Table 2.
Steps in Network Studies for Targeted Therapy of CNS Disorders.
| 1. Network identification—Human neuroimaging—CNS disorders |
| A. Examined in untreated patients |
| B. Evaluate changes with effective therapies (drugs and stimulation paradigms) |
| 2. Network modeling—Animal neuroimaging disorder modela |
| 3. Network operation—Model |
| A. Identification of critical hubsb—focal blockade |
| B. Identify neuron firing abnormalities in hubsc |
| 4. Animal model—Therapeutics |
| A. Determine effective therapies in model—Current, new, and repurposed drugs and stimulation paradigms—Animal neuroimaging changes |
| B. Administer therapeutic doses of drugs and evaluate hub neuron firing changes based on emergent properties |
| C. Evaluate stimulation therapies effect on hub neurons |
| D. Examine combination therapies action on hub neurons |
| 5. Animal model—Mechanistic studies |
| A. Evaluate emergent property action of drugs by local application onto neurons in vivo |
| B. Evaluate intracellular mechanisms in vitro |
| 6. Human trials with new and repurposed therapies |
| 7. Human neuroimaging of effective new therapies |
a
Without anesthesia.
b
Crucial to differentiate requisite from ancillary sites, because requisite hubs are critical future targets of therapy.
c
Critical for identification of abnormal neuronal firing patterns that the therapy is targeted to normalize.
Based on Faingold and Blumenfeld (2014c), with permission.