An important chemical in the brain’s memory region that enables us to censor unwanted thoughts has been pinpointed by a University of Cambridge study.
The finding helps scientists understand why people who suffer from disorders like depression, schizophrenia, post-traumatic stress disorder (PTSD), and anxiety often experience repeated intrusive thoughts when these circuits malfunction.
“Our ability to control our thoughts is fundamental to our wellbeing, When this capacity breaks down, it causes some of the most debilitating symptoms of psychiatric diseases: intrusive memories, images, hallucinations, ruminations, and pathological and persistent worries. These are all key symptoms of mental illnesses such as PTSD, schizophrenia, depression, and anxiety."
said Professor Michael Anderson from the Medical Research Council Cognition and Brain Sciences Unit at the University of Cambridge.
Play It Again, Sam
From time to time, we are confronted with reminders of unwanted thoughts — thoughts about unpleasant memories, images or worries. When this happens, the thought may be retrieved, making us think about it again even though we prefer not to.
Although being reminded in this way may not be a problem when our thoughts are positive, if the topic was unpleasant or traumatic, our thoughts may be very negative, worrying or ruminating about what happened, taking us back to the event.
[caption id=“attachment_92936” align=“aligncenter” width=“680”] Domain-specific modulation during thought and action suppression.
Credit: Taylor W. Schmitz, et al. CC-BY[/caption]
Professor Anderson compares our ability to intervene and stop ourselves retrieving particular memories and thoughts to stopping a physical action.
“We wouldn’t be able to survive without controlling our actions,” he says. “We have lots of quick reflexes that are often useful, but we sometimes need to control these actions and stop them from happening. There must be a similar mechanism for helping us stop unwanted thoughts from occurring."
Located at the front of the brain, the area known as the prefrontal cortex is known to play a key role in controlling our actions and has more recently been shown to play a similarly important role in stopping our thoughts. The prefrontal cortex acts as a master regulator, controlling other brain regions - the motor cortex for actions and the hippocampus for memories.
In their research, a team of scientists led by Dr Taylor Schmitz and Professor Anderson used a task known as the Think/No-Think procedure to identify a significant new brain process that enables the prefrontal cortex to successfully inhibit our thoughts.
In this task, participants learn to associate a series of words with a paired, but otherwise unconnected, word, for example ordeal/roach and moss/north. In the next stage, participants are asked to recall the associated word if the cue is green or to suppress it if the cue is red.
In other words, when shown ‘ordeal’ in red, they are asked to stare at the word but to stop themselves thinking about the associated thought ‘roach’.
[caption id=“attachment_92935” align=“aligncenter” width=“680”] Hippocampal GABA predicts DLPFC-Hippocampal connectivity during thought suppression.
a) Schematic of psychophysiological interaction analysis (PPI) with hippocampal (HIP) seed and conditions modulating HIP connectivity.
Significant PPI effects arose in right lateral prefrontal cortex: Brodmann’s area (BA) 46/9 (DLPFC) and BA45 (VLPFC), displayed as colored boundaries (see legend).
b) DLPFC activity during suppression (No-Think > Think) in the current (left) and in a prior study31 (right) overlapped with the PPI effects.
c) Functional connectivity: Suppression negatively modulated fronto-hippocampal coupling (PPI estimate, y axis), with the strength of negative coupling differing between low- and high-GABA subgroups (Independent samples t-test, *p < 0.05). Error bars represent standard error of the mean.
d) The six bidirectional dynamic causal models of the DLPFC–HIP network varied according to two parameters: Which Task modulated connectivity (horizontal lines: No-Think or Think) and source of Driving Input (Outer arrows: DLPFC, HIP, or BOTH).
e) Effective connectivity: for Low GABA participants, no clear evidence for a role of DLPFC in modulating connectivity emerged in any model.
For high hippocampal GABA participants, model evidence (exceedence probabilities) favored a model with inputs to DLPFC driving the network and the No-Think task modulating connectivity.
Credit: Taylor W. Schmitz, et al. CC-BY[/caption]
Using a combination of functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy, the researchers were able to observe what was happening within key regions of the brain as the participants tried to inhibit their thoughts. Spectroscopy allowed the researchers to measure brain chemistry, and not just brain activity, as is usually done in imaging studies.
Professor Anderson, Dr Schmitz and colleagues showed that the ability to inhibit unwanted thoughts relies on a neurotransmitter - a chemical within the brain that allows messages to pass between nerve cells - known as gamma-Aminobutyric acid (GABA). GABA is the main ‘inhibitory’ neurotransmitter in the brain, and its release by one nerve cell can suppress activity in other cells to which it is connected.
Anderson and colleagues discovered that GABA concentrations within the hippocampus - a key area of the brain involved in memory - predict people’s ability to block the retrieval process and prevent thoughts and memories from returning.
“What’s exciting about this is that now we’re getting very specific. Before, we could only say ‘this part of the brain acts on that part’, but now we can say which neurotransmitters are likely important - and as a result, infer the role of inhibitory neurons - in enabling us to stop unwanted thoughts.
Where previous research has focused on the prefrontal cortex - the command centre - we’ve shown that this is an incomplete picture. Inhibiting unwanted thoughts is as much about the cells within the hippocampus - the ‘boots on the ground’ that receive commands from the prefrontal cortex. If an army’s foot-soldiers are poorly equipped, then its commanders' orders cannot be implemented well,"
The researchers found that even within his sample of healthy young adults, people with less hippocampal GABA (less effective ‘foot-soldiers’) were less able to suppress hippocampal activity by the prefrontal cortex—and as a result much worse at inhibiting unwanted thoughts.
GABA In Schizophrenia
The discovery may answer one of the long-standing questions about schizophrenia. Research has shown that people affected by schizophrenia have ‘hyperactive’ hippocampi, which correlates with intrusive symptoms such as hallucinations.
Post-mortem studies have revealed that the inhibitory neurons (which use GABA) in the hippocampi of these individuals are compromised, possibly making it harder for the prefrontal cortex to regulate activity in this structure.
This suggests that the hippocampus is failing to inhibit errant thoughts and memories, which may be manifest as hallucinations.
According to Dr Schmitz,
“The environmental and genetic influences that give rise to hyperactivity in the hippocampus might underlie a range of disorders with intrusive thoughts as a common symptom."
In fact, studies have shown that elevated activity in the hippocampus is seen in a broad range of conditions such as PTSD, anxiety and chronic depression, all of which include a pathological inability to control thoughts - such as excessive worrying or rumination.
Although the study did not investigate any treatments, Professor Anderson believes it could offer a new approach to tackling intrusive thoughts in these disorders.
Taylor W. Schmitz, Marta M. Correia, Catarina S. Ferreira, Andrew P. Prescot & Michael C. Anderson Hippocampal GABA enables inhibitory control over unwanted thoughts Nature Communications 8, Article number: 1311 (2017) doi:10.1038/s41467-017-00956-z
Image: Jef Safi/Flickr