Help: Noise jumps when 2x4 HD is connected via USB

I've been using miniDSP crossovers for a decade. In order of acquisition, the models I've used are OpenDRC DA-8, 4x10 HD, and several units of the 2x4 HD. They have their limitations & foibles, but the decent user interface keeps me. Flex replacements (esp 8 or HT models) are on the horizon, but the USD225 2x4 HD is tough to replace with a USD495 Flex for a more modest 2-way.

Recently, working with a new 2x4 HD, I noticed the residual noise through the speakers jumped dramatically whenever it's connected via USB to the PC in my studio. The noise is a combination of slightly intermittent squealing & buzzing, probably 10 dB higher than the usual hiss that becomes inaudible beyond about a foot from a 90 dB/W sensitive tweeter. It doesn't matter which USB port is used, nor type (2.0 or 3.0), nor whether the USB is used as source input or control only. As long as the 2x4 HD is connected to the PC via USB, this noise exhibits. Unplugging the USB immediately stops the noise.

The W10 PC is under 10 years old, with good general performance (6 or 8 core CPU, iirc; NVME SSD, 16gb RAM) well-maintained, fairly speedy & reliable with all the audio related tasks it runs.

What are the most likely causes? Anyone run into a similar problem before? Any good solutions?

I'm guessing this is caused by noise on the PC's USB bus, some kind of interaction between the power supply of the 2x4 HD & the PC, or some kind of ground loop via USB -- if that's is even possible? Negative interaction with some other device connected to the PC via USB?

Help & suggestions welcome!
 
This sort of thing happens all the time, and that's why there's a whole bunch of USB isolator devices out there. I can't vouch for which one will actually work because I use a dedicated USB output card using external power only.