PMID-22017994[0] Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.
- Also reviewed by Rui Costa: PMID-22017983[1]
- Good, brief review -- with appropriate minimal references.
- Partial goal of the work: parameter determination and optimization can take a long time, and are typically only done every 3-6 months initially. But the actually changes of activity / responsiveness occur on a faster timescale in the disease, even instantaneous; other studies have shown that updating the stimulation parameters more frequently helps patients. (of course, this is a different form of closed-loop).
- Pathology: intermittent neuronal oscillations in the basal ganglia and motor cortex commonly observed.
- In MPTP treated primates these oscillations occur in the tremor band (theta, 4-7Hz), and double-tremor band (9-15Hz, alpha) (Bergman et al 1994 {120}, Ras et al 2000 PMID-11069964 ).
- Actual pathology still inconclusive; talk about disruption of pathological patterns and 'focal inhibition', but this is no thorough review by any estimate.
- "In recent years, the role of pathological discharge patterns in the parkinsonian brain has emerged as pivotal in the disease pathology
- Eusebio and Brown, 2007;
- Hammond et al., 2007;
- Kuhn et al., 2009;
- Tass et al., 2010;
- Vitek, 2008;
- Weinberger et al., 2009;
- Wichmann and DeLong, 2006;
- Zaidel et al., 2009.
- Automatic systems should disrupt this pattern of discharge (Feng 2006, Tass 2003).
- However, the role of these oscillations as the neuronal correlate of PD motor symptoms is still debated (Hammond et al., 2007; Leblois et al., 2007; Lozano and Eltahawy, 2004; McIntyre et al., 2004; Tass et al., 2010; Vitek, 2002; Weinberger et al., 2009 {1089}).
- 2 african green monkeys, MPTP treatment.
- Recorded from GPi & M1 (127 and 210 neurons); stimulated GPi, 7 pulses at 130Hz, 80ms after spike from reference area (M1 or GPi).
- 80ms delay coincided with the next double-tremor oscillatory burst (12.5Hz)
- State of neuronal oscillatory discharge of cortico-BG loops often accompanied by synchronization btw cortex and BG (see also quote below)
- GPi following M1 activity superior (GP|M1 in their notation).
- single pulses did not work.
- Stimulation: 80uA 200us bipolar biphasic (small and short!).
- Stimiulus protocol (M1 trigger) abolishes oscillatory activity in recorded GPi neurons.
- Also reduced akinesia as measured with an accelerometer & decreased firing rate in the GPi.
- Both work better than constant 130Hz DBS.
- Also much more irregular: fewer stimulation pulses at longer latency.
- Open loop control (the control) did much less regarding FR oscillations & bursts and reduction in firing rate.
- Dorval et al 2010: increasing the stimulus irregularity of open-loop DBS decreases its beneficial clinical effectcs. (also Baker et. al 2011).
- GP train stimulation triggered on GP firing significantly worsened akinesia, despite the fact that the pallidial FR decreased.
- Treatment increased spike oscillation at double-tremor frequency in M1.
- Oscillations more important than firing rate changes (new vs. old hypothesis).
- pallidal oscillatory activity was not correlated to the pallidal discharge rate either before or during the application of standard DBS or GP|M1.
- In our data, may have double-frequency tremor effects. Heterodyne should detect this.
- "Studies on the dynamics of the entire cortico-basal ganglia loops have frequently reported the emergence of intra-and interloop component synchrony and oscillatory activity."
- "Nevertheless, the somewhat intuitive connection between neuronal oscillations and parkinsonian motor symptoms, which include rest and action tremors, has been challenged (Hammond et al., 2007 PMID-17532060 ; Leblois et al., 2007 {1146}; Lozano and Eltahawy, 2004; Tass et al., 2010 {1147}; Vitek, 2002; Weinberger et al., 2009). For instance, while the parkinsonian rest tremor occurs mainly at the 4–7 Hz frequency band, the oscillatory neuronal activity is observed in several characteristic frequency bands in both human PD patients (Hutchison et al., 2004) {1156} and animal models (Bergman et al 1994, Gubellini et al 2009) {1074}"
- This also has import to our heterodyne results!
- Synchrony between globus pallidus and M1 is dynamic and state-dependent (whatever that means -- have to check the refs, Levy et al 2002 {829}, Timmerman et al 2003 {1087})
- Quote: "... it suggests that reduction of the abnormal parkinsonian oscillatory activity could in fact be the underlying mechanism by which DBS exerts its action and brings about the associated clinical improvement."
- Neuronal oscillatory activity occurs as high as the beta-band, 15-35Hz, hence clinical app. would need a tuned antiphase lag.
- Suggest that the closed-loop treatment may be applicable to other diseases with characteristic firing patterns, like schizophrenia.
- Since synchonization and oscillations hend to coincide, .. we found this too.
- Heimer et al 2006 {1076}: oscillations and synchrony can exist independently.
- Figure suck. Text inconsistent and frequently too small.
- Wavelet spectrograms are nice tho.
Other thoughts:
- Somebody should measure the transfer function of the BG / cortical loop. H(z).
- This seems like adding a comb-filter or zero at a particular frequency: GP|GP stimluation exacerbated the effect, GP|M1 minimized the effect as there is a negation in there. (e.g. GP actviity decreases firing of M1, and vice versa).
____References____
[0] Rosin B, Slovik M, Mitelman R, Rivlin-Etzion M, Haber SN, Israel Z, Vaadia E, Bergman H, Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.Neuron 72:2, 370-84 (2011 Oct 20) |
[1] Santos FJ, Costa RM, Tecuapetla F, Stimulation on demand: closing the loop on deep brain stimulation.Neuron 72:2, 197-8 (2011 Oct 20) |
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