Table 4

Stimulation of the post-commissural ventral fornix in rodents and human patients, along with main findings

StudyModelMain findings
Hamani et al 3 1 obese patientAcute 130 Hz DBS induced old memories recall
Laxton et al 20106 Patients with ADClinical trial phase I: forniceal DBS was safe and drove neural activity in the memory circuit, including the entorhinal and hippocampal areas, and activated the brain’s default mode network
Smith et al 20126 Patients with ADIncreased connectivity after 1 year of DBS is observed. The persistent cortical metabolic increases after 1 year of DBS were associated with better clinical outcomes
Sankar et al 2015Patients with ADIn addition to modulating neural circuit activity, forniceal DBS influenced the natural course of brain atrophy in a neurodegenerative disease
Lozano et al 2016Patients with ADClinical trial phase II: no significant differences in the primary cognitive outcomes in the ‘on’ vs ‘off’ stimulation group at 12 months, but in patients >65 years old was associated with a trend towards both benefit on clinical outcomes
Hescham et al 2015aRats1 hour of 100 Hz DBS increased c-Fos in CA1 and CA3 and led to ACh increase in hippocampus peaking 20 min after stimulus onset, and no change of glutamate
Zhang et al 2015Rats with hippocampal AP 1–4224-hour-long DBS facilitated hippocampus-dependent spatial memory 4 weeks later
Hescham et al 2016RatsAcute 100 Hz DBS improved performance in Morris Water Maze test
Hescham et al 2013Rats, IP scopolamineForniceal DBS reversed the memory impairing effects of scopolamine. DBS efficacy was not sensitive to the frequency of stimulation, but rather to current levels
Gondard et al 2015RatsForniceal DBS triggers hippocampal activity and rapidly modulates the expression of neurotrophic factors and markers of synaptic plasticity known to play key roles in memory processing
  • ACh, acetylcholine; AD, Alzheimer's disease; AP 1-42, amyloid peptide 1-42; DBS, deep brain stimulation; IP, intraperitoneal.