In recent years, growing research in brain sciences has suggested that cells in the brain connect together in networks to perform specific functions, and a disruption to some of these connections could alleviate conditions such as substance-use disorders, or alcohol addiction.
Now, clinical researchers at Sunnybrook think they have a living example to support this theory.
A patient case study with brain network mapping, reported by University of Toronto Psychiatry resident and lead author Dr. Saarah Haque and colleagues, was recently published in the journal Communications Medicine.
The findings from this study provide additional understanding of the causes of substance use disorders and could be helpful for developing new treatments in the future.
Sunnybrook cognitive neurologist and senior author of the paper, Dr. Matt Burke, provides for us a summary of his patient’s case, and helps us to make sense of what it could potentially mean for the direction of research and the treatment of chronic, debilitating, and otherwise “treatment-resistant” alcohol use disorder (AUD).
Dr. Matthew Burke, cognitive neurologist and associate scientist in the Hurvitz Brain Sciences Program at Sunnybrook.
Can you provide for us an overview of the events that led to this case study?
A few years ago, a 42-year-old Toronto woman with chronic AUD (since her early twenties), experienced a traumatic brain injury (TBI) as a result of falling down stairs while intoxicated. She struck her head and lost consciousness, with no memory of the incident.
While in intensive care, brain imaging showed bleeding in in the left frontal lobe of her brain.
A few weeks after her injury, I first met with this patient through my work at Sunnybrook’s Traumatic Brain Injury (TBI) Clinic. She reported a good recovery in many symptoms but still had some insomnia, mild short-term memory difficulties, and loss of smell and taste. Interestingly, she also independently reported a dramatic reduction in her cravings and interest in drinking alcohol – leading to her being abstinent from alcohol for the first time in years.
Keep in mind that before the incident, she didn’t respond well to any treatments. Previous attempts to reduce her alcohol consumption went unsuccessful, despite trying multiple approaches including psychosocial treatments – such as individual counselling and group supports, and pharmacological treatments – where she participated in clinical trials testing medications aimed at minimizing symptoms, such as cravings and a strong urge to drink. But they didn’t work for her.
So, this patient had tried a number of other treatments for her alcohol addiction – with little to no success – and was now suddenly showing signs of remission, after her fall?
That’s correct. You could say her addictive behaviour stopped becoming as much of a problem for her – in a way that was not seen before with clinical treatment.
At a one-year follow-up appointment, she had reported one relapse a few months after the TBI that was triggered by increased workplace stressors, in the context of the COVID pandemic.
After the relapse, she had successfully abstained from alcohol in the four months preceding her one-year follow-up appointment in our clinic (early remission), and she was discharged from the TBI clinic.
How did this incident lead to a research study?
We were obviously fascinated and very happy to learn about the relief she was experiencing from her addiction, albeit it was unfortunately in the context of a TBI with other consequences that can come with such an injury.
We were curious as to whether the damage to the specific brain region seen on the CT scan could be the reason for her marked reduction in cravings and interest in alcohol. In order to do so, we knew we would need to collaborate with previous colleagues at Harvard Medical School to map the brain region and see if it overlapped with regions/circuits previously implicated in remission from addiction.
What did you find?
We were able to trace a focal lesion – damage to tissue created when an object penetrates the skull and directly injures the area. In this case, the location of the lesion was in the orbitofrontal cortex – a part of the brain’s frontal lobe.
This is the same area that previous research in pre-clinical models and humans has been telling us plays a role in addictive behaviour – including the regulation of urges, compulsions, and reward decision-making processes.
We then looked to see what parts of the brain this lesion is connected to in a process called lesion network mapping. This map revealed that the lesion overlapped with previously identified circuits implicated in addiction remission.
What does this tell us?
This case study provides us with information that we normally would never be able to ethically do – in that you would never intentionally disrupt or create injury to one’s brain – for obvious reasons, unless there is very specific evidence indicating a measured controlled way for healthcare practitioners to do so that is proven to show therapeutic benefit with minimal risk.
An example of this includes some of the proven therapies offered in medicine and research for some other brain conditions, where non-invasive or minimally-invasive brain therapies have shown to carefully and precisely create either some form of connection disruption, or in some cases, produce a controlled lesion or “injury” to very specific parts deep within the brain to create a therapeutic effect.
In this case, this unintentional TBI appeared to somehow, by fluke, disrupt a brain connection in perhaps a specific way and/or in a critical spot, that contributes to, or is responsible for, this patient’s AUD.
To the best of our knowledge, there have been no published reports of focal lesions resulting in remission of isolated alcohol use disorder (without the use of more than one drug).
What is the take home message?
We describe a patient with longstanding alcohol use disorder who reported reduced cravings and stopped drinking alcohol following a traumatic brain injury that damaged part of her left frontal lobe.
We performed analyses on this damaged brain region and found that this area overlaps with previously-identified brain connections involved in substance use disorders.
Our findings provide additional understanding of the causes of substance use disorders and could be helpful for developing new treatment strategies.
How unusual is this case?
This is a fairly extraordinary situation. I would say there are probably a handful of other cases I have seen where patients report a paradoxical improvement of pre-existing symptoms (e.g. low mood) after a major head injury.
When I was previously working down at Harvard Medical School, I was involved in research that collected such rare lesion cases from the medical literature and combined them with brain network mapping – and they garnered unexpected media attention, probably in part due to the unusualness of these cases.
Does this mean a potential treatment for alcohol addiction? What are the next steps?
Not yet. But it does shine a new light in this area of research and highlights how changes to brain circuits may impact complex behaviours (the crux of neuropsychiatry).
Our findings suggest that potentially just disrupting this brain network could possibly facilitate remission, however, the intersection of brain injury and AUD is complicated and requires more study.
Importantly, we couldn’t control for other possible factors that could have been potential contributors to alcohol remission in our patient. This includes negative psychological associations with alcohol (given that the trauma occurred in the context of alcohol intoxication), less social interaction, the role of psychiatric factors, such as depression or post-traumatic stress disorder, or reduced exposure to triggers for alcohol use in the context of a recovery from TBI.
We therefore need to do more research and proceed with caution in further investigating any potential treatment looking to modulate the brain circuit implicated in our article.
