Background Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. Objective/Hypothesis We hypothesized that DBS applied to the fornix in patients with Alzheimer’s Disease (AD) could have an effect on brain structure. Methods In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. Results We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. Conclusion We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.

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Minimally conscious state (MCS) is characterized by inconsistent but clearly discernible behavioral evidence of consciousness, and can be distinguished from coma and the vegetative state (VS). Ten MCS patients were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury, and were treated by spinal cord stimulation (SCS). A flexible four-contact, cylinder electrode was inserted into the epidural space of the cervical vertebrae, and placed at the C2-C4 levels. Stimulation was applied for 5 minutes every 30 minutes during the daytime at an intensity that produced motor twitches of the upper extremities. We used 5 Hz for SCS, considering that the induced muscle twitches can be a useful functional neurorehabilitation for MCS patients. Eight of the 10 MCS patients satisfied the electrophysiological inclusion criteria, which we proposed on the basis of the results of deep brain stimulation for the treatment of patients in the VS. Seven patients recovered from MCS following SCS therapy, and were able to carry out functional interactive communication and/or demonstrate the functional use of two different objects. Cervical SCS increased cerebral blood flow (CBF) diffusely in the brain, and CBF increased by 22.2% during the stimulation period compared with CBF before stimulation in MCS patients (p º 0.0001, paired t-test). Five-Hz cervical SCS could increase CBF and induce muscle twitches of the upper extremities. This SCS therapy method may be suitable for treating MCS.