In Dead Space 2, a phantom of the late Nicole Brennan produced by the Site 12 Marker haunts Isaac throughout Dead Space 2 and is arguably the main antagonist of that game. As the game progresses, "Nicole" becomes more violent and disturbing, making attempts to hurt and even "kill" Isaac.

Later, "Nicole" threatens to kill Isaac unless he explains why he can't "let her go". When he does explain, "Nicole" loses her haunting visage and appears as she did when she was alive. From then on until closer to the end, "Nicole" continues to appear before Isaac, giving him encouragement and advice on how to destroy the Marker.

Things take a turn for the worst after Isaac finally reaches the Marker and dispatches Tiedmann. After "Nicole" embraces Isaac in front of the Marker, she then attempts to kill him again, this time in Isaac's own mind. She reveals that the makers of the Marker must be absorbed for the Convergence to be complete. Betrayed and infuriated, Isaac fights and defeats "Nicole" and in turn, destroys the Marker.