Jon Simons – Exploring How the Brain Helps You Keep a Grip on Reality

During Gatherings of Members, it rarely takes long for people to start reminiscing about their time as undergraduates. Amusing (sometimes, bawdy) tales might be told about events that occurred many years in the past.

As a listener, you can find yourself transported back in time to your heady student days, re-living a fondly remembered episode as if it were playing out in front of you once again. Except, how do you know you were actually there when the event originally took place? How can you be sure you’re remembering a faithful representation of what happened, as opposed to a fictitious recollection of an event that might have been entirely imagined? In short, how do we determine whether our memories are real?

My research group has spent the last few years pondering these questions, seeking answers by undertaking experiments using cognitive neuroscience methods such as functional brain imaging of healthy volunteers and studies of neurological and psychiatric disorders, as well as of normal ageing. Our aim is to understand how the brain supports our capacity to distinguish what is real from what we imagined, an ability termed ‘reality monitoring’ that is vital for maintaining confidence in our memories, and in understanding ourselves as individuals with a past and a future. In characterising how these processes might be organised in the brain, we can better understand the way in which they may break down in disorders like schizophrenia, in which perceptions of reality can be altered. We can also improve our understanding of how our memories change as we get older, and why some people seem to be better than others at accurately recalling the past. This year, our work was recognised by the award of the Experimental Psychology Society Prize. The EPS, which was founded in Cambridge just after World War II, is one of the most venerable and respected learned societies in the field, and it is a great honour for our work to have been recognised by them.

Among the research methods used in my group is the brain imaging technique of functional MRI. This method provides the ability to observe changes in brain activity that occur when people undertake a cognitive task such as remembering the context in which a previous event was experienced. We have used the technique to isolate the brain regions that are involved when people try to remember whether an event was previously imagined or did actually take place. One brain area that has emerged as playing a key role in discriminating imagination from reality is the anterior prefrontal cortex. This is a region right at the front of the brain, just behind the forehead. It is an area that, in relative terms, is roughly twice as large in the human brain as in even our closest non-human cousins, the great apes. It is thought to be among the last areas fully to achieve myelination, the neurodevelopmental process that continues into adolescence and enables nerve cells to transmit information more rapidly, allowing for more complex cognitive abilities. As such, although the functions performed by this area are not well understood, they have generally been considered likely to be among the ‘higher’ levels of complex cognition in humans.

In the field of memory research, scientists who used functional MRI to identify the brain areas involved in remembering the context of previous events, previously found it difficult to characterise what role the anterior prefrontal cortex might play. Some studies reported activation there whereas others, equally well conducted and apparently very similar, failed to identify activity in that region. We hypothesised that the discrepancy between studies might be because the kinds of information participants were being asked to remember differed according to whether it had been generated by internal cognitive functions such as thought and imagination, or derived from the outside world by perceptual processes.

In the last few years, we have tested this hypothesis in several experiments. We have shown, for example, that activity in the anterior prefrontal cortex differentiates between stimuli that were previously seen or imagined. To demonstrate this, in one experiment we presented volunteers either with well-known word-pairs such as ‘Laurel and Hardy’ or with the first word of a word-pair and a question mark (‘Laurel and ?’). In the latter case, participants were instructed to imagine the second word of the word-pair. Later, we scanned participants’ brains while they tried
to remember whether they had seen or imagined the second word of each previously encountered word-pair. Several areas showed activity that could be related to general memory retrieval processes. But the region consistently to emerge across a number of similar experiments as contributing to the distinction between seen and imagined information has been the anterior prefrontal cortex.

One of the applications of this work has been to inform understanding of the cognitive dysfunction seen in clinical disorders, such as schizophrenia. Although schizophrenia can vary in its presentation, among the symptoms often observed are hallucinations, whereby patients report, for example, hearing voices when none are present. It has been suggested that these symptoms may result from a difficulty in discriminating between information that is perceived in the external world and information that is imagined. For example, a sufferer might imagine a voice conveying a message, but misattribute that voice as real, coming from another person.

We have tested a number of the predictions that arise from this suggestion. First, individuals with schizophrenia have been shown to be impaired on the kinds of seen rather than imagined memory tasks that elicit anterior prefrontal cortex activity. Second, the anterior prefrontal area we have identified overlaps closely with an area that tends to be functionally disrupted in schizophrenia. Finally, healthy volunteers who exhibit reduced levels of activity in this region tend to make more of the misattribution errors typically observed in schizophrenia, mistakenly endorsing imagined items as having been seen.

Very recently, we have extended these findings to try to explain the variability in reality monitoring performance that is typically seen even in apparently healthy individuals. Given the same task to distinguish seen from imagined words or objects, some people will score highly, correctly attributing 80 per cent or more to the correct source, whereas others will struggle to perform that well. We have recently uncovered preliminary evidence that this variability may be linked to the presence or absence of a particular brain structural folding pattern in the anterior prefrontal cortex, known as the paracingulate sulcus. This structural variation, which is present in roughly half of the normal population, is one of the last cortical folds to develop in utero and for this reason varies greatly in size between individuals in the healthy population. We have discovered that adults whose MRI scans indicate an absence of the paracingulate sulcus appear to demonstrate reduced reality monitoring ability compared with other participants. As all those who took part in the experiment were healthy adult volunteers with typical educational backgrounds and no reported history of cognitive difficulties, the observed differences in monitoring reality are particularly interesting to us.

Thus, although there is much work to do before we can claim to understand the functions supported by the anterior prefrontal cortex, evidence is mounting that one of its key roles may be to help us keep a firm grip on reality.