Non-invasive brain stimulation holds promise for improving navigation skills in cognitively impaired patients

Targeted deep brain stimulation improves spatial navigation in virtual reality research and offers new hope for treating cognitive disorders such as dementia.

study: Non-invasive modulation of the hippocampal-entorhinal complex in human spatial navigation. Image credit: Gorodenkoff/Shutterstock.com

In a recent study published in scientific progressa group of researchers investigated the effects of transcranial temporal interference electrical stimulation (tTIS) on the hippocampal-entorhinal complex (HC-EC) in healthy volunteers and its relationship with spatial navigation ability.

background

Cognitive impairments in navigation and spatial memory are prevalent among older adults and people with neurodegenerative diseases, severely impacting daily life and independence.

Understanding the underlying brain networks is important for developing innovative therapeutic strategies. Studies have identified the medial temporal lobe, particularly the HC-EC, as essential for spatial cognition through the role of place cells and grid cells.

However, challenges remain in translating animal findings to humans due to the limitations of invasive recording. Therefore, further studies are needed to clarify the causal role of HC-EC and grid cell-like activity in human spatial cognition and how age and neurological status influence these functions. It's essential.

About research

Thirty young, healthy participants (16 females, mean age 23.63 ± 4.07 years) were recruited for this study. All participants were right-handed, unaware of the purpose of the study, and provided informed consent in accordance with the Declaration of Helsinki.

tTIS was administered using low-intensity current delivered through two constant current sources. The electrode montage targets the right hippocampus and was validated by computational modeling and measurements on human cadavers.

Participants received 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 adapted from previous studies. Participants navigated a circular arena with only distal landmarks for directional guidance while receiving stimulation.

This task included an encoding phase in which participants memorized the object's location, followed by a retrieval trial. Each participant completed six blocks of the task, applying stimulus conditions in a pseudorandomized order.

MRI data were collected using a 3T MRI scanner, capturing both structural and functional images. Preprocessing of functional MRI (fMRI) data was performed using Statistical Parametric Mapping 12 (SPM12), and analysis involved a variety of Changes in brain responses to stimulation protocols were assessed.

Research results

Participants completed six blocks of a VR spatial navigation task while receiving tTIS in one of three conditions: iTBS, cTBS, or a control condition applied in a pseudorandomized order.

Each block began with a 2.5-min encoding phase in which participants memorized the locations of three objects in the virtual arena. This was followed by a retrieval phase in which participants recalled the object locations one by one, with repeated trials lasting a total of 9 min per block.

Statistical analysis showed that there were significant differences in search times between stimulus conditions, with participants in the iTBS group having significantly shorter trial times compared to participants in the cTBS group.

This suggests improved time efficiency during navigation. This analysis also revealed that participants departed earlier when receiving iTBS than in cTBS or control conditions, supporting the idea that earlier departure times contributed to shorter retrieval periods.

However, there were no significant differences in navigation distance or overall time spent navigating, indicating that the improved performance in the iTBS condition was not the result of increased impulsivity or a trade-off between speed and accuracy.

Subsequent analysis of brain activity revealed that tTIS targeting right HC-ECs affected hexagonal lattice cell-like representation (GCLR). During the control condition, GCLR was significantly greater than zero, confirming the involvement of six-way coding during the task.

In contrast, both iTBS and cTBS significantly decreased the magnitude of GCLR compared to control. The decrease in GCLR indicated changes in grid cell-like activity due to the stimulation protocol.

Furthermore, analysis of blood oxygen level-dependent (BOLD) activity within the right hippocampus and entorhinal cortex suggested that changes in neural activity were correlated with behavioral performance.

Significant differences in hippocampal activation were observed during the cue+recovery period and correlated with the faster departure times observed during the iTBS condition. These findings suggest that faster retrieval of object locations is associated with increased activity in the right hippocampus, highlighting the important role of this region in spatial navigation.

Finally, a control condition was evaluated to ensure that there were no differential effects on behavior. Comparisons of participants who received high-frequency (HF) control and those who received sham stimulation showed no significant differences in behavior, supporting the validity of combining these control groups in analyses.

conclusion

In summary, the findings showed that iTBS reduced departure time compared to cTBS without affecting accuracy. Although entorhinal GCLR was decreased in both stimulation conditions, these changes did not fully explain the changes in navigational behavior.

Increased right hippocampal activity correlated with improved navigation performance during the Cue+Retrieval phase, indicating that tTIS can effectively modulate spatial navigation mechanisms.