The most common problem with getting Hotkeys to work in TextAloud is choosing key combinations that are too common, and are used in other programs. For example, you can't use something like Control-C, because Control-C in any program means Copy to windows clipboard. Depending on what other program is active in windows at the time, there could be hundreds of keyboard combinations that have special meanings as shortcut keys to that program. In those cases, the active program will intercept the keyboard combination and it would never be passed out to the global windows where TextAloud could receive it.
The best thing to do when trying to get TextAloud's global hotkeys to work is to start at least with very obscure combinations. Once you get those working and understand what hotkeys do, you can experiment with possibly shorter combinations that would work. Our suggestions for starting out with hotkeys are
Import News Control-Alt-Shift-N
Speak Text Control-Alt-Shift-S
Stop Speaking Control-Alt-Shift-Q
Try these settings until you are comfortable that the hotkeys work and understand their function, then if you desire you can try to reduce the number of keys, but understanding that you must use a combination that doesn't already have meaning within the program you are working in (such as Word or other editor).