The Roles of the Cortical Motor Areas in Sequential Movements.

The ability to learn and perform a sequence of movements is a key component of voluntary motor behavior. During the learning of sequential movements, individuals go through distinct stages of performance improvement. For instance, sequential movements are initially learned relatively fast and later learned more slowly. Over multiple sessions of repetitive practice, performance of the sequential movements can be further improved to the expert level and maintained as a motor skill. How the brain binds elementary movements together into a meaningful action has been a topic of much interest. Studies in human and non-human primates have shown that a brain-wide distributed network is active during the learning and performance of skilled sequential movements. The current challenge is to identify a unique contribution of each area to the complex process of learning and maintenance of skilled sequential movements. Here, I bring together the recent progress in the field to discuss the distinct roles of cortical motor areas in this process.

Inhibition of protein synthesis in M1 of monkeys disrupts performance of sequential movements guided by memory.

The production of action sequences is a fundamental aspect of motor skills. To examine whether primary motor cortex (M1) is involved in maintenance of sequential movements, we trained two monkeys (Cebus apella) to perform two sequential reaching tasks. In one task, sequential movements were instructed by visual cues, whereas in the other task, movements were generated from memory after extended practice. After the monkey became proficient with performing the tasks, we injected an inhibitor of protein synthesis, anisomycin, into M1 to disrupt information storage in this area. Injection of anisomycin in M1 had a marked effect on the performance of sequential movements that were guided by memory. In contrast, the anisomycin injection did not have a significant effect on the performance of movements guided by vision. These results suggest that M1 of non-human primates is involved in the maintenance of skilled sequential movements.

Sequential Reaching Task for the Study of Motor Skills in Monkeys.

The ability to perform a sequence of movements is a key component of motor skills, such as typing or playing a musical instrument. How the brain binds elementary movements together into meaningful actions has been a topic of much interest. Here, we describe two sequential reaching tasks that we use to investigate the neural substrate of skilled sequential movements in monkeys after long-term practice. The movement elements performed in these tasks are essentially identical, but are generated in two different contexts. In one task, monkeys perform reaching movements that are instructed by visual cues. In the other, the monkeys perform reaching movements that are generated from memory after extended practice. With this behavioral paradigm, we can dissociate the neural processes related to the acquisition and retention of motor skills from those related to movement execution.

Inactivation of the Dorsal Premotor Area Disrupts Internally Generated, But Not Visually Guided, Sequential Movements.

As skill on a sequence of movements is acquired through practice, each movement in the sequence becomes seamlessly associated with another. To study the neural basis of acquired skills, we trained two monkeys (Cebus apella) to perform two sequential reaching tasks. In one task, sequential movements were instructed by visual cues, whereas in the other task, movements were generated from memory after extended practice. Then, we examined neural activity in the dorsal premotor area (PMd) and the effects of its local inactivation during performance of each task. Comparable numbers of neurons in the PMd were active during the two tasks. However, inactivation of the PMd had a marked effect only on the performance of sequential movements that were guided by memory. These results emphasize the importance of the PMd in the internal generation of sequential movements, perhaps through maintaining arbitrary motor-motor associations. SIGNIFICANCE STATEMENT: The dorsal premotor cortex (PMd) has long been thought to be a critical node in the cortical networks responsible for visually guided reaching. Here we show that PMd neurons are active during both visually guided and internally generated sequential movements. In addition, we found that local inactivation of the PMd has a marked effect only on the performance of sequential movements that were internally generated. These observations suggest that, although the PMd may participate in the generation of visually guided sequences, it is more important for the generation of internally guided sequences.

Conversion of working memory to motor sequence in the monkey premotor cortex.

To plan a serial order behavior, we hold serial sensory information in our minds and convert it to a movement program. We trained monkeys to memorize a sequence of positional cues and to reproduce it by making saccades in either the original or reverse order. The order was determined in the middle of a trial on the basis of an instruction stimulus. Triggered by the instruction stimulus, single neurons in the dorsal premotor cortex became transiently active only when the order needed to be determined. These transient neurons, together with nearby sustained neurons that hold information on cue or movement sequences, appear to mediate the generation of a motor program from the maintained information.