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Frontal non-invasive neurostimulation modulates antisaccade preparation in non-human primates.

Valero-Cabre A, Wattiez N, Monfort M, François C, Rivaud-Péchoux S, Gaymard B, Pouget P - PLoS ONE (2012)

Bottom Line: We show that online single pulse TMS significantly modulated antisaccade latencies.Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS).Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes.

View Article: PubMed Central - PubMed

Affiliation: Université Pierre et Marie Curie, CNRS UMR 7225, INSERM UMRS 975, Institut du Cerveau et la Möelle (ICM), Paris, France. antoni.valerocabre@upmc.fr

ABSTRACT
A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes.

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Behavioral paradigm illustrating the experimental antisaccade paradigm.(Upper panel) Antisaccade paradigm practiced by the two monkeys under the online impact of sham (left panel) or active (right panel) TMS single pulses. After fixating on a central stimulus (red), monkeys were to initiate a fast saccade to a location in the opposite direction with respect to a peripheral target (green) appearing on the screen, simultaneously (no gap) to the disappearance of the central fixation. Animals performed within each block, no-TMS trials (white small rectangles) yielding no stimulation at all (Upper Left) and TMS trials (grey small rectangles) during which a single TMS pulse was delivered at a given postarget onset SOA prior to the AS initiation, to modulate the planning of visually guided oculomotor activity (Bottom panel) Example of an experimental session. Animals performed a total of 4 blocks of AS training per session. In one of the blocks they did not receive TMS (white long rectangle), whereas in the remaining 3, they received in half of the trials TMS pulses (see long grey-filled rectangles) at one of the 3 intensities used in the study (30%, 40% and 50%). The order of the four blocks (3 TMS blocks at 30%, 40% or 50% absolute TMS intensities and 1 noTMS block) was randomized within each session. Monkeys performed 100 trials per block (50 no-TMS and 50 TMS trials) for a total of 400 trials per session, and received 50 pulses per TMS block (i.e., only in 50% of the trials), amounting to 150 pulses per experimental session. Independent sessions comprising active TMS pulses delivered at 100 ms or 150 ms SOA post target onset on the FEF, sham TMS pulses and active TMS stimulation in a control location were carried over.
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pone-0038674-g001: Behavioral paradigm illustrating the experimental antisaccade paradigm.(Upper panel) Antisaccade paradigm practiced by the two monkeys under the online impact of sham (left panel) or active (right panel) TMS single pulses. After fixating on a central stimulus (red), monkeys were to initiate a fast saccade to a location in the opposite direction with respect to a peripheral target (green) appearing on the screen, simultaneously (no gap) to the disappearance of the central fixation. Animals performed within each block, no-TMS trials (white small rectangles) yielding no stimulation at all (Upper Left) and TMS trials (grey small rectangles) during which a single TMS pulse was delivered at a given postarget onset SOA prior to the AS initiation, to modulate the planning of visually guided oculomotor activity (Bottom panel) Example of an experimental session. Animals performed a total of 4 blocks of AS training per session. In one of the blocks they did not receive TMS (white long rectangle), whereas in the remaining 3, they received in half of the trials TMS pulses (see long grey-filled rectangles) at one of the 3 intensities used in the study (30%, 40% and 50%). The order of the four blocks (3 TMS blocks at 30%, 40% or 50% absolute TMS intensities and 1 noTMS block) was randomized within each session. Monkeys performed 100 trials per block (50 no-TMS and 50 TMS trials) for a total of 400 trials per session, and received 50 pulses per TMS block (i.e., only in 50% of the trials), amounting to 150 pulses per experimental session. Independent sessions comprising active TMS pulses delivered at 100 ms or 150 ms SOA post target onset on the FEF, sham TMS pulses and active TMS stimulation in a control location were carried over.

Mentions: Two captive-born macaques (one Maccaca Mulatta, “Y", and one Maccaca Fascicularis, “C") participated in this study. The monkeys were individually housed and handled in strict accordance with the recommendations of the Weatherall Report about good animal practice. Monkey housing conditions, surgical procedures and experimental protocols were all carried out in strict accordance with the National Institutes of Health guidelines (1996) and the recommendations of the EEC (86/609) and the French National Committee (87/848). The authorization for conducting our experiments in the institute was delivered by the Animal Health and Veterinary Medication Division of the Department of Public Veterinary Health, Nutrition and Food Safety of the French Ministry of Health (last renewals. no. Arrêté prefectoral N° DTPP 2010-424). Our routine laboratory procedures included an environmental enrichment program where monkeys had access to toys, mirrors and swings. Monkeys also had visual, auditory and olfactory contact with other animals and, when appropriate, could touch/groom each other. Any possible pain associated with surgeries was pharmacologically ameliorated by means of a daily injection of Ketofen (0.03 ml/kg) or Buprecare (0.067 ml/kg). The well-being and health conditions of the monkeys were constantly monitored by an institutional veterinary doctor. Prior to participating in the study, both animals were periodically chaired, head-posted and trained to perform an antisaccade (AS) paradigm (Figure 1, upper panel) for a period of 6–12 months, until they became regular and proficient performers.


Frontal non-invasive neurostimulation modulates antisaccade preparation in non-human primates.

Valero-Cabre A, Wattiez N, Monfort M, François C, Rivaud-Péchoux S, Gaymard B, Pouget P - PLoS ONE (2012)

Behavioral paradigm illustrating the experimental antisaccade paradigm.(Upper panel) Antisaccade paradigm practiced by the two monkeys under the online impact of sham (left panel) or active (right panel) TMS single pulses. After fixating on a central stimulus (red), monkeys were to initiate a fast saccade to a location in the opposite direction with respect to a peripheral target (green) appearing on the screen, simultaneously (no gap) to the disappearance of the central fixation. Animals performed within each block, no-TMS trials (white small rectangles) yielding no stimulation at all (Upper Left) and TMS trials (grey small rectangles) during which a single TMS pulse was delivered at a given postarget onset SOA prior to the AS initiation, to modulate the planning of visually guided oculomotor activity (Bottom panel) Example of an experimental session. Animals performed a total of 4 blocks of AS training per session. In one of the blocks they did not receive TMS (white long rectangle), whereas in the remaining 3, they received in half of the trials TMS pulses (see long grey-filled rectangles) at one of the 3 intensities used in the study (30%, 40% and 50%). The order of the four blocks (3 TMS blocks at 30%, 40% or 50% absolute TMS intensities and 1 noTMS block) was randomized within each session. Monkeys performed 100 trials per block (50 no-TMS and 50 TMS trials) for a total of 400 trials per session, and received 50 pulses per TMS block (i.e., only in 50% of the trials), amounting to 150 pulses per experimental session. Independent sessions comprising active TMS pulses delivered at 100 ms or 150 ms SOA post target onset on the FEF, sham TMS pulses and active TMS stimulation in a control location were carried over.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368878&req=5

pone-0038674-g001: Behavioral paradigm illustrating the experimental antisaccade paradigm.(Upper panel) Antisaccade paradigm practiced by the two monkeys under the online impact of sham (left panel) or active (right panel) TMS single pulses. After fixating on a central stimulus (red), monkeys were to initiate a fast saccade to a location in the opposite direction with respect to a peripheral target (green) appearing on the screen, simultaneously (no gap) to the disappearance of the central fixation. Animals performed within each block, no-TMS trials (white small rectangles) yielding no stimulation at all (Upper Left) and TMS trials (grey small rectangles) during which a single TMS pulse was delivered at a given postarget onset SOA prior to the AS initiation, to modulate the planning of visually guided oculomotor activity (Bottom panel) Example of an experimental session. Animals performed a total of 4 blocks of AS training per session. In one of the blocks they did not receive TMS (white long rectangle), whereas in the remaining 3, they received in half of the trials TMS pulses (see long grey-filled rectangles) at one of the 3 intensities used in the study (30%, 40% and 50%). The order of the four blocks (3 TMS blocks at 30%, 40% or 50% absolute TMS intensities and 1 noTMS block) was randomized within each session. Monkeys performed 100 trials per block (50 no-TMS and 50 TMS trials) for a total of 400 trials per session, and received 50 pulses per TMS block (i.e., only in 50% of the trials), amounting to 150 pulses per experimental session. Independent sessions comprising active TMS pulses delivered at 100 ms or 150 ms SOA post target onset on the FEF, sham TMS pulses and active TMS stimulation in a control location were carried over.
Mentions: Two captive-born macaques (one Maccaca Mulatta, “Y", and one Maccaca Fascicularis, “C") participated in this study. The monkeys were individually housed and handled in strict accordance with the recommendations of the Weatherall Report about good animal practice. Monkey housing conditions, surgical procedures and experimental protocols were all carried out in strict accordance with the National Institutes of Health guidelines (1996) and the recommendations of the EEC (86/609) and the French National Committee (87/848). The authorization for conducting our experiments in the institute was delivered by the Animal Health and Veterinary Medication Division of the Department of Public Veterinary Health, Nutrition and Food Safety of the French Ministry of Health (last renewals. no. Arrêté prefectoral N° DTPP 2010-424). Our routine laboratory procedures included an environmental enrichment program where monkeys had access to toys, mirrors and swings. Monkeys also had visual, auditory and olfactory contact with other animals and, when appropriate, could touch/groom each other. Any possible pain associated with surgeries was pharmacologically ameliorated by means of a daily injection of Ketofen (0.03 ml/kg) or Buprecare (0.067 ml/kg). The well-being and health conditions of the monkeys were constantly monitored by an institutional veterinary doctor. Prior to participating in the study, both animals were periodically chaired, head-posted and trained to perform an antisaccade (AS) paradigm (Figure 1, upper panel) for a period of 6–12 months, until they became regular and proficient performers.

Bottom Line: We show that online single pulse TMS significantly modulated antisaccade latencies.Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS).Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes.

View Article: PubMed Central - PubMed

Affiliation: Université Pierre et Marie Curie, CNRS UMR 7225, INSERM UMRS 975, Institut du Cerveau et la Möelle (ICM), Paris, France. antoni.valerocabre@upmc.fr

ABSTRACT
A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes.

Show MeSH