In a recent study published in the journal natural medicineResearchers investigated the effects of deep brain stimulation (DBS) within the central lateral thalamic (CL) nucleus and associated medial dorsal tegmental (CL/DTTm) tract in patients with moderate to severe traumatic brain injury (msTBI). Efficacy and safety were evaluated.
Studies have shown that the CL thalamic nucleus is an important node for executive function and information processing speed deficits in msTBI patients, impeding quality of life and social reintegration. Currently, there is no effective treatment for these abnormalities, and the “mesocircuit theory” points out that insufficient activation of the CL is the cause.
study: Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.. Image credit: SciePro / Shutterstock
About research
In the current Phase 1 randomized feasibility study, researchers evaluated the efficacy and safety of CL DBI in humans with chronic traumatic brain injury-related disorders, and aimed to improve daily functioning and employability. It made an impact.
The aim of the study was to develop a treatment for persistent cognitive impairment in msTBI patients using thalamic DBS electrodes. Lateral sections of the mediolateral nucleus of the thalamus and its associated DTTm fiber bundles were selected as stimulation targets. They performed biophysical modeling and aimed virtual brain stimulation electrodes at each individual’s CL/DTTm bundle depending on stimulation amplitude and location. Researchers investigated the safety and efficacy of thalamic DBS in the treatment of cognitive disorders.
This study also included patients with msTBI [Glasgow Coma Scale (GCS) scores of 3 to 12], functional impairment, and cognitive impairment (GOS-E score 5–7). The team received 419 requests for experiments and evaluated 15 people for eligibility. Six people were enrolled and randomly assigned between August 2018 and May 2021. The team excluded nine people who were ineligible, leaving six people for analysis: four men and two women with a history of traumatic brain injury.
Researchers randomly assigned participants to one of three baseline conditions lasting 30, 44, or 58 days after surgery. Participants were double-blinded after the titration phase, a 90-day open-label treatment period, and a 21-day treatment continuation or discontinuation condition to reduce the influence of participant and examiner bias on the final outcome assessment. I took the test. The primary efficacy outcomes are improvements in executive control as measured by processing speed and at least 10% of the time required to complete the Trail Making Test Part B (TMT-B) from baseline (preoperative) to conclusion. It was shortened. Out of a 3 month treatment period.
The researchers conducted semi-structured interviews and conducted post-hoc analyzes to examine the consistency of electrode implantation within human CL/DTTm structures. They built a customized data processing pipeline and identified CL neurons and DTTm fascicles as the key structures of her DBS activation for interpreting preclinical findings. Using white matter voided magnetic resonance imaging (MRI), automated thalamic segmentation, DTI, and biophysical modeling of applied electric fields, a synthetic atlas was constructed to coordinate electrode placement among five individuals. The researchers evaluated evoked responses in the EEG to assess the consistency of physiological effects between individuals and compared their results with those of two subgroups of msTBI patients.
result
Six people successfully achieved bilateral DBS leads. New imaging and thalamic segmentation procedures and biophysical estimation models allowed us to precisely localize the participant’s central nucleus and her DTTm fibers. Five patients completed all outcome measures and met the primary objective (10% improvement threshold from baseline to end of treatment phase in TMT-B, mean improvement 32%).
Two patients reached the improvement criterion, two patients remained stable, and one patient met the second end goal, the criterion for reduction in change in TBIQoL fatigue. Four study participants (average, 33%) showed an improvement of more than 10% in their study. All five subjects showed better TMT-A scores regarding visual search speed, which may be related to fronto-striatal function and data processing speed. Rough 2 & 7 trials, which measure selective attention in time-limited situations, revealed significant improvements among her four subjects who completed the test.
Two individuals progressed from low to moderate or above GOS-E disability category. The functional status of the remaining three of her patients remained stable. The research team assessed her TMT-B scores at two intervals (post-surgery and at the start of treatment) prior to DBS exposure. Three of the five voluntarily participated in the randomized blind withdrawal phase. Only one subject randomly assigned to the OFF condition showed a 34% decrease in TMT-B score, indicating a withdrawal effect.
Despite variations in atrophy, this study found a similar targeting approach to detect fiber outflow from the lateral wings of the CL to the DTTm across subjects. The hemispheric temporal course and spatial localization of her P4 in the frontal brain were comparable, indicating that P4 received therapeutic stimulation in both hemispheres.
Overall, the study results showed that deep brain stimulation (DBS) with CL/DTTm can improve executive control in msTBI patients throughout the chronic recovery period. Results showed that DBS enhanced executive function using primary and executive assessments and secondary measures addressing fatigue, psychological well-being, and global functioning. The targeting technique used in the study involved dense clustering of active electrode connections within a synthetic thalamic ring. However, some subjects experienced temporary sensory disturbances and other adverse effects.