Use of magnetic resonance spectroscopy to explore metacognitive ability and academic score

Background: Previous studies have reported the important roles of the precuneus in mediating metacognition and the prefrontal cortex in decision-making tasks. However, the underlying mechanisms of metacognition are still not fully elucidated. Long echo time proton magnetic resonance spectroscopy (MRS) was used to further explore the neurocognitive correlates of metacognition. Methods: Metacognition was based on a self-report questionnaire of nursing students. Magnetic resonance (MR) spectra were recorded from bilateral precuneus and medial prefrontal cortex. Results: Significant positive correlation was discovered between total metacognitive score and academic score (p = 0.007). Precuneus N-acetyl aspartate/creatine plus phosphocreatine (NAA/Cr+PCr) ratios were corresponded to metacognitive ability. Moreover, the correlation between precuneus NAA/Cr+PCr ratios and metacognitive ability was established for the right precuneus and not left precuneus. Furthermore, linear regression suggested that for every increase in the right precuneus NAA/Cr+PCr ratios, there is a predicted decrease in total metacognitive score (p = 0.020). Conclusions: These findings further indicated that the right precuneal region plays an important role in metacognition and learning.

reported that the prefrontal cortex is essentially involved in metacognition through decision-making tasks [6]. Lesions to anterior prefrontal cortex impair perceptual metacognitive accuracy while sparing memory metacognitive accuracy [7][8].
Macaque monkey's metacognitive capability of introspecting its own memory success is causally dependent on intact superior dorsolateral prefrontal cortices but not the orbitofrontal cortices [9]. Studies in the past have indicated that variation in memory metacognitive efficiency was correlated with the volume of the precuneus [10]. Despite recent studies indicating the neural architecture of metacognition in various cognitive domains [7][8][10][11][12][13], the complex relationships concerning metacognition are still not fully understood. Magnetic resonance spectroscopy (MRS) is a noninvasive technique increasingly used in recent times, which can provide information regarding the chemical or metabolic composition of the brain [14]. Some metabolite changes have been found in both patients with mild cognitive impairment and Alzheimer's disease, especially the latter [15][16][17]. We hypothesized that metabolite levels in related brain regions may be related to metacognitive ability. In contrast with earlier studies, MRS was used to further explore the complex neurocognitive correlates of metacognition.

Participants
A total of 117 nursing students (90 females; age range, 18-21 years) from Binzhou Medical University voluntarily participated in this study. All participants were healthy.
The exclusion criteria were brain injury, encephalitis, and psychiatric disorders. The aims and objectives of the study were introduced to each participant, and written consents from all participants were obtained prior to the test. The study was approved by the Ethics Committee of Binzhou Medical University.

Survey tools
A 24-item metacognitive ability scale was used [18], involving four factors: 4 metacognitive planning (seven items, including 7,9,16,17,18,21,24), metacognitive monitoring (six items, including 8,10,12,13,22,23), metacognitive regulating (six items, including 1,2,3,4,19,20), and metacognitive evaluating (five items, including 5,6,11,14,15). The response alternatives were on a five-point Likert scale (1, never; 2, seldom; 3, sometimes; 4, often; and 5, always). The total score range was from 24 to 120, with higher scores indicating better metacognitive ability. The Cronbach's alpha for the total score has been reported to be 0.93/0.87 for metacognitive planning, 0.83 for metacognitive monitoring, 0.85 for metacognitive regulating, and 0.79 for metacognitive evaluating. The content validity (experts) and construct validity (exploratory and confirmatory factor analyses) of the scale have been shown to be acceptable. The four factors explained 66.9% of the variance [18][19]. All participants were trained in order to fully understand the survey process and the meaning of the scale items. All questionnaires were issued and taken back on the spot, taking a class as a unit. There were 117 questionnaires returned, and all of them had complete data. Academic score referred to the sum of test scores for all subjects of the current semester.

Magnetic resonance spectroscopy
Magnetic resonance (MR) examinations were performed by a SIEMENS Skyra 3.0 T MR scanner with a standard quadrature head coil. A standard two-dimensional (2D) chemical-shift imaging point-resolved spectroscopy (CSI-PRESS) was used with the following parameters: TR, 1700 ms; TE, 135 ms; thickness, 15 mm; matrix, 160 mm × 160 mm; bandwidth, 1200 Hz; flip angle, 90; and average, 3. Axial, sagittal, and coronal T2 weighted imaging (T2WI) scans were acquired for locating. A rectangular volume of interest (VOI, A>>P 120 mm; R>>L, 150 mm; F>>H 15 mm) was placed to cover the precuneus and medial prefrontal lobe. MR spectra were observed from the bilateral precuneus and medial prefrontal cortex ( Fig. 1), with a voxel size of 10 mm × 10mm × 15mm. The voxel in the precuneus was selected in the front side of parietooccipital sulcus at the roof of the lateral ventricle level. The voxel in the prefrontal lobe was selected in the medial prefrontal cortex. The spectra were 5 analyzed using the Functool software package. Metabolite ratios, including N-acetyl aspartate/creatine plus phosphocreatine (NAA/Cr+PCr), phosphocholine plus glycerophosphocholine/creatine plus phosphocreatine (PC+GPC/Cr+PCr), and myo-inositol/creatine plus phosphocreatine (mI/Cr+PCr), were automatically calculated (Fig. 2).  Statistical methods 6 Statistical analysis was carried out using the Statistical Package for the Social Sciences (version 21.0). One-way ANOVA, pearson correlation analysis, and linear regression were utilized to describe the relationship between metacognitive scores, academic score, and metabolites ratios.

Results
Most students in the study population were female (76.9%; n = 90), and 23.1% were male (n = 27). The students' average age was 19. The Pearson correlation analysis with adjusted Bonferroni correction demonstrated a significant positive correlation between the total metacognitive score and academic score (p = 0.007; Table 1 and Fig. 3). Positive correlation was also observed between metacognitive evaluating score and academic score (Table 1)  Bonferroni correction: correlation is significant at the 0.05/5 level (2-tailed).

Discussion
Metacognitive ability is a powerful predictor of academic achievement [3,[20][21]. The results of this study are in agreement with results of previous studies. Significant positive correlation was found between metacognitive ability and academic score.
Self-monitoring of memory is necessary for successful learning and retention. It has been illustrated that metacognitive monitoring can be captured through Judgments of Learning (JOLs) [22]. Event-related potentials were used to compare neural correlates of JOLs and successful memory encoding. Therefore, ERP data indicate that JOLs do not reduce the encoding processes that predict the accuracy of memory judgments [23]. Previous findings reported that JOLs made during studying correlate with memory retrieval during test; however, this correlation is specific to recollection [24]. A previous study revealed that JOLs were accompanied by a positive slow wave over the medial frontal areas and a bilateral negative slow wave over occipital areas 10 [25]. A previous neuropsychological study indicated different processes for metacognitive and cognitive judgments in children by providing direct electrophysiological evidence of more negative slow wave over centroparietal areas [26]. The significant roles of the anterior prefrontal cortex in perceptual metacognition [7] and the precuneus in memory metacognition [8,10,[27][28] have been previously elucidated. The link between memory metacognitive efficiency and the precuneal gray matter density has been identified [10]. A similar relationship was discovered between mnemonic metacognitive efficiency and resting-state functional connectivity between the precuneus and medial anterior prefrontal cortex [12].
In this study, MRS measurement of the medial prefrontal cortex was not found to be related to metacognitive ability, which was not consistent with previous research.
The suggested explanation for this is that MR measurements of the medial prefrontal cortex were prone to artifact interference due to the anterior skull base and sinus.
However, some meaningful discoveries have been achieved in the precuneus.
Precuneus NAA/Cr+PCr ratios were correlated to metacognitive ability. Moreover, the correlation between precuneus NAA/Cr+PCr ratios and metacognitive ability was noted for the right precuneus, but not left precuneus. Further linear regression suggested that for every increase in the right precuneus NAA/Cr+PCr ratios, there is a predicted decrease in total metacognitive score. With regard to the relationship between the precuneus and metacognition, a possible circuit encompassing the precuneus and its mnemonic midbrain neighbor, the hippocampus, at the service of realizing our meta-awareness during memory recollection of episodic details has been presented [5]. NAA is commonly referred to as a neuronal marker, which is predominantly present in neurons [29]. NAA is a reasonably good surrogate marker of neuronal health in several neurologic and psychiatric disorders. Reduced NAA/Cr+PCr ratios have been manifested in Alzheimer's disease [16][17], which might reflect a loss of neuronal components and neuronal function disruption, or both [17]. However, this study reported negative correlations between the right precuneus NAA/Cr+PCr ratios and metacognitive ability. The suggested explanation for negative 11 correlations is that metacognitive activities may lead to increased oxygen consumption in the right precuneus, which then affects neuronal function.
There are several limitations to this present study. Participants in this study were mostly females and within a narrow age range. In addition, the MR spectra in this study were only recorded from the precuneus and medial prefrontal cortex. Further studies focusing on other regions, such as the anterior cingulate, are warranted.

Conclusion
In summary, cerebral metabolite levels are related to metacognitive ability. The right precuneal region plays an important role in metacognition and learning.