Abnormal motor cortical plasticity as a useful neurophysiological biomarker for Alzheimer's disease pathology.

OBJECTIVE: Amyloid-beta (Aß) and tau accumulations impair long-term potentiation (LTP) induction in animal hippocampi. We investigated relationships between motor-cortical plasticity and biomarkers for Alzheimer's disease (AD) diagnosis in subjects with cognitive decline. METHODS: Twenty-six consecutive subjects who complained of memory problems participated in this study. We applied transcranial quadripuse stimulation with an interstimulus interval of 5 ms (QPS5) to induce LTP-like plasticity. Motor-evoked potentials were recorded from the right first-dorsal interosseous muscle before and after QPS5. Cognitive functions, Aß42 and tau levels in the cerebrospinal fluid (CSF) were measured. Amyloid positron-emission tomography (PET) with11C-Pittsburg compound-B was also conducted. We studied correlations of QPS5-induced plasticity with cognitive functions or AD-related biomarkers. RESULTS: QPS5-induced LTP-like plasticity positively correlated with cognitive scores. The degree of LTP-like plasticity negatively correlated with levels of CSF-tau, and the amount of amyloid-PET accumulation at the precuneus, and correlated with the CSF-Aß42 level positively. In the amyloid-PET positive subjects, non-responder rate of QPS5 was higher than the CSF-tau positive rate. CONCLUSIONS: Findings suggest that QPS5-induced LTP-like plasticity is a functional biomarker of AD. QPS5 could detect abnormality at earlier stages than CSF-tau in the amyloid-PET positive subjects. SIGNIFICANCE: Assessing motor-cortical plasticity could be a useful neurophysiological biomarker for AD pathology.

[Awake surgery for preservation of higher brain functions].

Awake surgery for gliomas has become a widely accepted neurosurgical method worldwide. However, it is applied mainly to restore speech and simple motor functions, and intraoperative applications to restore higher brain functions have not been established yet. Preserving these functions is crucial to restoring the normal social lives of patients postoperatively. In this review article, we focused on preserving spatial attention and higher motor functions, and discussed their neural basis, as well as, the application of awake surgery practices using effective tasks. For spatial attention, the line bisection task is the most popular and reliable; however, other tasks, such as exploratory tasks, can be used, depending on the location of the brain. For higher motor functions, we developed two tasks: 1) the PEG & COIN task, which evaluates grasping and approaching skills, and 2) the sponge-control task, which assesses somatosensory-dependent movement. Although scientific knowledge and evidence are still limited in this field of neurosurgery, we believe that expanding our knowledge about higher brain functions and developing specific and efficient intraoperative tasks to evaluate them will eventually preserve patients'quality of life.

[Electrical Stimulation Mapping of Multilingualism].

Language mapping is commonly practiced in brain tumors and epilepsy surgeries. It is done by direct electrical stimulation of the brain during awake craniotomy or by placing subdural electrodes on the brain's surface, or both. Studies of the language mapping in bi- or multi-lingual patients have concluded that they have both "language-specific areas," in which symptoms are evoked upon stimulation in one specific language and not in the other languages, and "common areas" or "overlapping areas," in which positive findings are evoked in all languages evaluated. The distribution of the pattern of language areas associated with each language, however, varies widely from patient to patient due to multiple factors such as the age of language acquisition, the language proficiency level, the amount of exposure to each language, the location of the lesions, the duration of the diseases, and other factors. Language mapping in bi- or multi-lingual patients should be done by screening all languages the patient speaks.

Neural Basis of Language: An Overview of An Evolving Model.

The neural basis of language had been considered as a simple model consisting of the Broca's area, the Wernicke's area, and the arcuate fasciculus (AF) connecting the above two cortical areas. However, it has grown to a larger and more complex model based upon recent advancements in neuroscience such as precise imaging studies of aphasic patients, diffusion tensor imaging studies, functional magnetic resonance imaging studies, and electrophysiological studies with cortical and subcortical stimulation during awake surgery. In the present model, language is considered to be processed through two distinct pathways, the dorsal stream and the ventral stream. The core of the dorsal stream is the superior longitudinal fasciculus/AF, which is mainly associated with phonological processing. On the other hand, semantic processing is done mainly with the ventral stream consisting of the inferior fronto-occipital fasciculus and the intratemporal networks. The frontal aslant tract has recently been named the deep frontal tract connecting the supplementary motor area and the Broca's area and it plays an important role in driving and initiating speech. It is necessary for every neurosurgeon to have basic knowledge of the neural basis of language. This knowledge is essential to plan safer surgery and preserve the above neural structures during surgery.

Use of Network Analysis to Establish Neurosurgical Parameters in Gliomas and Epilepsy.

Cutting-edge neuroimaging technologies can facilitate preoperative evaluation in various neurosurgical settings. Surgery for gliomas and epilepsy requires precise localization for resection due to the need to preserve (or perhaps improve) higher cognitive functions. Accordingly, a hodological approach should be taken that considers subcortical networks as well as cortical functions within various functional domains. Resting state functional magnetic resonance imaging (fMRI) has the potential to provide new insights that are valuable for this approach. In this review, we describe recent developments in network analysis using resting state fMRI related to factors in glioma and epilepsy surgery: the identification of functionally dominant areas, evaluation of cognitive function by alteration of resting state networks (RSNs), glioma grading, and epileptic focus detection. One particular challenge that is close to realization is using fMRI for the identification of sensorimotor- and language-dominant areas during a task-free resting state. Various RSNs representative of the default mode network demonstrated at least some alterations in both patient groups, which correlated with behavioral changes including cognition, memory, and attention, and the development of psychosis. Still challenging is the detection of epileptic foci and propagation pathways when using only network analysis with resting state fMRI; however, a combined method with simultaneous electroencephalography has produced promising results. Consequently, network analysis is expected to continue to advance as neuroimaging technology improves in the next decade, and preoperative evaluation for neurosurgical parameters through these techniques should improve parallel with them.

A case of secondary somatosensory epilepsy with a left deep parietal opercular lesion: successful tumor resection using a transsubcentral gyral approach during awake surgery.

Few studies have examined the clinical characteristics of patients with lesions in the deep parietal operculum facing the sylvian fissure, the region recognized as the secondary somatosensory area (SII). Moreover, surgical approaches in this region are challenging. In this paper the authors report on a patient presenting with SII epilepsy with a tumor in the left deep parietal operculum. The patient was a 24-year-old man who suffered daily partial seizures with extremely uncomfortable dysesthesia and/or occasional pain on his right side. MRI revealed a tumor in the medial aspect of the anterior transverse parietal gyrus, surrounding the posterior insular point. Long-term video electroencephalography monitoring with scalp electrodes failed to show relevant changes to seizures. Resection with cortical and subcortical mapping under awake conditions was performed. A negative response to stimulation was observed at the subcentral gyrus during language and somatosensory tasks; thus, the transcortical approach (specifically, a transsubcentral gyral approach) was used through this region. Subcortical stimulation at the medial aspect of the anterior parietal gyrus and the posterior insula around the posterior insular point elicited strong dysesthesia and pain in his right side, similar to manifestation of his seizure. The tumor was completely removed and pathologically diagnosed as pleomorphic xanthoastrocytoma. His epilepsy disappeared without neurological deterioration postoperatively. In this case study, 3 points are clinically significant. First, the clinical manifestation of this case was quite rare, although still representative of SII epilepsy. Second, the location of the lesion made surgical removal challenging, and the transsubcentral gyral approach was useful when intraoperative mapping was performed during awake surgery. Third, intraoperative mapping demonstrated that the patient experienced pain with electrical stimulation around the posterior insular point. Thus, this report demonstrated the safe and effective use of the transsubcentral gyral approach during awake surgery to resect deep parietal opercular lesions, clarified electrophysiological characteristics in the SII area, and achieved successful tumor resection with good control of epilepsy.

Intraoperative subcortical mapping of a language-associated deep frontal tract connecting the superior frontal gyrus to Broca's area in the dominant hemisphere of patients with glioma.

OBJECT: The deep frontal pathway connecting the superior frontal gyrus to Broca's area, recently named the frontal aslant tract (FAT), is assumed to be associated with language functions, especially speech initiation and spontaneity. Injury to the deep frontal lobe is known to cause aphasia that mimics the aphasia caused by damage to the supplementary motor area. Although fiber dissection and tractography have revealed the existence of the tract, little is known about its function. The aim of this study was to determine the function of the FAT via electrical stimulation in patients with glioma who underwent awake surgery. METHODS: The authors analyzed the data from subcortical mapping with electrical stimulation in 5 consecutive cases (3 males and 2 females, age range 40-54 years) with gliomas in the left frontal lobe. Diffusion tensor imaging (DTI) and tractography of the FAT were performed in all cases. A navigation system and intraoperative MRI were used in all cases. During the awake phase of the surgery, cortical mapping was performed to find the precentral gyrus and Broca's area, followed by tumor resection. After the cortical layer was removed, subcortical mapping was performed to assess language-associated fibers in the white matter. RESULTS: In all 5 cases, positive responses were obtained at the stimulation sites in the subcortical area adjacent to the FAT, which was visualized by the navigation system. Speech arrest was observed in 4 cases, and remarkably slow speech and conversation was observed in 1 case. The location of these sites was also determined on intraoperative MR images and estimated on preoperative MR images with DTI tractography, confirming the spatial relationships among the stimulation sites and white matter tracts. Tumor removal was successfully performed without damage to this tract, and language function did not deteriorate in any of the cases postoperatively. CONCLUSIONS: The authors identified the left FAT and confirmed that it was associated with language functions. This tract should be recognized by clinicians to preserve language function during brain tumor surgery, especially for tumors located in the deep frontal lobe on the language-dominant side.

Evaluation of resting state networks in patients with gliomas: connectivity changes in the unaffected side and its relation to cognitive function.

In this study, we investigated changes in resting state networks (RSNs) in patients with gliomas located in the left hemisphere and its relation to cognitive function. We hypothesized that long distance connection, especially between hemispheres, would be affected by the presence of the tumor. We further hypothesized that these changes would correlate with, or reflect cognitive changes observed in patients with gliomas. Resting state functional MRI datasets from 12 patients and 12 healthy controls were used in the analysis. The tumor's effect on three well-known RSNs including the default mode network (DMN), executive control network (ECN), and salience network (SN) identified using independent component analysis were investigated using dual regression analysis. Scores of neuropsychometric testing (WAIS-III and WMS-R) were also compared. Compared to the healthy control group, the patient group showed significant decrease in functional connectivity in the right angular gyrus/inferior parietal lobe of the ventral DMN and in the dorsolateral prefrontal cortex of the left ECN, whereas a significant increase in connectivity in the right ECN was observed in the right parietal lobe. Changes in connectivity in the right ECN correlated with spatial memory, while that on the left ECN correlated with attention. Connectivity changes in the ventral DMN correlated with attention, working memory, full IQ, and verbal IQ measures. Although the tumors were localized in the left side of the brain, changes in connectivity were observed in the contralateral side. Moreover, these changes correlated with some aspects of cognitive function indicating that patients with gliomas may undergo cognitive changes even in the absence of or before the onset of major symptoms. Evaluation of resting state networks could be helpful in advancing our hodological understanding of brain function in glioma cases.