reward stimuli cues might drive DBS‐treated patients to higher food intake and subsequent weight gain.

Horizontal and vertical eye movement metrics: What is important?

OBJECTIVE To assist other eye movement investigators in the design and analysis of their studies. METHODS We examined basic saccadic eye movements and smooth pursuit in the horizontal and vertical directions with video-oculography in a group of 145 healthy subjects between 19 and 82 years of age. RESULTS Gender and education level did not influence eye movement metrics. With age, the latency of leftward and vertical pro- and antisaccades increased (p<0.001), velocity of upward prosaccades decreased (p<0.001), gain of rightward and upward prosaccades diminished (p<0.001), and the error rate of antisaccades increased (p<0.001). Prosaccades and antisaccades were influenced by the direction of the target, resulting in a right/left and up/down asymmetry. The skewness of the saccade velocity profile was stable throughout the lifespan, and within the range of saccades analyzed in the present study, correlated with amplitude and duration only for antisaccades (p<0.001). CONCLUSIONS Some eye movement metrics must be separated by the direction of movement, others according to subject age, while others may be pooled. SIGNIFICANCE This study provides important information for new oculomotor laboratories concerning the constitution of subject groups and the analysis of eye movement metrics.

Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus

Significance The involvement of the subthalamic nucleus (STN) in affective processing has been suggested with the appearance of neuropsychiatric side effects of deep brain stimulation in Parkinson’s disease (PD), but direct evidence has been lacking. In our study, we recorded single-neuron activity from the STN during affective picture presentation to PD patients intraoperatively. We discovered two spatially distinct populations of “affective” neurons responding to the emotional dimensions of the stimuli: valence (pleasantness-unpleasantness) and arousal (intensity). As previously believed, neural circuits underlying these two affective dimensions are functionally segregated. Here we observed separated emotional processing even at the single neuron level. These results extend our knowledge regarding the emotional role of the STN and the neural basis of emotions. Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson’s disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

Sex, Food and Threat: Startling Changes after Subthalamic Stimulation in Parkinson's Disease

BACKGROUND Changes in motivational processing may play a role in weight gain and other non-motor side effects in Parkinsons disease (PD) patients treated with deep brain stimulation of the subthalamic nucleus. OBJECTIVE/HYPOTHESIS We aimed to assess changes in aversive and appetitive motivational activation using modulation of the acoustic blink reflex (ABR) by rewarding and aversive stimuli. METHODS ABR elicited during the viewing of erotic, food, aversive and neutral pictures was recorded in 11 off-medicated patients with the subthalamic stimulation switched ON and OFF, and in 11 control subjects. RESULTS ABR to erotic stimuli was larger in patients in the ON compared to the OFF condition and controls (P < 0.01). Aversive stimuli caused a larger increase in the ABR in patients with the ON condition than in controls (P < 0.05). Additionally, we found a negative correlation of the ABR magnitude to food pictures in the ON condition with weight gain following subthalamic stimulation (P < 0.01, after adjustment to OFF condition). CONCLUSIONS Our results suggest that subthalamic stimulation affects motivational processing. Subthalamic stimulation may disturb appetitive engagement by erotic cues and increase aversive activation in PD patients. Additionally, postoperative weight gain may be related to changes in the processing of food cues due to subthalamic stimulation.

Eye Movements in Ephedrone-Induced Parkinsonism

Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinsons disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system.

Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

A Loud Auditory Stimulus Overcomes Voluntary Movement Limitation in Cervical Dystonia

Background Patients with cervical dystonia (CD) present with an impaired performance of voluntary neck movements, which are usually slow and limited. We hypothesized that such abnormality could involve defective preparation for task execution. Therefore, we examined motor preparation in CD patients using the StartReact method. In this test, a startling auditory stimulus (SAS) is delivered unexpectedly at the time of the imperative signal (IS) in a reaction time task to cause a faster execution of the prepared motor programme. We expected that CD patients would show an abnormal StartReact phenomenon. Methods Fifteen CD patients and 15 age matched control subjects (CS) were asked to perform a rotational movement (RM) to either side as quick as possible immediately after IS perception (a low intensity electrical stimulus to the II finger). In randomly interspersed test trials (25%) a 130 dB SAS was delivered simultaneously with the IS. We recorded RMs in the horizontal plane with a high speed video camera (2.38 ms per frame) in synchronization with the IS. The RM kinematic-parameters (latency, velocity, duration and amplitude) were analyzed using video-editing software and screen protractor. Patients were asked to rate the difficulty of their RMs in a numerical rating scale. Results In control trials, CD patients executed slower RMs (repeated measures ANOVA, p<0.10−5), and reached a smaller final head position angle relative to the midline (p<0.05), than CS. In test trials, SAS improved all RMs in both groups (p<0.10−14). In addition, patients were more likely to reach beyond their baseline RM than CS (χ2, p<0.001) and rated their performance better than in control trials (t-test, p<0.01). Conclusion We found improvement of kinematic parameters and subjective perception of motor performance in CD patients with StartReact testing. Our results suggest that CD patients reach an adequate level of motor preparation before task execution.

Brainstem dysfunction in variegate porphyria

Introduction: Variegate porphyria (VP) is a rare metabolic disorder that may present as an acute predominantly motor neuropathy. Cranial nerves and brainstem functions have been only scarcely studied. Methods: Brainstem reflexes were examined in symptomatic and non‐symptomatic VP mutation carriers of a single family. Results: Similar results were found in the 2 patients with a history of porphyric crises. The blink reflex showed an absence of late responses (R2 and R2c) to stimulation of both sides. The masseter inhibitory reflex showed reduced inhibition of the second phase. The jaw jerk was normal. The asymptomatic carriers did not show any of the abnormalities just noted. Conclusions: Our results are compatible with a central lower pons–upper medulla disorder in the brainstem. We hypothesize that brainstem dysfunction in VP patients with a history of porphyric crises may be due to neurotoxic effects of porphyrin precursors as well as subclinical osmolarity changes due to hyponatremia. Muscle Nerve 46: 426–433, 2012

The impact of non-motor symptoms on the health-related quality of life in patients with functional movement disorders

OBJECTIVE Pain, fatigue, cognitive complaints and psychiatric comorbidities are common in patients with functional movement disorder and may significantly affect their quality of life. The aim of the study was to assess the impact of motor and non-motor symptoms on health-related quality of life in patients with functional movement disorder. METHODS Sixty-one patients with clinically established functional movement disorder and 61 matched healthy controls completed standardized questionnaires for depression, anxiety, cognitive complaints, fatigue, pain, sleepiness, apathy and health-related quality of life. Motor disorder severity was assessed using The Simplified Functional Movement Disorders Rating Scale. Personality traits were assessed using the 44-Item Big Five Inventory. RESULTS Compared to controls, patients reported significantly lower health-related quality of life and higher levels of all assessed non-motor symptoms except for apathy. No difference was found in personality traits. In both groups, health-related quality of life scores negatively correlated with depression, anxiety, pain, cognitive complaints, apathy, and neuroticism. No correlation was found between health-related quality of life and motor symptom severity in patients with functional movement disorder. Multiple regression analysis of the predictors of health-related quality of life showed significant impact of trait anxiety and cognitive complaints scores. CONCLUSIONS Multiple non-motor symptoms but not motor symptom severity correlated with impaired health-related quality of life in patients with functional movement disorder. Impaired health-related quality of life was predicted by anxiety and cognitive complaints. Our results highlight the importance of assessing and treating both motor and non-motor symptoms in patients with functional movement disorder.