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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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Schematic of TMS sites.Modified picture showing a top view of each of the two monkey’s scalp profiles (animals ‘Y’ and ‘C’), while posted and under training. The dotted line corresponds to the stereotaxic zero bar; the grey dot signals the location and size of the head-post; the orange dot corresponds to the location where digit movements were evoked by TMS pulses; the red dot FEF region of stimulation; the double white/grey dots is an approximate schematic representation of the TMS figure-of-eight coil which was located on the FEF region.
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pone-0038674-g002: Schematic of TMS sites.Modified picture showing a top view of each of the two monkey’s scalp profiles (animals ‘Y’ and ‘C’), while posted and under training. The dotted line corresponds to the stereotaxic zero bar; the grey dot signals the location and size of the head-post; the orange dot corresponds to the location where digit movements were evoked by TMS pulses; the red dot FEF region of stimulation; the double white/grey dots is an approximate schematic representation of the TMS figure-of-eight coil which was located on the FEF region.

Mentions: The surgical procedures for titanium headpost implant were the same as previously described [42], [43]. Each animal was deeply anaesthetized with ketamine hydrochloride (5 mg/kg i.m.) for initial sedation and anesthesia was induced with 2–4% isofluoran gas and then maintained during surgery. Heart rate, temperature and respiration were carefully monitored and kept within physiological range. Pain medication was given prior the surgery and routinely given after surgery. Head posts (9/32″ or 7.1 mm internal diameter) were commercially available as Part #6-FHP-X2F produced by Crist Instrument, Hagerstown, MD, USA. They had an “X"-shaped footplate designed for attachment to the skull with a total of 12 titanium bone screws. The vertical post had a tapered cross section, designed to mate with a headpost holder (see Part #6-FHB-S2B, Crist Instrument, Hagerstown, MD, USA). In monkey ‘Y’ the center of the head post was located adjacently caudal to the stereotaxic zero bar, aligned with the interauricular scalp line. In monkey ‘C’ the headpost was placed slightly more rostral than in monkey ‘Y’ (Figure 2). The non-ferromagnetic properties of the titanium material of the head-post prevented the very unlikely (brief or lasting) magnetization and heating of these elements under the influence of isolated TMS single pulses.


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)

Schematic of TMS sites.Modified picture showing a top view of each of the two monkey’s scalp profiles (animals ‘Y’ and ‘C’), while posted and under training. The dotted line corresponds to the stereotaxic zero bar; the grey dot signals the location and size of the head-post; the orange dot corresponds to the location where digit movements were evoked by TMS pulses; the red dot FEF region of stimulation; the double white/grey dots is an approximate schematic representation of the TMS figure-of-eight coil which was located on the FEF region.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038674-g002: Schematic of TMS sites.Modified picture showing a top view of each of the two monkey’s scalp profiles (animals ‘Y’ and ‘C’), while posted and under training. The dotted line corresponds to the stereotaxic zero bar; the grey dot signals the location and size of the head-post; the orange dot corresponds to the location where digit movements were evoked by TMS pulses; the red dot FEF region of stimulation; the double white/grey dots is an approximate schematic representation of the TMS figure-of-eight coil which was located on the FEF region.
Mentions: The surgical procedures for titanium headpost implant were the same as previously described [42], [43]. Each animal was deeply anaesthetized with ketamine hydrochloride (5 mg/kg i.m.) for initial sedation and anesthesia was induced with 2–4% isofluoran gas and then maintained during surgery. Heart rate, temperature and respiration were carefully monitored and kept within physiological range. Pain medication was given prior the surgery and routinely given after surgery. Head posts (9/32″ or 7.1 mm internal diameter) were commercially available as Part #6-FHP-X2F produced by Crist Instrument, Hagerstown, MD, USA. They had an “X"-shaped footplate designed for attachment to the skull with a total of 12 titanium bone screws. The vertical post had a tapered cross section, designed to mate with a headpost holder (see Part #6-FHB-S2B, Crist Instrument, Hagerstown, MD, USA). In monkey ‘Y’ the center of the head post was located adjacently caudal to the stereotaxic zero bar, aligned with the interauricular scalp line. In monkey ‘C’ the headpost was placed slightly more rostral than in monkey ‘Y’ (Figure 2). The non-ferromagnetic properties of the titanium material of the head-post prevented the very unlikely (brief or lasting) magnetization and heating of these elements under the influence of isolated TMS single pulses.

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