scholarly journals Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque

2020 ◽  
Author(s):  
Anil Bollimunta ◽  
Samantha R. Santacruz ◽  
Ryan W. Eaton ◽  
Pei S. Xu ◽  
John H. Morrison ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Motor Behavior ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Calcium Dynamics ◽  
Dorsal Premotor Cortex ◽  
Plug And Play ◽  
Grin Lens

SummaryA major effort is now underway across the brain sciences to identify, characterize and manipulate mesoscale neural circuits in order to elucidate the mechanisms underlying sensory perception, cognition and behavior. Optical imaging technologies, in conjunction with genetically encoded sensors and actuators, serve as important tools toward these goals, allowing access to large-scale genetically defined neuronal populations. In particular, one-photon miniature microscopes, coupled with genetically encoded calcium indicators and microendoscopic gradient-refractive index (GRIN) lenses, enable unprecedented readout of neural circuit dynamics in cortical and deep subcortical brain regions during active behavior in rodents. This has already led to breakthrough discoveries across a wide array of rodent brain regions and behaviors. However, in order to study the neural circuit mechanisms underlying more complex and clinically relevant human behaviors and cognitive functions, it is crucial to translate this technology to non-human primates. Here, we describe the first successful application of this technology in the rhesus macaque. We identified a viral strategy for robust expression of GCaMP, optimized a surgical protocol for microendoscope GRIN lens insertion, and created a chronic cranial chamber and lens mounting system for imaging in gyral cortex. Using these methods, we demonstrate the ability to perform plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from over 100 genetically-targeted neurons simultaneously in dorsal premotor cortex while the macaque performs a naturalistic motor reach task with the head unrestrained and freely moving. The recorded population of neurons exhibited calcium dynamics selective to the direction of reach, which we show can be used to decode the animal’s trial-by-trial motor behavior. Recordings were stable over several months, allowing us to longitudinally track large populations of individual neurons and monitor their relationship to motor behavior over time. Finally, we demonstrate the ability to conduct simultaneous, multi-site imaging in bilateral dorsal premotor cortices, offering an opportunity to study distributed networks underlying complex behavior and cognition. Together, this work establishes head-mounted microendoscopic calcium imaging in macaque as a powerful new approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.HighlightsFirst demonstration of head-mounted microendoscopic calcium imaging in behaving macaque.Surgical protocols developed for preparing the animal for calcium imaging, including virus injections to express GCaMP and chronic implantation of a GRIN lens to enable optical access to gyral cortex.Proof of concept plug-and-play calcium imaging in behaving macaques with months long stable recording capability allowing populations of individual neurons to be tracked longitudinally.Bilateral calcium imaging from dorsal premotor cortex exhibited dynamics selective to the animal’s direction of reach and allowed decoding of the animal’s motor behavior

scholarly journals Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque

Cell Reports ◽  
2021 ◽  
Vol 35 (11) ◽  
pp. 109239
Author(s):  
Anil Bollimunta ◽  
Samantha R. Santacruz ◽  
Ryan W. Eaton ◽  
Pei S. Xu ◽  
John H. Morrison ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Calcium Imaging ◽  
Premotor Cortex ◽  
Dorsal Premotor Cortex

Conditional Selection of Contra- and Ipsilateral Forelimb Movements by the Dorsal Premotor Cortex in Monkeys

2010 ◽  
Vol 103 (1) ◽  
pp. 262-277 ◽  
Author(s):  
Kiyoshi Kurata
Keyword(s):  
Motor Behavior ◽  
Premotor Cortex ◽  
Body Movement ◽  
Low Frequency ◽  
Dorsal Premotor Cortex ◽  
Movement Initiation ◽  
Reaching Task ◽  
Instruction Selection ◽  
The Right ◽  
Selection Of

It has been suggested that the dorsal premotor cortex (PMd) may contribute to conditional motor behavior. Thus when a selection is instructed by arbitrary conditional cues, it is possible that the unilateral PMd affects behavior, regardless of which arm, contra- or ipsilateral, is to be used. We examined this possibility by recording neuronal activity and injecting muscimol into the caudal PMd (PMdc) of monkeys while they were performing a reaching task toward visuospatial targets with either the right or left arm, as instructed by low-frequency or high-frequency tone signals. Following the injection of a small amount of muscimol (1 μL; 5 μg/μL) into the unilateral PMdc, monkeys exhibited two major deficits in behavioral performance: 1) erroneous selection of the arm not indicated by the instruction (selection errors) and 2) no movement initiation in response to a visuospatial target cue serving as a trigger signal for reaching within the reaction time limit (movement initiation errors). Errors were observed following unilateral muscimol injection into both right and left PMdc, although selection errors occurred with significantly greater frequency in the arm contralateral to the injection site. By contrast, movement initiation errors were more commonly observed in left-arm trials, regardless of whether the right or left PMdc was inactivated. Notably, errors rarely occurred following a ventral PM muscimol injection. These results suggest that the left and right PMdc cooperate to transform conditional sensory cues into appropriate motor output and can affect both contra- and ipsilateral body movement.

Organization of Action Sequences and the Role of the Pre-SMA

2004 ◽  
Vol 91 (2) ◽  
pp. 978-993 ◽  
Author(s):  
Steve W. Kennerley ◽  
K. Sakai ◽  
M.F.S. Rushworth
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Motor Behavior ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Premotor Cortex ◽  
Special Role ◽  
Dorsal Premotor Cortex ◽  
Key Press ◽  
Action Sequences

To understand the contribution of the human presupplementary motor area (pre-SMA) in sequential motor behavior, we performed a series of finger key-press experiments. Experiment 1 revealed that each subject had a spontaneous tendency to organize or “chunk” a long sequence into shorter components. We hypothesized that the pre-SMA might have a special role in initiating each chunk but not at other points during the sequence. Experiment 2 therefore examined the effect of 0.5-s, 10-Hz repetitive transcranial magnetic stimulation (rTMS) directed over the pre-SMA. As hypothesized, performance was disrupted when rTMS was delivered over the pre-SMA at the beginning of the second chunk but not when it was delivered in the middle of a chunk. Contrary to the hypothesis, TMS did not disrupt sequence initiation. Experiments 3 and 4 examined whether the very first movement of a sequence could be disrupted under any circumstances. Pre-SMA TMS did disrupt the initiation of sequences but only when subjects had to switch between sequences and when the first movement of each sequence was not covertly instructed by a learned visuomotor association. In conjunction, the results suggest that for overlearned sequences the pre-SMA is primarily concerned with the initiation of a sequence or sequence chunk and the role of the pre-SMA in sequence initiation is only discerned when subjects must retrieve the sequence from memory as a superordinate set of movements without the aid of a visuomotor association. Control experiments revealed such effects were not present when rTMS was applied over the left dorsal premotor cortex.

scholarly journals Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  
Keyword(s):  
Animal Behavior ◽  
Neural Circuit ◽  
Concentration Level ◽  
Brain Regions ◽  
Mild Stress ◽  
Depression Effect ◽  
Monoamine Neurotransmitters ◽  
Reward Circuitry ◽  
High Doses ◽  
The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

scholarly journals Interactions between pairs of transcranial magnetic stimuli over the human left dorsal premotor cortex differ from those seen in primary motor cortex

2007 ◽  
Vol 578 (2) ◽  
pp. 551-562 ◽  
Author(s):  
Giacomo Koch ◽  
Michele Franca ◽  
Hitoshi Mochizuki ◽  
Barbara Marconi ◽  
Carlo Caltagirone ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Dorsal Premotor Cortex

Modest Gaze-Related Discharge Modulation in Monkey Dorsal Premotor Cortex During a Reaching Task Performed With Free Fixation

2002 ◽  
Vol 88 (2) ◽  
pp. 1064-1072 ◽  
Author(s):  
Paul Cisek ◽  
John F. Kalaska
Keyword(s):  
Premotor Cortex ◽  
Cell Activity ◽  
Delay Period ◽  
Gaze Direction ◽  
Dorsal Premotor Cortex ◽  
Experimental Conditions ◽  
Reaching Task ◽  
Oculomotor Behavior ◽  
Arm Reaching ◽  
Gaze Angle

Recent studies have shown that gaze angle modulates reach-related neural activity in many cortical areas, including the dorsal premotor cortex (PMd), when gaze direction is experimentally controlled by lengthy periods of imposed fixation. We looked for gaze-related modulation in PMd during the brief fixations that occur when a monkey is allowed to look around freely without experimentally imposed gaze control while performing a center-out delayed arm-reaching task. During the course of the instructed-delay period, we found significant effects of gaze angle in 27–51% of PMd cells. However, for 90–95% of cells, these effects accounted for <20% of the observed discharge variance. The effect of gaze was significantly weaker than the effect of reach-related variables. In particular, cell activity during the delay period was more strongly related to the intended movement expressed in arm-related coordinates than in gaze-related coordinates. Under the same experimental conditions, many cells in medial parietal cortex exhibited much stronger gaze-related modulation and expressed intended movement in gaze-related coordinates. In summary, gaze direction-related modulation of cell activity is indeed expressed in PMd during the brief fixations that occur in natural oculomotor behavior, but its overall effect on cell activity is modest.

A novel dual-site transcranial magnetic stimulation paradigm to probe fast facilitatory inputs from ipsilateral dorsal premotor cortex to primary motor cortex

NeuroImage ◽  
2012 ◽  
Vol 62 (1) ◽  
pp. 500-509 ◽  
Author(s):  
Sergiu Groppa ◽  
Nicole Werner-Petroll ◽  
Alexander Münchau ◽  
Günther Deuschl ◽  
Matthew F.S. Ruschworth ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Dorsal Premotor Cortex ◽  
Stimulation Paradigm ◽  
Dual Site

scholarly journals Seizures start as silent microseizures by neuronal ensembles

2018 ◽  
Author(s):  
Michael Wenzel ◽  
Jordan P. Hamm ◽  
Darcy S. Peterka ◽  
Rafael MD Yuste
Keyword(s):  
Calcium Imaging ◽  
Travelling Wave ◽  
Inhibitory Neurons ◽  
Neural Activation ◽  
Calcium Dynamics ◽  
Neuronal Ensembles ◽  
Two Photon ◽  
Step Model

AbstractUnderstanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.

scholarly journals Voluntary Movements Discipline Audiovisual Perception

2020 ◽  
Author(s):  
Ahmad Yousef
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Voluntary Movements ◽  
Deep Breathing ◽  
Audiovisual Perception ◽  
Cognitive Action ◽  
Actual Material

We had shown that deep breathing had been able to effectively and timely alter visual and auditory bistable perception, see reference 1, 2. Deep breathing requires cognitive control, and therefore, in this study, we decide to investigate whether voluntary movements of human hands are able to govern the audiovisual perception using an integrative stimulus that’s built up with the aforementioned visual and auditory stimuli. Astoundingly, when the human subjects moves the pen towards the actual physical direction, even without touching the screen; the original materials of the audiovisual stimulus appear. Reversed perception, namely, illusory motion reversals and illusory word appear when the pen is moved in the opposite direction of the actual motion. Cognitive actions’ brain areas, namely, dorsolateral prefrontal cortex, premotor cortex, and primary motor cortex may require high concentration of oxygenated hobgoblin red blood cells to achieve fulsome executive movements; and this could results in significant reduction of the concentrations of the oxygenated hobgoblin red blood cells in the visual and auditory cortices. Reductions that disallow one of two; the central versus the peripheral conscious brains dedicated for audiovisual perceptions, to rapidly alternate their conscious productions; and therefore, stoppage against bistable audiovisual perception will occur. We thus hypothesis that the DLPFC may send signals to deactivate the peripheral areas in the sensory brain regions when the cognitive action is harmonized with the actual material; but it may send a contrary signal to deactivate the central areas in the sensory brain regions when the cognitive action and the actual material are disharmonized.

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