Brain Lesion Location Influences Addiction Behaviors

Jordan Grafman, PhD, professor of Physical Medicine and Rehabilitation and of Psychiatry and Behavioral Sciences, was a co-author of the study published in Nature Medicine.

Damage to particular regions of the brain may influence addiction behaviors, providing insight into potential therapeutic targets for substance use disorders, according to findings published in Nature Medicine.

“By examining whether damage to selected brain regions in humans can cause changes in addictive behaviors, we provided complementary and novel evidence about brain networks critically involved in addictive behaviors,” said Jordan Grafman, PhD, professor of Physical Medicine and Rehabilitation, of Psychiatry and Behavioral Sciences and a co-author of the study; Grafman also directs Brain Injury Research at Shirley Ryan AbilityLab.

Substance use disorders are considered a public health crisis in the US and internationally; Effective treatments are still needed, and rates of long-term remission remain poor. However, previous work had uncovered a potential link between damage to specific parts of the brain and repetitive addictive behaviors, specifically reward or pleasure-seeking behaviors.

In the current study, investigators studied two patient cohorts — 67 patients and 62 patients, respectively — who were active cigarette smokers at the time of having focal brain damage from either stroke or traumatic brain injury. They also studied 186 patients with penetrating traumatic brain injuries who experienced addiction to alcohol.

Some lesions associated with smoking addiction remission intersected the insula (a) but many others did not (b). Each slice represents a different patient and lesion locations are shown in red.

Patients’ CT and MRI brain scans were then used to create outlines of each lesion location, resulting in a total of 129 brain lesions due to stroke and 186 brain lesions due to penetrating traumatic brain injuries. Lesion locations were mapped to a brain atlas, and the brain network functionally connected to each lesion location was determined using human connectome data.

The investigators found that lesionsing smoking and alcohol addiction behaviors occurred in many different brain regions and were disrupted by a specific pattern of brain connectivity. Notably, positive connectivity was observed in the dorsal cingulate (cognition and motor control), lateral prefrontal cortex (cognition), and insula (sensory) regions. Negative connectivity was seen in the medial prefrontal and temporal cortex regions, which are involved in numerous cognitive functions and object recognition, among other functions.

Regions of the brain with similar connectivity profiles as seen in patients undergoing remission were the paracingulate gyrus (cognitive and affective regulation), the left frontal operculum (language) and the medial fronto-polar cortex (cognition).

The identified regions may serve as potential sites for targeted therapeutic interventions that could help remediate addictive behaviors, according to the authors.

“We have potential target sites for trying to reduce addictive behaviors and one potential approach is to combine behavioral and cognitive strategies that reduce addictive behaviors with non-invasive brain stimulation — techniques such as transcranial magnetic or electrical stimulation,” Grafman said.

Furthermore, identifying the precise roles of these regions within the identified brain network may highlight which parts of the neural circuits are key to modifying addictive behaviors, enabling more precise therapeutic targets using a neuromodulation strategy, according to Grafman.

This work was supported by the Academy of Finland (no. 295580), the Finnish Medical Foundation, the Instrumentarium Research Foundation, the Finnish Foundation for Alcohol Studies and Turku University Hospital (ERVA funds).

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