Medial Premotor Cortex

Nomenclature, Location, Function, Connectivity

Nomenclature:

    Medial Premotor Cortex; SMA and PreSMA; areas F3 & F6

    (History)

    1952 - The term "supplementary motor area" introduced by Woolsey et al for the simunculus on mesial cortical surface revealed by stimulation mapping and somatotopy established (Woolsey, Settlage et al. 1952).

    1985-1992 - SMA and Pre-SMA (F3/F6) are distinguished by many criteria including histochemistry (Matelli, Luppino et al. 1985), cytoarchitectontics (Matelli, Luppino et al. 1991), connectivity (Luppino, Matelli et al. 1990) and physiology (Rizzolatti, Gentilucci et al. 1990; Matsuzaka, Aizawa et al. 1992).

Location:

1)  F1 -> F3 boundary

    a. ~ at AP level of the superior precentral dimple

    b. drop in numbers of giant V "Betz" cells

    c. increase in threshold for intracortical microstimulation (ICMS) (>15 microamps)

    d. reversed somatotopy by ICMS, sensory exam and connectivity

2)  F3 -> F6

    a. ~ 2 mm anterior to the AP level of the genu of arcuate sulcus. (~ anterior commisure in humans, (Picard and Strick 1996) see figure.)

    b. reduced microexcitation (threshold > 30 microamps or long stim. trains).

    c. increased prevalence of visual sensory reponses

3)  F3/F6 -> cingulate boundary

    a. at the middle of the dorsal bank of cingulate sulcus

Function:

Lesion/inactivation studies

- Large unilateral lesions cause transient akinesia (paucity of movement and spontaneous speech (Goldberg 1985)) and bimanual dyscoordination (akin to mirror movements, (Brinkman 1981)).

- Bilateral SMA/pre-SMA lesions cause a lasting deficit in selecting and initiating movement in the absence of sensory instructions telling the animal what to do ("when " is not as important (Thaler, Chen et al. 1995; Chen, Cohen et al. 1997).  Simple movements are impaired.

- Inactivation of pre-SMA or SMA impairs the learning of new motor sequence (Nakamura, Sakai et al. 1999) and the performance of sequences from memory (without visual cues (Kermadi, Liu et al. 1997; Shima and Tanji 1998).

- Neurological case reports (i.e., poorly controlled): unilateral mesial lesions cause impaired intermanual coordination (load transfer task), alien hand syndrome, apraxia, mirror movements.

Physiology

1. Peri-Movement activity

    - Large proportion of SMA cells (41%) have perimovement activity only.  Activity is similar to that observed in M1 (same latencies and directionality (Crutcher and Alexander 1990; Chen, Hyland et al. 1991)). (2- and 3-D tuning in SMA not done!)

    - Reflects limb kinematics (direction) or dynamics (muscle-like activity) in roughly equal proportions (similar to M1) (Crutcher and Alexander 1990).  Seldom reflects target when dissociated from movement.

    - Peri-movement activity is more common in SMA than in pre-SMA (Matsuzaka, Aizawa et al. 1992).

2. Delay period activity

    - More common in SMA (~50% of cells) than in M1 (~35%) (Alexander and Crutcher 1990).  More common in pre-SMA than in SMA (Matsuzaka, Aizawa et al. 1992).

    - Reflects limb or target direction in roughly equal proportions (Alexander and Crutcher 1990).

    - Many pre-SMA neurons are activated during delay periods when subjects change a motor plan (Matsuzaka and Tanji 1996).

3. Signal-related or visual responses

    - Pre-SMA has far more visual responses than SMA proper (Chen, Hyland et al. 1991; Matsuzaka, Aizawa et al. 1992).

4. Internal selection of movement

    - Lesion studies cited above

    - SMA neurons are preferentially active with internally selected movement (i.e., mvt. not guided by sensory instructions (Mushiake, Inase et al., 1991)).  But, this is a preference only, it is not exclusive.

    - Slow scalp potential centered on SMA and preceding movement (the Bereitschaftspotential) is accentuated when movements are internally selected (Praamstra, Stegeman et al. 1995).

5. Already-learned sequences (Tanji et al)

    - Perimovement activity in SMA (61%) is movement-specific independent of sequence.  Perimovement activity pre-SMA instead reflects a particular movement in a particular sequence.

    - Most SMA delay period activity (80% of cells) is influenced by sequence.  SMA activity often (40% of cells) is interval-selective for two specific movements in a sequence (Shima and Tanji 2000).  Interval selective activity links component movements of a sequence, relating one movement to the next.

    - Nearly all pre-SMA activity (98%) is influenced by sequence.  Pre-SMA activity often reflects the ordinal position of next movement (rank order selective) independent of what movement it is (40% of cells) (Shima and Tanji, 2000).  Rank order selective activity specifies the sequence position independent of the component movements

    - A few cells (<10%) in both SMA and pre-SMA had sequence-selective activity either preparatory before the first movement or perimovement

    - Only in pre-SMA, 18% of cells fire selectively only when a new sequence was presented visually.

    Conclusion: Pre-SMA is more involved in monitoring task performance and switching between tasks while SMA is involved in linking between component movements of a sequence.

6. Sequence learning

    - PET and fMRI consistently show activation of SMA during learning of a new sequence (Grafton, Hazeltine et al. 1998, black blob in figure).

    - SMA bilateral lesions block new sequence learning.

7. Trial-and-Error learning (Hikosaka et al)

    - 2x5 task = learning a series of forced choices.  Accurate performance requires first guessing and then remembering the correct response to a given stimulus (choice of two targets).

    - Pre-SMA inactivation blocks new learning but has no effect on overlearned sequences.  (But injections were unilateral).

    - Neurons preferring new sequences are more common in pre-SMA (~25% of task-related) than in SMA (~10%).

    - fMRI in humans confirms activation of pre-SMA during initial trial-and-error-learning.  Pre-SMA is not active during performance of overlearned sequence.

    Conclusion: Pre-SMA may be especially active when performance monitoring is most needed.

8. Relations to bimanual coordination

    Small proportion of cells (5%) fire exclusively w/ bimanual tasks (coordinated movement of both hands), while more (19%) fire non-exclusively with similar ipsi- contra- or bimanual movement (versus 5% in M1 - Kazennidov et al '90, Neurosci 89:661).  Similar non-exclusive activity patterns in the lateral premotor areas and parietal regions.

    Conclusion: SMA is not specially involved in bimanual coordination.

Connectivity:

* mot = motor loop, assoc = "associative" loops projecting also to dorsolateral prefrontal, BG = basal ganglia, Cb = cerebellum, SS? = spinothalamic somatosensory input

- Different retrograde tracers injected into M1 and prefrontal cortex (principal sulcus - 9/46) (Lu, Preston et al. 1994, see figure).  There is no overlap between PF-projecting (including F6) and M1-projecting SMA.

References

Alexander, G. E. and M. D. Crutcher (1990).  "Prepartation for movement: neural representations of intended direction in three motor areas of the monkey." J. Neurophysiology. 64: 133-150.

Brinkman, C. (1981). "Lesions in supplementarymotor area interfere with a monkey's performance of a bimanual coordination task." Neurosci Letters 27: 267-270.

Chen, D. F., B Hyland, et al. (1991). "Comparison of neural activity in the supplementary motor area and in the primary motor cortex in monkeys." Somatosens Mot Res 8(1): 27-44.

Chen, R., L. G. Cohen, et al. (1997). "Role of the ipsilateral motor cortex in voluntary movement." Can J Neurol Sci 24(4): 284-91.

Crutcher, M. D. and G. E. Alexander (1990). "Movement-related neuronal activity selectively coding either direction or muscle pattern in three motor areas of the monkey." J. Neurophysiol. 64: 151-163.

Goldberg, G. (1985). "Supplementary motor area structure and function: review and hypotheses." Behav. Brain Sci. 8: 567-616.

Grafton, S. T., E. Hazeltine, et al. (1998). "Abstract and effector-specific representations of motor sequences identified with PET." J Neurosci 18(22): 9420-8.

Kermadi, I., Y. Liu, et al. (1997). "Effects of reversible inactivation of the supplementary motor area (SMA) on unimanual grasp and bimanual pull and grasp performance in monkeys." Somatosens Mot Res 14(4): 268-80.

Lu, M. T., J. B. Preston, et al. (1994). "Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe." J Comp Neurol 341 (3): 375-92.

Luppino, G., M. Matelli, et al. (1990). "Cortico-cortical connections of two electrophysiologically identified arm representations in the mesial agranular frontal cortex." Exp Brain Res 82(1): 214-8.

Matelli, M., G. Luppino, et al. (1985). "Patterns of cytochrome oxidase activity in the frontal agranular cortex of macaque monkey." Behav. Brain Res. 18: 125-137.

Matelli, M., G. Luppino, et al. (1991). "Architecture of superior and mesial are 6 and of adjacent cingulate cortex." J. Comp. Neurol. 311: 445-462.

Matsuzaka, Y., H. Aizawa, et al. (1992). "A motor area rostral to the supplementary motor area (presupplementary motor area) in the monkey: neuronal acitivty during a learned motor task." J. Neurophysiol 68: 653-662.

Matsuzaka, Y. and J. Tanji (1996). "Changing directions of forthcoming arm movements: neuronal acitivty in the presupplementary and suppleme ntary motor area of monkey cerebral cortex." J Neurophysiol. 76(4): 2327-42.

Mushiake, H., M. Inase, et al. (1991). "Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements." J. Neurophysiol. 66: 705-718.

Nakamura, K., K. Sakai, et al. (1999). "Effects of local inactivation of monkey medial frontal cortex in learning of sequential procedures." J Neurophysiol 82(2): 1063-8.

Picard, N. and P. L. Strick (1996). "Motor areas of the medial wall: a review of their location and functional activation." Cereb Cortex 6: 342-353.

Praamstra, P., D. F. Stegeman, et al. (1995). "Movement-related potentials preceding voluntary movement are modulated by the mode of movement selection." Exp Brain Res 103(3): 429-39.

Rizzolatti, G., M. Gentilucci, et al. (1990). "Neurons related to reaching-grasping arm movements in the rostral part of area 6 (area 6a beta)." Exp Brain Res 82(2): 337-50.

Shima, K. and J. Tanji (1998). "Both supplementary and presupplementary motor areas are crucial for the temporal organization of multiple movements." J Neurophysiol 80(6): 3247-60.

Shima, K. and J. Tanji (2000). "Neuronal activity in the supplementary and presupplementary motor areas for temporal organization of multiple movements." J Neurophysiol 84(4): 2148-60.

Tanji, J. (1996). "New concepts of the supplementary motor area." Curr Opin Neurobiol 6(6): 782-7.

Thaler, D., Y. C. Chen, et al. (1995). "The functions of the medial premotor cortex. I. Simple learned movements." Exp Brain Res 102(3): 445-60.

 Woolsey, C.N., P.H. Settlage, et al. (1952). "Patterns of localization in precentral and 'supplementary' motor areas and their relation to the concept of a premotor area." REs Publ Assoc Res Nerv Ment Dis 30: 238-264.

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