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The events of the game take place shortly after the ending of the first game. The devastating zombie invasion, caused by the scientist Dr. Cooger and his resurrection medicine, was finally stopped, and the young hero Cole could marry his sweetheart Sheila. But alas, if only everything could be so simple... A biker gang starts terrorizing the town. Sheila and Cole find a dead body in Cole's apartment. And soon they discover that not all the traces of the resurrection medicine were destroyed...

Like its predecessor, Dead of the Brain 2 is a horror adventure. The gameplay follows the Japanese template - no puzzles, no physical movement, reduced interaction. The interface has been greatly simplified: all the actions except moving (automatically takes Cole to another location) can be performed by highlighting an object or a person on the screen and confirming. Like in the first game, there are timed tasks (mostly involving enemy encounters), during which the player has to perform an action before time runs out. Failure to do so, or performing an incorrect action, leads to Game Over.

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