If you consider that prior to the cognitive revolution 50,000 years back it’s believed we lacked the ability to speak based on genetics, so humans prior to it could never have spoken, I’d say that’s a big genetic change and there likely will have been others. Though of course it’s all subjective and depends what you class as a big change.

Once it did happen selections based on behaviour would have become a thing, who knows how this would have changed the makeup of our brains, but I’d imagine there would have been change, and a decent amount at the that.

But like I say, it’s all subjective! Thanks for the comment, Buffy!