Subthalamic nucleus stimulation affects a frontotemporal network: A PET study

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective strategy in the treatment of motor symptoms in advanced Parkinson's disease. However, clinical studies have shown that DBS can affect verbal fluency. Seven Parkinson's disease patients with bilateral DBS of the STN were studied with positron emission tomography (PET) to investigate the effects of STN stimulation on regional cerebral blood flow during a verbal fluency task. Activation of the right orbitofrontal cortex and verbal fluency-associated activation within a left-sided frontotemporal network were decreased during STN stimulation compared with the OFF state. Our results offer an explanation for the commonest neuropsychological side effect of STN stimulation and show that STN stimulation affects a frontotemporal network during a fluency task.

STN Stimulation Alters Pallidal—Frontal Coupling during Response Selection under Competition

“…For example, Mink and Thach (1993) proposed a 'centre-surround' inhibition model, based on the two pathways from the cortex to the basal ganglia output through the GPi namely via the STN or striatum, acting in parallel to inhibit potentially competing programmes and to enable the cortically selected programme. The present results and those of Schroeder et al (2002Schroeder et al ( , 2003 suggest that for tasks such as RNG, phonemic verbal fluency, and the Stroop which involve response selection under competition, STN stimulation alters/interferes with suppression of habitual or prepotent responses necessary for selection of the appropriate response. This would account for the increased habitual counting during RNG observed in the present study, and worse performance on phonemic verbal fluency and reduced accuracy on the Stroop reported with STN stimulation compared with when the stimulators are switched off (Schroeder et al, 2002(Schroeder et al, , 2003Jahanshahi et al, 2000a).…”

“…This conclusion is supported by the present results, showing that the rCBF decrease in the prefrontal and cingulate areas and the increased rCBF in GPi were specific to the RNG task and not observed for the COUNT task. Similarly, the rCBF decreases in prefrontal or cingulate cortices or the ventral striatum reported by Schroeder et al (2002Schroeder et al ( , 2003 were specific to the verbal fluency and Stroop tasks and not the control tasks. The proposal that the effects of DBS STN are task-specific and depend on the particular networks engaged by specific tasks is in agreement with the results of animal studies suggesting that striatofrontal connectivity as well functional connectivity between different nuclei of the basal ganglia depend on brain state, such as whether the animal is at rest or active (Magill et al, 2004).…”

“…In carefully selected PD patients, DBS of the STN does not produce any major adverse effects on intellectual ability or general cognitive functioning (Ardouin et al, 1999). However, detailed neuropsychological assessment has revealed consistent deficits on two cognitive tasks with DBS of the STN: verbal fluency and Stroop (Ardouin et al, 1999;Saint-Cyr et al, 2000;Jahanshahi et al, 2000a;Schroeder et al, 2002Schroeder et al, , 2003Witt et al, 2004), which imaging has shown to be associated with reduced prefrontal or ACC activation compared with when the stimulators are off (Schroeder et al, 2002(Schroeder et al, , 2003. In 16 PD patients with DBS of the STN, we (Jahanshahi et al, in preparation) recently found that at a fast rate of 1 Hz, STN stimulation decreased the ability of patients to generate numbers randomly and resulted in a significant increase of CS1 scores by 25.7% (mean 110.279.5) compared with when the stimulators were off (mean 81.977.2).…”

Subthalamic stimulation affects homophone meaning generation in Parkinson's disease

“…Impaired performance on the HMGT is consistent with the numerous studies that have linked STN stimulation with impaired performance on verbal fluency tests (e.g., Cilia et al, 2007;De Gaspari et al, 2006;Saint-Cyr et al, 2000;Schroeder et al, 2003;Smeding et al, 2006). While performance on both semantic and phonemic fluency tests is related to performance on the HMGT (Kave et al, 2007), there are some distinct differences between them.…”

“…Numerous studies have now associated STN DBS with significant improvements in the motor complications of PD (see Kleiner-Fisman et al, 2006, for a review), yet changes in neuropsychological status as a function of STN stimulation are not as clearly defined. Whereas STN DBS has generally been considered as a cognitively safe procedure, declines in verbal fluency have frequently been reported (e.g., Cilia et al, 2007;De Gaspari et al, 2006;Saint-Cyr et al, 2000;Schroeder et al, 2003;Smeding et al, 2006). Saint-Cyr and colleagues (2000) in a comprehensive study of the neuropsychological consequences of STN DBS, compared preoperative semantic and phonemic verbal fluency scores, including measures of switching (number of switches from one semantic subcategory to another) and clustering (mean number of words per semantic subcategory) with postoperative scores in 10 patients who received STN DBS.…”