Neural representation and modulation of volitional motivation in response to escalating efforts.

Task-dependent volitional control of the selected neural activity in the cortex is critical to neuroprosthetic learning to achieve reliable and robust control of the external device. The volitional control of neural activity is driven by a motivational factor (volitional motivation), which directly reinforces the target neurons via real-time biofeedback. However, in the absence of motor behaviour, how do we evaluate volitional motivation? Here, we defined the criterion (ΔF/F) of the calcium fluorescence signal in a volitionally controlled neural task, then escalated the efforts by progressively increasing the number of reaching the criterion or holding time after reaching the criterion. We devised calcium-based progressive threshold-crossing events (termed 'Calcium PTE') and calcium-based progressive threshold-crossing holding-time (termed 'Calcium PTH') for quantitative assessment of volitional motivation in response to progressively escalating efforts. Furthermore, we used this novel neural representation of volitional motivation to explore the neural circuit and neuromodulator bases for volitional motivation. As with behavioural motivation, chemogenetic activation and pharmacological blockade of the striatopallidal pathway decreased and increased, respectively, the breakpoints of the 'Calcium PTE' and 'Calcium PTH' in response to escalating efforts. Furthermore, volitional and behavioural motivation shared similar dopamine dynamics in the nucleus accumbens in response to trial-by-trial escalating efforts. In general, the development of a neural representation of volitional motivation may open a new avenue for smooth and effective control of brain-machine interface tasks. KEY POINTS: Volitional motivation is quantitatively evaluated by M1 neural activity in response to progressively escalating volitional efforts. The striatopallidal pathway and adenosine A