PMID-19559747[0] Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.
- Wow, DBS has been used since the 1950s for localization of lesion targets; in the 1960's was discovered to alleviate tremor; 70s and 80s targeted at the cerebellum for treatimng movement disorders or epilepsy.
- Extensive list of all the other studies & their stimulation protocols.
- Large mylenated fibers have chronaxies ranging aruond 30-200 us, while cell bodies and dendrites this value is around 1-10ms. (Rank, 1975).
- Lapique: minimum energy is a/b, where b is the rhreobase (the minimal electric current of infinite duration that results in an action potential), and chronaxie is the minimum time over which an electric current double the strength of the rheobase needs to be applied in order ti stimulate a nerve cell.
- where is the rheobase and is the chronaxie.
- you can simplify this to: where is the rheobase current and is the threshold current (Irnich, 2002).
- Measurements of chronaxie in VIM and GPi found values of 60-75us, hence DBS effects are likely mediated through the activation of afferent and efferent axons. (Holsheimer et al 2000a, 2000b)
- In line with these findings, cortical stimulation also results in the activation of afferent and efferent axons (Nowak and Bullier, 1998a, 1998b PMID-9504844).
- Ustim can result in cell body hyperpolarization coupled with action potential initiation in the axon (McIntyre and Grill, 1999; Nowak and Bullier 1998a b).
- Stimulation depends on the direction of the electric field, obviously. When the axons and are ||.
- Acute stimulation is different from chronic DBS (as used in patients); it may be a mistake to extrapolate conclusions.
- DBS electrodes become encapsulated, and current delivered hence decreases.
- Strong placebo effect of just the DBS surgery.
- Implantation of electrodes alone had therapeutic benefit in 6-mo trial. (Mann et al 2009).
- mean lead impedance is 400-120 ohms in clinical DBS leads, PT-IR.
- platinum is relatively non-toxic to the brain when compared to metals such as gold or rhodium.
- If stimulation exceeds 30 uC/cm^2/phase, there is a risk of tissue damage. This equates to 30ma.
- Stainless steel electrodes are damadged by days of in vivo stimulation -- metal ions are lost.
- STN neurons spontaneously oscillate due to leak Ca currents and C-activated K channels.
- STN DBS seems to disrupt abnormal synchronized activity recorded in the BG-thalamocortical loops in PD. (meta-analysis of several studies).
- STN DBS seems to reduce FR in the SNr.
- STN excitotoxic leasion in rats causes increased impulsivity, impaired accuracy, premature responses, and more attention to food reward location in rats.
- There is a hyperdirect pathway from the medial prefrontal cortex to the STN; breaking this decreases attention and perseverance.
- STN HFS sometimes induces impulsive behavior in humans, with which this is consistent. (This may be sequelae from levodopa treatment).
- STN HFS often causes weight gain in patients. But it might be because they can eat more or are more 'motivated at life'.
- Controlled studies in rats show that STN lesion does not effect quantity consumed, either food, ehanol, or cocaine.
- Differential effect when the reward was food vs. cocaine -- the STN may modulate the reward system based on the nature of the reward.
- Huh: HFS of the ZI (zona incerta) has been reported to be superior to STN HFS for improving contralateral parkinsonism in PD patients.
- Could be current diffusion into the STN, however, as lesioning this structure in rats has less effect than lesioning STN.
- See also {1098}.
- Chronic GPi DBS does not allow reducing L-DOPA dosage, unlike STN stimulation, but it is a good treatment for dyskinesia.
- VIM treatment is very effective for tremor, but it does not treat the other motor symptoms of PD. Furthermore, it wears off after a few years.
- CM/Pf seems like an even better target (Center median / parafasicular complex of the thalamus -- see {1119}.
- DBS in the PPN (pedunculo pontine nucleus, brainstem target of the BG) at 10 HZ induces a feeling of well-being , concomitant with a modest improvement in motor function; no effect at 80 Hz.
- Dystonia: GPi is a efficacious target for DBS.
- Full effect takes a year (!), suggesting that the effect is through reorganization of the BG / neuroplascticity.
- ET : lesions of the VIM, STN, or cerebellum can reduce symptoms. DBS of the VIM, STN, or ZI all have been found effective.
- Huntington's disease involves degeneration of the projection neurons from the caudate and putamen.
- HD affects motor, cognitive, and psychiatric functioning.
- Drug addiction: inactivating the Nucelus accumbens (NAc) may reduce motivation to obtain the drug, but it may also reduce the motivation to do anything (apathy).
- GPi DBS also a target for reducing chorea.
- STN DBS may worsen treatment-resistant-depression; this seen in an animal model, and anecdotally in humans with PD.
- OCD can be treated with DBS through the internal capsule extending toward the NAc / ventral striatum.
- side effects include hypomania or anxiety.
- Alas there is no satisfactory animal model of OCD, which hampers research.
____References____
[0] Gubellini P, Salin P, Kerkerian-Le Goff L, Baunez C, Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.Prog Neurobiol 89:1, 79-123 (2009 Sep) |
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