Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease

Abstract

In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood. Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel corticostriatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery. To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions.

Psychiatric considerations in deep brain stimulation for Parkinson’s disease

“…Hypomania and mania have been associated with dopaminergic medications. Patients treated with L-dopa or STN stimulation perceive similar subjective improvements in euphoria, motivation, fatigue, anxiety, and tension, suggesting mechanistic overlaps (Funkiewiez et al, 2006). In a study of two patients with reproducible stimulation-induced mania, using an interactive brain atlas, the active contacts were localized to the…”

Animal models of Parkinson's disease and their applications

“…41,42 In addition, paraquat induces an increase in α-synuclein and the formation of Lewy-like bodies in dopaminergic SNpc neurons. 10,43 However, in several cases of paraquat-induced PD models, there is not a patent decrease in the striatal dopaminergic innervation, and there is only a transient decrease in the striatal TH levels, 42,43 suggesting that it takes care to make the paraquat model.…”

“…10 However, although selective dopaminergic or serotonergic neuronal cell loss occurs in rodents following the administration of high doses of methamphetamine, this model is not very reliable; 44 the results only produce a long-term loss of TH enzyme but are not examined in the PD-dependent behavioral tests.…”

“…7,8 Although l-DOPA therapy has been found to improve anxiety disorders in PD, 9 in general, the non-motor disorders are not improved or are even sometimes worsened by chronic l-DOPA administration. 10,11 many bioactive and natural adjunctive agents have been developed that relieve the symptoms of PD (described in the "Experimental applications of animal models and the related clinical studies" section). Here, the main animal models of PD and their applications are introduced in order to aid the development of therapeutic and/or adjuvant agents.…”

“…57 Although the function of α-synuclein was recently revealed, the continual expression of α-synuclein is required for the disease progression, 57 and the actual role of α-synuclein in PD still remains elusive. 10 In addition, α-synuclein aggregation can be modulated by the formation of toxic oligomer by including interaction with lipids or small molecules, phosphorylation of α-synuclein at Ser129 and Ser87, oxidative stress, and truncation (review). 58 The level of total and oligomeric forms of normal and phosphorylated α-synuclein (at Ser129) from PD patients as a prospective diagnosis marker is detected by the immune detection method of plasma samples and other Lewy body disease.…”