In a 69-year-old man with chronic multi-therapy resistant bipolar depression, combining intravenous ketamine three times per week with sequential theta burst stimulation led to complete remission that persisted at a two-year follow-up. The patient had previously failed numerous antidepressants, mood stabilizers, electroconvulsive therapy, and standalone brain stimulation. Clinical improvement was measured by a drop in the Hamilton Depression Rating Scale from 15 to 8 and eventually to remission. Electroencephalography showed corrected dysregulated brain activity patterns, suggesting changes in short-term adaptive plasticity. This combination may offer a treatment path for patients who do not respond to standard therapies.
A computational model of the brain's thalamo-cortico-thalamic network, built from twelve neural populations, reproduces the abnormal EEG oscillations seen in schizophrenia by simulating the effects of ketamine, which blocks NMDAR receptors. The model shows that ketamine increases excitatory activity and alters gamma and sigma band oscillations, matching experimental observations. Adding a neuroplasticity model of transcranial direct current stimulation (tDCS) and applying simulated current to selected pathways reverses these ketamine-induced changes. The work suggests that neural mass models can help predict personalized tDCS protocols for treating schizophrenia.