Multi-scale analysis of acupuncture mechanisms for motor and sensory cortex activity based on SEEG data.

Acupuncture, a traditional Chinese therapy, is gaining attention for its impact on the brain. While existing electroencephalogram and functional magnetic resonance image research has made significant contributions, this paper utilizes stereo-electroencephalography data for a comprehensive exploration of neurophysiological effects. Employing a multi-scale approach, channel-level analysis reveals notable $\delta $-band activity changes during acupuncture. At the brain region level, acupuncture modulated connectivity between the paracentral lobule and the precentral gyrus. Whole-brain analysis indicates acupuncture's influence on network organization, and enhancing $E_{glob}$ and increased interaction between the motor and sensory cortex. Brain functional reorganization is an important basis for functional recovery or compensation after central nervous system injury. The use of acupuncture to stimulate peripheral nerve trunks, muscle motor points, acupoints, etc., in clinical practice may contribute to the reorganization of brain function. This multi-scale perspective provides diverse insights into acupuncture's effects. Remarkably, this paper pioneers the introduction of stereo-electroencephalography data, advancing our understanding of acupuncture's mechanisms and potential therapeutic benefits in clinical settings.

Bilateral Whisker Representations in the Primary Somatosensory Cortex in Robo3cKO Mice Are Reflected in the Primary Motor Cortex.

In Robo3cKO mice, midline crossing defects of the trigeminothalamic projections from the trigeminal principal sensory nucleus result in bilateral whisker maps in the somatosensory thalamus and consequently in the face representation area of the primary somatosensory (S1) cortex (Renier et al., 2017; Tsytsarev et al., 2017). We investigated whether this bilateral sensory representation in the whisker-barrel cortex is also reflected in the downstream projections from the S1 to the primary motor (M1) cortex. To label these projections, we injected anterograde viral axonal tracer in S1 cortex. Corticocortical projections from the S1 distribute to similar areas across the ipsilateral hemisphere in control and Robo3cKO mice. Namely, in both genotypes they extend to the M1, premotor/prefrontal cortex (PMPF), secondary somatosensory (S2) cortex. Next, we performed voltage-sensitive dye imaging (VSDi) in the left hemisphere following ipsilateral and contralateral single whisker stimulation. While controls showed only activation in the contralateral whisker barrel cortex and M1 cortex, the Robo3cKO mouse left hemisphere was activated bilaterally in both the barrel cortex and the M1 cortex. We conclude that the midline crossing defect of the trigeminothalamic projections leads to bilateral whisker representations not only in the thalamus and the S1 cortex but also downstream from the S1, in the M1 cortex.

Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans.

BACKGROUND: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. OBJECTIVE/HYPOTHESIS: The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. METHODS: We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). RESULTS: Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. CONCLUSIONS: Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.

Motor cortex activation during visuomotor transformations: evoked potentials during overt and imagined movements.

Despite the prevalence of visuomotor transformations in our motor skills, their mechanisms remain incompletely understood, especially when imagery actions are considered such as mentally picking up a cup or pressing a button. Here, we used a stimulus-response task to directly compare the visuomotor transformation underlying overt and imagined button presses. Electroencephalographic activity was recorded while participants responded to highlights of the target button while ignoring the second, non-target button. Movement-related potentials (MRPs) and event-related desynchronization occurred for both overt movements and motor imagery (MI), with responses present even for non-target stimuli. Consistent with the activity accumulation model where visual stimuli are evaluated and transformed into the eventual motor response, the timing of MRPs matched the response time on individual trials. Activity-accumulation patterns were observed for MI, as well. Yet, unlike overt movements, MI-related MRPs were not lateralized, which appears to be a neural marker for the distinction between generating a mental image and transforming it into an overt action. Top-down response strategies governing this hemispheric specificity should be accounted for in future research on MI, including basic studies and medical practice.

Motor cortex transcranial direct current stimulation improves non-motor symptoms in early-onset Parkinson's disease: a pilot study.

Early-onset Parkinson's Disease (EOPD) demands tailored treatments. The younger age of patients might account for a higher sensitivity to transcranial direct current stimulation (tDCS) based non-invasive neuromodulation, which may raise as an integrative therapy in the field. Accordingly, here we assessed the safety and efficacy of the primary left motor cortex (M1) anodal tDCS in EOPD. Ten idiopathic EOPD patients received tDCS at 2.0 mA per 20 min for 10 days within a crossover, double-blind, sham-controlled pilot study. The outcome was evaluated by measuring changes in MDS-UPDRS part III, Non-Motor Symptoms Scale (NMSS), PD-cognitive rating scale, and PD Quality of Life Questionnaire-39 scores. We showed that anodal but not sham tDCS significantly reduced the NMSS total and "item 2" (sleep/fatigue) scores. Other parameters were not modified. No adverse events occurred. M1 anodal tDCS might thus evoke plasticity changes in cortical-subcortical circuits involved in non-motor functions, supporting the value as a therapeutic option in EOPD.

The Effects of Different Brain Regions on fNIRS-based Task-state Detection in Speech Imagery.

Brain-computer interface (BCI) based on speech imagery can decode users' verbal intent and help people with motor disabilities communicate naturally. Functional near-infrared spectroscopy (fNIRS) is a commonly used brain signal acquisition method. Asynchronous BCI can response to control commands at any time, which provides great convenience for users. Task state detection, defined as identifying whether user starts or continues covertly articulating, plays an important role in speech imagery BCIs. To better distinguish task state from idle state during speech imagery, this work used fNIRS signals from different brain regions to study the effects of different brain regions on task state detection accuracy. The imagined tonal syllables included four lexical tones and four vowels in Mandarin Chinese. The brain regions that were measured included Broca's area, Wernicke's area, Superior temporal cortex and Motor cortex. Task state detection accuracies of imagining tonal monosyllables with four different tones were analyzed. The average accuracy of four speech imagery tasks based on the whole brain was 0.67 and it was close to 0.69, which was the average accuracy based on Broca's area. The accuracies of Broca's area and the whole brain were significantly higher than those of other brain regions. The findings of this work demonstrated that using a few channels of Broca's area could result in a similar task state detection accuracy to that using all the channels of the brain. Moreover, it was discovered that speech imagery with tone 2/3 tasks yielded higher task state detection accuracy than speech imagery with other tones.

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OBJECTIVES: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. METHODS: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). RESULTS: The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). CONCLUSIONS: Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Emergence of cortical network motifs for short-term memory during learning.

Learning of adaptive behaviors requires the refinement of coordinated activity across multiple brain regions. However, how neural communications develop during learning remains poorly understood. Here, using two-photon calcium imaging, we simultaneously recorded the activity of layer 2/3 excitatory neurons in eight regions of the mouse dorsal cortex during learning of a delayed-response task. Across learning, while global functional connectivity became sparser, there emerged a subnetwork comprising of neurons in the anterior lateral motor cortex (ALM) and posterior parietal cortex (PPC). Neurons in this subnetwork shared a similar choice code during action preparation and formed recurrent functional connectivity across learning. Suppression of PPC activity disrupted choice selectivity in ALM and impaired task performance. Recurrent neural networks reconstructed from ALM activity revealed that PPC-ALM interactions rendered choice-related attractor dynamics more stable. Thus, learning constructs cortical network motifs by recruiting specific inter-areal communication channels to promote efficient and robust sensorimotor transformation.

Layer 5 Intratelencephalic Neurons in the Motor Cortex Stably Encode Skilled Movement.

The primary motor cortex (M1) and the dorsal striatum play a critical role in motor learning and the retention of learned behaviors. Motor representations of corticostriatal ensembles emerge during motor learning. In the coordinated reorganization of M1 and the dorsal striatum for motor learning, layer 5a (L5a) which connects M1 to the ipsilateral and contralateral dorsal striatum, should be a key layer. Although M1 L5a neurons represent movement-related activity in the late stage of learning, it is unclear whether the activity is retained as a memory engram. Here, using Tlx3-Cre male transgenic mice, we conducted two-photon calcium imaging of striatum-projecting L5a intratelencephalic (IT) neurons in forelimb M1 during late sessions of a self-initiated lever-pull task and in sessions after 6 d of nontraining following the late sessions. We found that trained male animals exhibited stable motor performance before and after the nontraining days. At the same time, we found that M1 L5a IT neurons strongly represented the well-learned forelimb movement but not uninstructed orofacial movements. A subset of M1 L5a IT neurons consistently coded the well-learned forelimb movement before and after the nontraining days. Inactivation of M1 IT neurons after learning impaired task performance when the lever was made heavier or when the target range of the pull distance was narrowed. These results suggest that a subset of M1 L5a IT neurons continuously represent skilled movement after learning and serve to fine-tune the kinematics of well-learned movement.SIGNIFICANCE STATEMENT Motor memory persists even when it is not used for a while. IT neurons in L5a of the M1 gradually come to represent skilled forelimb movements during motor learning. However, it remains to be determined whether these changes persist over a long period and how these neurons contribute to skilled movements. Here, we show that a subset of M1 L5a IT neurons retain information for skilled forelimb movements even after nontraining days. Furthermore, suppressing the activity of these neurons during skilled forelimb movements impaired behavioral stability and adaptability. Our results suggest the importance of M1 L5a IT neurons for tuning skilled forelimb movements over a long period.

Individual Differences in Decision Strategy Relate to Neurochemical Excitability and Cortical Thickness.

The speed-accuracy trade-off (SAT), whereby faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during the performance of almost all daily tasks. To date, computational modeling has implicated the latent decision variable of response caution (thresholds), the amount of evidence required for a decision to be made, in the SAT. Previous imaging has associated frontal regions, notably the left prefrontal cortex and the presupplementary motor area (pre-SMA), with the setting of such caution levels. In addition, causal brain stimulation studies, using transcranial direct current stimulation (tDCS), have indicated that while both of these regions are involved in the SAT, their role appears to be dissociable. tDCS efficacy to impact decision-making processes has previously been linked with neurochemical concentrations and cortical thickness of stimulated regions. However, to date, it is unknown whether these neurophysiological measures predict individual differences in the SAT, and brain stimulation effects on the SAT. Using ultra-high field (7T) imaging, here we report that instruction-based adjustments in caution are associated with both neurochemical excitability (the balance between GABA+ and glutamate) and cortical thickness across a range of frontal regions in both sexes. In addition, cortical thickness, but not neurochemical concentrations, was associated with the efficacy of left prefrontal and superior medial frontal cortex (SMFC) stimulation to modulate performance. Overall, our findings elucidate key neurophysiological predictors, frontal neural excitation, of individual differences in latent psychological processes and the efficacy of stimulation to modulate these.SIGNIFICANCE STATEMENT The speed-accuracy trade-off (SAT), faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during most daily tasks. The SAT is often investigated by explicitly instructing participants to prioritize speed or accuracy when responding to stimuli. Using ultra-high field (7T) magnetic resonance imaging (MRI), we found that individual differences in the extent to which participants adjust their decision strategies with instruction related to neurochemical excitability (ratio of GABA+ to glutamate) and cortical thickness in the frontal cortex. Moreover, brain stimulation to the left prefrontal cortex and the superior medial frontal cortex (SMFC) modulated performance, with the efficacy specifically related to cortical thickness. This work sheds new light on the neurophysiological basis of decision strategies and brain stimulation.

The severity of acute hypoxaemia determines distinct changes in intracortical and spinal neural circuits.

The purpose of this study was to examine how two common methods of continuous hypoxaemia impact the activity of intracortical circuits responsible for inhibition and facilitation of motor output, and spinal excitability. Ten participants were exposed to 2 h of hypoxaemia at 0.13 fraction of inspired oxygen ( F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol) and 80% of peripheral capillary oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol) using a simulating altitude device on two visits separated by a week. Using transcranial magnetic and peripheral nerve stimulation, unconditioned motor evoked potential (MEP) area, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and F-wave persistence and area were assessed in the first dorsal interosseous (FDI) muscle before titration, after 1 and 2 h of hypoxic exposure, and at reoxygenation. The clamping protocols resulted in differing reductions in S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ by 2 h ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol: 81.9 ± 1.3%, F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol: 90.6 ± 2.5%). Although unconditioned MEP peak to peak amplitude and area did not differ between the protocols, SICI during F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping was significantly lower at 2 h compared to S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping (P = 0.011) and baseline (P < 0.001), whereas ICF was higher throughout the F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping compared to S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping (P = 0.005). Furthermore, a negative correlation between SICI and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (rrm  = -0.56, P = 0.002) and a positive correlation between ICF and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (rrm  = 0.69, P = 0.001) were determined, where greater reductions in S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ correlated with less inhibition and less facilitation of MEP responses. Although F-wave area progressively increased similarly throughout the protocols (P = 0.037), persistence of responses was reduced at 2 h and reoxygenation (P < 0.01) during the S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol compared to the F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol. After 2 h of hypoxic exposure, there is a reduction in the activity of intracortical circuits responsible for inhibiting motor output, as well as excitability of spinal motoneurones. However, these effects can be influenced by other physiological responses to hypoxia (i.e., hyperventilation and hypocapnia). NEW FINDINGS: What is the central question of this study? How do two common methods of acute hypoxic exposure influence the excitability of intracortical networks and spinal circuits responsible for motor output? What is the main finding and its importance? The excitability of spinal circuits and intracortical networks responsible for inhibition of motor output was reduced during severe acute exposure to hypoxia at 2 h, but this was not seen during less severe exposure. This provides insight into the potential cause of variance seen in motor evoked potential responses to transcranial magnetic stimulation (corticospinal excitability measures) when exposed to hypoxia.

Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.

Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in deep layer pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 µm-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disrupted dendritic arbors and a significant reduction in spine densities in neurons surrounding devices. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents, a reduction in sag amplitude, an increase in spike frequency adaptation, and an increase in filopodia density. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes. STATEMENT OF SIGNIFICANCE: Implanted electrodes in the brain can be used to treat sources of pathology and understand normal physiology by recording or stimulating electrical signals generated by local neurons. However, a foreign body response following implantation undermines the performance of these devices. While several studies have investigated the biological mechanisms of device-tissue interactions through histology, transcriptomics, and imaging, our study is the first to directly interrogate effects on the function of neurons surrounding electrodes using single-cell electrophysiology. Additionally, we provide new, detailed assessments of the impacts of electrodes on the dendritic structure and spine morphology of neurons, and we assess effects for both traditional (silicon) and newer polymer electrode materials. These results reveal new potential mechanisms of electrode-tissue interactions.

Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics.

Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, and dendritic synapse locations are constrained by experimental data. The model includes long-range inputs from seven thalamic and cortical regions and noradrenergic inputs. Connectivity depends on cell class and cortical depth at sublaminar resolution. The model accurately predicts in vivo layer- and cell-type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blockade and thalamus inactivation). We generate mechanistic hypotheses underlying the observed activity and analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell-type-specific multiscale dynamics associated with several experimental conditions and behaviors.

Event-Related Desynchronization Induced by Tactile Imagery: an EEG Study.

It is well known that both hand movements and mental representations of movement lead to event-related desynchronization (ERD) of the electroencephalogram (EEG) recorded over the corresponding cortical motor areas. However, the relationship between ERD in somatosensory cortical areas and mental representations of tactile sensations is not well understood. In this study, we employed EEG recordings in healthy humans to compare the effects of real and imagined vibrotactile stimulation of the right hand. Both real and imagined sensations produced contralateral ERD patterns, particularly in the µ-band and most significantly in the C3 region. Building on these results and the previous literature, we discuss the role of tactile imagery as part of the complex body image and the potential for using EEG patterns induced by tactile imagery as control signals in brain-computer interfaces (BCIs). Combining this approach with motor imagery (MI) could improve the performance of BCIs intended for rehabilitation of sensorimotor function after stroke and neural trauma.

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex.

AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.

Whole brain inputs to major descending pathways of the anterior lateral motor cortex.

The anterior lateral motor cortex (ALM) is critical to subsequent correct movements and plays a vital role in predicting specific future movements. Different descending pathways of the ALM are preferentially involved in different roles in movements. However, the circuit function mechanisms of these different pathways may be concealed in the anatomy circuit. Clarifying the anatomy inputs of these pathways should provide some helpful information for elucidating these function mechanisms. Here, we used a retrograde trans-synaptic rabies virus to systematically generate, analyze, and compare whole brain maps of inputs to the thalamus (TH)-, medulla oblongata (Med)-, superior colliculus (SC)-, and pontine nucleus (Pons)-projecting ALM neurons in C57BL/6J mice. Fifty-nine separate regions from nine major brain areas projecting to the descending pathways of the ALM were identified. Brain-wide quantitative analyses revealed identical whole brain input patterns between these descending pathways. Most inputs to the pathways originated from the ipsilateral side of the brain, with most innervations provided by the cortex and TH. The contralateral side of the brain also sent sparse projections, but these were rare, emanating only from the cortex and cerebellum. Nevertheless, the inputs received by TH-, Med-, SC-, and Pons-projecting ALM neurons had different weights, potentially laying an anatomical foundation for understanding the diverse functions of well-defined descending pathways of the ALM. Our findings provide anatomical information to help elucidate the precise connections and diverse functions of the ALM.NEW & NOTEWORTHY Distinct descending pathways of anterior lateral motor cortex (ALM) share common inputs. These inputs are with varied weights. Most inputs were from the ipsilateral side of brain. Preferential inputs were provided by cortex and thalamus (TH).

Task-specific modulation of corticospinal neuron activity during motor learning in mice.

Motor skill learning relies on the plasticity of the primary motor cortex as task acquisition drives cortical motor network remodeling. Large-scale cortical remodeling of evoked motor outputs occurs during the learning of corticospinal-dependent prehension behavior, but not simple, non-dexterous tasks. Here we determine the response of corticospinal neurons to two distinct motor training paradigms and assess the role of corticospinal neurons in the execution of a task requiring precise modulation of forelimb movement and one that does not. In vivo calcium imaging in mice revealed temporal coding of corticospinal activity coincident with the development of precise prehension movements, but not more simplistic movement patterns. Transection of the corticospinal tract and optogenetic regulation of corticospinal activity show the necessity for patterned corticospinal network activity in the execution of precise movements but not simplistic ones. Our findings reveal a critical role for corticospinal network modulation in the learning and execution of precise motor movements.

Parietal/premotor lesions effects on visuomotor cognition in neuro-oncology patients: A multimodal study.

BACKGROUND: Assessing prior to surgery the functionality of brain areas exposed near the tumor requires a multimodal approach that combines the use of neuropsychological testing and fMRI tasks. Paradigms based on motor imagery, which corresponds to the ability to mentally evoke a movement, in the absence of actual action execution, can be used to test sensorimotor areas and the functionality of mental motor representations. METHODS: The most commonly used paradigm is the Limb Laterality Recognition Task (LLRT), requiring judgments about whether a limb belongs to the left or right side of the body. The group studied included 38 patients with high-grade (N = 21), low-grade (N = 11) gliomas and meningiomas (N = 6) in areas anterior (N = 21) and posterior (N = 17) to the central sulcus. Patients before surgery underwent neuropsychological assessment and fMRI. They performed the LLRT as an fMRI task. Accuracy, and neuroimaging data were collected and combined in a multimodal study. Structural MRI data analyses were performed by subtracting the overlap of volumes of interest (VOIs) plotted on lesions from the impaired patient group vs the overlap of VOIs from the spared group. The fMRI analyses were performed comparing the impaired patients and spared group. RESULTS: In general, patients were within normal limits on many neuropsychological screening tests. Compared with the control group, 17/38 patients had significantly different performance. The subtraction between the VOIs overlay of the impaired patients' group vs. the VOIs overlay of the spared group revealed that the areas maximally involved by lesions in the impaired patients' group were the right postcentral gyrus, right inferior parietal lobe, right supramarginal gyrus, right precentral gyrus, paracentral lobule, left postcentral gyrus, right superior parietal lobe, left inferior parietal lobe, and left superior and middle frontal gyrus. Analysis of the fMRI data showed which of these areas contributes to a correct LLRT performance. The task (vs. rest) in the group comparison (spared vs. impaired patients) activated a cluster in the left inferior parietal lobe. CONCLUSION: Underlying the altered performance at LLRT in patients with lesions to the parietal and premotor areas of the right and left hemispheres is a difference in activation of the left inferior parietal lobe. This region is involved in visuomotor processes and those related to motor attention, movement selection, and motor planning.

Motor cortex projections to red and pontine nuclei have distinct roles during movement in the mouse.

Motor control largely depends on the deep layer 5 (L5) pyramidal neurons that project to subcortical structures. However, it is largely unknown if these neurons are functionally segregated with distinct roles in movement performance. Here, we analyzed mouse motor cortex L5 pyramidal neurons projecting to the red and pontine nuclei during movement preparation and execution. Using photometry to analyze the calcium activity of L5 pyramidal neurons projecting to the red nucleus and pons, we reveal that both types of neurons activate with different temporal dynamics. Optogenetic inhibition of either kind of projection differentially affects forelimb movement onset and execution in a lever press task, but only the activity of corticopontine neurons is significantly correlated with trial-by-trial variations in reaction time. The results indicate that cortical neurons projecting to the red and pontine nuclei contribute differently to sensorimotor integration, suggesting that L5 output neurons are functionally compartmentalized generating, in parallel, different downstream information.

A C-shaped miniaturized coil for transcranial magnetic stimulation in rodents.

Objective.Transcranial magnetic stimulation (TMS) is a non-invasive technique widely used for neuromodulation. Animal models are essential for investigating the underlying mechanisms of TMS. However, the lack of miniaturized coils hinders the TMS studies in small animals, since most commercial coils are designed for humans and thus incapable of focal stimulation in small animals. Furthermore, it is difficult to perform electrophysiological recordings at the TMS focal point using conventional coils.Approach.We designed, fabricated, and tested a novel miniaturized TMS coil (4-by-7 mm) that consisted of a C-shaped iron powder core and insulated copper wires (30 turns). The resulting magnetic and electric fields were characterized with experimental measurements and finite element modeling. The efficacy of this coil in neuromodulation was validated with electrophysiological recordings of single-unit activities (SUAs), somatosensory evoked potentials (SSEPs), and motor evoked potentials (MEPs) in rats (n= 32) following repetitive TMS (rTMS; 3 min, 10 Hz).Main results.This coil could generate a maximum magnetic field of 460 mT and an electric field of 7.2 V m-1in the rat brain according to our simulations. With subthreshold rTMS focally delivered over the sensorimotor cortex, mean firing rates of primary somatosensory and motor cortical neurons significantly increased (154±5% and 160±9% from the baseline level, respectively); MEP and SSEP amplitude significantly increased (136±9%) and decreased (74±4%), respectively.Significance.This miniaturized C-shaped coil enabled focal TMS and concurrent electrophysiological recording/stimulation at the TMS focal point. It provided a useful tool to investigate the neural responses and underlying mechanisms of TMS in small animal models. Using this paradigm, we for the first time observed distinct modulatory effects on SUAs, SSEPs, and MEPs with the same rTMS protocol in anesthetized rats. These results suggested that multiple neurobiological mechanisms in the sensorimotor pathways were differentially modulated by rTMS.