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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 34-37

Functional remodeling of brain language networks

Department of Neurosurgery, Glioma Surgery Division, Huashan Hospital, Fudan University, Shanghai, China

Date of Submission11-May-2020
Date of Acceptance26-May-2020
Date of Web Publication27-Jun-2020

Correspondence Address:
Prof. Jinsong Wu
Department of Neurosurgery, Glioma Surgery Division, Huashan Hospital, Fudan University, Shanghai 200040
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/glioma.glioma_12_20

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How to cite this article:
Hameed NU, Wu J. Functional remodeling of brain language networks. Glioma 2020;3:34-7

How to cite this URL:
Hameed NU, Wu J. Functional remodeling of brain language networks. Glioma [serial online] 2020 [cited 2023 Oct 2];3:34-7. Available from: http://www.jglioma.com/text.asp?2020/3/2/34/288177

  From Language Centers, Language Models to Language Networks Top

Broca and Wernicke discovered the motor and sensory language centers, respectively, in the 19th century. These were described in classic textbooks by their descendants. Synonyms have been used for these structures for more than 150 years. Over the past decades, with the advancement of science and technology, and especially the emergence and application of high-resolution noninvasive imaging technology, Graph theory, and precise electrophysiological technology, the concept of language centers has been questioned and replaced by language network. This has raised questions regarding our perception of medical history and the lessons to be learned from it.

First, we should understand that due to the limitations of the development of science and technology, in the 19th century, the two pioneering studies of Broca and Wernicke were limited to only observation and autopsy. As they pointed out themselves, there may be deep structural damage underlying the corresponding damaged cerebral cortex. Wernicke went on to further illustrate the idea of the language network. However, due to the limitations of the time, he was not able to confirm this. More contemporarily, Lichteim (1845–1928) described the “network graph” in the Wernicke–Lichteim model which can predict five types of aphasia: (1) Broca aphasia; (2) Wernicke aphasia; (3) conductive aphasia; (4) transcortical motor aphasia; and (5) transcortical sensory aphasia. In the 20th century, an American neurologist Geschwind (1926–1984) proposed the Wernicke–Lichteim–Geschwind model based on the predecessors. According to the model, the signal of the word sound passes through the auditory gyrus to the auditory cortex and is then processed in the Wernicke area to generate meaning. To form phonemes, the vocalization is coded through the arcuate fasciculus to the Broca area and finally coordinates the vocal cords and larynx muscles by the motor programing cortex to generate language. Although the above two language models outline the prototype of the language network, they are incomplete. The anatomical location of the Broca and Wernicke areas is not clear and there is still limited objective evidence. Many patients' clinical manifestations are difficult to incorporate into these two language models. For example, electrical stimulation of the anterior fusiform gyrus of the dominant hemisphere (which does not involve the Wernicke area) can cause severe dysfunction of lexia and sentence comprehension.[1] The arcuate fasciculus is completely damaged and the patient's ability to repeat is retained or can be fully recovered despite the lesion.[2] The cortex in the Broca area is completely damaged, causing only temporary or incomplete motor aphasia. During epilepsy surgery, electrical stimulation of the supramarginal gyrus can cause conductive aphasia.[3] In cases of primary progressive aphasia, severe semantic aphasia and syntactic aphasia are associated with the anterior temporal lobe. The anterior temporal lobe has never been included in the Wernicke language model.[4] The lesions in the classic Wernicke area only cause difficulties in sentence comprehension, mostly without difficulties in word comprehension. The latter is mostly observed in the left temporal pole or adjacent anterior temporal lobe cortical injury. In addition to the temporoparietal area, sentence comprehension disorder also involves the dorsal part of the Broca and the premotor areas. To understand words and sentences, the cortex around the Wernicke area and its underlying white matter pathways are as crucial as the cortex in the Wernicke area itself.[5] Notably, the brain specimens of the two patients first studied by Broca are well preserved in a Paris museum. These were recently examined with 1.5 T magnetic resonance imaging, which revealed that in addition to lesions in the posterior part of the inferior frontal gyrus, there were additional obvious lesions in the inferior white matter and superior longitudinal fasciculus.[6]

Through the observation and research of humans and primates, Hickok and Poeppel[7] proposed a new language model based on brain networks, namely the dual-stream model. According to this model, (1) the bilateral brain ventral streams extend from the front and middle of the temporal lobe to the base of the temporo-occipital lobe and are responsible for semantic understanding; (2) the main dorsal stream extends from the posterior superior temporal gyrus to the inferior frontal gyrus and premotor cortex via the arcuate fasciculus and the temporoparietal junction area and is responsible for vocal output. The dual-stream model originates from classic anatomy and is not based on lesions. However, it has been verified clinically for conditions such as aphasia after stroke. Lesions in different cortical areas cause similar aphasia reflecting the same language network damage. In a recent report on 99 patients with persistent acquired aphasia, high-resolution neuroimaging structural maps were used to analyze the relationship between language disorders and anatomy.[8] The report confirmed language production in the superior lateral fissure area, which is consistent with the dorsal stream. The lateral inferior lateral fissure area and the ventral stream were consistent with sound recognition and semantic production and understanding barriers were found to involve nonlateral fissure areas. The anterior temporal lobe is related to semantic aphasia. The frontal lobe is connected to the white matter of other brain regions namely the uncinate fasciculus and the inferior frontal occipital fasciculus, which converge into an isthmus-like white matter region (temporal stem) near the insular lobe. Even if undamaged, this can cause a disorder to semantic understanding. Corresponding semantic aphasia to other brain regions require extensive lesions.[8] This involves centers and pathways in the relationship between nodes in Graph theory and networks. These centers and pathway lines exist in the dual-stream model. The primary hubs in the ventral stream are the superior temporal gyrus, superior temporal sulcus, middle temporal gyrus, inferior temporal gyrus, temporal pole, inferior gyrus, precentral gyrus, anterior insula, posterior insula, and supramarginal gyrus. The ventral stream comprises the external capsule, the inferior frontal occipital fasciculus, the inferior longitudinal fasciculus, and the uncinate fasciculus. The “backflow” has the arcuate fasciculus and the anterior and posterior parts of the superior longitudinal fasciculus. However, the dual-stream model is still imperfect because (1) it does not include the cerebellum and cerebellar lesions can cause aphasia.[9] The cerebellum participates in a wide range of cognitive, emotional, and language activities;[10] (2) thalamus and basal ganglia participate in language activities; (3) positron emission tomography and functional magnetic resonance imaging studies show that nonclassical areas participate in language activities, such as the right hemisphere and cerebellum, suggesting that language activity involves the whole brain. The brain network theory partially supports the functional holistic theory, but is not entirely opposed to localizing theory.

  Primary and Secondary Networks Top

In the past two decades, the invention of high-field magnetic resonance and the development of neural function imaging technology have made the understanding of brain networks clearer. Through high-resolution imaging and diffusion tensor imaging, the cerebral cortex and white matter fibers can be visually reconstructed to show the brain structural network. The development of cognitive science and Graph theory has enhanced the ability of scholars to study and analyze the spatial and topological organization of neural connections. Through the design of functional experiments, brain regions that perform similar functions are divided, and the concept of brain function network is interpreted. It has even been found that tasks that require external attention are widely distributed in specific areas of the cortex.[11] In value judgment, situational memory, and future assumptions, these areas are active and the concept of the default network is established.

Based on the evidence of the reconstruction of the structural network, functional experiments have shown that cortical and white matter fibers in different locations can participate in the execution of similar functions.[12] For example, the “gold standard” intraoperative electrical stimulation of language suggests that the ventral steam includes a direct pathway (inferior occipital fasciculus) and an indirect pathway (inferior longitudinal fasciculus and uncinate fasciculus).[12] The direct inferior frontal occipital fasciculus connects the posterior occipital lobe to the anterior frontal cortex, while the bypass inferior longitudinal fasciculus connects the optic cortex to the temporal pole, and the uncinate fasciculus connects the temporal pole to the orbital part of the inferior frontal gyrus. As another example in the study of motor networks, functional imaging suggests that the pathway between the parietal lobe–lateral premotor area–cerebellum in the complex motor learning process produces spatial action guidance.[13] Parallel pathways are also involved in motor guidance, that is, the supplemental motor area–basal ganglia–medial temporal lobe system. Acute brain injury disease model and brain functional area gliomas can be observed after surgery. After the disruption of the indirect ventral semantic pathway, the patient's semantic understanding is not significantly impaired. Following disconnection of the direct pathway, however, the function is significantly impaired. After the primary area of the motor network is obviously damaged, or after the connection between the primary motor area and the supplemental motor area is damaged, it is very difficult to perform simple or complex movements. All of us have reason to believe that there are several extremely important central nodes in the brain structure and functional network. There are also extremely important connecting fibers between these central nodes. The connected nodes constitute the primary pathway of a functional network. The fibers between the central nodes and some peripheral nodes form side branches or functional bypasses, which constitute the secondary network of the function.

Graph theory has proposed a similar concept. It is believed that the brain network conforms neither to the regular network nor to the completely random network, but is a network with small world statistical properties between the two. Some nodes are classified through the probabilistic model. Within the same subnetwork, according to the execution function of the sub-network, it is further divided into motor, visual, auditory networks, and so on. Subsequent research has shown that similar connection and distribution patterns exist within these functional subnetworks.[14] The default mode network comprises multiple widely distributed regional clusters. The latest view also suggests that the default mode network is not a single network but consists of at least two spatially significant differences between the front and rear of the midline structure. Although the two subnetworks are heterogeneous in thinking theoretical and memory tasks, they are thought to share the same functional mode, and the hub with strong centrality is responsible for information interaction and task guidance. Some scholars believe that this is a group of network hubs arranged along the midline structure.[15] It has also been inferred that the triangle zone of the parahippocampal gyrus and the posterior cingulate gyrus is the hub of the default network by injecting fiber tracers from rhesus monkeys.[16] The default mode network is a functional network built on the results of functional research. These studies do not only constitute the structural basis for them and provide evidence for the primary and secondary networks; the brain structure of primates that are highly homologous to humans also suggests that there may also be network branches.[15]

  Neuroplasticity Top

Neuroplasticity is also called brain plasticity. The nervous system has the ability to change its own circuit altering information processing at any time. Neuroplasticity describes a person's continuous brain changes over a period of time. In the past, it was believed that the brain had plasticity potential only in infants and young children. However, it has been confirmed that under certain conditions, both in adulthood and in childhood, plasticity can occur in the brain structure or function. This is not only dependent on the biological potential of the individual, but also influenced by environmental stimuli and emotions. The process of adaptive changes in nerve function and structure due to changes in the internal and external environment is consequently called reorganization. The significance of remodeling relates not only to normal physiological processes, such as infant development and learning and memory, but also to the compensation for pathological conditions such as cortical damage or subcortical fiber damage. Functional imaging technology can measure the location and progress of compensation after clinical injury. For example, for the first time, Chollet et al.[17] observed a compensatory increase in blood flow on the ischemic side after stroke with positron emission tomography, as well as increased blood flow in the sensorimotor area on the opposite side of the cerebral hemisphere. Duffau[18] observed in glioma surgery that following the removal of the posterior part of the left temporal gyrus, the functional connection with the inferior parietal lobe may be compensated by the remodeling of brain structure. During the perioperative period, it was found that in addition to activation of compensation around the lesion, functional compensation was also observed in the distant brain area (left supramarginal gyrus and inferior frontal gyrus). Gili's team found increased functional connections in multiple areas in the right cerebral hemisphere of patients with poststroke aphasia and showed high eigenvector centrality in the ventral premotor cortex and ventral middle temporal gyrus of the right hemisphere. Functional improvements exist.[19] According to the above experimental conclusions, it can be found that remodeling not only occurs in the surrounding structures of the lesion, but can also be observed at remote locations. Therefore, the description of remodeling can be extended to the scale of brain networks. However, it is often observed in the clinic that irreversible, permanent hemiplegia or visual field defects may occur in the primary motor cortex and pyramidal tract injury or occipital cortical and visual tract destruction. Therefore, it can be found that the reshaping potential of the primary and the secondary networks of the function is heterogeneous. How to accurately locate the primary and the secondary networks is not only related to protecting from permanent damage caused by organic damage, but also related to the remodeling between the secondary networks to achieve maximum functional rehabilitation.

In a study of stroke aphasia, the relationship between cortical damage and aphasia in the common language area is classified according to the type of language impairment.[20] Subsequent literature also pointed out that after the damage to the cortical language center, an alternative cortical center appears and compensates for part of the impaired function.[21] Some surgical case reports have suggested that the aphasia caused by the white matter fiber damage of the language pathway is more serious, and the destruction of the white matter fiber may cause permanent aphasia.[22] We believe that the difference in compensability may not lie in the plasticity of gray matter or white matter, but in the primary and secondary natures of the aforementioned functional network. Understanding the difference between the remodeling of the primary and the secondary networks not only provides a new therapeutic target for rehabilitation such as noninvasive transcranial magnetic stimulation (TMS), but also provides a basis for intraoperative verification and protection of the primary functional network.

The primary motion cortex, supplemental motor area, and premotor area of the neural network are important nodes. For the first time, Bestmann et al.[23] used TMS to give high-frequency facilitation stimulation in the contralateral premotor area in patients with hemiplegia after stroke and observed that the outgoing signal of the affected hemisphere was more easily transmitted to the spinal cord. This shows that the remodeling efficiency of network nodes can be improved after application of external intervention. Naeser et al.[24] enrolled patients with long-term aphasia for more than 5 years after stroke in the frontal lobe. TMS treatment was applied to the right-sided hemisphere Broca for 10 days. The results showed that the ability of patients to name pictures gradually improved within 2 months. While studies have shown TMS to be effective, the treatment benefit is not universal and not applicable to the use of TMS to promote remodeling. It should depend on the repair process of the brain network and its repairability. For example, the affected side of the hemisphere is already in the process of maximum compensation, and repeated application of TMS stimulation intervention may inhibit compensation. The function of the original damaged cortex is replaced by the cortex in other locations after long-term recovery of stroke patients. There is no remodeling effect in the functional cortex when TMS applied. Therefore, we can use functional magnetic resonance to determine the remaining functional area or brain network structure and then navigate the location of TMS intervention or dynamically observe the brain network to determine the time window for intervention. The remodeling activity and remodeling effect expressed by the primary network and the secondary network after TMS are topics for future research.

The primary and secondary natures of neural function network exist not only in sensorimotor network or language network but also in cognitive network. Like the default network mentioned above, there is still a gap in research on the reshaping of advanced cognitive networks. Through the mapping of the lesion network of the human brain connectome method, it can be determined whether different parts of the brain that cause similar mental symptoms are located in the same brain network. This is an advancement in the analysis of traditional lesions. A complex cognitive behavior is a comprehensive manifestation of multiple connections in the brain area, and damage to any of these areas can disrupt normal behavior and cause cognitive impairment or mental symptoms. Through functional imaging, scientists believed that compensation for cognitive impairment is compensation for symptoms, not structural changes. The purpose of this change may be to suppress the abnormal activation of signals in a certain area and prevent the deterioration of symptoms. This inference not only explains the remodeling of advanced cognitive networks but also extends the definition of brain network remodeling from structural to functional plasticity, providing a theoretical basis for functional prognosis and treatment.

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