Elena Torre

Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus

Placebo administration is known to affect the brain both in pain and in Parkinson disease. Here we show that placebo treatment caused reduced activity in single neurons in the subthalamic nucleus of placebo-responsive Parkinsonian patients. These changes in activity were tightly correlated with clinical improvement; no decrease in activity occurred when the clinical placebo response was absent.

Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients.

Expectations about future events are known to trigger neural mechanisms that affect both perception and action. Here we report that different and opposite expectations of bad and good motor performance modulate the therapeutic effects of subthalamic nucleus stimulation in Parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation. By analyzing the effects of subthalamic stimulation on the velocity of movement of the right hand, we found hand movement to be faster when the patients expected a good motor performance. The expectation of good performance was induced through a placebo-like procedure, thus indicating that placebo-induced expectations have influence on the treatment outcome. All these effects occurred within minutes, suggesting that expectations induce neural changes very quickly.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: comparison of pre- and postoperative neuropsychological evaluation

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of advanced Parkinsons disease (PD). The aim of this study was to assess the effect of the bilateral surgical procedure and STN DBS on the neuropsychological functions. Twenty Parkinsons disease patients underwent a neuropsychological assessment before and 6 months after surgery in four different conditions: medication on (with levodopa) and medication off (without levodopa) during the preoperative period, medication on/stimulation on (levodopa plus stimulators switched on) and medication off/stimulation on (stimulators switched on without levodopa) during the postoperative period. We did not find any significant difference in the four conditions for all the neuropsychological tests, confirming the lack of an overall cognitive decline after surgery. From a neuropsychological point of view, these results seem to indicate that bilateral STN DBS is a safe treatment for advanced PD.

Motor and Nonmotor Symptom Follow-Up in Parkinsonian Patients after Deep Brain Stimulation of the Subthalamic Nucleus

Objective: To evaluate motor and nonmotor symptoms in patients with Parkinson’s disease undergoing bilateral deep brain stimulation of the subthalamic nucleus (STN DBS). Methods: Thirty-six consecutive patients receiving bilateral STN stimulation implants were evaluated preoperatively as well as 12 and 24 months after surgery. Motor symptoms were assessed through the Unified Parkinson’s Disease Rating Scale (UPDRS). Data concerning nonmotor symptoms were collected from items of the UPDRS and 2 additional questions from clinical charts regarding constipation and urological dysfunction. Results: STN DBS was effective in controlling motor symptoms; concerning nonmotor symptoms, sleep quality and constipation improved after surgery as compared to baseline. Salivation, swallowing and sensory complaints were ameliorated to a comparable degree by the medication on state, whether preoperatively or postoperatively. With a lower dose of dopaminergic medication, however, the medication on state appeared to be a much larger percentage of the day postoperatively. No significant variations were detected in intellectual impairment, depression, thought disorders, motivation, falling unrelated to freezing, nausea, orthostatic hypotension and urological dysfunction. Conclusions: STN DBS effectively controls motor symptoms, while nonmotor features of advanced Parkinson’s disease patients are mostly unchanged after surgery, even though some specific aspects, notably sleep complaints and constipation, are ameliorated.

Autonomic and emotional responses to open and hidden stimulations of the human subthalamic region

We performed a microstimulation study of the subthalamic region of Parkinsonian patients who underwent bilateral electrode implantation in the subthalamic nuclei and whose heart rate and heart rate variability were recorded. The stimulation of the dorsalmost region, which includes the zona incerta and the dorsal pole of the subthalamic nucleus, produced autonomic responses that were constant over time. In fact, hidden stimulations (the patient is not aware of being stimulated) and open stimulations (the patient is aware of being stimulated) always induced the same responses. By contrast, the stimulation of the ventralmost region, which includes the ventral pole of the subthalamic nucleus and the substantia nigra pars reticulata, produced autonomic and emotional responses that were inconstant over time and varied according to the condition. In fact, different responses were elicited with hidden and open stimulations. These data suggest that the dorsal subthalamic nucleus and/or the zona incerta are involved in autonomic control, whereas the ventral subthalamic nucleus and/or the substantia nigra reticulata are involved in associative/limbic-related autonomic activity. The difference between the open and hidden stimulations in the ventral subthalamic region can explain previous studies in which open and hidden stimulations produced different therapeutic outcomes.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up.

Abstract. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be an effective therapy for the treatment of advanced Parkinsons disease (PD). Fortyseven patients were bilaterally implanted for STN DBS and clinically evaluated according to the Core Assessment Program for Intracerebral Transplantations before surgery and 3, 12 and 24 months after surgery. Electrical stimulation led to a significant improvement in motor symptoms and in the quality of life, allowing a significant reduction of dopaminergic drugs with a consequent improvement of drug-induced dyskinesias. Statistical differences were observed between UPDRS parts II, III and IV values and daily levodopa dosage in the pre- and postoperative periods, while no differences were evident between the 3 postoperative conditions.

Expectation enhances autonomic responses to stimulation of the human subthalamic limbic region

Recent studies show that the placebo component of a treatment can be investigated by administering therapies either overtly or covertly, without the administration of any placebo. Here, we analyze the effects of open (i.e., expected) versus hidden (i.e., unexpected) stimulations of the human subthalamic region on autonomic responses in Parkinson patients. To do this, we mapped the whole subthalamic region, from the dorsal to the ventral part, and recorded both heart rate and sympathetic responses by using spectral analysis of heart rate variability. We found that open stimulations were more effective than hidden ones only in the ventral subthalamic region, whereas no difference between the two conditions was found in the dorsal aspect. By analyzing the stimulus-response curves in the dorsal, middle, and ventral subthalamic regions, we found that the autonomic response threshold was higher in the hidden than open condition for both heart rate and sympathetic responses only in the ventral part. As this ventralmost portion of the subthalamic region is involved in associative-limbic functions, these data suggest that expectation enhances autonomic responses only if these are elicited in the limbic system. These results extend previous findings on the open-hidden paradigm in deep brain stimulation [Benedetti, F., Colloca, L., Lanotte, M., Bergamasco, B., Torre, E., Lopiano, L., 2004a. Autonomic and emotional responses to open and hidden stimulations of the human subthalamic region. Brain Res. Bull. 63, 203-211.], and indicate that expectation plays a major role in the therapeutic outcome. In light of the interactions between the sympathetic adrenergic system and the immune system, the open-hidden difference in autonomic responses might be relevant to the understanding of how expectations might affect the immune system.

Sexual well being in parkinsonian patients after deep brain stimulation of the subthalamic nucleus

Objectives: To evaluate changes in sexual well being in a group of patients with Parkinson’s disease following deep brain stimulation (DBS) of the subthalamic nucleus (STN). Methods: 31 consecutive patients with Parkinson’s disease (21 men and 10 women), bilaterally implanted for DBS of STN, were evaluated one month before and 9–12 months after surgery. Sexual functioning was assessed using a reduced form of the Gollombok Rust inventory of sexual satisfaction (GRISS). Depression (Beck depression inventory) and anxiety (STAI-X1/X2) were also evaluated. Relations between sexual functioning and modifications in the severity of disease (Hoehn and Yahr stage), reduction in levodopa equivalent daily dosage (LEDD), age, and duration of disease were analysed. Results: While no modifications were found in female patients, male patients reported slightly but significantly more satisfaction with their sexual life after DBS of STN. When only male patients under 60 years old were considered, a greater improvement in sexual functioning was found, though still small. Modifications in depressive symptoms and anxiety, as well as duration of the disease, reduction in LEDD, and improvement in the severity of disease, showed no relation with changes in sexual functioning after DBS of STN. Conclusions: DBS of STN appears to affect sexual functioning in a small but positive way. Male patients with Parkinson’s disease, especially when under 60, appeared more satisfied with their sexual well being over a short term follow up period.

Deep brain stimulation of subthalamic nucleus: behavioural modifications and familiar relations

Abstract The present study investigated behavioural modifications and familiar relations in a group of 15 parkinsonian patients treated with bilateral deep brain stimulation of the subthalamic nucleus. In 70% of the patients, during the first months after surgery we observed a euphoric mood owing to motor sugins amelioration, but a series of problems (fear to come back to the pre-operative condition, sense of failure, slowness in changing the old habits) arose when it was necessary to adjust the parameters of stimulation and the pharmacological therapy to obtain a stable clinical picture. The caregivers showed an aggressive behaviour as reaction to the persistent psychological dependence of the patients. This distressed condition could be the cause of the onset of incomprehensions within the couple.

Q-band EPR investigations of neuromelanin in control and Parkinson's disease patients

New insights into the understanding of the changes induced in the iron domain of neuromelanin (NM) upon development of Parkinsons disease (PD) have been gained by electron paramagnetic spectroscopy (EPR). The results of this study are compared with a previously reported variable temperature analysis of X-band EPR spectra of a NM specimen obtained from control brain tissues. The availability of high sensitivity instruments operating in the Q-band (34.4 GHz) allows us to deal with the low amounts of NM available from PD brains. The organization of iron in NM is in the form of polynuclear superparamagnetic/antiferromagnetic aggregates, but the lack of one or more signals in the EPR spectra of NM from PD suggests that the development of the pathology causes NM to decrease its ability to bind iron. Furthermore, the detection of the Mn(II) signal in the Q-band spectra is exploited as an additional internal probe to assess minor structural differences in iron domains of PD and control NM specimens.