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The pedunculopontine nucleus (PPN) is a target for deep brain stimulation for the control of gait and postural disability, but its role in gait control is not understood. Here, using extracellular single-unit recordings in awake patients, the authors show that neurons in the PPN respond to limb movement and imagined gait by dynamically changing network activity and decreasing alpha phase locking. The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and is thought to be important for the initiation and maintenance of gait. Lesions of the PPN induce gait deficits, and the PPN has therefore emerged as a target for deep brain stimulation for the control of gait and postural disability. However, the role of the PPN in gait control is not understood. Using extracellular single-unit recordings in awake patients, we found that neurons in the PPN discharged as synchronous functional networks whose activity was phase locked to alpha oscillations. Neurons in the PPN responded to limb movement and imagined gait by dynamically changing network activity and decreasing alpha phase locking. Our results indicate that different synchronous networks are activated during initial motor planning and actual motion, and suggest that changes in gait initiation in Parkinson's disease may result from disrupted network activity in the PPN.

Abstract BACKGROUND Pedunculopontine nucleus (PPN) stimulation is a novel therapy for Parkinson disease. However, controversies remain regarding the clinical application of this new therapy, including patient selection, electrode positioning, and how best to assess outcomes. OBJECTIVE To clarify the clinical application of PPN stimulation in Parkinson disease. METHODS Five consecutive patients with Parkinson disease complicated by severe gait freezing, postural instability, and frequent falls (all persisting even while the patient was on medication) received bilateral stimulation of the mid-lower PPN without costimulation of other brain targets. Outcomes were assessed prospectively over 2 years with gait-specific questionnaires and the Unified Parkinson Disease Rating Scale (part III). RESULTS The primary outcome, the Gait and Falls Questionnaire score, improved significantly with stimulation. Benefits were maintained over 2 years. Unified Parkinson Disease Rating Scale (part III) items assessing gait and posture were relatively insensitive to these treatment effects. Beneficial effects often appeared to outlast stimulation for hours or longer. Thus, single-session on- vs off-stimulation assessments may be susceptible to “delayed washout effects.” Stimulation of the PPN did not change akinesia scores or dopaminergic medication requirements. CONCLUSION Bilateral stimulation of the mid-lower PPN (more caudal than previous reports) without costimulation of other brain targets may be beneficial for the subgroup of patients with Parkinson disease who experience severe gait freezing and postural instability with frequent falls, which persist even while on medication. Choosing appropriate outcome measures and accounting for the possibility of prolonged stimulation washout effects appear to be important for detecting the clinical benefits.

ObjectivesAttentional augmentation and enhanced motor function are potential mechanisms by which stimulation of the region of the pedunculopontine nucleus (PPN) may improve gait in parkinsonism. Here, the authors assess the impact of stimulation of this region on attentional and motor aspects of reaction task performance in patients with parkinsonism.MethodsEleven patients implanted with PPN stimulators underwent computerised assessment of simple, choice and digit vigilance reaction tasks. Patients were assessed ‘off medication’ during stimulation at different frequencies (0 Hz, 5 Hz, 10 Hz and ‘therapeutic’ 20–35 Hz). There were two primary endpoints: ‘Speed of Reaction’ (sum of the mean task reaction times) and ‘Accuracy of Reaction’ (reflecting omissions and percentage of correct responses). Baseline performance was compared with age- and sex-matched healthy controls. Clinical effects of stimulation were assessed using the Unified Parkinson's Disease Rating Scale and a falls frequency scale.ResultsCompared with healthy controls, subjects had significant deficits in ‘Speed of Reaction’ and in all mean task reaction times. ‘Accuracy of Reaction’ was not different from healthy controls and did not improve with stimulation. ‘Speed of Reaction’ significantly improved with stimulation at therapeutic frequencies (20–35 Hz). Of the individual tasks, only simple reaction time improved significantly. Simple reaction time distribution analysis revealed a general speeding of responses rather than a selective reduction in outliers. Acute PPN stimulation improved gait and balance but not akinesia scores. Chronic PPN stimulation significantly improved falls frequency. Falls score improvement significantly correlated with changes to simple reaction time with therapeutic stimulation.ConclusionThe pattern of reaction time improvement with stimulation of the PPN area suggests a benefit on motor performance, rather than augmentation of attention.

PurposeDysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance.MethodsTo determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt.ResultsThe fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean − 8.3% versus − 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005).ConclusionPPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.

This paper presents the Brisbane experience of pedunculopontine nucleus (PPN) deep brain stimulation (DBS) in Parkinson’s disease (PD). Clinical outcomes along with studies of the mechanisms and neurophysiology of PPN in PD patients with severe freezing of gait (FoG) and postural imbalance (PI) are summarised and presented. Our results indicate that PPN DBS improves FoG and falls in the relatively uncommon group of PD patients who respond well to medication other than for continuing on time FoG and falls. Our studies indicate that bilateral DBS is more beneficial than unilateral DBS, and that the more caudal region of the PPN seems preferable for stimulation. There is evidence that rapid-release programs for initiation and correction of gait and posture are modulated by the PPN, possibly to some extent independently of the cerebral cortex. These functions were found to be impaired in PD patients with severe FoG/PI, but to some extent corrected by bilateral PPN DBS.

We present the case of a 32-year-old Caucasian woman with severe treatment-refractory obsessive compulsive disorder (OCD) and Tourette's syndrome. Both conditions were present prior to age 5 and impacted significantly on the patient's functioning. Multiple trials of evidence-based pharmacological and behavioural therapies had not achieved remission of symptoms. Bilateral deep brain stimulation of the nucleus accumbens was undertaken to treat both illnesses but with a particular focus on OCD, as the patient identified this as the more debilitating of the two disorders. Following surgery there was an immediate improvement in OCD and tic severity. At follow-up 8 months later, there was a 90% improvement in OCD symptoms and a 57% improvement in tic severity. No intraoperative or postoperative complications or adverse events occurred and there were no undesired effects of stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in individuals with Parkinson's disease (PD) has often been associated with reduced verbal fluency performance. This study aimed to directly assess semantic switching as a function of STN stimulation in PD participants with the Homophone Meaning Generation Test (HMGT). Seventeen participants with PD who had received STN DBS completed the HMGT in on and off stimulation conditions. Twenty-one non-neurologically impaired participants acted as controls. PD participants (in both on and off stimulation conditions) generated significantly fewer meanings than control participants and consistent with the previous reports of verbal fluency impairment, PD participants produced fewer definitions in the on stimulation condition. PD participants (in both on and off stimulation conditions) also had greater difficulty generating definitions for nonhomographic homophones compared with homographic homographs. The results of this study indicate that STN stimulation exacerbates impairment in semantic switching. (JINS, 2008, 14, 890–894.)

To assess the efficacy of percutaneous transluminal angioplasty. A retrospective case study covering the period January 1990 to December 1992. A tertiary-care referral centre. Thirteen patients, ranging in age from 23 to 57 years, who had suffered an aneurysmal subarachnoid hemorrhage and subsequent symptomatic vasospasm that had not responded to aggressive medical therapy. Percutaneous transluminal angioplasty of spastic cerebral arteries Neurologic improvement (improved level of consciousness or resolution of focal deficit) immediately after angioplasty and functional status at 6 months after angioplasty. Four (31%) patients showed neurologic improvement immediately after angioplasty. At 6 months, 5 (38%) of the 13 were independent, 2 (15%) were dependent (severely disabled), and 6 (46%) had died. Poor clinical grade at the time of angioplasty was associated with a poor outcome. Percutaneous transluminal angioplasty appears to be a safe procedure that is beneficial in some patients with symptomatic vasospasm refractory to aggressive hypervolemic, hypertensive therapy. The best results likely are obtained in patients of good clinical grade in whom new neurologic deficits have not become established, and angioplasty should not be delayed if medical therapy does not rapidly reverse the symptoms of vasospasm.

We present the case of a 32-year-old Caucasian woman with severe treatment-refractory obsessive compulsive disorder (OCD) and Tourette's syndrome. Both conditions were present prior to age 5 and impacted significantly on the patient's functioning. Multiple trials of evidence-based pharmacological and behavioural therapies had not achieved remission of symptoms. Bilateral deep brain stimulation of the nucleus accumbens was undertaken to treat both illnesses but with a particular focus on OCD, as the patient identified this as the more debilitating of the two disorders. Following surgery there was an immediate improvement in OCD and tic severity. At follow-up 8 months later, there was a 90% improvement in OCD symptoms and a 57% improvement in tic severity. No intraoperative or postoperative complications or adverse events occurred and there were no undesired effects of stimulation.