Deep brain stimulation of the subthalamic nucleus improves sense of well‐being in parkinson's disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short‐term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self‐reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty‐three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better‐coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short‐term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day‐to‐day management of patients with deep brain stimulation of the subthalamic nucleus are discussed. © 2012 Movement Disorder Society     

Neurosurgery in Parkinson＇s disease： Social adjustment, quality of life and coping strategies

Subthalamic nucleus deep brain stimulation has become a standard neurosurgical therapy for ad- vanced Parkinson＇s disease. Subthalamic nucleus deep brain stimulation can dramatically improve the motor symptoms of carefully selected patients with this disease. Surprisingly, some specific dimensions of quality of life, ＂psychological＂ aspects and social adjustment do not always improve, and they could sometimes be even worse. Patients and their families should fully understand that subthalamic nucleus deep brain stimulation can alter the motor status and time is needed to readapt to their new postoperative state and lifestyles. This paper reviews the literatures regarding effects of bilateral subthalamic nucleus deep brain stimulation on social adjustment, quality of life and coping strategies in patients with Parkinson＇s disease. The findings may help to understand the psychoso-cial maladjustment and poor improvement in quality of life in some Parkinson＇s disease patients.     

Pathological gambling in Parkinson's disease: Subthalamic oscillations during economics decisions

Pathological gambling develops in up to 8% of patients with Parkinson's disease. Although the pathophysiology of gambling remains unclear, several findings argue for a dysfunction in the basal ganglia circuits. To clarify the role of the subthalamic nucleus in pathological gambling, we studied its activity during economics decisions. We analyzed local field potentials recorded from deep brain stimulation electrodes in the subthalamic nucleus while parkinsonian patients with (n = 8) and without (n = 9) pathological gambling engaged in an economics decision‐making task comprising conflictual trials (involving possible risk‐taking) and non conflictual trials. In all parkinsonian patients, subthalamic low frequencies (2–12 Hz) increased during economics decisions. Whereas, in patients without gambling, low‐frequency oscillations exhibited a similar pattern during conflictual and non conflictual stimuli, in those with gambling, low‐frequency activity increased significantly more during conflictual than during non conflictual stimuli. The specific low‐frequency oscillatory pattern recorded in patients with Parkinson's disease who gamble could reflect a subthalamic dysfunction that makes their decisional threshold highly sensitive to risky options. When parkinsonian patients process stimuli related to an economics task, low‐frequency subthalamic activity increases. This task‐related change suggests that the cognitive‐affective system that drives economics decisional processes includes the subthalamic nucleus. The specific subthalamic neuronal activity during conflictual decisions in patients with pathological gambling supports the idea that the subthalamic nucleus is involved in behavioral strategies and in the pathophysiology of gambling. © 2013 International Parkinson and Movement Disorder Society     

Weight variation before and after surgery in Parkinson's disease: A noradrenergic modulation?

Changes in the nutritional profile of patients with Parkinson's disease have been reported before and after deep brain stimulation surgery. The major determinants of the weight variation in Parkinson's disease are not yet understood, and the mechanism seems complex. Based on the influence of the sympathetic nervous system in metabolic syndrome obesity, the intent of the present review is to consider the role of noradrenergic modulation on weight variations in Parkinson's disease. In this review the authors raise the following hypothesis: weight variation in Parkinson's disease before and after deep brain stimulation of the subthalamic nucleus could be influenced by noradrenergic interaction between the locus coeruleus, subthalamic nucleus, and hypothalamic nucleus. © 2012 Movement Disorder Society     

Weight gain following subthalamic nucleus deep brain stimulation: A PET study

Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was calculated and brain activity prospectively measured using 2‐deoxy‐2[18F]fluoro‐D ‐glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinson's disease. Motor complications (United Parkinson's Disease Rating Scale [UPDRS]‐IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m² (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease. © 2014 International Parkinson and Movement Disorder Society     

Functional imaging of subthalamic nucleus deep brain stimulation in Parkinson's disease

Deep brain stimulation of the subthalamic nucleus is an accepted treatment for the motor complications of Parkinson's disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clinical neurophysiology suggests that the effects of subthalamic nucleus‐deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Positron emission tomography/single‐photon emission computed tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus‐deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarifying whether clinically relevant effects from subthalamic nucleus‐deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or antidromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus‐deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation. © 2011 Movement Disorder Society     

A cost analysis of intraoperative microelectrode recording during subthalamic stimulation for Parkinson's disease

Deep brain stimulation of the subthalamic nucleus is the standard of care for treating medically intractable Parkinson's disease. Although the adjunct of microelectrode recording improves the targeting accuracy of subthalamic nucleus deep brain stimulation in comparison with image guidance alone, there has been no investigation of the financial cost of intraoperative microelectrode recording. This study was performed to address this issue. A comprehensive literature search of large subthalamic nucleus deep brain stimulation series (minimum, 75 patients) was performed, revealing a mean operating room time of 223.83 minutes for unilateral and 279.79 minutes for simultaneous bilateral implantation. The baseline operating room time was derived from the published operating room time for subthalamic nucleus deep brain stimulation without microelectrode recording. The total cost (operating room, anesthesia, neurosurgery) was then calculated based on hospitals geographically representative of the entire United States. The average cost for subthalamic nucleus deep brain stimulation implantation with microelectrode recording per patient is $26,764.79 for unilateral, $33,481.43 for simultaneous bilateral, and $53,529.58 for staged bilateral. For unilateral implantation, the cost of microelectrode recording is $19,461.75, increasing the total cost by 267%. For simultaneous bilateral implantation, microelectrode recording costs $20,535.98, increasing the total cost by 159%. For staged bilateral implantation, microelectrode recording costs $38,923.49, increasing the total cost by 267%. Microelectrode recording more than doubles the cost of subthalamic nucleus deep brain stimulation for Parkinson's disease and more than triples the cost for unilateral and staged bilateral procedures. The cost burden of microelectrode recording to subthalamic nucleus deep brain stimulation requires the clinical efficacy of microelectrode recording to be proven in a prospective evidence‐based manner in order to curtail the potential for excessive financial burden to the health care system. © 2011 Movement Disorder Society     

Deep brain stimulation for Parkinson's disease: the experience of the Policlinico-San Paolo Group in Milan

Neurological Sciences - Thirty patients with idiopathic Parkinson's disease were treated with deep brain stimulation electrode in the subthalamic nucleus. After surgery, the patients' best...     

Involvement of the subthalamic nucleus and globus pallidus internus in attention

We studied the appearance of cognitive event-related potentials (ERPs) and event-related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and globus pallidus internus (GPi). We particularly focused on the rare non-target (distractor) stimuli processing. ERPs and ERD/S in the alpha and beta frequency range were analyzed in seven Parkinson’s disease patients and one primary dystonia patient with implanted deep brain stimulation (DBS) electrodes. A visual three-stimulus protocol was used (frequent stimulus, target stimulus, and distractor). The non-target and distractor-related waveforms manifested similar shapes. A specific positive ERP peak around 200 ms and a low alpha frequency ERS were detected from the STN as a response to the distractor stimuli in six of the patients with Parkinson’s disease and also in the primary dystonia patient’s GPi. This positivity probably reflects an attentional orienting response to the distractor stimuli. The STN and GPi are probably involved in attentional cerebral networks.     

Eight-years Failure of Subthalamic Stimulation Rescued by Globus Pallidus Implant

BackgroundDeep brain stimulation is the surgical procedure of choice in patients with Parkinson's disease. The subthalamic nucleus and the globus pallidus interna are the two most common targets used to treat Parkinson's disease.MethodsWe describe three patients with previous effective subthalamic deep brain stimulation in whom globus pallidus interna deep brain stimulation was performed as “rescue” surgery, 8 years after the original operation.ResultsTwo years after globus pallidus surgery the reduction of dystonia and dyskinesias led to an improvement of motor symptoms. In two patients, painful dystonias disappeared and motor fluctuations markedly improved. One patient achieved an improvement in freezing.ConclusionAfter 24 months of follow up, our observations suggest that globus pallidus deep brain stimulation, can improve motor fluctuations, dyskinesia and axial symptoms.     

Apathie et stimulation cérébrale profonde dans la maladie de Parkinson

Apathy was defined by Marin as diminished motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Up to 42% of Parkinson's disease patients could be concerned. It has a pejorative impact on quality of life and could be predictive of cognitive decline. It has been shown that deep brain stimulation in Parkinson's disease may induce apathy. It seems directly related to the stimulation target, i.e. the subthalamic nucleus, since such an effect has not been observed so far in thalamic and pallidal stimulation. It should certainly not make us question the remarkable effectiveness of subthalamic stimulation in Parkinson's disease patients, but encourages us to be very careful about operability criteria. We must, in this sense, improve identification of at risk patients, seeking a thoroughly diminished motivation, loss of interest or blunting affects.     

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

BackgroundChanges in motivational processing may play a role in weight gain and other non-motor side effects in Parkinson's disease (PD) patients treated with deep brain stimulation of the subthalamic nucleus.Objective/hypothesisWe aimed to assess changes in aversive and appetitive motivational activation using modulation of the acoustic blink reflex (ABR) by rewarding and aversive stimuli.MethodsABR 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.ResultsABR 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).ConclusionsOur 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.     

Addiction in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation

In Parkinson's disease, dopamine dysregulation syndrome (DDS) is characterized by severe dopamine addiction and behavioral disorders such as manic psychosis, hypersexuality, pathological gambling, and mood swings. Here, we describe the case of 2 young parkinsonian patients suffering from disabling motor fluctuations and dyskinesia associated with severe DDS. In addition to alleviating the motor disability in both patients, subthalamic nucleus (STN) deep brain stimulation greatly reduced the behavioral disorders as well as completely abolished the addiction to dopaminergic treatment. Dopaminergic addiction in patients with Parkinson's disease, therefore, does not constitute an obstacle to high‐frequency STN stimulation, and this treatment may even cure the addiction. © 2005 Movement Disorder Society     

Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study

In predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson''s disease. They completed a cued go/no‐go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non‐operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto‐basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.     

Subthalamic nucleus neuronal firing rate increases with Parkinson's disease progression

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic cells in the central nervous system, in particular the substantia nigra, resulting in an unrelenting loss of motor and nonmotor function. Animal models of Parkinson's disease reveal hyperactive neurons in the subthalamic nucleus that have increased firing rates and bursting activity compared with controls. Although subthalamic nucleus activity has been characterized in patients with advanced‐stage Parkinson's disease, it has not been described in patients with early‐stage Parkinson's disease. Here we present the results of subthalamic nucleus neuronal recordings from patients with early‐stage Parkinson's disease (Hoehn and Yahr stage II) enrolled in an ongoing clinical trial compared with recordings from age‐ and sex‐matched patients with advanced Parkinson's disease. Subthalamic nucleus neurons had a significantly lower firing rate in early versus advanced Parkinson's disease (28.7 vs 36.3 Hz; P < .01). The overall activity of the subthalamic nucleus was also significantly lower in early versus late Parkinson's disease, as measured by background neuronal noise (12.4 vs 14.0 mV; P < .05). No significant difference was identified between groups in the bursting or variability of neuronal firing in the subthalamic nucleus, as measured by a burst index or the interspike interval coefficient of variability. The results suggest that neuronal firing in the subthalamic nucleus increases with Parkinson's disease progression. © 2011 Movement Disorder Society     

Directional Stimulation in Parkinson's Disease and Essential Tremor: The Cleveland Clinic Experience

ObjectiveTo assess use of directional stimulation in Parkinson's disease and essential tremor patients programmed in routine clinical care.Materials and MethodsPatients with Parkinson's disease or essential tremor implanted at Cleveland Clinic with a directional deep brain stimulation (DBS) system from November 2017 to October 2019 were included in this retrospective case series. Omnidirectional was compared against directional stimulation using therapeutic current strength, therapeutic window percentage, and total electrical energy delivered as outcome variables.ResultsFifty-seven Parkinson's disease patients (36 males) were implanted in the subthalamic nucleus (105 leads) and 33 essential tremor patients (19 males) were implanted in the ventral intermediate nucleus of the thalamus (52 leads). Seventy-four percent of patients with subthalamic stimulation (65% of leads) and 79% of patients with thalamic stimulation (79% of leads) were programmed with directional stimulation for their stable settings. Forty-six percent of subthalamic leads and 69% of thalamic leads were programmed on single segment activation. There was no correlation between the length of microelectrode trajectory through the STN and use of directional stimulation.ConclusionsDirectional programming was more common than omnidirectional programming. Substantial gains in therapeutic current strength, therapeutic window, and total electrical energy were found in subthalamic and thalamic leads programmed on directional stimulation.     

Modulation of gait coordination by subthalamic stimulation improves freezing of gait

The effect of subthalamic deep brain stimulation on gait coordination and freezing of gait in patients with Parkinson's disease is incompletely understood. The purpose of this study was to investigate the extent to which modulation of symmetry and coordination between legs by subthalamic deep brain stimulation alters the frequency and duration of freezing of gait in patients with Parkinson's disease. We recruited 13 post‐subthalamic deep brain stimulation patients with Parkinson's disease with off freezing of gait and evaluated them in the following 4 conditions: subthalamic deep brain stimulation on (ON) and stimulation off (OFF), 50% reduction of stimulation voltage for the leg with shorter step length (worse side reduction) and for the leg with longer step length (better side reduction). Gait analysis was performed on a treadmill and recorded by an optoelectronic analysis system. We measured frequency and duration of freezing of gait episodes. Bilateral coordination of gait was assessed by the Phase Coordination Index, quantifying the ability to generate antiphase stepping. From the OFF to the ON state, freezing of gait improved in frequency (2.0 ± 0.4 to 1.4 ± 0.5 episodes) and duration (12.2 ± 2.6 to 2.6 ± 0.8 seconds; P = .005). Compared with the ON state, only better side reduction further reduced freezing of gait frequency (0.2 ± 0.2) and duration of episodes (0.2 ± 0.2 seconds; P = .03); worse side reduction did not change frequency (1.3 ± 0.4) but increased freezing of gait duration (5.2 ± 2.1 seconds). The better side reduction–associated improvements were accompanied by normalization of gait coordination, as measured by phase coordination index (16.5% ± 6.0%), which was significantly lower than in the other 3 conditions. Reduction of stimulation voltage in the side contralateral to the leg with longer step length improves frequency and duration of freezing of gait through normalization of gait symmetry and coordination in subthalamic deep brain stimulation patients with Parkinson's disease. This identifies poor leg coordination as a risk factor for causing freezing of gait. © 2011 Movement Disorder Society     

Coordinated reset has sustained aftereffects in Parkinsonian monkeys

Coordinated reset neuromodulation consists of the application of consecutive brief high‐frequency pulse trains through the different contacts of the stimulation electrode. In theoretical studies, by achieving unlearning of abnormal connectivity between neurons, coordinated reset neuromodulation reduces pathological synchronization, a hallmark feature of Parkinson's disease pathophysiology. Here we show that coordinated reset neuromodulation of the subthalamic nucleus has both acute and sustained long‐lasting aftereffects on motor function in parkinsonian nonhuman primates. Long‐lasting aftereffects were not observed with classical deep brain stimulation. These observations encourage further development of coordinated reset neuromodulation for treating motor symptoms in Parkinson disease patients. ANN NEUROL 2012;72:816–820     

Subthalamic Nucleus Activity during Cognitive Load and Gait Dysfunction in Parkinson's Disease

Background

Gait freezing is a common, disabling symptom of Parkinson's disease characterized by sudden motor arrest during walking. Adaptive deep brain stimulation devices that detect freezing and deliver real-time, symptom-specific stimulation are a potential treatment strategy. Real-time alterations in subthalamic nucleus firing patterns have been demonstrated with lower limb freezing, however, whether similar abnormal signatures occur with freezing provoked by cognitive load, is unknown.

Methods

We obtained subthalamic nucleus microelectrode recordings from eight Parkinson's disease patients performing a validated virtual reality gait task, requiring responses to on-screen cognitive cues while maintaining motor output.

Results

Signal analysis during 15 trials containing freezing or significant motor output slowing precipitated by dual-tasking demonstrated reduced θ frequency (3–8 Hz) firing compared to 18 unaffected trials.

Conclusions

These preliminary results reveal a potential neurobiological basis for the interplay between cognitive factors and gait disturbances including freezing in Parkinson's disease, informing development of adaptive deep brain stimulation protocols. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.