26 February 2012. Intensive cognitive training can aid neural and cognitive impairments found in schizophrenia, according to a study published on February 23 in Neuron. A team of researchers, led by Sophia Vinogradov of the University of California, San Francisco, found that 80 hours of computerized cognitive training improved reality monitoring (the ability to distinguish information generated internally from external experiences), increased medial prefrontal cortex (mPFC) activation, and the boost to mPFC activity was associated with improved social functioning six months later.
Although antipsychotics are useful in improving positive symptoms of schizophrenia, they have little effect on the cognitive deficits that most strongly predict functional outcome (Green et al., 2000). To improve cognition, many researchers are exploring non-pharmacological “cognitive remediation” strategies that seek to strengthen a person’s capacity to think. These approaches can improve cognitive functioning (McGurk et al., 2007) and induce changes in brain activity (Haut et al., 2010) in schizophrenia, and are the subject of a recent SRF Webinar that included a presentation by Vinogradov.
Detecting the internal versus the external
Reality monitoring is a higher-order cognitive process that depends, in part, on the activity of the mPFC (Frith and Frith, 1999). Individuals with schizophrenia have difficulty recognizing self-generated items during reality monitoring, and exhibit mPFC hypofunction, even when they can accurately identify the source of information (Vinogradov et al., 2008). Abnormal reality monitoring in the illness is associated with deficits in more basic cognitive components such as attention, memory, executive function, and social cognition, suggesting that tuning up these elementary aspects of cognition may improve higher-order processes such as reality monitoring (Fisher et al., 2008).
First author Karuna Subramaniam administered a baseline reality monitoring task during fMRI to 31 schizophrenia patients and 15 healthy controls. Prior to the task, subjects were presented with simple sentences (noun-verb-noun) in which the final noun was either created by the subject or provided by the experimenter. Once inside the scanner, the subjects were required to differentiate between the words they had provided (internally generated) from those given by the experimenter (externally generated).
Consistent with prior data, schizophrenia subjects exhibited impaired reality monitoring: they were significantly worse at identifying the source of the words than were healthy subjects. In addition, also similar to previous studies, while healthy controls exhibited greater mPFC activation during identification of self-generated words than those that were externally generated, this increase in mPFC activity was absent in schizophrenia subjects.
Restored reality and pumped-up PFC
The schizophrenia subjects were then randomly assigned to one of two groups who each received 80 hours of computer training over 16 weeks: one group received active cognitive training while the control condition played computer games. The active training comprised three modules, each focused on a different component cognitive process: auditory processing exercises for 10 weeks, visual processing exercises for six weeks, and emotion identification exercises throughout. All exercises became progressively harder as a subject’s performance improved.
After 16 weeks of this, both groups and the healthy controls performed the reality monitoring fMRI task a second time. Only the subjects who had received cognitive training improved their accuracy, correctly identifying the source of more words than at baseline. In contrast, neither the healthy controls nor the schizophrenia subjects who played computer games exhibited significant improvement, arguing that the improved reality monitoring was specific to those who received the targeted cognitive training.
Activation of the mPFC was also improved by cognitive training. Although healthy controls and the computer game-playing subjects did not exhibit differences in activation between the two scans, subjects who received cognitive training exhibited significantly more mPFC activity than at baseline.
Improved cognition and enhanced social functioning
Subramaniam and colleagues also tested all schizophrenia subjects on clinical and cognitive measures at baseline and after training. No change emerged in the Positive and Negative Syndrome Scale (PANSS) symptoms ratings between the two time points; however, consistent with prior results from the authors (see SRF related news story; Fisher et al., 2010), improvements in cognitive functioning were picked up. Active training subjects (but not those who played computer games) exhibited significant improvement on a test of delayed verbal memory recall from the Neuropsychological Test Battery relative to baseline. Importantly, delayed verbal memory recall performance was significantly correlated with both the accuracy of source word identification on the reality monitoring task, and with mPFC activity, only after active training. No such correlations were present in the subjects who played computer games. Active training also improved executive functioning, as measured by the Tower of London task, which probes planning skills, and reality monitoring performance after training was significantly correlated with Tower of London performance, but not at baseline. In contrast, no correlations were observed between mPFC activity and executive functioning.
But could these lab-based improvements generalize to real-world function? To explore this, the researchers also assessed social functioning of the schizophrenia subjects six months after training. The Social Functioning Subscale of the Quality of Life Scale revealed no change in social function between the groups. However, mPFC activity immediately after training was significantly correlated with ratings of social functioning six months after training, though this correlation was absent at baseline. These data suggest that cognitive training provided some improvement in patients’ functional outcome and quality of life, key outcomes of any successful cognitive remediation strategy.
The promise of cognitive training
The findings suggest, tantalizingly, that a non-pharmacological treatment can contribute to improvements in higher-order cognitive function, mPFC activity, and social functioning in schizophrenia. Worth noting is the fact that subjects did not receive training on the specific reality monitoring task on which they improved, indicating that they were able to generalize their training on specific cognitive components to the more complex task of reality monitoring. Moreover, the mean length of illness of the schizophrenia subjects included in this study was 19 years, demonstrating that cognitive improvements are possible in chronically ill patients with appropriate training.
Just how this cognitive training improved patients’ behavioral and neural functioning, and what specific components of the training were most beneficial, remains to be determined. In the meantime, the broader implications of this study offer hope and, as noted by the authors, suggest that “neural impairments in schizophrenia—and undoubtedly other neuropsychiatric illnesses—are not immutably fixed, but instead may be amenable to well-designed interventions that target restoration of neural system functioning.”—Allison A. Curley.
Subramaniam K, Luks TL, Fisher M, Simpson GV, Nagarajan S, Vinogradov S. Computerized Cognitive Training Restores Neural Activity within the Reality Monitoring Network in Schizophrenia. Neuron . 2012 Feb 23 ; 73(4):842-53. Abstract