Introduction: Working memory (WM) refers to the temporary storage and manipulation of information. Short-term memory storage can be divided into separate subsystems for verbal information and visual information. We explored the capacity of visual WM in patients with temporal lobe glioma. Methods: In this study, we assessed 30 patients with temporal lobe glioma and 30 healthy controls (HCs) using a method that combined memory tests with visual WM tasks (digital span task, spatial capacity N-back task, and emotional N-back task). Results: The results revealed that groups did not differ in terms of demographics, estimated intelligence, and level of psyc distress. For visual WM tasks, statistically significant differences were not found on the 1-back tasks and forward versions of simple span tasks between the temporal patient (TP) group and the HC group. Analysis of correct responses of the experimental tasks suggested that the TP group was significantly different from the HC group in the 2-back tasks and backward versions of simple span tasks. For reaction times, spatial capacity 2-back task and emotional 2-back task showed the TP group was significantly different from the HC group. Conclusion: These findings revealed that visual WM scores of temporal glioma patients were lower than HCs, and hence, the temporal lobe may be a certain neuroanatomical structure in the WM network.

© 2022 The Author(s). Published by S. Karger AG, Basel

Introduction

Working memory (WM) is an important cognitive function that is frequently used in everyday life. It requires a complex interaction between different cognitive functions such as stimulus encoding, storage, retrieval, replacement, and manipulation [1]. In broad terms, models of WM can be differentiated by their emphasis on content material (e.g., verbal and visuospatial) versus constituent processes (e.g., updating and maintenance). With respect to content, previous behavioral, neuropsychological, and neuroimaging research has consistently indicated that WM can be separated into verbal and visuospatial stores which mainly subserve maintenance functions [2, 3]. Although the verbal storage system has been well characterized, the storage capacity of visual working memory (VWM) has not yet been established.

Neurobiological and neuroimaging findings over the last decades have conveyed the idea that WM might depend on specific anatomical structures. Neuroimaging studies to date have largely focused on the dorsolateral prefrontal cortex and parietal cortex, key regions involved in WM processing [4, 5]. Though a larger network of WM-related dysfunction including the anterior cingulate cortex and left frontal pole has also been proposed [6-8], evidence for local generators of WM theta oscillations in humans has been found in the occipital/parietal and temporal cortices and hippocampus using intracranial EEG [9]. A growing body of research indicates that the medial temporal lobe (MTL) is essential not only for long-term episodic memory but also for VWM [10-12]. Additional analyses suggested that the MTL per se was critical for accurate conjunction WM. They proposed that the MTL was critically involved in memory for conjunctions at both short and long delays [13]. Consequently, these studies have provided evidence that the temporal lobe contributes to WM processes.

However, there have been limited studies of a role for the temporal glioma in WM. Therefore, we are the first to attempt to explore the VWM in patients with temporal glioma in multiple dimensions. Our present study primarily investigates the influence of WM in a group of homogenous patients with a glioma relatively limited to the temporal lobe. In our study, we enrolled patients for evaluation within 1 week after seizure symptom onset because there is evidence that long-term epilepsy-impaired recognition is a component of the neuropsychological profile that is associated with epilepsy [14, 15].

In the present study, we simultaneously assessed WM in temporal patients (TPs) through VWM paradigms. Based on previous behavioral, functional, and anatomical data, we hypothesized that (1) the TP group would show deficits in VWM and (2) the temporal lobe may be a neuroanatomic structure in VWM.

Materials and MethodsParticipants

Thirty right-handed patients with a localized glioma that was limited to the temporal lobe (TP, N = 30) that were evaluated before operation and chemoradiotherapy in the Department of Neurosurgery, the First Affiliated Hospital of USTC, from September 2019 to March 2021 were considered for participation in the present study. Patients were excluded if they failed to recognize frank hemiplegia and suffered from language deficits, anosognosia, or motor limitations that could have affected their performance in the neuropsychological tasks in the present experiment. All patients were examined using MRI scans before the experiment. They were identified and contacted based on these imaging data.

Additionally, 30 right-handed healthy controls (HCs, N = 30) were matched with the patients for age, gender, education, and ethnicity. All participants had normal color vision and no previous or current neurological or psychiatric diseases.

Tasks (digital span task, spatial capacity N-back task, emotional N-back task, and neuropsychological assessment) were performed in a random order. Picture stimulus, questions, and instructions were programmed into E-Prime (version 2.0), which was presented on a regular PC or notebook. Every participant was instructed to perform several exercises before the tasks. Each participant was given 300 Chinese yuan (about $50) at the end of the experiment as financial compensation.

A professional neurosurgeon who was blinded to the study’s hypotheses and the neuropsychological data performed the anatomical classification based on acute or recent MRIs. This study was approved by the Ethics Committee of the hospital.

Experimental MeasuresNeuropsychological Examinations

All participants completed the Beijing version of the Montreal Cognitive Assessment (MoCA). The NEO-Five-Factor Inventory was used to assess general personality traits [16], and Raven’s Progressive Matrices [17] was applied to estimate basic intelligence. The Self-Rating Depression Scale (translated into Chinese) [18] was administered to obtain a measure of depressive symptoms for the participants.

WM Tests

The visual WM test battery included six VWM tests that encompassed three different task paradigms: simple digital span task, spatial capacity N-back task, and emotional N-back task.

Simple Digital Span Task

Simple span tasks are assumed to predominantly tap WM storage (Fig. 1a). In simple span tasks, lists of stimulus items with varying lengths are to be reproduced while maintaining the order of presentation. Both forward versions (repeating the list in the same order) and backward versions (repeating the list in the reverse order) have been used extensively in the literature, and they are part of common standardized neuropsychological and IQ tests. Within the verbal domain, the backward version is generally more difficult than its forward counterpart, while the pattern is somewhat less clear when it comes to visuospatial material.

Fig. 1.

a Simple digital span task. Response screens in the simple span tasks. b Spatial capacity N-back task. Schematic representation of the 1-back and 2-back conditions. c Emotional N-back task. Schematic representation of the 1-back and 2-back conditions.

For the simple span tasks used here, stimulus lists (digits) of unpredictable length were presented. At the end of each list, participants were required to report the items in the exact order in which they had been presented in the forward version of the task, while the items were to be reported in the reverse order in the backward version of the task. Each test included two initial practice trials that consisted of one three-item list and one four-item list. In case of error, the practice trials were repeated until the participant answered correctly or until the practice was presented three times. This practice was followed by an additional practice trial consisting of a list with nine items (longest list length) to demonstrate the range. None of the practice trials were included in the dependent measures. The actual tests included seven trials involving list lengths ranging from three to nine.

Spatial Capacity and Emotional N-Back Task

The N-back tests used here consisted of 1- and 2-back tasks. In the 1-back task, the participant was to respond whether the currently visible item was the same (target), or not (no target), as the previous item by pressing the N (target) and M (no target) keys on the computer keyboard. In the 2-back task, the participant was required to indicate whether the currently presented item was the same as the item that was presented two steps back.

Spatial squares were used as the major stimuli in spatial WM (Fig. 1b). There were two blocks, and each block was composed of 40 trials. Each trial sequence began with the presentation of a memory item for 1,500 ms. Then, a memory item was presented for 6,000 ms. Next, a test item was presented for 6,000 ms. If the spatial test stimulus was the “same” as the memory array stimuli, subjects were instructed to press “N,” otherwise, press “M.”

Emotional pictures were used as the major stimuli in object WM (Fig. 1c). Eight blocks were included, and each block comprised 40 trials. Each trial sequence began with the presentation of a fixation for 1,500 ms. Then, a memory item was presented for 6,000 ms. Next, a test item was presented for 6,000 ms. Subsequently, participants were instructed to press a button. If the test stimulus was the “same” as the memory array stimuli, subjects were instructed to press “N,” otherwise, press “M.”

Statistical Methods

All statistical analyses were performed using SPSS 23.0, and the level of significance was set at p = 0.05 after correction. We utilized the mean values (the standard deviations) that denoted the results that were normally distributed and used medians (P75-P25) to express the results that were not normally distributed. We compared demographic characteristics between groups using independent samples t-tests for continuous variables and χ2 tests for categorical variables.

ResultsParticipants Characteristics

A summary of participant characteristics is given in Table 1. In this study, 30 right-handed patients and healthy participants were enrolled. In the TP group, there were 15 males and 15 females, with an average age of 42.27 ± 6.31 years. In the HC group, there were 13 males and 17 females, with an average age of 41.57.1 ± 6.41 years. There was no significant difference between the two groups (p > 0.05). The majority of tumors were on the right side (17 patients); the average volume of tumors was 31.91 ± 9.87 cm3. Definite pathological diagnosis included glioblastoma (26.67%), astrocytoma (43.33%), oligodendroglioma (30.00%). 40% of patients had seizure history, and 46.67% of patients have taken antiepileptic drugs.

Table 1.

Clinical and demographic characteristics of the study groups

Neuropsychological Functioning

The independent samples t-tests revealed no significant difference between the groups with regard to MoCA scores (26.00 vs. 26.00), NEO Five-Factor Inventory (120.03 ± 9.46 vs. 118.27 ± 10.40), Raven’s Progressive Matrices (44.43 ± 3.17 vs. 45.37 ± 3.09), and Self-Rating Depression Scale (38.16 ± 5.86 vs. 39.40 ± 6.84). See Table 1.

WM TestsSimple Digital Span Task, Spatial Capacity N-Back Task, Emotional N-Back Task

The mean, standard deviations, independent samples t-test analysis of group differences in these tasks are reported in Table 2. Statistically significant differences were not found on the spatial capacity 1-back task (percent correct: 0.79 ± 0.10 vs. 0.80 ± 0.09; RT: 2,632.81 ms ± 443.29 vs. 2,447.12 ms ± 440.44), emotional 1-back task (percent correct: 0.83 ± 0.08 vs. 0.90 ± 0.06; RT: 2,993.27 ms ± 359.19 vs. 2,759.61 ms ± 339.04), and forward versions of simple span tasks (4.00 vs. 4.00). Analysis of correct responses of the experimental tasks demonstrated that TP group was significantly different from the HC group in the spatial capacity 2-back task (percent correct: 0.61 ± 0.05 vs. 0.86 ± 0.06), emotional 2-back task (percent correct: 0.62 ± 0.06 vs. 0.75 ± 0.08), and backward versions of simple span tasks (2.00 vs. 5.00). For reaction times, spatial capacity 2-back task (RT: 3,388.20 ms ± 680.23 vs. 2,351.35 ms ± 770.85) and emotional 2-back task (RT: 4,093.27 ms ± 772.22 vs. 2,992.95 ms ± 461.09) showed the TP group were significantly different from the HC group. See details in Table 2.

Table 2.

Behavioral data of span tasks, 1-back and 2-back conditions

Discussion

In this case-control study, we investigated the central neuroanatomic structure underlying VWM in TPs and healthy participants. We assessed VWM abilities with paradigms (simple digital span task, spatial capacity N-back task, emotional N-back task). The present study provides neuropsychological evidence of: (1) VWM being impaired in patients with a temporal lobe glioma when compared to a healthy group matched on sex, age, education, and ethnicity and (2) the temporal cortex may be a neuroanatomic structure in VWM.

WM is a capacity-limited short-term memory system that is engaged in the processing of currently active information [19]. The key role of WM in goal-directed behavior makes it a significant predictor of a number of skills and abilities ranging from fluid intelligence to language learning, mathematical skills, and academic achievement [20, 21]. Due to the critical role that WM plays in human behavior, considerable research effort has focused on describing its structure, that is, its cognitive building blocks and their interrelationships, in more detail. In contrast to some earlier studies, we included an extensive VWM test battery and a large and diverse adult sample. The present tasks represented typical hypothetical VWM processes: simple span tasks have been argued to primarily tap WM maintenance, complex span tasks have been considered to reflect both maintenance and manipulation [22], and running memory tasks as well as N-back tasks are thought to measure higher order WM processes, including updating and attention control [23]. In our study, TPs had significantly lower scores in the backward version of span tasks and 2-back tasks.

In accord with the presumed role of the temporal in subjective WM and previous neuroimaging studies that reported temporal activation during the observation and experience of WM tests, the temporal is typically related to WM. However, some studies have reported that the temporal may also be involved in processes of WM [24-26]. To date, these results do not yet provide causal evidence for the role of the temporal in VWM. We are the first to evaluate VWM in a comprehensive manner, wherein we observe lower scores in backward version of span task and significantly poorer performance on the 2-back tasks in those TPs. Thus, our results suggested that the damaged temporal impaired the VWM based on the VWM paradigms.

Limitation

One limitation of our study is the fact that some gliomas infiltrated the operculo-insula rather than purely the temporal cortex. Prominent subcortical fiber bundles, including the uncinate and the arcuate fascicle, connect to the fronto-orbital regions. Damage to the fronto-orbital regions or fiber might have impacted the performance on WM in some patients [27]. Furthermore, a larger sample size would have allowed for comparisons according to the particular location of the temporal cortex lesions (lateral anterior, lateral posterior vs. medial), which could be of special interest given the functional segregation within the temporal cortex revealed by functional imaging and intracerebral electrical stimulation studies [28, 29]. Finally, we did not explore the difference between WM in left temporal versus right temporal lesions, although a recent study suggests that patients with LTL glioma exhibited more memory impairments than RTL patients [30, 31].

Conclusion

By simultaneously measuring VWM paradigms in the homogenous, well-matched cohort of temporal glioma patients and demographically matched healthy volunteers, we confirmed previous results associating WM impairment with exposure to temporal damage. Finally, we could not identify obvious laterality effects on VWM and deficits in intelligence and personality in temporal lesions. Although the study does not provide mechanistic evidence and has limitations, these results are consistent with (1) temporal lobe glioma patients having impaired VWM and (2) the temporal lobe contributing to VWM processing. In the past few years, we have been attempting to better understand the neural basis of VWM. Identifying critical subcomponents and brain network interactions that are involved in WM contributes to understanding the generation of this multifaceted experience at the crucial intersection of human emotional and social behavior. Therefore, such studies may also guide the development of clinical and subclinical groups that are associated with deficient VWM ability, such as individuals with conduct disorder, autism spectrum disorder [32], and alexithymia [33]. Clinicians should recognize this important social disability, and appropriate counseling should be provided to guardians.

Acknowledgments

We are grateful to the participants involved in our study.

Statement of Ethics

This study protocol was reviewed and approved by the Ethics Committee of University of Science and Technology of China, approval number (2020048). All study participants provided written informed consent.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

Scientific research project of Anhui provincial health and Health Commission (No. AHWJ2021a004).

Author Contributions

Shengyuan Ni, Peng Chen, Yang Yang, and Dejun Bao contributed to the manuscript’s conception, design, preparation, conducting experiments, acquisition, analysis, and interpretation. Rui Zhang and Pang Qi made substantial contributions in drafting the manuscript and revising it critically for important intellectual content. All authors read and approved the final manuscript.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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