1 Department of Physiology, University of Toronto; 2 Toronto Western Research Institute; and 3 Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada
Submitted 31 July 2008;
...accepted in final form 7 November 2008
Rest tremor is one of the main symptoms in Parkinson's disease (PD), although in contrast to rigidity and akinesia, the severity of the tremor does not correlate well with the degree of dopamine deficiency or the progression of the disease. Studies suggest that akinesia in PD patients is related to abnormal increased beta (15–30 Hz) and decreased gamma (35–80 Hz) synchronous oscillatory activity in the basal ganglia. Here we investigated the dynamics of oscillatory activity in the subthalamic nucleus (STN) during tremor. We used two adjacent microelectrodes to simultaneously record neuronal firing and local field potential (LFP) activity in nine PD patients who exhibited resting tremor during functional neurosurgery. We found that neurons exhibiting oscillatory activity at tremor frequency are located in the dorsal region of STN, where neurons with beta oscillatory activity are observed, and that their activity is coherent with LFP oscillations in the beta frequency range. Interestingly, in 85% of the 58 sites examined, the LFP exhibited increased oscillatory activity in the low gamma frequency range (35–55 Hz) during periods with stronger tremor. Furthermore, in 17 of 26 cases where two LFPs were recorded simultaneously, their coherence in the gamma range increased with increased tremor. When averaged across subjects, the ratio of the beta to gamma coherence was significantly lower in periods with stronger tremor compared with periods of no or weak tremor. These results suggest that resting tremor in PD is associated with an altered balance between beta and gamma oscillations in the motor circuits of STN.
Address for reprint requests and other correspondence: J. O. Dostrovsky, Dept of Physiology, Med Sci Bldg 3302, 1 King's College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada (E-mail: j.dostrovsky{at}utoronto.ca )
Abstract Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease which produces bradykinesia, rigidity, tremor and ...postural instability. The dopamine precursor levodopa ( L -Dopa) is the most effective treatment for the amelioration of PD signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L -Dopa-induced dyskinesias. In animal models of PD, a form of plasticity called depotentiation, or the reversal of previous potentiation, is selectively lost after the development of dyskinetic movements following L -Dopa treatment. We investigated whether low frequency stimulation (LFS) in the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr) could induce depotentiation at synapses that had already undergone high frequency stimulation (HFS)-induced potentiation. To do so, we measured the field potentials (fEPs) evoked by stimulation from a nearby microelectrode in 28 patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN) or GPi. We found that GPi and SNr synapses in patients with less severe dyskinesia underwent greater depotentiation following LFS than in patients with more severe dyskinesia. This demonstration of impaired depotentiation in basal ganglia output nuclei in PD patients with dyskinesia is an important validation of animal models of levodopa-induced dyskinesia. The ability of a synapse to reverse previous potentiation may be crucial to the normal function of the BG, perhaps by preventing saturation of the storage capacity required in motor learning and optimal motor function. Loss of this ability at the output nuclei may underlie, or contribute to the cellular basis of dyskinetic movements.
We studied the time course and nature of interactions between the subthalamic nucleus (STN) and the motor cortex in 8 Parkinson disease (PD) patients with chronically implanted STN deep-brain ...stimulation (DBS) electrodes. We first identified the cortical evoked potentials following STN stimulation. The most consistent potential was positive wave with peak latency of 22.2 ± 1.2 ms from stimulation of clinically effective contacts. We then stimulated the motor cortex with transcranial magnetic stimulation (TMS) at 2–15 ms and at the latency of the evoked potential (∼ 23 ms) following STN DBS. TMS induced currents in 3 directions: lateral–medial (LM) direction activated corticospinal axons directly, posterior–anterior (PA), and anterior–posterior (AP) directions activated corticospinal neurons transynaptically. Motor-evoked potentials (MEP) elicited by AP and PA TMS were facilitated at short (2–4 ms) and medium latencies (21–24 ms). However, MEPs elicited by LM TMS were not modified by STN DBS. Short-latency antidromic stimulation of the corticosubthalamic projections and medium latency transmission likely through the basal ganglia–thalamocortical circuit led to cortical evoked potentials and increased motor cortex excitability at specific intervals following STN stimulation at clinically effective contacts. Cortical activation may be related to the clinical effects of STN DBS in PD.
The oscillation model of Parkinson disease (PD) states that, in the subthalamic nucleus (STN), increased θ (4-10 Hz) and β (11-30 Hz) frequencies were associated with worsening whereas γ frequencies ...(31-100 Hz) were associated with improvement of motor symptoms. However, the peak STN frequency in each band varied widely from subject to subject. We hypothesized that STN deep brain stimulation (DBS) at individualized γ frequencies would improve whereas θ or β frequencies would worsen PD motor signs.
We prospectively studied 13 patients with PD. STN local field potential (LFP) was recorded after electrode implantations, in the OFF and then in ON dopaminergic medication states while patients performed wrist movements. Six individual peak frequencies of the STN LFP power spectra were obtained: the greatest decrease in θ and β and greatest increase in γ frequencies in the ON state (MED) and during movements (MOVE). Eight DBS frequencies were applied including 6 MED and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no stimulation. The patients were assessed using the motor Unified Parkinson's Disease Rating Scale (mUPDRS).
STN DBS at γ frequencies (MED and MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and both γ frequencies were not different from HF. DBS at θ and β frequencies did not worsen mUPDRS scores compared to no stimulation.
Short-term administration of STN DBS at peak dopamine-dependent or movement-related γ frequencies were as effective as HF for reducing parkinsonian motor signs but DBS at θ and β frequencies did not worsen PD motor signs.
This study provides Class III evidence that STN DBS at patient-specific γ frequencies and at usual high frequencies both improved mUPDRS scores compared to no stimulation and did not differ in effect.
Trigeminal neuralgia (TN), one of the most intense forms of facial pain, has been the subject of great clinical interest. Significant advances have been made in its management, including surgical ...treatment and imaging of the trigeminal nerve and associated neurovascular compression. The different options for surgical treatment, recent advances in each as well as novel methods of imaging of the trigeminal nerve focusing on diffusion tensor imaging/tractography will be discussed.
BACKGROUND AND PURPOSEVestibular schwannomas are common cerebellopontine angle tumors arising from the vestibulocochlear nerve and can result in cranial nerve dysfunction. Conventional MR imaging ...does not provide information that could correlate with cranial nerve compression symptoms of hearing loss or imbalance. We used multitensor tractography to evaluate the relationship between the WM microstructural properties of cranial nerves and tumor volume in a cohort of patients with vestibular schwannomas. MATERIALS AND METHODSA retrospective study was performed in 258 patients with vestibular schwannomas treated at the Gamma Knife clinic at Toronto Western Hospital between 2014 and 2018. 3T MR images were analyzed in 160 surgically naïve patients with unilateral vestibular schwannomas. Multitensor tractography was used to extract DTI-derived metrics (fractional anisotropy and radial, axial, and mean diffusivities of the bilateral facial and vestibulocochlear nerves cranial nerves VII/VIII). ROIs were placed in the transition between cisternal and intracanalicular segments, and images were analyzed using the eXtended Streamline Tractography reconstruction method. Diffusion metrics were correlated with 3D tumor volume derived from the Gamma Knife clinic. RESULTSDTI analyses revealed significantly higher fractional anisotropy values and a reduction in axial diffusivity, radial diffusivity, and mean diffusivity (all P < .001) within the affected cranial nerves VII and VIII compared with unaffected side. All specific diffusivities (axial, radial, and mean diffusivity) demonstrated an inverse correlation with tumor volume (axial, radial, and mean diffusivity, P < .01). CONCLUSIONSMultitensor tractography allows the quantification of cranial nerve VII and VIII WM microstructural alterations in patients with vestibular schwannomas. Our findings support the hypothesis that tumor volume may cause microstructural alterations of the affected cranial nerves VII and VIII. This type of advanced imaging may represent a possible avenue to correlate diffusivities with cranial nerve function.
The authors describe long-term follow-up (mean, 5 years) in patients with anterior (AN) (n = 6) or centromedian (n = 2) thalamic deep brain stimulation (DBS) for epilepsy. Five patients (all AN) had ...> or = 50% seizure reduction, although benefit was delayed in two until years 5 to 6, after changes in antiepileptic drugs. DBS electrode implantation in AN patients was followed by seizure reduction 1 to 3 months before active stimulation, raising the possibility of a beneficial microthalamotomy effect.
Abstract Decreased inhibition and aberrant plasticity are key features in the pathophysiology of dystonia. Impaired short interval cortical inhibition and resultant increased excitability have been ...described for various forms of dystonia using paired pulse methods with transcranial magnetic stimulation of motor cortex. It is hypothesized that, in addition to cortical abnormalities, impairments in basal ganglia function may lead to dystonia but a deficit of inhibition within the basal ganglia has not been demonstrated to date. To examine the possibility that impaired inhibition and synaptic plasticity within the basal ganglia play a role in dystonia, the present study used a pair of microelectrodes to test paired pulse inhibition in the globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr) of dystonia and PD patients undergoing implantation of deep brain stimulating (DBS) electrodes. We found that there was less paired pulse depression of local field evoked potentials in the basal ganglia output nuclei of dystonia patients compared with Parkinson's disease patients on dopaminergic medication. Paired pulse depression could be restored following focal high frequency stimulation (HFS). These findings suggest that abnormalities exist in synaptic function of striatopallidal and/or striatonigral terminals in dystonia patients and that these abnormalities may contribute to the pathophysiology of dystonia, either independent of, or in addition to the increased excitability and plasticity observed in cortical areas in dystonia patients. These findings also suggest that HFS is capable of enhancing striatopallidal and striatonigral GABA release in basal ganglia output nuclei, indicating a possible mechanism for the therapeutic benefits of DBS in the GPi of dystonia patients.
Parkinson's disease, caused by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease characterized by bradykinesia, rigidity, tremor and postural ...instability. The dopamine precursor levodopa (l-dopa) is the most effective treatment for the amelioration of Parkinson's disease signs and symptoms, but long-term administration can lead to disabling motor fluctuations and l-dopa -induced dyskinesias (LIDs). Studies in rat striatal slices have shown dopamine to be an essential component of activity-dependent synaptic plasticity at the input to the basal ganglia, but dopamine is also released from ventrally projecting dendrites of the substantia nigra pars compacta (SNc) on the substantia nigra pars reticulata (SNr), a major output structure of the basal ganglia. We characterized synaptic plasticity in the SNr using field potentials evoked with a nearby microelectrode (fEPs), in 18 Parkinson's disease patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFS—four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral l-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau). Our findings suggest that extrastriatal dopamine modulates activity-dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.
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