A study by UCLA psychologists provides strong evidence that a certain region of the brain plays a critical role in memory recall.
The research, published in the Journal of Cognitive Neuroscience, also shows for the first time that using an electrical current to stimulate that region, the left rostrolateral prefrontal cortex, improves people’s ability to retrieve memories.
“We found dramatically improved memory performance when we increased the excitability of this region,” said Jesse Rissman, a UCLA assistant professor of psychology, and of psychiatry and biobehavioral sciences, the study’s senior author.
The left rostrolateral prefrontal cortex is important for high-level thought, including monitoring and integrating information processed in other areas of the brain, Rissman said.
This area is located behind the left side of the forehead, between the eyebrow and the hairline.
“We think this brain area is particularly important in accessing knowledge that you formed in the past and in making decisions about it,” said Rissman, who also is a member of the UCLA Brain Research Institute.
The psychologists conducted experiments with three groups of people whose average age was 20. Each group contained 13 women and 11 men.
Participants were shown a series of 80 words on a computer screen.
For each word, participants were instructed to either imagine either themselves or another person interacting with the word, depending on whether the words “self” or “other” also appeared on the screen.
(For example, the combination of “gold” and “other” might prompt them to imagine a friend with a gold necklace.)
The following day, the participants returned to the laboratory for three tests – one of their memory, one of their reasoning ability and one of their visual perception.
Each participant wore a device that sent a weak electrical current through an electrode on the scalp to decrease or increase the excitability of neurons in the left rostrolateral prefrontal cortex.
Increasing their excitability makes neurons more likely to fire, which enhances the connections between neurons, Rissman said.
(The technique, called transcranial direct current stimulation, or tDCS, gives most people a warm, mild tingling sensation for the first few minutes, said the study’s lead author, Andrew Westphal, who conducted the study as a UCLA doctoral student and is now a postdoctoral scholar in neurology at UC San Francisco.)
For the first half of the hour-long study, all participants received “sham” stimulation – meaning that the device was turned on just briefly, to give the sensation that something was happening, but then turned off so that no electrical stimulation was applied.
This allowed the researchers to measure how well each participant performed the tasks under normal conditions.
For the next 30 minutes, one group of participants received an electrical current that increased their neurons’ excitability, the second group received current that suppressed neuron activity and the third group received only the sham stimulation.
The researchers analyzed which group had the best recall of the words they saw the previous day.
First, the scientists noted that there were no differences among the three groups during the first half of the study – when no brain stimulation was used – so any differences in the second half of the experiment could be attributed to the stimulation, Westphal said.
Memory scores for the group whose neurons received excitatory stimulation during the second half of the study were 15.4 percentage points higher than their scores when they received the sham stimulation.
Scores for those who received fake stimulation during both sessions increased by only 2.6 percentage points from the first to the second session – a statistically insignificant change that was likely was due to their increased familiarity with the task, according to the paper.
And scores for the group whose neuron activity was temporarily suppressed increased by just five percentage points, which the authors also wrote was not statistically significant.
“Our previous neuroimaging studies showed the left rostrolateral prefrontal cortex is highly engaged during memory retrieval,” Rissman said.
“Now the fact that people do better on this memory task when we excite this region with electrical stimulation provides causal evidence that it contributes to the act of memory retrieval.
“We didn’t expect the application of weak electrical brain stimulation would magically make their memories perfect, but the fact that their performance increased as much as it did is surprising and it’s an encouraging sign that this method could potentially be used to boost people’s memories.”
The study’s reasoning task asked participants to decide in seven seconds whether certain pairs of words were analogies. Half of the trials featured word pairs that were true analogies, such as “‘moat’ is to ‘castle’ as ‘firewall’ is to ‘computer.'” (In both pairs, the first word protects the second from invasion.)
The other half had word pairs that were related but not actually analogous.
Researchers found no significant differences in performance among the three groups.
For the final task, focusing on perception, subjects were asked to select which of four words has the most straight lines in its printed form.
(One example: Among the words “symbol,” “museum,” “painter” and “energy,” the word “museum” has the most straight lines.)
Again, the researchers found no significant differences among the three groups – which Rissman said was expected.
“We expected to find improvement in memory, and we did,” Rissman said.
“We also predicted the reasoning task might improve with the increased excitability, and it did not.
We didn’t think this brain region would be important for the perception task.”
Why do people forget names and other words? Sometimes it’s because they don’t pay attention when they first hear or see it, so no memory is even formed.
In those cases, the electrical stimulation wouldn’t help. But in cases where a memory does form but is difficult to retrieve, the stimulation could help access it.
“The stimulation is helping people to access memories that they might otherwise have reported as forgotten,” Westphal said.
Although tDCS devices are commercially available, Rissman advises against anyone trying it outside of supervised research.
“The science is still in an early stage,” he said. “If you do this at home, you could stimulate your brain in a way that is unsafe, with too much current or for too long.”
Rissman said other areas of the brain also play important roles in retrieving memories. Their future research will aim to better understand the contributions of each region, as well as the effects of brain stimulation on other kinds of memory tasks.
The human frontal cortex is often thought to be organized as a hierarchy, ranging from caudal motor areas, via caudal prefrontal areas involved in higher-order control processes, to the most rostral areas involved in the most abstract levels of control , .
The anterior part of the prefrontal cortex sits at the top of this cortical hierarchy.
It is often activated in tasks requiring the integration of outcomes of separate cognitive operations, especially when dealing with information outside direct environmental demands .
Anterior prefrontal cortex’s functional interactions can reflect upcoming rather than current task demands .
However, although there has been substantial progress in the understanding of anterior prefrontal function, little is known about its anatomy.
This is partly due to a lack of data from comparable regions in experimental animals.
Recordings in the most anterior part of the cortex in the macaque monkey have been sparse and have yielded results that differ substantially from what was predicted based on human neuroimaging studies , leading some authors to suggest that part of the human anterior prefrontal cortex might be uniquely human .
To investigate the organization of the human frontal lobe, a number of recent studies used diffusion MRI to parcellate this part of the cortex based on structural connections to the rest of the brain.
Areas identified this way often are highly similar to those identified using traditional cytoarchitectonic methods .
A study by Neubert and colleagues revealed an area of the anterior prefrontal cortex located between the traditional area 10 and dorsolateral prefrontal cortex area 46, which was labeled lateral frontal pole (FPl) . Although its connectivity fingerprint was similar to that of area 46, the two areas differed in their connectivity with medial frontal and inferior parietal cortex.
The lateral part was similar in location and had a similar connectivity profile to FPl. Importantly, Neubert and colleagues compared each human frontal area to areas in the macaque monkey.
In a separate line of research, Bunge and colleagues reported an area of the left rostrolateral prefrontal cortex that is involved specifically in processing higher-order relations between mental representations .
This type of information processing goes beyond the learning of visuospatial, temporal, or semantic relationships that are first-order in nature, defining relations between relations. In a series of studies, they ruled out that activation of this part of prefrontal cortex was due to task difficulty and demonstrated its involvement across different paradigms , .
Recently, Vendetti and Bunge  integrated these two research lines, suggesting that the lateral frontal pole identified by Neubert and colleagues is the same region that was activated during relational processing.
Non-human primates can solve the kind of tasks used in humans to probe processing of higher-order relations, but might do so using alternative, often much less efficient strategies .
This suggests the presence of specializations for this type of information processing in the human lineage, possibly involving FPl.
Consistent with this suggestion, integrating different domains of knowledge or abstracting away from familiar items to apply their rules to novel stimuli has been suggested to emerge only late in the human lineage .
Here we tested two suggestions originating from this idea.
First, we aimed to test whether the region identified by Bunge and colleagues on functional grounds is indeed the same as the region Neubert and colleagues identified on anatomical grounds. We used the paradigm developed by Bunge and colleagues  identifying the lateral prefrontal locus for relational integration to localize this region in our participants (Fig. 1, left panel).
Using resting state functional MRI we investigated the similarity in whole-brain functional connectivity of regions identified in the relational processing task with that of FPl and related regions, testing the hypothesis that the functional connectivity of FPl most closely matches that of the relational integration area (Fig. 1, right panel).
Using diffusion MRI-based tractography we then determined the pattern of connections of the reported regions with the main association fibers of the brain and compared them with the patterns of different anterior prefrontal regions, again testing whether the pattern of FPl most closely matches the relational integration region (Fig. 1, right panel).
Second, we reasoned that if this region’s role in indeed characterized by the processing of higher-order relations we would expect this to be domain-general.
Therefore, we also tested a variant of the relational integration paradigm using different stimuli, testing whether FPl is involved independent of the types of stimuli.
Together, this project thus tested the anatomical area involved in processing higher-order relations and its domain-generality.
More information: Andrew J. Westphal et al. Anodal Transcranial Direct Current Stimulation to the Left Rostrolateral Prefrontal Cortex Selectively Improves Source Memory Retrieval, Journal of Cognitive Neuroscience(2019). DOI: 10.1162/jocn_a_01421
Journal information: Journal of Cognitive Neuroscience
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