Schizophrenia is a mental disorder that affects 23 million people worldwide. The key features of schizophrenia include distortions in: sense of self, behavior, emotions, thinking, and perception. To date, research has been unable to identify a single factor causing schizophrenia.[1]
Mazes are useful for assessing cognition in schizophrenic patients. Cognition is not an easy thing to measure because there are so many aspects and processes intertwined.
Mazes offer an efficient and focused strategy for testing and measuring the many aspects of cognition. The cognitive skills which are most likely to be compromised in schizophrenic patients can be quantified through several maze solving tasks which are easy to administer.
The brain carries on many complex cognitive tasks during daily life, like planning, decision making, reasoning, and problem-solving. Collectively, these tasks are referred to as executive function. In schizophrenic patients, this collection of cognitive skills is weakened, leading to the disruption of daily activities and disorganized thinking.
In this article, we will take a look at what hand-drawn or two-dimensional maze-solving tasks have taught us about cognition in schizophrenic patients.
We will introduce the different types of mazes that are commonly used in research practice for assessing cognition in schizophrenia. Throughout the article, we will see what maze-solving has shown us about the characteristics of schizophrenia. Towards the end of the article, we will also take a special look at how maze-solving tasks have been used in clinical trials. Then, we will conclude by discussing the new directions happening in the realm of maze solving for conducting cognitive assessment in schizophrenic patients.
4 Commonly Used Mazes in Assessing Schizophrenia in Humans
As promised, we will begin this article by introducing the hand-drawn or two-dimensional mazes that are used for testing the neuropsychology of schizophrenic patients.
1. The Porteus Maze
The Porteus Maze is frequently used for assessing the cognitive abilities of schizophrenic patients. In order to perform well on the Porteus Maze, it is necessary to have: visuomotor coordination, perceptual organization, foresight and planning, as well as coordination and speed. All of these cognitive abilities are potentially compromised by schizophrenia.
The Porteus Maze Procedure
When completing the Porteus Maze, participants are expected to trace and complete a maze without crossing the maze lines, backtracking or going over the same path twice, or entering a dead-end or ‘blind alley’. If these requirements are at any point violated, the participants are given a new copy of the same maze to complete but for a reduced score.
The participants are expected to complete a certain number of mazes, all of which increase in difficulty as the test progresses.
Scoring and Measurements from the Porteus Maze
Maze difficulty is determined by the typical number of failed attempts encountered while completing that maze. The final measurement acquired is the total number of trials needed in order to complete the particular maze. Cognitive efficiency is also measured but by the number of seconds it takes to complete the task.
In the Porteus Maze, scores are calculated by adding up all the errors that have been performed. Errors include: touching lines of the maze, lifting the finger/pin, or cutting corners. Also, the time that it takes to complete the test is taken into account.[2]
A mental age is calculated as the main outcome of the participant’s performance. The ‘mental age’ is calculated by using two pre-established standard procedures for calculating the: test quota (TQ) and qualitative (Q) score.[3]
The Porteus Maze Can Measure Impulsivity
The Porteus Maze test was originally developed to measure intelligence. However, a few studies have also used it as a proxy of measuring impulsiveness, given the likelihood that intelligence and impulsivity are differentiated from each other. Using the Q score, it is possible to obtain a measure indicative of impulse control which can be used to distinguish different groups with regards to their impulsivity.[4]
Example of the Porteus Maze Test for Assessing Cognition of Schizophrenic Patients
Below is an example of how the Porteus Maze test is administered in schizophrenic patients and what it can reveal about their cognitive abilities.
In an experiment by Lis et al., 25 schizophrenic patients who were treated with atypical antipsychotic agents were matched to 25 healthy controls based on education, age, and sex.
The participants were expected to solve a series of mazes on a computer. (Increasingly, cognitive research using the Porteus Maze is using an electronic adaptation of it that can be completed on the computer, instead of using the traditional paper and pencil approach.)
There were two experimental conditions:
- In one scenario, the participants could see the trail they left behind as they progressed through the maze, essentially providing feedback with what route they have covered in that trial (as is the case in the traditional pencil-and-paper approach). This was the low-demand condition.
- In a different condition, the cursor did not leave any trail behind (but that information was available to the researcher). So, in the second condition, the participant was completing the maze with the cursor and the maze remained blank, without any trails, challenging the participant to complete the maze without any feedback. This was considered to be the high-demand condition.
The results revealed that:
- Healthy controls performed equally well in the low-demand and high-demand tasks, proving they were uninfluenced by the experimental condition and that normal cognition does not need feedback (visual reference from the moving cursor) in order to complete the task.
- In the low-demand condition, where the trail/trace or the cursor was visible, the schizophrenic patients performed similarly to healthy controls but at the expense of increased time demands.
- Thus, it may be possible for schizophrenic patients to be successful in performing executive functions, granted that they are subjected to lower demands of maintenance tasks.[5]
2. NAB Maze Tests
The Neuropsychological Assessment Battery (NAB) is a collection of tests that measure different types of higher cognition including executive functions, language, and spatial abilities using multiple modules. The NAB Maze Tests have been traditionally administered as one of the tests in the NAB Executive Functions Module.[6]
NAB Maze Tests are currently available as independent assessments, too.[7][8] Thus, researchers are now able to only use NAB Maze Tests for assessing executive functions, if they want to, instead of having to administer the entire NAB.
NAB Maze Test Features
The NAB Maze Tests:
- Quickly measure and assess a participant’s organizational and planning skills, as well as their foresight abilities.
- Are sensitive to the executive function impairments created by frontal lobe dysfunction or lesions.
- Consists of seven mazes which progressively increase in difficulty. Scores are based on maze completeness and completion time.
- Come with a detailed Record Form which guides the researcher through the procedure, including ways to make the test quick and efficient, as well as instructions on scoring.
- Contain equivalent parallel forms, ultimately allowing for easy retesting.
- Are specially designed to avoid ceiling and floor effects which are potential confounds that exist in many maze tests.
NAB Mazes and the MATRICS MCCB
NAB Mazes, as mentioned previously, traditionally are a part of a neuropsychological test battery. Recently, the NAB Mazes have been included in a different test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Project. The battery developed by the MATRICS project is called the MATRICS Consensus Cognitive Battery (MCCB) to assess cognition in schizophrenic patients.[9]
The MCCB is a collection of tests carefully selected to test cognition specifically in schizophrenic patients. Domains that the MCCB covers include: verbal learning, processing speed, visual learning, social cognition, working memory, attention/vigilance, and problem-solving/reasoning. NAB Mazes are used to quantify the problem-solving and reasoning domain.[10]
The MCCB has been approved by the Food & Drug Administration (FDA) for use in clinical trials to assess cognitive improvement in schizophrenic patients.
NAB Mazes Findings on Schizophrenic Cognition
Below is a summary of findings that have been established as a result of using the NAB Mazes portion of the MCCB:
- Age matters. Depending on how old a schizophrenic patient is or their age of disease onset, different performances in the reasoning/problem-solving are bound to be observed. Older schizophrenics have less effective problem-solving in the NAB Mazes. However, a younger age of onset is associated with better NAB Maze problem-solving. Furthermore, the longer the disease duration, the worse the performance when completing the NAB Mazes.[11]
- Lurasidone and ziprasidone. Composite scores do not always tell the whole story. Drugs like lurasidone and ziprasidone are being tested for their efficacy in managing schizophrenic symptoms. However, these two drugs do not significantly change the MCCB composite score. But, these drugs affect different realms of cognition. Looking at the sub-scales, for example, patients that are treated with ziprasidone are likely to show improvement in their reasoning and problem-solving skills in the NAB maze test, while those that take lurasidone do not.[12]
- Pregnenolone. Pregnenolone is another drug that is being assessed for its potential to improve schizophrenic symptoms. Although it does not improve the composite MCCB score, it has been found to specifically improve the problem-solving and reasoning subscale measured by NAB Mazes.[13]
- Cognitive training may improve schizophrenic symptoms. Recent directions in research have shown that cognitive training or remediation may be a promising solution in alleviating schizophrenic symptoms. A randomized controlled trial by Mendella et al. demonstrated that after 12-weeks of Compensatory Cognitive Training (CCT), schizophrenia patients have a significantly improved MCCB score when compared to the Treatment as Usual group. The significant improvement in the MCCB had a non-significant but medium effect in the improvement in the reasoning and problem-solving subscale as measured by the NAB Mazes test.[14]
3. Groton Maze Learning Test
Another type of maze that’s used to assess cognition in schizophrenic patients is the Groton Maze Learning Test (GMLT). The GMLT measures spatial problem-solving and error monitoring cognition. This maze is a computerized form of the Milner Stylus and the Austin Maze.
The GMLT is commonly used as a part of an early phase battery by major global pharmaceutical companies and academic researchers when investigating the potential of new nutraceutical or pharmaceutical compounds in phase I studies on improving schizophrenic symptoms.[15]
The GMLT task essentially involves finding and navigating through a hidden maze. Such a task requires many cognitive processes, in order to be completed successfully, including:
- Visuomotor processing speed
- Various aspects of executive function, like decision-making
- Error monitoring
- Attention
The GMLT Procedure
In order to complete the maze successfully, individuals must employ trial and error learning. These are the features of the GMLT procedure:
- There is a hidden 28-step pathway located under a 10 x 10 matrix of tiles.
- In successive trials, participants are expected to find the same pathway.
- Correct tile selections are indicated with a ‘check mark’ while incorrect selections are signaled with a cross.
- Only the participant’s current location in the pathway is visible.
- Upon finding the entire pathway, the participant must repeatedly complete the same pathway for an additional four trials.
- The GMLT can be modified so that the pathways which are generated across different assessments are either constant (i.e., the same) or random. By having these two conditions, the effect of practice can be measured through the constant-pathway condition.[16]
The participants are given a set of rules to adhere to when completing this task:
- Only one tile can be moved at a time
- Moving diagonally is prohibited
- If they select an incorrect tile, they must return to the last correct location.
In the next sections, we will see how the GMLT is involved in research with schizophrenic patients.
GLMT and the CogState Schizophrenia Battery
The CogState schizophrenia battery is a collection of tests that can assess all of the cognitive domains as suggested by the MATRICS group.[17] This battery is frequently seen in research with schizophrenic patients and is used as an alternative to the MCCB battery (mentioned previously).
The CogState has been used by a number of leading pharmaceutical companies, including GlaxoSmithKline, Abbott, Bristol-Myers Squibb, Johnson & Johnson, and Pfizer Inc.[15]
GMLT Findings on Schizophrenic Cognition
- Schizophrenic patients have significant impairments in the GMLT task. Schizophrenic patients have significantly lower performance in the GMLT than healthy normal controls. Compared to matched controls, schizophrenic patients are significantly more impaired in the following GMLT measures: chase task, rule break errors, perseverative errors, total time, total errors, and efficiency.[18]
- Antipsychotic medication improves GMLT performance. A study by Snyder et al. showed that one month of antipsychotic treatment is associated with significant improvement in the change of performance in the GMLT when compared with healthy normal controls. Schizophrenic patients will improve across the majority of GMLT domains. The greatest magnitude and improvement occur for the rule break, perseverative and total errors. Moderate, but significant, improvement is seen for total time and efficiency. A small improvement in the chase task performance and legal errors is seen after 30 days of antipsychotic treatment.[18]
- Ketamine psychosis may be related to schizophrenia. Spatial problem-solving performance varies with ketamine use. Patients with ketamine associated persisting psychosis perform at the level of schizophrenic patients when solving the GMLT. Also, individuals with ketamine associated persisting psychosis perform worse than patients that are non-psychotic ketamine users. This suggests that there may be a relationship between the way cognition (especially spatial reasoning) is compromised in psychosis and schizophrenia.[20]
- GMLT performance improves in schizophrenic patients taking TC-5619. Alpha7 nicotinic receptor partial agonist (TC-5619) acts on a neural nicotinic acetylcholine receptor subtype. When given TC-5619, schizophrenic patients’ cognitive dysfunction will improve. Executive function, as measured by the GMLT, statistically improves as a result of this drug.[20]
- D-Amphetamine improves executive function in schizophrenic patients. When schizophrenic patients are given D-amphetamine and tested with the constant form of the GMLT, no improvement is observable. However, when they are subjected to the random-form, they show significant improvements in GMLT performance after being given D-amphetamine.[16]
4. WISC-R and WISC-III Mazes
One of the classic forms of intelligence tests for adults is the Wechsler Adult Intelligence Scale (WAIS). The equivalent test that is given to children specifically is the Wechsler Intelligence Scale for Children (WISC) of which the WISC-R and WISC-III are two modified versions published in 1974 and 1991, respectively. However, a subscale of the WISC-R and WISC-III, the WISC-R Mazes Test, is given to adults as a supplementary cognitive assessment since the traditional WAIS does not feature a maze test.[21]
The WISC-R and WISC-III Mazes have been around for a few decades, thus they are more likely than NAB Mazes to be used in international research since there are multilingual translations of the test available.
- Schizophrenic patients perform significantly worse on the WISC-R Maze. When compared to normal controls, schizophrenics score significantly lower on the WISC-R Maze Test. While healthy controls are expected to score approximately 11.5, schizophrenic patients score 7.5.[22]
- Clozapine improves WISC-R Maze performance in schizophrenic patients. A noteworthy study by Hagger et al. showed that after 6 months of treatment with clozapine schizophrenic patients improve in many cognitive measures, including the WISC-R Maze Test.[22]
- Sarcosine improves reasoning and problem-solving in schizophrenic patients. A randomized, double-blind, placebo-controlled clinical trial run by Lin et al. in 2015 showed that sarcosine administration can improve reasoning and problem-solving in schizophrenic patients as measured by the WISC-III after 12-weeks of 2 g/day treatments.[23]
- Risperidone alleviates schizophrenic cognitive symptoms. Risperidone, typically given at 2.2 mg/day, can improve cognitive symptoms in schizophrenic patients. In fact, it has been shown that 6-months of treatment significantly impact reasoning and problem-solving and leads to better performance on the WISC-R Mazes Test.[24]
New Directions
Mazes are an efficient way to measure cognition in schizophrenic patients. Increasingly, new mazes and variations are developing in order to have even more methods that can assess different aspects of cognition.
For example, a study by Bertholet et al. adapted the traditional Radial Arm Maze as it is used in rodents in order to be suitable for humans. Their modifications led to four different versions of the maze:
- Fingertip texture-groove maze
- Tactile screen maze
- Virtual radial maze
- Walking size maze
These mazes employ distal and local relational cues and can measure spatial short-term and long-term memory.
Such a variety of mazes and scale, from small to life-size, allow for flexibility to accommodate different participants and research hypotheses.[25]
Conclusion
Schizophrenia is an ailment that places a heavy burden on the individual (and also the economy).[26] In fact, experts and researchers recommend therapeutic solutions to move in the direction of cognitive functioning improvement, not just symptom management.[26]
In the development of effective therapies, pharmaceutical, and nutraceutical solutions, maze solving tasks play a key role. With maze solving tasks, it is possible to measure and quantify several subtle aspects of cognition pre- and post-intervention.
In this article, we covered the top mazes used in assessing executive and cognitive function in schizophrenia, but there will be more mazes developed for this purpose in the future.
References
- World Health Organization. (2018). Schizophrenia [Fact sheet]. Retrieved from https://www.who.int/en/news-room/fact-sheets/detail/schizophrenia
- Butcher, James N., Spielberge, John Charles D. . A Theory of Justice.Advances in Personality Assessment. Lawrence Erlbaum. 1992. ISBN 9780805812268.
- Ayers, Susan; Baum, Andrew; Newman, Stanton; Wallston, Kenneth; Weinman, John; West, Robert (23 August 2007). Cambridge Handbook of Psychology, Health and Medicine. Cambridge University Press. ISBN 978-1-139-46526-7.
- Leshem, Rotem, and Joseph Glicksohn. “The construct of impulsivity revisited.” Personality and individual Differences 43.4 (2007): 681-691.
- Lis, Stefanie, et al. “Feedback about previous action improves executive functioning in schizophrenia: An analysis of maze solving behaviour.” Schizophrenia research 78.2-3 (2005): 243-250.
- “NAB Neuropsychological Assessment Battery (NAB)” Hogrefe, https://www.hogrefe.co.uk/shop/neuropsychological-assessment-battery-nab-writing-test.html.
- “NAB – Neuropsychological Assessment Battery – Mazes Test.” Psychology Resource Centre, 9 Oct. 2018, https://psycentre.apps01.yorku.ca/wp/nab-neuropsychological-assessment-battery-mazes-test/.
- “NAB Mazes Test.” Ann Arbor Publishers Limited – Suppliers of Testing Resources, https://www.annarbor.co.uk/index.php?main_page=index&cPath=416_249_334.
- Keefe, Richard SE, et al. “Characteristics of the MATRICS Consensus Cognitive Battery in a 29-site antipsychotic schizophrenia clinical trial.” Schizophrenia Research 125.2-3 (2011): 161-168.
- Nuechterlein, Keith H., et al. “The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity.” American Journal of Psychiatry 165.2 (2008): 203-213.
- Linke, Magdalena, et al. “Age or age at onset? Which of them really matters for neuro and social cognition in schizophrenia?.” Psychiatry research 225.1-2 (2015): 197-201.
- Harvey, Philip D., et al. “Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone.” Schizophrenia research 127.1-3 (2011): 188-194.
- Marx, Christine E., et al. “Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia.” Psychopharmacology 231.17 (2014): 3647-3662.
- Mendella, Paul D., et al. “Compensatory cognitive training for people with first-episode schizophrenia: results from a pilot randomized controlled trial.” Schizophrenia research 162.1-3 (2015): 108-111.
- Pietrzak, Robert H., et al. “An examination of the construct validity and factor structure of the Groton Maze Learning Test, a new measure of spatial working memory, learning efficiency, and error monitoring.” Archives of Clinical Neuropsychology 23.4 (2008): 433-445.
- Pietrzak, Robert H., Peter J. Snyder, and Paul Maruff. “Amphetamine-related improvement in executive function in patients with chronic schizophrenia is modulated by practice effects.” Schizophrenia research 124.1-3 (2010): 176-182.
- Pietrzak, Robert H., et al. “A comparison of the CogState Schizophrenia Battery and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery in assessing cognitive impairment in chronic schizophrenia.” Journal of clinical and experimental neuropsychology 31.7 (2009): 848-859.
- Snyder, Peter J., et al. “Spatial working memory and problem solving in schizophrenia: the effect of symptom stabilization with atypical antipsychotic medication.” Psychiatry Research 160.3 (2008): 316-326.
- Cheng, Wan-Ju, et al. “Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia.” Schizophrenia research 199 (2018): 313-318.
- Lieberman, Jeffrey A., et al. “A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia.” Neuropsychopharmacology 38.6 (2013): 968.
- Gass, Carlton S., Jane Ansley, and Sherry Boyette. “Emotional correlates of fluency test and maze performance.” Journal of Clinical Psychology 50.4 (1994): 586-590.
- Hagger, Corinne, et al. “Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine.” Biological psychiatry 34.10 (1993): 702-712.
- Lin, Chun-Yuan, et al. “Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial.” The World Journal of Biological Psychiatry 18.5 (2017): 357-368.
- Chua, L., et al. “The effect of risperidone on cognitive functioning in a sample of Asian patients with schizophrenia in Singapore.” Singapore medical journal 42.6 (2001): 243-246.
- Bertholet, Léa, et al. “Spatial radial maze procedures and setups to dissociate local and distal relational spatial frameworks in humans.” Journal of neuroscience methods 253 (2015): 126-141.
- Cloutier, Martin, et al. “The economic burden of schizophrenia in the United States in 2013.” The Journal of clinical psychiatry 77.6 (2016): 764-771.