The Role Of The Lateral Intraparietal Area (LIP) During The Sequential Saccades

Sequential learning occurs frequently and plays a crucial role in daily life,such as writing,playing the piano,tying shoelaces,handing things,etc.The smooth completion of sequential movements is based on the learning of sequential movements.Some people with disabilities,especially those with functional brain disorders,have difficulty completing these daily behaviors due to impaired ability to learn and complete sequential movements,which causes considerable distress in their lives.However,the question of how the brain plans,executes and regulates sequential movements is still open to research.Previous studies have shown that the Lateral Intraparietal Cortex(LIP)is a key brain region for sequence planning,but the organization of sequence learning and the neural mechanisms of sequence motor control are not clear.To investigate the neural mechanisms of sequence learning,we trained macaques to learn two sequence saccades tasks: left-left-right-right(L-L-R-R)and right-right-left-left(R-R-L-L),using sequence saccades as a behavioral paradigm.When macaques were proficient in the sequential saccades task,LIP neuronal activity was recorded by in vivo electrophysiology to explore the representation of sequential saccades behavior in this brain region.It was found that 68.6 % of neurons in the left hemisphere LIP and 84.4 %of neurons in the right hemisphere LIP characterized individual saccade of the sequence in the L-L-R-R sequence saccades task;15.6 % of neurons in the left LIP and 10.8 % of neurons in the right LIP issued significantly to the first or last movement,suggesting possible characterization of the sequence start or stop in the left hemisphere LIP,15.8 %of neurons and 4.3 % of neurons in the right hemisphere LIP showed significant firing for the second or third action,suggesting the possibility of characterizing the switch of the sequence.Since the L-L-R-R sequence saccades task contains directional information,this one sequence task alone is not sufficient to indicate whether cells actually encode sequence start,stop,and switching.Therefore,for the latter two types of neurons,we used their representations in the R-R-L-L sequence saccades task as a control for further analysis.The majority(72.4 % in the left hemisphere brain and 89.3 % in the right hemisphere brain)of neurons were found to encode sequences embodied in the subsequence(i.e.,LL or R-R)hierarchy.Of these,the most represented neurons characterized the stop of the subsequence in the ipsilateral direction(38.1 % in the left hemisphere brain and 44.0 %in the hemisphere right brain);secondly,for subsequences in the contralateral direction of the brain,left brain LIP neurons characterized the signal of the stop of the subsequence(28.6 %)slightly more than the signal of the start(22.6 %),while right hemisphere LIP neurons characterized the signal of the start(32 %)of the subsequence.The right hemisphere LIP neurons showed more representation of the start(32 %)signal than the stop(16 %)signal;the least represented was the ipsilateral direction of the start(10.7 %in the left hemisphere and 8 % in the right hemisphere).This shows that although there are slight differences between the left and right hemisphere,both of them mainly characterize the stop of ipsilateral directional subsequences at the subsequence level.To further investigate the causal contribution of the LIP to the sequence saccades behavior,we performed microstimulation of the LIP to observe the effect on the sequence structure during the execution of the L-L-R-R sequence saccades task in macaques.We found that microstimulation of the LIP did not change the sequence structure for more than 60 % of the time,and that macaques were able to flexibly integrate external triggers into the sequence,suggesting that the LIP may be located at a higher level of sequence eye-movement control.At the same time,microstimulation could also change the sequence structure to some extent,as shown by: when stimulating the left hemisphere LIP,it showed more of a shortening of the L-L subsequence length,i.e.,the subsequence was terminated earlier,indicating that the LIP may be involved in the stop of subsequences in the ipsilateral direction of the brain;when stimulating the right hemisphere LIP,it showed more of an increase in the L-L subsequence length,i.e.,the subsequence may have undergone multiple initiations,indicating that the LIP may be involved in the initiation of subsequences in the contralateral direction of the brain.Pharmacological inactivation of LIP revealed a significant decrease in the correct rate of performing the sequential saccades task in macaques,and the decrease in correct rate(error cases)was mainly manifested by the incomplete execution of subsequences in the contralateral direction of the brain(e.g.,the right hemisphere corresponding to the LL subsequence);the total duration of sequence execution was significantly increased,and saccades at different locations in the sequence was affected to different degrees,mainly by the increase in the time required for switching within subsequence.The time required to switch between actions within a sequence increases.This indicates that LIP is involved in sequence saccades at the subsequence level.In summary,the LIP characterizes not only the individual movement(Element)level,but also the Sub Sequence level in the sequence saccades task.At the Sub Sequence level,LIP may be involved in the stop of subsequences in the ipsilateral direction of the hemisphere and the start of subsequences in the contralateral direction of the hemisphere,and is at a higher level of control of sequential saccades.