Commun Bio: The epilepsy team of Xuanwu Hospital of Capital Medical University directly revealed the functional diversity of the basal ganglia of the human brain for the first time in the world

On October 23, 2022, Communications Biology published online a report from the epilepsy team of Xuanwu Hospital of Capital Medical University entitled “Intracranial direct electrical mapping reveals the functional architecture of the human basal ganglia” Based on the team's previous research work, with the help of stereotactic EEG electrode placement, the use of direct electrical stimulation technology revealed that the function and circuit of human basal ganglia nucleus are not only limited to sensorimotor function, but also involve vestibular system, autonomic nervous system and higher cognitive function, providing direct evidence
of the diversity of human basal ganglia nucleus and corresponding circuit functions for the first time.

This study marks an important step towards a comprehensive mapping of human basal ganglia function, provides mechanistic explanations for non-motor symptoms of brain loop diseases, and has potentially important value
in developing novel therapeutic modalities.

The basal ganglia nucleus is located in the center of the brain and is present in all vertebrates, and its basic structure was basically mature
as early as 500 million years ago in lampreys.
In humans, basal ganglia nuclei include striatum, globus pallidus, subthalamic nucleus and substantia nigra, etc.
, which have delicate and complex functions, through the cortex-thalamus-basal ganglia-cortical circuit, regulating a variety of human daily behaviors, and there is also an inseparable relationship
with brain circuit diseases.

The preliminary understanding of the function of human basal ganglia nuclei mainly stems from the clinical manifestations
of focal basal ganglion nucleologies and neurodegenerative diseases.
Through physiological and anatomical observations of nonhuman primates, GE.
Alexander, MR.
DeLong and PL.
In the 80s of the 20th century, Strick proposed a five-functional loop model of basal ganglion nuclei, which provided the neurobiological basis for the function of basal ganglion nuclei, which is of landmark significance
for the functional study of basal ganglion nuclei.
The basal ganglion nucleus participates in the learning, coordination and execution of a series of movements through direct, indirect and ultradirect pathways
.
In recent years, with the continuous advancement and updating of research methods and the rise of functional neuroimaging research, a series of new functional circuits of basal ganglia nuclei have been discovered, including higher cognitive and emotional processing
.
In 2021, the journal Nature published the latest research results on the basal ganglia loop, in which researchers discovered six functional loops in rodents that pass through the basal ganglia in parallel
.

Since Robert Bartholow first applied direct electrical stimulation technology to locate functional areas of the human brain at the end of the 19th century, direct electrical stimulation has been considered the "gold standard" for determining brain function.
It is widely used in the division of primary and advanced functions of the
cerebral cortex.
However, because the basal ganglia nucleus is located deep in the brain, it is difficult to characterize
it with conventional neurosurgery.
There are also sporadic reports of non-motor functions of basal ganglia nuclei during deep brain stimulation surgery for movement disorders, but because the surgical path and target are relatively fixed, and the evidence is mostly from patients
with basal ganglia dysfunction.
Therefore, there is a lack of direct evidence
for the physiological function of the human basal ganglia nucleus.

In this study, using direct electrical stimulation techniques, the researchers revealed the diversity of basal ganglia nucleus functions, including sensorimotor functions, as well as involvement in higher cognitive functions
such as vestibular sensation, autonomic nervous system, and language.
The specificity of the spatial location of different functions of the basal ganglia in the nucleus also reflects the specificity of the functional circuit of the basal ganglia, which provides a new perspective
for the symptomatic interpretation of brain circuit diseases associated with the nucleus of the basal ganglia.
For example, direct evidence is provided for the hypothesis of the central origin of sensory dysfunction and autonomic dysfunction in Parkinson's disease; The discovery of vestibular sensation provides new ideas
for explaining gait instability in patients with Parkinson's disease.

Schematic of the grouped electrodes through the MNI spatial BG (ICBM 2009b), electrode configuration, and stimulation parameters (Figure from Communications Biology).

It is worth noting that the researchers found that the direct electrical stimulation of the basal ganglia nucleus caused the phenomenon of confusion in thinking, which indicates that the basal ganglia nucleus is also involved in decision-making, memory information and other high-level cognitive function circuits, which also provides clues
to explain the obsessive thinking of patients with OCD.
The above findings are verified by the prediction model obtained based on the meta-analysis of functional imaging studies, and the spatial distribution location of many specific functions cannot be completely predicted, and the findings of this study further make up for the current lack
of understanding of human basal ganglia function.

This study is a further expansion of the previous research work of the epilepsy team of Xuanwu Hospital of Capital Medical University (some of the research results were published in the international classic authoritative journals of neurology Brain and Annals of 2020 in 2018 and 2020, respectively Neurology）
。 Associate Professor Qi Lei and Associate Researcher Xu Cuiping are the co-first authors of this paper, and Professor Zhao Guoguang, Professor Yu Tao and Professor Ren Liankun are the co-corresponding authors
.
This research was strongly supported
by Professor Shu Yousheng's team from the Institute of Translational Brain Science of Fudan University and Cui Zaijie, a researcher at the Beijing Center for Brain Science and Brain-like Research.

This study marks an important step towards the goal of comprehensively mapping the function of the human basal ganglia, providing direct evidence
for revealing the diversity of nuclei of the basal ganglia of the human brain.
It provides a new perspective for the mechanism interpretation of brain circuit disease symptoms, and also has potential clinical translational application value
for neuromodulation treatment of brain circuit diseases including epilepsy and other movement disorders, especially for the improvement of non-motor symptoms.

Original link: