TABLE 2.
Possible Targets, Potential Surrogates, and Current Developmental Hurdles
| Disease | Stimulation targets | Surrogate/biomarker | Biomarker development challenges |
|---|---|---|---|
| Epilepsy | Anterior thalamic nucleus, CM thalamus, localized seizure focus, vagal nerve | Intracranial: abnormal synchrony and excitability noted on EEG, ECoG and depth electrodes | Ability to sense pre-ictal event, validate clinical efficacy in human trials |
| Extracranial: heart rate (VNS) | |||
| Parkinson (rigidity and bradykinesia) | STN, GPi | Beta hyper synchrony (Beta band oscillations) | Direct correlation with clinical symptom improvement |
| Phase amplitude coupling | Signal differentiation | ||
| Parksinon (dyskinesia) | STN + Gpi (dual electrode) | Gamma oscillations | |
| Parkinson (FOG) | Pedunculopontine nucleus | DBS: Increased beta frequency or cholinergic neuron action potentials | |
| SCS: Spinal cord evoked recordings or secondary sensory evoked recordings | |||
| Tourette | Centromedian nucleus of thalamus and GPi | Low frequency thalamic oscillations, cortical oscillations | Identify best control system mode (continuous versus adaptive versus responsive) |
| Essential tremor | Vim (of thalamus) | Internal: ECAP External: EMG, accelerometry | Signal stability over time; signal variability between patients; signal to noise ratio |
| Alzheimer's disease | Fornix, entorhinal cortex, hippocampus, cingulate, precuneous, frontal cortex | Electrophysiological: hippocampal evoked potentials chemical: cholinergic activity | Very theoretical, stimulation target/biomarker identification |
| Depression | Subcallosal cingulate (SCC) and | Imaging based: tractography | Leading biomarker identification |
| Area 25 (medial forebrain bundle), | intersection of 3 fiber bundles near | ||
| nucleus accumbens | SCC, frontal lobe evoked potentials |
These sites summarize the disease-based discussion in the text. (CM – centromedian nucleus (of the thalamus); PET – positron emission tomography; SPECT – single photon emission computed tomography; STN – substantia nigra; EEG – electroencephalogram; ECoG – electrocorticography.)