Targeted deep brain stimulation improves spatial navigation in virtual reality research and offers new hope for the treatment of cognitive disorders such as dementia.
Study: Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Image credits: Gorodenkoff/Shutterstock.com
From a recent study published in Scientific progressa group of researchers investigated the effects of transcranial temporal interference electrical stimulation (tTIS) on the hippocampus-entorhinal complex (HC-EC) and its relationship with spatial navigation performance in healthy volunteers.
Background
Cognitive deficits in navigation and spatial memory are common among the aging population and in people with neurodegenerative diseases, significantly affecting daily life and independence.
Understanding the underlying brain networks is crucial for developing innovative treatment strategies. Research has shown that the medial temporal lobe, specifically the HC-EC, is essential for spatial cognition through the role of place and grid cells.
However, challenges remain in translating findings from animals to humans due to invasive recording restrictions. Therefore, further research is essential to clarify the causal role of the HC-EC and grid cell-like activity in human spatial cognition and how age or neurological conditions influence these functions.
About the study
Thirty young, healthy participants (16 females, mean age 23.63 ± 4.07 years) were recruited for this study. All participants were right-handed, naïve to the purpose of the study and gave informed consent in accordance with the Declaration of Helsinki.
tTIS was administered using low-intensity currents delivered via two constant current sources. The electrode montage targeted the right hippocampus, verified through computational modeling and measurements of human cadavers.
Participants underwent three different stimulation protocols: intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), or a control condition.
The spatial navigation task used magnetic resonance imaging (MRI), which is compatible with virtual reality (VR) and was adapted from previous research. Participants navigated a circular arena using only distal landmarks for orientation cues while receiving stimulation.
The task included an encoding phase, during which participants memorized object locations, followed by retrieval trials. Each participant completed six blocks of the task, with the stimulation conditions applied in a pseudorandomized order.
MRI data were collected using a 3T MRI scanner, capturing both structural and functional images. Preprocessing of the functional MRI (fMRI) data was performed using Statistical Parametric Mapping 12 (SPM12), and analyzes assessed changes in brain responses to different stimulation protocols, applying different statistical methods for interpretation of behavioral and neural data.
Study results
Participants completed six blocks of a VR spatial navigation task while undergoing tTIS with one of three conditions: iTBS, cTBS, or a control condition, applied in a pseudorandomized order.
Each block began with a 2.5-minute encoding phase, during which participants memorized the locations of three objects in the virtual arena. This was followed by a retrieval phase in which participants retrieved the object locations one at a time, leading to repeated trials over a total duration of nine minutes per block.
Statistical analyzes indicated a significant difference in retrieval times across the stimulation conditions, with participants in the iTBS group showing significantly shorter trial times compared to those in the cTBS group.
This suggests increased temporal efficiency during navigation. The analysis also found that participants left earlier when undergoing iTBS than in cTBS and control conditions, supporting the idea that faster departure times contributed to shorter pick-up times.
However, there was no significant difference in the distance navigated or the total navigation time, indicating that the improved performance in the iTBS condition was not due to increased impulsivity or a trade-off between speed and accuracy.
Subsequent analyzes of brain activity revealed that tTIS targeting the right HC-EC affected hexadirectional grid cell-like representations (GCLR). During the control condition, the GCLR was significantly greater than zero, confirming the involvement of hexadirectional coding during the task.
In contrast, both iTBS and cTBS significantly reduced GCLR magnitudes compared to control. The reductions in GCLR were indicative of changes in grid cell-like activity as a result of the stimulation protocols.
Furthermore, analysis of Blood Oxygen Level Dependent (BOLD) activity within the right hippocampus and entorhinal cortex suggested that changes in neural activity correlated with behavioral performance.
Significant differences in hippocampal activation were observed during the Cue+Retrieval periods, which correlated with the faster departure times noted during the iTBS condition. These findings imply that faster retrieval of object locations is associated with increased activity of the right hippocampus, highlighting the critical role of this region in spatial navigation.
Finally, the control conditions were assessed to ensure that there were no differential effects on behavior. Comparisons between participants who received high-frequency (HF) control and those who received sham stimulation indicated no significant behavioral differences, supporting the validity of combining these control groups in the analysis.
Conclusions
In summary, the findings showed that iTBS resulted in faster departure times compared to cTBS without affecting accuracy. Although both stimulation conditions reduced entorhinal GCLR, these changes did not fully explain the changes in navigation behavior.
Increased right hippocampal activity correlated with improved navigation performance during the Cue+Retrieval phase, indicating that tTIS can effectively modulate spatial navigation mechanisms.