Evaluation of Medial Olivocochlear Neural Efferent Pathway in Tinnitus Perception in Normal-hearing Individuals.

OBJECTIVE: The objective of this study is to investigate a possible role of the Medial Olivocochlear (MOC) efferent neural pathway and neural connections responsible for tinnitus generation in silence/sensory deprivation. DESIGN: By placing normal hearing participants in a sound booth for 10 minutes, silence/sensory deprivation was created. This offered assessment of MOC neural pathway in normal hearing participants in silence. Hyperactivity of MOC neural pathway was assessed by its more suppressive effect on Transient Otoacoustic Emissions (TEOAEs) in silence. The required auditory measurements were recorded in the sound booth using recommended diagnostic protocols to ensure the effect of 'only silence' on auditory structures. TEOAE were recorded from the right ear and suppression was measured by placing noise in the left ear. Fifty-eight normal hearing male individuals between age 18-35 years were recruited as participants in this study. RESULTS: Approximately, forty-one percent of the participants perceived some type of tinnitus during/after 10 minutes of silence. No statistically significant difference was found in the total TEOAE amplitude and TEOAE suppression amplitude before and after ten minutes of silence. Post silence total TEOAE suppression between tinnitus perceiving and non-perceiving tinnitus participants were not statistically significantly different. CONCLUSION: These results suggest that the medial olivocochlear efferent pathway or lower brain stem area does not appear to play a role in the emergence of temporary tinnitus in silence however indicate the involvement of higher central auditory nervous system structures in perception of the tinnitus which support the well-accepted notion that tinnitus is the central auditory processing phenomenon.

The medial olivocochlear reflex strength is modulated during a visual working memory task.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (13 males, mean age 25.3 yr) with normal hearing performed a visual change detection task with different VWM load conditions (high load = 4 visual objects; low load = 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAEs) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n = 21) compared with control experiments (n = 10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.NEW & NOTEWORTHY The auditory efferent system has been proposed to function as a biological filter of cochlear responses during selective attention. Here, we recorded electroencephalographic activity and otoacoustic emissions in response to auditory distractors during a visual working memory task in humans. We found that the olivocochlear efferent activity is modulated during the visual working memory period suggesting a common mechanism for suppressing cochlear responses during selective attention and working memory.

Central Neurocircuits Regulating Food Intake in Response to Gut Inputs-Preclinical Evidence.

The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake.

Transcranial Random Noise Stimulation Acutely Lowers the Response Threshold of Human Motor Circuits.

Transcranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioral effect is stochastic resonance (SR), a mechanism that explains how signal processing in nonlinear systems can benefit from added noise. While acute noise benefits of electrical RNS have been demonstrated at the behavioral level as well as in in vitro preparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Here, we hypothesized that acute tRNS will increase the responsiveness of primary motor cortex (M1) when probed with transcranial magnetic stimulation (TMS). Neural responsiveness was operationalized via the well-known concept of the resting motor threshold (RMT). We showed that tRNS acutely decreases RMT. This effect was small, but it was consistently replicated across four experiments including different cohorts (total N = 81, 46 females, 35 males), two tRNS electrode montages, and different control conditions. Our experiments provide critical neurophysiological evidence that tRNS can acutely generate noise benefits by enhancing the neural population response of human M1.SIGNIFICANCE STATEMENT A hallmark feature of stochastic resonance (SR) is that signal processing can benefit from added noise. This has mainly been demonstrated at the single-cell level in vitro where the neural response to weak input signals can be enhanced by simultaneously applying random noise. Our finding that transcranial random noise stimulation (tRNS) acutely increases the excitability of corticomotor circuits extends the principle of noise benefits to the neural population level in human cortex. Our finding is in line with the notion that tRNS might affect cortical processing via the SR phenomenon. It suggests that enhancing the response of cortical populations to an external stimulus might be one neurophysiological mechanism mediating performance improvements when tRNS is applied to sensory cortex during perception tasks.

Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice.

The parabrachial nucleus (PB) is a complex structure located at the junction of the midbrain and hindbrain. Its neurons have diverse genetic profiles and influence a variety of homeostatic functions. While its cytoarchitecture and overall efferent projections are known, we lack comprehensive information on the projection patterns of specific neuronal subtypes in the PB. In this study, we compared the projection patterns of glutamatergic neurons here with a subpopulation expressing the transcription factor Foxp2 and a further subpopulation expressing the neuropeptide Pdyn. To do this, we injected an AAV into the PB region to deliver a Cre-dependent anterograde tracer (synaptophysin-mCherry) in three different strains of Cre-driver mice. We then analyzed 147 neuroanatomical regions for labeled boutons in every brain (n = 11). Overall, glutamatergic neurons in the PB region project to a wide variety of sites in the cerebral cortex, basal forebrain, bed nucleus of the stria terminalis, amygdala, diencephalon, and brainstem. Foxp2 and Pdyn subpopulations project heavily to the hypothalamus, but not to the cortex, basal forebrain, or amygdala. Among the few differences between Foxp2 and Pdyn cases was a notable lack of Pdyn projections to the ventromedial hypothalamic nucleus. Our results indicate that genetic identity determines connectivity (and therefore, function), providing a framework for mapping all PB output projections based on the genetic identity of its neurons. Using genetic markers to systematically classify PB neurons and their efferent projections will enhance the translation of research findings from experimental animals to humans.

Anatomical evidence for the efferent pathway from the hypothalamus to autonomic innervation in the anterior chamber structures of eyes.

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.

Spatially coherent and topographically organized pathways of the human globus pallidus.

Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.

Agent-dependent modulation of corticospinal excitability during painful transcutaneous electrical stimulation.

Pain has an inhibitory effect on the corticospinal excitability that has been interpreted as an evolutionary mechanism, directed to down-regulate cortical activity in order to facilitate rapid protective spinal reflexes. Here, we focused on the link between defensive mechanisms and motor system and we asked whether voluntary actions can modulate the corticospinal excitability during painful stimulations. To this aim, we manipulated the volition-related aspects of our paradigm by comparing conditions in which either the participant (self-generated action) or the experimenter (other-generated action) pressed the button to deliver painful high-intensity transcutaneous electric shocks to the right digit V. MEPs to TMS were recorded from the FDI and APB muscles of the stimulated hand. A compelling agent-dependent modulation of the corticospinal excitability was found, showing, in self-generated compared to other-generated actions, a significantly lower inhibitory effect, as measured by greater MEP amplitude. This finding suggests a top-down modulation of volitional actions on defensive mechanisms, promoting the view that predictive information from the motor system attenuates the responses to the foreseeable adverse events generated by one's own actions as compared to unpredictable events generated by someone else's actions.

Measuring conduction velocity distributions in peripheral nerves using neurophysiological techniques.

OBJECTIVE: To determine how long it takes for neural impulses to travel along peripheral nerve fibers in living humans. METHODS: A collision test was performed to measure the conduction velocity distribution of the ulnar nerve. Two stimuli at the distal and proximal sites were used to produce the collision. Compound muscle or nerve action potentials were recorded to perform the measurements on the motor or mixed nerve, respectively. Interstimulus interval was set at 1-5 ms. A quadri-pulse technique was used to measure the refractory period and calibrate the conduction time. RESULTS: Compound muscle action potential produced by the proximal stimulation started to emerge at the interstimulus interval of about 1.5 ms and increased with the increment in interstimulus interval. Two groups of motor nerve fibers with different conduction velocities were identified. The mixed nerve showed a wider conduction velocity distribution with identification of more subgroups of nerve fibers than the motor nerve. CONCLUSIONS: The conduction velocity distributions in high resolution on a peripheral motor and mixed nerve are different and this can be measured with the collision test. SIGNIFICANCE: We provided ground truth data to verify the neuroimaging pipelines for the measurements of latency connectome in the peripheral nervous system.

Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway.

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Cochlea and auditory nerve.

The transduction process in the cochlea requires patent hair cells. Population responses that reflect this patency are the cochlear microphonic (CM) and summating potential (SP). They can be measured using electrocochleography (ECochG). The CM reflects the sound waveform in the form of outer hair cell (OHC) depolarization and hyperpolarization, and the SP reflects the average voltage difference of the OHC membrane potential for depolarization and hyperpolarization. The CM can be measured using ECochG or via the so-called otoacoustic emissions, using a sensitive microphone in the ear canal. Neural population responses are called the compound action potentials (CAPs), which by frequency selective masking can be decomposed into narrow-band action potentials (NAPs) reflecting CAPs evoked by activity from small cochlear regions. Presence of CM and absence of CAPs are the diagnostic hallmarks of auditory neuropathy. Increased and prolonged SPs are often found in Ménière's disease but are too often in the normal range to be diagnostic. When including NAP waveforms, Ménière's disease can be differentiated from vestibular schwannomas, which often feature overlapping symptoms such as dizziness, hearing loss, and tinnitus. The patency of the efferent system, particularly the olivocochlear bundle, can be tested using the suppressive effect of contralateral stimulation on the otoacoustic emission amplitude.

Medial olivocochlear suppression in musicians versus non-musicians.

The medial olivocochlear efferent (MOCE) branch synapses with outer hair cells (OHCs), and the efferent pathway can be activated via a contralateral acoustic stimulus (CAS). The activation of MOCE can change OHC motile responses and convert signals that are capable of controlling the sensitivity of the peripheral hearing system in a frequency-specific manner. The aim of this study was to examine the MOCE system activity in professional musicians using transient evoked otoacoustic emission test and CAS. Musician group showed stronger suppression in all frequency bands in the presence of CAS.

Gentle Perineal Skin Stimulation for Control of Nocturia.

One of the major causes of nocturia is overactive bladder (OAB). Somatic afferent nerve stimuli are used for treating OAB. However, clinical evidence for the efficacy of this treatment is insufficient due to the lack of appropriate control stimuli. Studies on anesthetized animals, which eliminate emotional factors and placebo effects, have demonstrated an influence of somatic stimuli on urinary bladder functions and elucidated the underlying mechanisms. In general, the effects of somatic stimuli are dependent on the modality, location, and physical characteristics of the stimulus. Recently we showed that gentle stimuli applied to the perineal skin using a soft elastomer roller inhibited micturition contractions to a greater extent than a roller with a hard surface. Studies aiming to elucidate the neural mechanisms of gentle stimulation-induced inhibition reported that 1-10 Hz discharges of low-threshold cutaneous mechanoreceptive Aß, Aδ, and C fibers evoked during stimulation with an elastomer roller inhibited the micturition reflex by activating the spinal cord opioid system, thereby reducing both ascending and descending transmission between bladder and pontine micturition center. The present review will provide a brief summary of (1) the effect of somatic electrical stimulation on the micturition reflex, (2) the effect of gentle mechanical skin stimulation on the micturition reflex, (3) the afferent, efferent, and central mechanisms underlying the effects of gentle stimulation, and (4) a translational clinical study demonstrating the efficacy of gentle skin stimuli for treating nocturia in the elderly with OAB by using the two roller types inducing distinct effects on rat micturition contractions. Anat Rec, 302:1824-1836, 2019. © 2019 American Association for Anatomy.

Functional MRI evidence of the cortico-olivary efferent pathway during active auditory target processing in humans.

Auditory target detection has been explored by a number of studies, but none have demonstrated activity in the auditory subcortical centers evoked by the top-down attentional mechanism related to target detection in humans. We applied functional magnetic resonance imaging (fMRI) with sparse sampling to explore activity in the auditory centers, particularly in the subcortex, during an active auditory target detection task. Fourteen healthy subjects with normal hearing tapped the left index finger in response to target tonal stimuli presented among other (non-target) stimuli during continuous white noise stimulation. General linear model, region-of-interest, and connectivity analyses were performed. In the cortex, bilateral auditory cortices as well as the cingulate gyrus, thalamus, and supramarginal gyrus were activated to target stimuli and functionally connected to each other. In the subcortex, the superior olivary complex (SOC) and locus coeruleus were activated to the target but not to the non-target or background noise stimuli. The SOC was the only auditory subcortical center that displayed connectivity to the auditory cortical areas as well as the cingulate and supramarginal gyri during target presentation but not during other conditions. SOC activation appears to be the first fMRI evidence of direct cortico-olivary projections in the human brain as well as SOC participation in auditory target detection. Our results may be an initial step towards developing a noninvasive methodology to evaluate the functional integrity of the auditory efferent system in humans.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.

OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.

Auditory event-related potentials and function of the medial olivocochlear efferent system in children with auditory processing disorders.

OBJECTIVE: The objectives were to investigate the function of central auditory pathways and of the medial efferent olivocochlear system (MOCS). DESIGN: Event-related potentials (ERP) were recorded following the delivery of the stimulus /da/ in quiet and in ipsilateral, contralateral, and binaural noise conditions and correlated to the results of the auditory processing disorders (APD) diagnostic test battery. MOCS function was investigated by adding ipsilateral, contralateral, and binaural noise to transient evoked otoacoustic emission recordings. Auditory brainstem responses and pure tone audiogram were also evaluated. STUDY SAMPLE: Nineteen children (7 to 12 years old) with APD were compared with 24 age-matched controls. RESULTS: Otoacoustic emissions and ABR characteristics did not differ between groups, whereas ERP latencies were significantly longer and of higher amplitudes in APD children than in controls, in both quiet and noise conditions. The MOCS suppression was higher in APD children. CONCLUSIONS: Findings indicate that children with APD present with neural deficiencies in both challenging and nonchallenging environments with an increase in the timing of several central auditory processes correlated to their behavioural performances. Meanwhile, their modulation of the auditory periphery under noisy conditions differs from control children with higher suppression.

A Sensorimotor Pathway via Higher-Order Thalamus.

We now know that sensory processing in cortex occurs not only via direct communication between primary to secondary areas, but also via their parallel cortico-thalamo-cortical (i.e., trans-thalamic) pathways. Both corticocortical and trans-thalamic pathways mainly signal through glutamatergic class 1 (driver) synapses, which have robust and efficient synaptic dynamics suited for the transfer of information such as receptive field properties, suggesting the importance of class 1 synapses in feedforward, hierarchical processing. However, such a parallel arrangement has only been identified in sensory cortical areas: visual, somatosensory, and auditory. To test the generality of trans-thalamic pathways, we sought to establish its presence beyond purely sensory cortices to determine whether there is a trans-thalamic pathway parallel to the established primary somatosensory (S1) to primary motor (M1) pathway. We used trans-synaptic viral tracing, optogenetics in slice preparations, and bouton size analysis in the mouse (both sexes) to document that a circuit exists from layer 5 of S1 through the posterior medial nucleus of the thalamus to M1 with glutamatergic class 1 properties. This represents a hitherto unknown, robust sensorimotor linkage and suggests that the arrangement of parallel direct and trans-thalamic corticocortical circuits may be present as a general feature of cortical functioning.SIGNIFICANCE STATEMENT During sensory processing, feedforward pathways carry information such as receptive field properties via glutamatergic class 1 synapses, which have robust and efficient synaptic dynamics. As expected, class 1 synapses subserve the feedforward projection from primary to secondary sensory cortex, but also a route through specific higher-order thalamic nuclei, creating a parallel feedforward trans-thalamic pathway. We now extend the concept of cortical areas being connected via parallel, direct, and trans-thalamic circuits from purely sensory cortices to a sensorimotor cortical circuit (i.e., primary sensory cortex to primary motor cortex). This suggests a generalized arrangement for corticocortical communication.

Cerebral blood flow features in chronic subcortical stroke: Lesion location-dependent study.

We investigated the influence of lesion location on cerebral blood flow (CBF) in chronic subcortical stroke patients. Three-dimensional pseudocontinuous arterial spin labeling was employed to obtain CBF images in normal controls (NC) and patients with left hemisphere subcortical infarctions involving motor pathways. Stroke patients were divided into two subgroups based on the infarction location (basal ganglia (BS) or pontine (PS). We mapped CBF alterations in a voxel-wise manner and compared them to detect differences among groups with height-level false discovery rate correction. Regions with significant group differences were extracted to perform post hoc analyses among the BS, PS and NC groups using a general linear model with age, gender, years of education, and interval after stroke as covariates. The BS group displayed significantly increased CBF in the contralesional putamen relative to NC and significantly decreased CBF in the ipsilesional sensorimotor cortex, ipsilesional thalamus and contralesional cerebellum. The PS group displayed significantly increased CBF in the contralesional inferior frontal gyrus relative to both the NC and BS groups. Nevertheless, the PS group showed significantly decreased CBF mainly in the cerebellum. Our results suggest different alteration patterns of CBF in chronic stroke patients with different infarct locations within subcortical motor pathways, potentially providing important information for the initiation of individualized rehabilitation strategies for subcortical stroke patients involving different infarct types.

Distinct descending motor cortex pathways and their roles in movement.

Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer 5. A key question is how preparatory activity is maintained without causing movement, and is ultimately converted to a motor command to trigger appropriate movements. Here, using single-cell transcriptional profiling and axonal reconstructions, we identify two types of pyramidal tract neuron. Both types project to several targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex; populations of these neurons produced early preparatory activity that persisted until the movement was initiated. The second type projects to motor centres in the medulla and mainly produced late preparatory activity and motor commands. These results indicate that two types of motor cortex output neurons have specialized roles in motor control.