Biology subjects

Lomber, S. G.

Publications and source records attributed to Lomber, S. G..

6 recordsLinked to original sources

bioRxiv2020

Causal roles of frontoparietal cortical areas in feedback control of the limb

Goal-directed motor corrections are surprisingly fast and complex, but little is known on how they are generated by the central nervous system. Here we show that temporary cooling of dorsal premotor cortex (PMd) or parietal area 5 (A5) in behaving monkeys caused impairments in corrective responses to mechanical perturbations of the forelimb. Deactivation of PMd impaired both spatial accuracy and response speed, whereas deactivation of A5 impaired spatial accuracy, but not response speed. Simulations based on optimal feedback control demonstrated that deactivation of the control policy (reduction of feedback gain) impaired both spatial accuracy and response speed, whereas deactivation in state estimation (reduction of Kalman gain) impaired spatial accuracy but not response speed, paralleling the impairments observed from deactivation of PMd and A5, respectively. Furthermore, combined deactivation of both cortical regions led to additive impairments of individual deactivations, whereas reducing the amount of cooling (i.e. milder cooling) to PMd led to impairments in response speed, but not spatial accuracy, both also predicted by the model simulations. These results provide causal support that higher order motor and somatosensory regions beyond primary somatosensory and primary motor cortex are involved in generating goal-directed motor responses. As well, the computational models suggest that the distinct patterns of impairments associated with these cortical regions reflect their unique functional roles in goal-directed feedback control.

neuroscience↗

bioRxiv2019

Assessment of anesthesia on physiological stability and bold signal reliability during visual or acoustic stimulation in the cat

BackgroundNeuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animals physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane - the latter of which is known to suppress cortical function. New MethodHere, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7T to assess mean signal strength and between-subjects signal variability. Results in Comparison with Existing MethodsWe show that alfaxalone results in more stable respiratory rates over the 120 minutes testing period, with evidence of smaller between measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed. ConclusionsAlfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.

neuroscience↗

bioRxiv2019

Cortico-cortical feedback from V2 exerts a powerful influence over the visually evoked local field potential and associated spike timing in V1

The local field potential (LFP) is generally thought to be dominated by synaptic activity within a few hundred microns of the recording electrode. The sudden onset of a visual stimulus causes a large downward deflection of the LFP recorded in primary visual cortex, known as a visually evoked potential (VEP), followed by rhythmic oscillations in the gamma range (30-80 Hz) that are often in phase with action potentials of nearby neurons. By inactivating higher visual areas that send feedback projections to V1, we produced a large decrease in amplitude of the VEP, and a strong attenuation of gamma rhythms in both the LFP and multi-unit activity, despite an overall increase in neuronal spike rates. Our results argue that much of the recurrent, rhythmic activity measured in V1 is strongly gated by feed-back from higher areas, consistent with models of coincidence detection that result in burst firing by layer 5 pyramidal neurons.

neuroscience↗

bioRxiv2019

Frontal eye field inactivation alters the readout of superior colliculus activity for saccade generation in a task-dependent manner

Saccades require a spatiotemporal transformation of activity between the intermediate layers of the superior colliculus (iSC) and downstream brainstem burst generator. The dynamic linear ensemble-coding model (Goossens and Van Opstal, 2006) proposes that each iSC spike contributes a fixed mini-vector to saccade displacement. Although biologically-plausible, this model assumes cortical areas like the frontal eye fields (FEF) simply provide the saccadic goal to be executed by the iSC and brainstem burst generator. However, the FEF and iSC operate in unison during saccades, and a pathway from the FEF to the brainstem burst generator that bypasses the iSC exists. Here, we investigate the impact of large yet reversible inactivation of the FEF on iSC activity in the context of the model across four saccade tasks. We exploit the overlap of saccade vectors generated when the FEF is inactivated or not, comparing the number of iSC spikes for metrically-matched saccades. We found that the iSC emits fewer spikes for metrically-matched saccades during FEF inactivation. The decrease in spike count is task-dependent, with a greater decrease accompanying more cognitively-demanding saccades. Our results show that FEF integrity influences the readout of iSC activity in a task-dependent manner. We propose that the dynamic linear ensemble-coding model be modified so that FEF inactivation increases the gain of a readout parameter, effectively increasing the influence of a single iSC spike. We speculate that this modification could be instantiated by a direct pathway from the FEF to the omnipause region that modulates the excitability of the brainstem burst generator.\n\nSignificance statementOne of the enduring puzzles in the oculomotor system is how it achieves the spatiotemporal transformation, converting spatial activity within the intermediate layers of the superior colliculus (iSC) into a rate code within the brainstem burst generator. The spatiotemporal transformation has traditionally been viewed as the purview of the oculomotor brainstem. Here, within the context of testing a biologically-plausible model of the spatiotemporal transformation, we show that reversible inactivation of the frontal eye fields (FEF) decreases the number of spikes issued by the iSC for metrically-matched saccades, with greater decreases accompanying more cognitively-demanding tasks. These results show that signals from the FEF influence the spatiotemporal transformation.

neuroscience↗

bioRxiv2017

Frontal eye field inactivation reduces saccade preparation in the superior colliculus, but does not alter how preparatory activity relates to saccade latency

A neural correlate for saccadic reaction times (SRTs) in the gap saccade task is the level of preparatory activity in the intermediate layers of the superior colliculus (iSC) just before visual target onset: greater levels of iSC preparatory activity precede shorter SRTs. The frontal eye fields (FEF) are one likely source of such iSC preparatory activity, since FEF preparatory activity is also inversely related to SRT. To better understand the FEFs role in saccade preparation, and the way in which such preparation relates to SRT, in two male rhesus monkeys we examined iSC preparatory activity during unilateral reversible cryogenic inactivation of the FEF. FEF inactivation increased contralesional SRTs, and lowered ipsilesional iSC preparatory activity. FEF inactivation also reduced fixation-related activity in the rostral iSC. Importantly, the distributions of SRTs generated with or without FEF inactivation overlapped, enabling us to conduct a novel population-level analyses examining iSC preparatory activity just before generation of SRT-matched saccades. These analyses revealed no change during FEF inactivation in the relationship between iSC preparatory activity and SRT-matched saccades across a range of SRTs, even for the occasional express saccade. Thus, while our results emphasize that the FEF has an overall excitatory influence on preparatory activity in the iSC, the communication between the iSC and downstream oculomotor brainstem is unaltered for SRT-matched saccades, suggesting that the integration of preparatory and visual signals in the SC just before saccade initiation is largely independent of the FEF for saccades generated in this task.\n\nSignificance statementHow does the brain decide when to move? Here, we investigate the role of two oculomotor structures, the superior colliculus (SC) and frontal eye fields (FEF), in dictating visually-guided saccadic reaction times (SRTs). In both structures, higher levels of preparatory activity precede shorter SRTs. Here, we show that FEF inactivation increases SRTs and decreases SC preparatory activity. Surprisingly, a population-level analysis of SC preparatory activity showed a negligible impact of FEF inactivation, providing one examines SRT-matched saccades. Thus, while the FEF is one source of preparatory input to the SC, it is not a critical source, and it is not involved in the integration of preparatory activity and visual signals that precedes saccade initiation in simple visually-guided saccade tasks.

neuroscience↗

bioRxiv2017

Frontal Eye Field inactivation diminishes Superior Colliculus activity, but delayed saccadic accumulation governs reaction time increases

Stochastic accumulator models provide a comprehensive framework for how neural activity could produce behavior. Neural activity within the frontal eye fields (FEF) and intermediate layers of the superior colliculus (iSC) support such models for saccade initiation, by relating variations in saccade reaction time (SRT) to variations in parameters such as baseline, rate of accumulation of activity, or threshold. Here, by recording iSC activity during reversible cryogenic inactivation of the FEF in non-human primates, we causally test which parameter(s) best explains concomitant increases in SRT. While FEF inactivation decreased all aspects of ipsilesional iSC activity, decreases in accumulation rate and threshold poorly predicted accompanying increases in SRT. Instead, SRT increases best correlated with delays in the onset of saccade-related accumulation. We conclude that FEF signals govern the onset of saccade-related accumulation within the iSC, and that the onset of accumulation is a relevant parameter for stochastic accumulation models of saccade initiation.\n\nSignificance StatementThe superior colliculus (SC) and frontal eye fields (FEF) are two of the best-studied areas in the primate brain. Surprisingly, little is known about what happens in the SC when the FEF is temporarily inactivated. Here, we show that temporary FEF inactivation decreases all aspects of functionally-related activity in the SC. This combination of techniques also allowed us to relate changes in SC activity to concomitant increases in saccadic reaction time (SRT). Although stochastic accumulator models relate SRT increases to reduced rates of accumulation or increases in threshold, such changes were not observed in the SC. Instead, FEF inactivation delayed the onset of saccade-related accumulation, emphasizing the importance of this parameter in biologically-plausible models of saccade initiation.

neuroscience↗