Is there something in your mind? = Are you completely stupid?
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Husband: I just drove up to the house and saw our dog running down the street two blocks away. I had to chase him down and bring him back. How did he get out??
Wife: Oh, I went out to get the mail and must've left the door open.
Husband: Is there something in your mind, or is it just air?!

Is there something in your mind? = Is there a certain defect in your psyche that accounts for the way you act?
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Father: The police say you not only robbed that man, but you also kicked him in the face while he was unconscious. Where does all this rage and violence come from? Is there something in your mind that makes you do these things?

Is there something on your mind? = Are you worried about something?
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Husband: I thought this was your favorite restaurant.
Wife: It is...
Husband: Well, is there something on your mind? You haven't said a word all evening.

Is there something on your mind? = Is there something you need/want to talk about with me?
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Worker: Mr. Phillips, do you have five minutes? I need to talk to you.
Boss: Of course. Is there something on your mind?