Targeted deep brain stimulation improves spatial navigation in virtual reality study, offering new hope for treating cognitive impairments like dementia.
Study: Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Image Credit: Gorodenkoff/Shutterstock.com
In a recent study published in Science Advances, a group of researchers investigated the effects of transcranial temporal interference electric stimulation (tTIS) on the hippocampal-entorhinal complex (HC-EC) and its relationship with spatial navigation performance in healthy volunteers.
Background
Cognitive deficits in navigation and spatial memory are prevalent among the aging population and individuals with neurodegenerative diseases, significantly affecting daily life and independence.
Understanding the underlying brain networks is crucial for developing innovative treatment strategies. Research has identified the medial temporal lobe, particularly the HC-EC, as essential for spatial cognition through the role of place and grid cells.
However, challenges remain in translating animal findings to humans due to invasive recording limitations. Therefore, further research is essential to clarify the causal roles of the HC-EC and grid cell-like activity in human spatial cognition and how age or neurological conditions impact 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, naive to the study's purpose, and provided informed consent in accordance with the Declaration of Helsinki.
tTIS was administered using low-intensity currents delivered through two constant current sources. The electrode montage targeted the right hippocampus, verified through computational modeling and human cadaver measurements.
Participants underwent three different stimulation protocols: intermittent theta-burst stimulation (iTBS), continuous theta-burst stimulation (cTBS), or a control condition.
The spatial navigation task utilized magnetic resonance imaging (MRI), which is compatible with virtual reality (VR) and was adapted from prior research. Participants navigated through a circular arena with only distal landmarks for orientation cues while receiving stimulation.
The task included an encoding phase, where participants memorized object locations, followed by retrieval trials. Each participant completed six blocks of the task, with stimulation conditions applied in a pseudo-randomized order.
MRI data were collected using a 3T MRI scanner, capturing both structural and functional images. Preprocessing of the functional MRI (fMRI) data was conducted using Statistical Parametric Mapping 12 (SPM12), and analyses assessed changes in brain responses to different stimulation protocols, with various statistical methods applied for behavioral and neural data interpretation.
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 pseudo-randomized order.
Each block began with a 2.5-minute encoding phase, where participants memorized the locations of three objects within the virtual arena. This was followed by a retrieval phase where participants recalled the object locations one by one, leading to repeated trials over a total duration of nine minutes per block.
Statistical analyses indicated a significant difference in retrieval times across stimulation conditions, with participants in the iTBS group exhibiting notably shorter trial times compared to those in the cTBS group.
This suggests increased temporal efficiency during navigation. The analysis also revealed that participants departed earlier when undergoing iTBS than in cTBS and control conditions, supporting the notion that faster departure times contributed to shorter retrieval durations.
However, there was no significant difference in the navigated distance or the overall time spent in navigation, indicating that the enhanced performance in the iTBS condition was not a result of increased impulsivity or a speed-accuracy trade-off.
Subsequent analyses of brain activity revealed that tTIS targeting the right HC-EC impacted hexadirectional grid cell-like representations (GCLR). During the control condition, GCLR was significantly greater than zero, confirming engagement of hexadirectional coding during the task.
In contrast, both iTBS and cTBS significantly decreased GCLR magnitudes compared to the control. The reductions in GCLR were indicative of alterations in grid cell-like activity due to 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, correlating with the faster departure times noted during the iTBS condition. These findings imply that more rapid retrieval of object locations is associated with increased right hippocampal activity, highlighting the critical role of this region in spatial navigation.
Finally, control conditions were assessed to ensure no differential effects on behavior. Comparisons between participants receiving high-frequency (HF) control and those receiving sham stimulation indicated no significant behavioral differences, supporting the validity of combining these control groups in the analysis.
Conclusions
To summarize, the findings showed that iTBS resulted in faster departure times compared to cTBS without affecting accuracy. Although both stimulation conditions decreased entorhinal GCLR, these changes did not fully explain the alterations 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.
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