A study in teenagers showed the "reward hub", which is involved in addiction, was larger in regular players.
A report in Translational Psychiatry said it was unknown if games changed the brain or if brain differences made people more likely to play.
Experts said more studies were needed for parents and teenagers to make sense of the findings.
Playing computer games has been linked to a range of effects from addiction to improved reasoning.
An international group of researchers investigated whether playing changed the structure of the brain.
They ranked 154 14-year-olds by the number of hours played in a week, with the middle teenagers playing about nine hours a week.
Those playing more than nine hours were classed as frequent players. None were classed as addicted.Enlarged
Brain scans showed a larger ventral striatum, which is the hub of the brain's reward system, in regular gamers.Continue reading the main story
For teenagers, parents, and clinicians to make sense of this finding, we need research monitoring brain structure over time”End Quote Dr Luke Clark University of Cambridge Dr Simone Kuhn, one of the researchers from Ghent University in Belgium, said the region is "usually activated when people anticipate positive environmental effects or experience pleasure such as winning money, good food, sex".
The region has been implicated in drug addiction.
The authors said it "cannot be determined" whether this was a "consequence" of gaming or if naturally larger regions led to a "vulnerability for preoccupation with gaming".
Dr Luke Clark, from the department of experimental psychology at the University of Cambridge, said the findings were "really provocative because this is a central hub in the brain's motivational system".
"But the burning question that this study does not resolve is whether the structural difference is a change caused by the frequent game play, or whether individual differences in this system naturally dispose some people to more excessive play," he added.
In drug users, Dr Clark said it was probably a combination of the two process - long-term drug use affecting the brain as well as some people being more susceptible.
He told the BBC that: "It certainly seems very plausible that playing video games for half a day a week may well actually structurally change the brain."
But said there was no evidence for this and that: "For teenagers, parents, and clinicians to make sense of this finding, we need research monitoring brain structure over time."
Dr Henrietta Bowden-Jones, of the division of neurosciences at Imperial College London, said: "These findings, linking ventral striatum abnormalities to compulsive computer gaming in young people, are highly relevant to clinical practice as they further close the gap between this activity and other addictions, giving us a better understanding of possible long-term treatment interventions."
The researchers are now asking adults, who have never used computer games, to start gaming. They are going to see if this has any effect on the brain.
Dr Kuhn said: "This will hopefully inform us whether the bigger ventral striatum in gamers is a phenomenon that makes them like computer games better or whether this structure did grow due to computer gaming."