Separating standard and non-standard reaches: Topographical differences within PMd

P. F. Sayegh, K. M. Hawkins & L. E. Sergio

`

School of Kinesiology and Health Science, Centre for Vision Research, York University, Toronto, Ontario, Canada.

Introduction
It is well established that reaching movements rely on a network of brain regions including the dorsal premotor (PMd) and superior parietal lobule (SPL) (1-3), which are regions located within the dorsomedial parieto-frontal network (4). However what is less understood is how the regions within this network are modulated during a reaching movement when there is a dissociation between the action of the eye and the hand, termed a non-standard movement(4). It has been suggested that during non-standard reaching movements, a specific set of transformations must occur in order to break the tight linkage between the eye and the hand (3,4). As a result, non-standard reaching movements likely depend on neural circuitry that is different albeit interconnected with the circuitry important for controlling natural (standard) reaching movements (3,5,6). We observed distinct task related as well as topographical differences between the local field potentials in PMdr and PMdc. Our results emphasize the necessity within the field to separate research analyzing standard reaches from those analyzing non-standard reaching. Additionally, our results also strengthen the functional differences between PMdr and PMdc during visually-guided reaching. PMdr may code for more rule-based aspects of a visually-guided reach, while PMdc may reflect more movement related activity.
A

Neurophysiological Results
PMdr shows stronger activity when planning non-standard reaches, PMdc shows stronger activity when planning standard reaches PMdr IDP Period
Frequency (Hz) 100 80 60 40 20 0 -0.4 0.4 0.8 0.4 0.8 -0.4 0 0 0 0.4 0.8 -0.4 Time (sec) Time (sec) Time (sec)

PMdc
B Non-standard
condition

Standard condition

C Non-standard
- Standard
Frequency (Hz) 80 60 40 20 0

D
100

Standard condition

E Non-standard
condition

F Non-standard
- Standard

-0.4

0.4 0.8 0 0 0.4 0.8 -0.4 0 0.4 0.8 -0.4 Time (sec) Time (sec) Time (sec)

Figure 4: Population time-frequency spectrograms of oscillatory activity during the IDP epoch for PMdr (A-C) and PMdc activity (D-F). C, F: Population spectrogram showing only significant differences between conditions. Activity was masked at 95% CI based on bootstrapped data. Colors above zero indicate stronger power within the non-standard condition and colors below zero indicate stronger power within the standard condition. Black line indicates movement onset. Power is color-coded on a log scale.

PMdc shows stronger activity when executing non-standard reaches PMdr MOVE Period
A
Frequency (Hz) 100 80 60 40 20 0 -.5 -.25 0 .25 .5 -.5 -.25 0 .25 .5 -.5 -.25 0 .25 .5 Time (sec) Time (sec) Time (sec)

PMdc
B Non-standard
condition

Standard condition

C Non-standard
- Standard
Frequency (Hz) 80 60 40 20 0

D
100

Standard condition

E Non-standard
condition

F Non-standard
- Standard

-.5

-.25 0 .25 Time (sec)

.5 -.5 -.25 0 .25 Time (sec)

.5-.5 -.25 0 .25 .5 Time (sec)

Methods
A B
M L

Figure 5: Population time-frequency spectrograms of oscillatory activity during the move epoch for PMdr (A-C) and PMdc activity (D-F). C,F: Population spectrogram showing only significant differences between conditions. Activity was masked at 95% CI based on bootstrapped data. Colors above zero indicate stronger power within the non-standard condition and colors below zero indicate stronger power within the standard condition. Black line indicates movement onset. Power is color-coded on a log scale.

PMdr and PMdc showed different patterns of oscillatory activity

A
P

CS

CS AS
AS

Normalized z-scores

LF

LF

IDP Period
12 Rostral 30-45Hz 8 4 0 -4 12 Caudal 30-45Hz 8 Caudal 10-30Hz 8 4 4 0 0 -0.4 -0.2 0 0.2 0.4 0.6 0.8 -4 -0.4 -0.2 0 0.2 0.4 0.6 0.8 Time (sec) Time (sec)

12 Rostral 0-10Hz 8 4 0 -4 12 Caudal 0-10Hz 8 4 0 -4 -0.4 -0.2 0 0.2 0.4 0.6 0.8 Time (sec)

Normalized z-scores

Figure 1: Cortical regions accessed by chamber placement: A) The black circle represents location of PMd chamber B) Penetration sites for monkey A (left panel) and monkey B (right panel). Larger dots indicate where recordings were obtained on more than one occasion. AS: arcuate sulcus. CS: central sulcus. LF: Longitudinal fissure. Arrows show anterior, posterior, medial, and lateral directions, dotted line denotes division between penetration sites classified as rostral (left of line) or caudal (right of line). Adapted from Kalaska et.al., Curr. Op. Neurobiol. 1997.

B
10 5 0 5 -10 20 10 0 10

MOVE Period
Rostral 0-10Hz 10 0 10 -20 Caudal 0-10Hz 20 0 -0.4 -0.2 0 0.2 Time (sec) 0.4 20 -0.4 -0.2 0 0.2 Time (sec) 0.4 Caudal 10-30Hz 10 0 -10 -0.4 -0.2 0 0.2 Time (sec) 0.4 Caudal 40-70Hz 10 5 0 -5 Rostral 10-30Hz

Standard condition Non-standard condition

Caudal 70-100Hz

Standard condition
Eye and hand congruent

Non-standard condition
Eye and hand decoupled

IDP Period

MOVE Period

-0.4

-0.2

0 0.2 Time (sec)

0.4

Figure 6: Population time plots showing significant task related difference during the delay (A) and MOVE (B) epochs. Black line represents peripheral cue onset A, and movement onset B. Shaded region represents when the oscillatory activity between standard and nonstandard reaches were significantly different.

CHT
500ms 2000

IDP
500ms

RT

MT

THT
500ms

PMdr more active during IDP period PMdc more active during MOVE period IDP Period
A
PMdc > PMdr PMdr > PMdc Normalized z-scores 15 10 5 0 -5 10 0 0.4 Time (sec) 0.8

Eye fixation, central target

Standard condition

B
PMdc > PMdr PMdr > PMdc Normalized z-scores 15 10 5 0 -5 10

Non-standard condition

70-100Hz 45-70Hz 30-45Hz 10-30Hz 0-10Hz PMdc > PMdr PMdr > PMdc Normalized z-scores 20 10 0 10

MOVE Period
C
Standard condition
PMdc > PMdr PMdr > PMdc Normalized z-scores 20 10 0 10

Non-standard condition

Figure 2: Experimental setup and trial timing. A) Schematic of the standard and dissociated conditions. B) During each trial, one of eight equally spaced (45) peripheral targets were presented on either a touch-sensitive screen placed over the animals lap or on a monitor positioned vertically 40 cm away from the animals frontal plane. Arm movements were always made over the horizontal touch screen. Light grey circles represent the eight possible target locations (not illuminated before cue). Epochs - CHT: centre hold time, IDP: instructed delay period, RT: reaction time, MT: movement time, THT: target hold time. Red horizontal line represents the time in which the animal had to maintain fixation and hand inside the central target. The animal's head was fixed throughout the experiment.

We examined eye and hand movement related LFP activity within PMd during standard and nonstandard situations (Figure 2). Monkeys (2 female macaca mulatta) were trained to fixate on a central target throughout the instructed delay period, then to move their eyes and hand to one of eight peripherally cued targets and hold them there throughout the target hold period. The full trajectory of the hand and eye were recorded to ensure that the motor task remained similar between conditions. Eye movements were monitored using the ISCAN-ETL 200 Eye Tracking System . Hand paths were monitored using a touch sensitive screen. A four electrode microdrive (FHC Inc.) was used in conjunction with a multi-unit recording system (Alpha-Omega Engineering, Israel) to collect single unit (12.5kHz) and waveform (1562.5 Hz) activity. Data were analyzed in Matlab (Mathworks, USA) using both custom written and open source (Chronux.org) programmes.

-20 -0.4 -0.2 0 0.2 Time (sec) 0.4

-20 -0.4 -0.2 0 0.2 Time (sec) 0.4

-15 -0.4

-15 -0.4

0 0.4 Time (sec)

0.8

Figure 7: Line plots show the mean difference between PMdr and PMdc oscillatory activity for each frequency range. Positive z-score values reflect stronger oscillatory activity within PMdr whereas negative z-score values represent stronger activity within PMdc. Color bars represent when the difference in activity between PMdr and PMdc were significant. Vertical black bars represent onset of peripheral cue (A,B) and movement onset (C,D)

Conclusions
During movement planning: -PMdr is more active during non-standard reaches when compared to standard reaches. During movement execution: -PMdc is more active during non-standard reaches when compared to standard reaches.

Behavioural Results
Monkey A Standard
100 100

Monkey A Non-Standard
100

Monkey B Standard
100

Monkey B Non-Standard

**
0

*
0 0 -100 -100 -100 -100

* *
0 100

-100 -100

100

-100 -100

100

100

Figure 3: Mean reach trajectories. Black lines: mean movement trajectories, black tick marks: standard deviations. Yellow asterisks denote trajectory segments that were significantly (p < .05) more variable in comparison to the standard condition for each monkey.

Our results strengthen the functional differences between PMdr and PMdc during visually-guided reaching. Additionally, these finding highlight the importance of accounting for differences in task when analyzing data from premotor cortex, particularity when comparing tasks that use standard reaches from those that use non-standard reaching.
1. J. A. Granek, et al. Cortex 46, 1165 (2010). 2. D. J. Gorbet, et al. Neuroimage 23(3), 1100 (2004). 3. L. E. Sergioet al. Cortical mechanisms of vision, M. Jenkins, L. Harris, Eds. (Cambridge University Press, Cambridge, 2009). 4. S. P. Wise, et al. Can. J. Physiol. Pharmacol. 74, 469 (1996). 5. A. Gail, et al. J. Neurosci. 29, 9490 (2009). 6 S. Clavagnier, et al. Neuroscientist 13, 22 (2007).