Clinically-Driven to Study Memory

Q&A with Muireann Irish

Clinical populations can provide a wealth of data to cognitive neuroscientists working to understand the brain. By seeing what happens in the brain of someone who has a cognitive disorder, researchers can better identify the fundamental underlying mechanisms. That is certainly true for memory research, where individuals with dementia and Alzheimer’s disease are providing critical information to scientists that could eventually translate to improving diagnosis and management of clinical disorders.

For Muireann Irish of the University of Sydney, a winner of the CNS 2019 Young Investigator Award, her study of dementia patients to better understand memory processes is very personal — beginning with when her grandmother was diagnosed with Alzheimer’s disease. Irish spoke with CNS about this experience, her work with clinical populations, and what she is looking forward to at CNS 2019 in San Francisco this March.

CNS: What first got you interested in neurodegenerative diseases and memory?

Irish: Memory has always been a source of fascination for me. As a child, I was known for my ability to recall the precise details of events and was often called upon to adjudicate during playground disputes or to remember who last did the washing up at home! My interest in memory was thrown into sharp relief, however, when my grandmother was diagnosed with Alzheimer’s disease. This was a formative experience as it impressed on me the frailty and vulnerability of memory and just how little we know about neurodegenerative disorders. I decided then that I wanted to study memory, to learn about how memory processes were disrupted in dementia, and hopefully contribute knowledge that might alleviate or help individuals affected by these devastating disorders.

CNS: Can you broadly describe what studies of patients with Alzheimer’s disease and dementia are telling us about memory and the brain? 

Irish: Some very exciting findings are emerging from the application of sophisticated neuroimaging techniques to understand how large-scale brain networks, such as the default mode network, are affected by the dementias. I find it quite amazing that the default mode network, which appears to support some of our most complex cognitive endeavours, appears to be most susceptible to pathology in Alzheimer’s disease. How changes in network connectivity relate to profiles of cognitive dysfunction and the underlying distribution of tau or amyloid pathology remains unclear, but the field is making significant strides in tackling these questions.

A common misconception about dementia in general is that there is a “loss” of the self, whereby the inability to retrieve memories from the past translates into a complete absence of self-concept. I find this misconception not only inaccurate but also quite damaging, as it has serious implications for how we interact and treat individuals living with dementia.

CNS: You had some recent research on mind wandering. Can you briefly describe how mind wandering is altered in dementia and the importance of that finding?

Irish: We recently finalized a study exploring spontaneous cognition in frontotemporal dementia, which is a younger-onset dementia that selectively targets the frontal and temporal cortices. Using our “Shapes Expectations” task, we found that frontotemporal dementia patients do not engage in mind wandering, but rather get “stuck” or captured by perceptual stimuli in their immediate surroundings. This profile of cognition bears striking overlap with their behavioral disturbances in everyday life, as these patients are commonly unable to disengage from the immediate sensorium to introspect or to consider the perspectives of others.

Our neuroimaging findings revealed an important role for the hippocampus in the generation of spontaneous internal thought, which parallels other lesion work recently published in this field. The next step is to determine the exact nature of the thoughts produced by these patients and, hopefully, use these findings to inform the clinical management and care of individuals affected by this disorder.

CNS: What do you find to be a common misconception about Alzheimer’s disease or dementia?

Irish: A common misconception about dementia in general is that there is a “loss” of the self, whereby the inability to retrieve memories from the past translates into a complete absence of self-concept. I find this misconception not only inaccurate but also quite damaging, as it has serious implications for how we interact and treat individuals living with dementia. We have recently posted a preprint of a review paper on this topic, outlining a new approach to thinking about and studying the self in dementia. The challenge is for us to overcome our preconceptions about what the patient “should” say and align our expectations with their experience. A great example of this is when my grandmother was moved into a care home and believed that she was back on the hospital wards working as a midwife. Rather than admonishing her for wandering the corridors, the care staff brought her on the morning rounds and let her serve morning tea, giving her a sense of purpose and tailoring her care to the epoch from which her memories were intact.

CNS: How about memory — what is a common misconception there?

Irish: A common misconception about memory is that it operates akin to a vast filing cabinet, enabling us to dip back to replay events or experiences in their entirety. As cognitive neuroscientists, however, we know that this is not accurate and that memory is reconstructive by nature. This means that we actively recreate or reconstruct experiences every time we remember, a finding that may account for the fallibility of memory and its susceptibility to distortion.

CNS: What do you most want people to understand about your work?

Irish: If people could take one point away from my work, it would be the importance of studying memory in clinical populations and the novel insights that this approach can yield. My work to date has revealed fascinating profiles of loss and sparing in the dementias, leading us to rethink the sharp distinction between the episodic and semantic memory systems. We need to consider interdependencies between episodic memory and semantic representations if we are to arrive at a comprehensive understanding of such processes as autobiographical memory and imagination.

CNS: What are the next steps for your work?

Irish: My research team is doing some really fantastic work investigating how processes such as scene construction, future thinking, and mind wandering are compromised in the dementias, using novel tasks and advanced neuroimaging techniques. We are exploring how compromised connectivity between the hippocampus and anterior/posterior brain networks potentially mediates distinct profiles of cognitive dysfunction across dementia syndromes and will soon launch some new studies looking at the contents of mind wandering in dementia. Some of my team members will be presenting posters at CNS 2019, so please make sure to find them and say hello!

CNS: What are you most looking forward to about the CNS meeting in San Francisco?

Irish: I’m really excited to meet everyone and hear all about the latest updates in the field, particularly given the strong emphasis on memory this year. The very first time I attended CNS was as a Ph.D. student in 2006 and the meeting was held in San Francisco so it feels apt that I will be returning there to receive the Young Investigator Award. I’m also looking forward to meeting some of my Twitter collaborators/colleagues in real life!

CNS: Is there anything else you would like to add?

Irish: I’d like to acknowledge the amazing support I have had since moving to Sydney and joining the FRONTIER research group, most notably from John Hodges and Olivier Piguet. I am also extremely lucky to have wonderful international collaborators including Donna Rose Addis and Jessica Andrews-Hanna, not to mention my brilliant students and research staff in the Memory and Imagination in Neurological Disorders (MIND) team. It’s a great feeling to look forward to going to work every day!

-Lisa M.P. Munoz