Deep brain stimulation

Abstract

Deep brain stimulation (DBS) has provided remarkable benefits for people with a variety of neurologic conditions. Stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. Multiple groups are attempting to extend this mode of treatment to other conditions. Yet, the precise mechanism of action of DBS remains uncertain. Such studies have importance that extends beyond clinical therapeutics. Investigations of the mechanisms of action of DBS have the potential to clarify fundamental issues such as the functional anatomy of selected brain circuits and the relationship between activity in those circuits and behavior. Although we review relevant clinical issues, we emphasize the importance of current and future investigations on these topics.

Figure 1

Simplified schematic of subcortical motor systems circuitry. Blue arrows represent excitatory synapses, and open red circles represent inhibitory synapses. Dotted line across the thalamus indicates the segregation between striatal and cerebellar connections. CBL CTX, cerebellar cortex; CBL NUC, cerebellar nuclei; GPe, globus pallidus external segment; GPi, globus pallidus internal segment; PN, pontine nuclei; SNr, substantia nigra pare reticulate; STN, subthalamic nucleus; STR, striatum; THAL, thalamus.

Figure 2

The neuronal response of a GPi cell during subthalamic nucleus stimulation. Top trace shows analog signal overlays of 100 sweeps made by triggering at 10-ms intervals in the prestimulation period and by triggering on the stimulation pulse in the on-stimulation period. Arrows indicate residual stimulation artifacts after artifact-template subtraction. Middle traces display peristimulus time histograms (PSTHs) reconstructed from successive 7.0-ms time periods in the prestimulation period and from the interstimulus periods in the on-stimulation period. The first PSTH bin is omitted in the on-stimulation period because of signal saturation and residual stimulation artifacts. Asterisks represent significant increase at p ≤ 0.01; Daggers represent significant decrease at p ≤ 0.01; Wilcoxon signed rank test. Bottom plot represents the mean firing rate calculated every 1 s on the basis of the PSTH illustrating the time course of the firing rate. From Hashimoto et al. 2003.

Figure 3

Sustained inhibition of thalamic neuron produced by 120-Hz stimulation of the GPi. (a) 100-pulse stimulus train. (b) 1000-pulse stimulus train. From Anderson et al. 2003.

Figure 4

Blood flow changes associated with the presence of tremor or other movement of the upper extremities during 1-min positron emission tomography (PET) scans in patients (n = 8) with subthalamic nucleus deep brain stimulation (STN DBS). These scans were collected with STN DBS off as part of a larger study of stimulation (Hershey et al. 2003). The image represents an averaged change in blood flow comparing paired scans for each patient with both STN stimulators off. During one scan there was no movement detected by videography or direct observation and no excessive activity seen on surface electromyography. During another scan there was movement or tremor. Arrows indicate peak blood flow increase of 5% in sensorimotor cortex. Such changes in motor behavior during PETs to investigate effects of DBS can confound the interpretation of findings. The scans collected during movement were excluded from our analysis of STN DBS effects (Hershey et al. 2003).