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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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Saccade latencies in TMS or no-TMS trials.Relative modulation of antisaccades latencies (mean and SD) under the impact of online FEF TMS normalized by the effects of sham TMS (white columns; (real TMS-noTMS)-(sham TMS-noTMS)) on the FEF, or active stimulation on a control cortical site (black columns; (real TMS-noTMS)-(active control TMS-noTMS)). Data are shown in millisecond differences for each of the two monkeys (‘C’ and ‘Y’) with TMS delivered at a SOA of 150 ms pre-target onset and at high intensity (50%), at which the effects of active FEF TMS were mostly noted in both monkeys (see Supplementary Table S1 for details). Decreases in normalized AS latency differences suggest a TMS-induced acceleration of AS preparation time with regards to the observed effects for sham TMS (white columns) or active TMS (black columns) in a control site and vice-versa. Notice that in both animals (‘C’ and ‘Y’) active TMS pulses decreased the average latency differences of the AS towards the hemifield ipsilateral to the stimulated FEF, whereas changes were marginal or  for contralateral AS.
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pone-0038674-g005: Saccade latencies in TMS or no-TMS trials.Relative modulation of antisaccades latencies (mean and SD) under the impact of online FEF TMS normalized by the effects of sham TMS (white columns; (real TMS-noTMS)-(sham TMS-noTMS)) on the FEF, or active stimulation on a control cortical site (black columns; (real TMS-noTMS)-(active control TMS-noTMS)). Data are shown in millisecond differences for each of the two monkeys (‘C’ and ‘Y’) with TMS delivered at a SOA of 150 ms pre-target onset and at high intensity (50%), at which the effects of active FEF TMS were mostly noted in both monkeys (see Supplementary Table S1 for details). Decreases in normalized AS latency differences suggest a TMS-induced acceleration of AS preparation time with regards to the observed effects for sham TMS (white columns) or active TMS (black columns) in a control site and vice-versa. Notice that in both animals (‘C’ and ‘Y’) active TMS pulses decreased the average latency differences of the AS towards the hemifield ipsilateral to the stimulated FEF, whereas changes were marginal or for contralateral AS.

Mentions: In order to control for the potential lateralized biases generated by TMS accompanying sensory phenomena, we normalized by subtraction the AS latency modulations induced by active TMS at the 150 ms SOA by those observed in homologue experiments under sham TMS ((real TMS-noTMS)-(sham TMS-noTMS)) or active TMS on a control cortical area ((real TMS-noTMS)-(active control TMS-noTMS)). This allowed us to eliminate inter-session variability, with regards to baseline AS latency value and to better define the characteristics (direction and field specific effects) of such modulation in each of the two monkeys. Indeed, whereas the raw AS latency effects were not always fully consistent across the two monkeys (see Supplementary Table S1), data showed inter-individual consistence only when such normalized values were employed (see Figure 5).


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)

Saccade latencies in TMS or no-TMS trials.Relative modulation of antisaccades latencies (mean and SD) under the impact of online FEF TMS normalized by the effects of sham TMS (white columns; (real TMS-noTMS)-(sham TMS-noTMS)) on the FEF, or active stimulation on a control cortical site (black columns; (real TMS-noTMS)-(active control TMS-noTMS)). Data are shown in millisecond differences for each of the two monkeys (‘C’ and ‘Y’) with TMS delivered at a SOA of 150 ms pre-target onset and at high intensity (50%), at which the effects of active FEF TMS were mostly noted in both monkeys (see Supplementary Table S1 for details). Decreases in normalized AS latency differences suggest a TMS-induced acceleration of AS preparation time with regards to the observed effects for sham TMS (white columns) or active TMS (black columns) in a control site and vice-versa. Notice that in both animals (‘C’ and ‘Y’) active TMS pulses decreased the average latency differences of the AS towards the hemifield ipsilateral to the stimulated FEF, whereas changes were marginal or  for contralateral AS.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038674-g005: Saccade latencies in TMS or no-TMS trials.Relative modulation of antisaccades latencies (mean and SD) under the impact of online FEF TMS normalized by the effects of sham TMS (white columns; (real TMS-noTMS)-(sham TMS-noTMS)) on the FEF, or active stimulation on a control cortical site (black columns; (real TMS-noTMS)-(active control TMS-noTMS)). Data are shown in millisecond differences for each of the two monkeys (‘C’ and ‘Y’) with TMS delivered at a SOA of 150 ms pre-target onset and at high intensity (50%), at which the effects of active FEF TMS were mostly noted in both monkeys (see Supplementary Table S1 for details). Decreases in normalized AS latency differences suggest a TMS-induced acceleration of AS preparation time with regards to the observed effects for sham TMS (white columns) or active TMS (black columns) in a control site and vice-versa. Notice that in both animals (‘C’ and ‘Y’) active TMS pulses decreased the average latency differences of the AS towards the hemifield ipsilateral to the stimulated FEF, whereas changes were marginal or for contralateral AS.
Mentions: In order to control for the potential lateralized biases generated by TMS accompanying sensory phenomena, we normalized by subtraction the AS latency modulations induced by active TMS at the 150 ms SOA by those observed in homologue experiments under sham TMS ((real TMS-noTMS)-(sham TMS-noTMS)) or active TMS on a control cortical area ((real TMS-noTMS)-(active control TMS-noTMS)). This allowed us to eliminate inter-session variability, with regards to baseline AS latency value and to better define the characteristics (direction and field specific effects) of such modulation in each of the two monkeys. Indeed, whereas the raw AS latency effects were not always fully consistent across the two monkeys (see Supplementary Table S1), data showed inter-individual consistence only when such normalized values were employed (see Figure 5).

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