Cerebral blood flow changes in maintenance hemodialysis patients with restless legs syndrome and their clinical significance:a cross-sectional case-control study.

OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.

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.

Beyond boundaries: investigating shared and divergent connectivity in the pre-/postcentral gyri and supplementary motor area.

OBJECTIVE: This study aimed to comprehensively investigate the functional connectivity of key brain regions involved in motor and sensory functions, namely the precentral gyrus, postcentral gyrus and supplementary motor area (SMA). Using advanced MRI, the objective was to understand the neurophysiological integrative characterizations of these regions by examining their connectivity with eight distinct functional brain networks. The goal was to uncover their roles beyond conventional motor and sensory functions, contributing to a more holistic understanding of brain functioning. METHODS: The study involved 198 healthy volunteers, with the primary methodology being functional connectivity analysis using advanced MRI techniques. The bilateral precentral gyrus, postcentral gyrus and SMA served as seed regions, and their connectivity with eight distinct brain regional functional networks was investigated. This approach allowed for the exploration of synchronized activity between these critical brain areas, shedding light on their integrated functioning and relationships with other brain networks. RESULTS: The study revealed a nuanced landscape of functional connectivity for the precentral gyrus, postcentral gyrus and SMA with the main functional brain networks. Despite their high functional connectedness, these regions displayed diverse functional integrations with other networks, particularly in the salience, visual, cerebellar and language networks. Specific data and statistical significance were not provided in the abstract, but the results suggested unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor and sensory functions. CONCLUSION: The study emphasized the multifaceted roles of the precentral gyrus, postcentral gyrus and SMA. Beyond their crucial involvement in motor and sensory functions, these regions exhibited varied functional integrations with different brain networks. The observed disparities, especially in the salience, visual, cerebellar and language networks, indicated a nuanced and specialized involvement of these regions in diverse cognitive functions. The study underscores the importance of considering the broader neurophysiological landscape to comprehend the intricate roles of these brain areas, contributing to ongoing efforts in unraveling the complexities of brain function.

Pharmacological adjuncts and transcranial magnetic stimulation-induced synaptic plasticity: a systematic review.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have been used to improve our fundamental understanding of TMS-induced synaptic plasticity. METHODS: We systematically reviewed the literature pairing pharmacological adjuncts with TMS plasticity-induction protocols in humans. We searched MEDLINE, PsycINFO, and Embase from 2013 to Mar. 10, 2023. Studies published before 2013 were extracted from a previous systematic review. We included studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. RESULTS: Thirty-six studies met our inclusion criteria (28 in healthy and 8 in clinical populations). Most pharmacological agents have targeted the glutamatergic N-methyl-d-aspartate (NMDA; 15 studies) or dopamine receptors (13 studies). The NMDA receptor is necessary for TMS-induced plasticity; however, sufficiency has not been shown across protocols. Dopaminergic modulation of TMS-induced plasticity appears to be dose-dependent. The GABAergic, cholinergic, noradrenergic, and serotonergic neurotransmitter systems have small evidence bases supporting modulation of TMS-induced plasticity, as do voltage-gated calcium and sodium channels. Studies in clinical populations suggest that pharmacological adjuncts to TMS may rescue motor cortex plasticity, with implications for therapeutic applications of TMS and a promising clinical trial in depression. LIMITATIONS: This review is limited by the predominance in the literature of studies with small sample sizes and crossover designs. CONCLUSION: Pharmacologically enhanced TMS largely parallels findings from ex vivo preparations. As this area expands and novel targets are tested, adequately powered samples in healthy and clinical populations will inform the mechanisms of TMS-induced plasticity in health and disease.

Communication defects with astroglia contribute to early impairments in the motor cortex plasticity of SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1G93A mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 of SOD1G93A mice, throughout disease progression. Results showed that astrocytes are involved in synaptic dysfunction observed in presymptomatic SOD1G93A mice, since astrocytic glutamate transport currents are diminished and pharmacological inhibition of astrocytes only impaired long-term potentiation and basal transmission in wild-type mice. Proteomic analysis revealed major differences in neuronal transmission, metabolism, and immune system in upper synapses, confirming early communication deficits between neurons and astroglia. These results provide valuable insights into the early impact of upper synapses in ALS and the lack of supportive functions of cortical astrocytes, highlighting the possibility of manipulating astrocytes to improve synaptic function.

Cerebellar Purkinje cell firing promotes conscious recovery from anesthesia state through coordinating neuronal communications with motor cortex.

Background: The neurobiological basis of gaining consciousness from unconscious state induced by anesthetics remains unknown. This study was designed to investigate the involvement of the cerebello-thalamus-motor cortical loop mediating consciousness transitions from the loss of consciousness (LOC) induced by an inhalational anesthetic sevoflurane in mice. Methods: The neural tracing and fMRI together with opto-chemogenetic manipulation were used to investigate the potential link among cerebello-thalamus-motor cortical brain regions. The fiber photometry of calcium and neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA) and norepinephrine (NE), were monitored from the motor cortex (M1) and the 5th lobule of the cerebellar vermis (5Cb) during unconsciousness induced by sevoflurane and gaining consciousness after sevoflurane exposure. Cerebellar Purkinje cells were optogenetically manipulated to investigate their influence on consciousness transitions during and after sevoflurane exposure. Results: Activation of 5Cb Purkinje cells increased the Ca2+ flux in the M1 CaMKIIα+ neurons, but this increment was significantly reduced by inactivation of posterior and parafascicular thalamic nucleus. The 5Cb and M1 exhibited concerted calcium flux, and glutamate and GABA release during transitions from wakefulness, loss of consciousness, burst suppression to conscious recovery. Ca2+ flux and Glu release in the M1, but not in the 5Cb, showed a strong synchronization with the EEG burst suppression, particularly, in the gamma-band range. In contrast, the Glu, GABA and NE release and Ca2+ oscillations were coherent with the EEG gamma band activity only in the 5Cb during the pre-recovery of consciousness period. The optogenetic activation of Purkinje cells during burst suppression significantly facilitated emergence from anesthesia while the optogenetic inhibition prolonged the time to gaining consciousness. Conclusions: Our data indicate that cerebellar neuronal communication integrated with motor cortex through thalamus promotes consciousness recovery from anesthesia which may likely serve as arousal regulation.

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.

Participation of the nucleus tractus solitarius in the therapeutic effect of electroacupuncture on post-stroke dysphagia through the primary motor cortex.

BACKGROUND: Post-stroke dysphagia (PSD), a common and serious disease, affects the quality of life of many patients and their families. Electroacupuncture (EA) has been commonly used effectively in the treatment of PSD, but the therapeutic mechanism is still under exploration at present. We aim to investigate the effect of the nucleus tractus solitarus (NTS) on the treatment of PSD by EA at Lianquan (CV23) through the primary motor cortex (M1). METHODS: C57 male mice were used to construct a PSD mouse model using photothrombotic technique, and the swallowing function was evaluated by electromyography (EMG) recording. C-Fos-positive neurons and types of neurons in the NTS were detected by immunofluorescence. Optogenetics and chemical genetics were used to regulate the NTS, and the firing rate of neurons was recorded via multichannel recording. RESULTS: The results showed that most of the activated neurons in the NTS were excitatory neurons, and multichannel recording indicated that the activity levels of both pyramidal neurons and interneurons in the NTS were regulated by M1. This process was involved in the EA treatment. Furthermore, while chemogenetic inhibition of the NTS reduced the EMG signal associated with the swallowing response induced by activation of M1 in PSD mice, EA rescued this signal. CONCLUSION: Overall, the NTS was shown to participate in the regulation of PSD by EA at CV23 through M1.

Reshaping the Cortical Connectivity Gradient by Long-Term Cognitive Training During Development.

The organization of the brain follows a topological hierarchy that changes dynamically during development. However, it remains unknown whether and how cognitive training administered over multiple years during development can modify this hierarchical topology. By measuring the brain and behavior of school children who had carried out abacus-based mental calculation (AMC) training for five years (starting from 7 years to 12 years old) in pre-training and post-training, we revealed the reshaping effect of long-term AMC intervention during development on the brain hierarchical topology. We observed the development-induced emergence of the default network, AMC training-promoted shifting, and regional changes in cortical gradients. Moreover, the training-induced gradient changes were located in visual and somatomotor areas in association with the visuospatial/motor-imagery strategy. We found that gradient-based features can predict the math ability within groups. Our findings provide novel insights into the dynamic nature of network recruitment impacted by long-term cognitive training during development.

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.

Short-Term Effects of Gamma Stimulation on Neuroinflammation at the Tissue-Electrode Interface in Motor Cortex.

OBJECTIVES: The reliability of long-term neural recordings as therapeutic interventions for motor and sensory disorders is hampered by the brain tissue response. Previous work showed that flickering light at gamma frequencies (ie, 20-50 Hz) causes enhanced microglial recruitment in the visual cortex. The effects of gamma stimulation on glial cells surrounding implanted neural electrodes are not well understood. We hypothesized that invasive stimulation in the gamma frequency band increases microglial recruitment in the short term and reduces astrogliosis at the tissue-electrode interface. MATERIALS AND METHODS: Male Long Evans rats were implanted with dual-shank silicon microelectrode arrays into the motor cortex. After implantation, rats received one hour of 40-Hz stimulation at a constant current of 10 µA using charge-balanced, biphasic pulses on one shank, and the other shank served as the nonstimulated control. Postmortem, tissue sections were stained with ectodermal dysplasia 1 (ED1) for activated microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and 4',6-diamidino-2-phenylindole (DAPI) for nonspecific nuclei. Fluorescent intensity and cell number as a function of distance from the tissue-electrode interface were used to quantify all stained sections. RESULTS: Fluorescent intensity for ED1 was nearly 40% lower for control than for stimulated sites (0-500 µm away from the implant), indicating increased microglial recruitment to the stimulated site (p < 0.05). Fluorescent intensity for GFAP was >67% higher for control than for stimulated sites (0-500 µm away from the implant), indicating reduced astrogliosis at the stimulated site (p < 0.05). No differences were observed in DAPI-stained sections between conditions. CONCLUSIONS: These results suggest that short-term gamma stimulation modulates glial recruitment in the immediate vicinity of the microelectrode. Future studies will investigate the long-term effects of gamma stimulation on glial recruitment at the tissue-electrode interface as a strategy to improve long-term recording reliability.

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.

Impact of the baseline temporal selection on the ERD/ERS analysis for Motor Imagery-based BCI.

Motor Imagery-based Brain-Computer Interfaces (MI-BCIs) are neurotechnologies that exploit the modulation of sensorimotor rhythms over the motor cortices, respectively known as Event-Related Desynchronization (ERD) and Synchronization (ERS). The interpretation of ERD/ERS is directly related to the selection of the baseline used to estimate them, and might result in a misleading ERD/ERS visualization. In fact, in BCI paradigms, if two trials are separated by a few seconds, taking a baseline close to the end of the previous trial could result in an over-estimation of the ERD, while taking a baseline too close to the upcoming trial could result in an under-estimation of the ERD. This phenomenon may cause a functional misinterpretation of the ERD/ERS phenomena in MI-BCI studies. This may also impair BCI performances for MI vs Rest classification, since such baselines are often used as resting states. In this paper, we propose to investigate the effect of several baseline time window selections on ERD/ERS modulations and BCI performances. Our results show that considering the selected temporal baseline effect is essential to analyze the modulations of ERD/ERS during MI-BCI use.

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.

A thalamocortical pathway controlling impulsive behavior.

Planning and anticipating motor actions enables movements to be quickly and accurately executed. However, if anticipation is not properly controlled, it can lead to premature impulsive actions. Impulsive behavior is defined as actions that are poorly conceived and are often risky and inappropriate. Historically, impulsive behavior was thought to be primarily controlled by the frontal cortex and basal ganglia. More recently, two additional brain regions, the ventromedial (VM) thalamus and the anterior lateral motor cortex (ALM), have been shown to have an important role in mice. Here, we explore this newly discovered role of the thalamocortical pathway and suggest cellular mechanisms that may be involved in driving the cortical activity that contributes to impulsive behavior.

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.

Neuronal Plasticity and Age-Related Functional Decline in the Motor Cortex.

Physiological aging causes a decline of motor function due to impairment of motor cortex function, losses of motor neurons and neuromuscular junctions, sarcopenia, and frailty. There is increasing evidence suggesting that the changes in motor function start earlier in the middle-aged stage. The mechanism underlining the middle-aged decline in motor function seems to relate to the central nervous system rather than the peripheral neuromuscular system. The motor cortex is one of the responsible central nervous systems for coordinating and learning motor functions. The neuronal circuits in the motor cortex show plasticity in response to motor learning, including LTP. This motor cortex plasticity seems important for the intervention method mechanisms that revert the age-related decline of motor function. This review will focus on recent findings on the role of plasticity in the motor cortex for motor function and age-related changes. The review will also introduce our recent identification of an age-related decline of neuronal activity in the primary motor cortex of middle-aged mice using electrophysiological recordings of brain slices.

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.