Cortical System Research Articles

Layer specificity of inputs from supplementary motor area and dorsal premotor cortex to primary motor cortex in macaque monkeys

The primate frontal lobe processes diverse motor information in parallel through multiple motor-related areas. For example, the supplementary motor area (SMA) is mainly involved in internally-triggered movements, whereas the premotor cortex (PM) is highly responsible for externally-guided movements. The primary motor cortex (M1) deals with both aspects of movements to execute a single motor behavior. To elucidate how the cortical motor system is structured to process a variety of information, the laminar distribution patterns of signals were examined between SMA and M1, or PM and M1 in macaque monkeys by using dual anterograde tract-tracing. Dense terminal labeling was observed in layers 1 and upper 2/3 of M1 after one tracer injection into SMA, another tracer injection into the dorsal division of PM resulted in prominent labeling in the deeper portion of layer 2/3. Weaker labeling was also visible in layer 5 in both cases. On the other hand, inputs from M1 terminated in both the superficial and the deep layers of SMA and PM. The present data indicate that distinct types of motor information are arranged in M1 in a layer-specific fashion to be orchestrated through a microcircuit within M1.

Cell-autonomous impact of polysialic acid-producing enzyme ST8SIA2 on developmental migration and distribution of cortical interneurons.

In humans, variations in the polysialic acid-producing enzyme ST8SIA2 and disturbances in the cortical inhibitory system are associated with neurodevelopmental psychiatric disorders such as schizophrenia and autism. In mice, the ST8SIA2-dependent formation of polysialic acid during embryonic development is crucial for the establishment of interneuron populations of the medial prefrontal cortex. However, the spatial pattern and the neurodevelopmental mechanisms of interneuron changes caused by loss of ST8SIA2 function have not been fully characterized. Here, we use immunohistochemical analysis to demonstrate that densities of parvalbumin-positive interneurons are not only reduced in the medial prefrontal cortex, but also in the adjacent motor and somatosensory cortices of St8sia2-deficient male mice. These reductions, however, were confined to the rostral parts of the analyzed region. Mice with conditional knockout of St8sia2 under the interneuron-specific Lhx6 promoter, but not mice with a deletion under the Emx1 promoter that targets cortical excitatory neurons and glia, largely recapitulated the area-specific changes of parvalbumin-positive interneurons in the anterior cortex of St8sia2-/- mice. Live imaging of interneuron migration in slice cultures of the developing cortex revealed a comparable reduction of directional persistence accompanied by increased branching of leading processes in slice cultures obtained from St8sia2-/- embryos or from embryos with interneuron-specific ablation of St8sia2. Together, the data demonstrate a cell-autonomous impact of ST8SIA2 on cortical interneuron migration and the distribution of parvalbumin-positive interneurons in the anterior cortex. This provides a neurodevelopmental mechanism for how dysregulation of ST8SIA2 may lead to disturbed inhibitory balance as observed in schizophrenia and autism.

Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors.

Polymorphic variants of the gene encoding for metabotropic glutamate receptor 3 (mGlu3) are linked to schizophrenia. Because abnormalities of cortical GABAergic interneurons lie at the core of the pathophysiology of schizophrenia, we examined whether mGlu3 receptors influence the developmental trajectory of cortical GABAergic transmission in the postnatal life. mGlu3-/- mice showed robust changes in the expression of interneuron-related genes in the prefrontal cortex (PFC), including large reductions in the expression of parvalbumin (PV) and the GluN1 subunit of NMDA receptors. The number of cortical cells enwrapped by perineuronal nets was increased in mGlu3-/- mice, suggesting that mGlu3 receptors shape the temporal window of plasticity of PV+ interneurons. Electrophysiological measurements of GABAA receptor-mediated responses revealed a more depolarized reversal potential of GABA currents in the somata of PFC pyramidal neurons in mGlu3-/- mice at postnatal d 9 associated with a reduced expression of the K+/Cl- symporter. Finally, adult mGlu3-/- mice showed lower power in electroencephalographic rhythms at 1-45 Hz in quiet wakefulness as compared with their wild-type counterparts. These findings suggest that mGlu3 receptors have a strong impact on the development of cortical GABAergic transmission and cortical neural synchronization mechanisms corroborating the concept that genetic variants of mGlu3 receptors may predispose to psychiatric disorders.-Imbriglio, T., Verhaeghe, R., Martinello, K., Pascarelli, M. T., Chece, G., Bucci, D., Notartomaso, S., Quattromani, M., Mascio, G., Scalabrì, F., Simeone, A., Maccari, S., Del Percio, C., Wieloch, T., Fucile, S., Babiloni, C., Battaglia, G., Limatola, C., Nicoletti, F., Cannella, M. Developmental abnormalities in cortical GABAergic system in mice lacking mGlu3 metabotropic glutamate receptors.

Impact of auditory feedback alterations in individuals with stuttering

IntroductionElectrophysiological evidence has reinforced the hypothesis that stuttering is associated with a deficit in modulation of the cortical auditory system during speech planning, contributing to an inefficient auditory feedback monitoring and, consequently, resulting in disfluencies. ObjectiveTo verify the impact of auditory feedback modifications on the spontaneous speech of individuals with stuttering. MethodsSixteen individuals, of both genders, aged 8–17 years and 11 months, with a diagnosis of persistent neurodevelopmental stuttering, were divided into two groups: Moderate Stuttering Group and Severe Stuttering Group. The testing procedures consisted of three stages: collection of identification data, audiological assessment and fluency evaluation of spontaneous speech in four auditory feedback conditions (non-altered, delayed, masked and amplified). The speech sample obtained in the non-altered feedback was considered the control; the others were considered as modified listening conditions. ResultsRegarding the stuttering-like disfluencies, a statistically significant difference was observed in the intragroup analysis of the Moderate Stuttering Group between non-altered and masked auditory feedback (p = 0.042), as well as between non-altered and amplified (p = 0.042). There was a statistically significant difference in the Severe Stuttering Group for all auditory feedback modifications in relation to the non-altered (delayed p = 0.012, masked p = 0.025 and amplified p = 0.042). There was also a reduction in flows of syllables and words-per-minute in the Moderate Stuttering Group for the delayed auditory feedback, as compared to non-altered (p = 0.017 and p = 0.025, respectively). ConclusionThe effect of delayed auditory feedback was favorable for the Severe Stuttering Group, promoting speech fluency. The conditions of masked and amplified auditory feedback resulted in speech benefits in both groups, decreasing the number of stuttering-like disfluencies. The speech rate was not impaired by any listening condition analyzed.

Graph-theoretical analysis for energy landscape reveals the organization of state transitions in the resting-state human cerebral cortex.

The resting-state brain is often considered a nonlinear dynamic system transitioning among multiple coexisting stable states. Despite the increasing number of studies on the multistability of the brain system, the processes of state transitions have rarely been systematically explored. Thus, we investigated the state transition processes of the human cerebral cortex system at rest by introducing a graph-theoretical analysis of the state transition network. The energy landscape analysis of brain state occurrences, estimated using the pairwise maximum entropy model for resting-state fMRI data, identified multiple local minima, some of which mediate multi-step transitions toward the global minimum. The state transition among local minima is clustered into two groups according to state transition rates and most inter-group state transitions were mediated by a hub transition state. The distance to the hub transition state determined the path length of the inter-group transition. The cortical system appeared to have redundancy in inter-group transitions when the hub transition state was removed. Such a hub-like organization of transition processes disappeared when the connectivity of the cortical system was altered from the resting-state configuration. In the state transition, the default mode network acts as a transition hub, while coactivation of the prefrontal cortex and default mode network is captured as the global minimum. In summary, the resting-state cerebral cortex has a well-organized architecture of state transitions among stable states, when evaluated by a graph-theoretical analysis of the nonlinear state transition network of the brain.

Multimodality Language Mapping Using Cortical Stimulation in Paediatric Patients With Epilepsy

Abstract INTRODUCTION Pediatric patients with epilepsy often undergo language mapping using electrical cortical stimulation. Previous studies have shown general localization of auditory naming in the anterior temporal lobe and visual naming in the posterior parietal and temporal lobe. No probabilistic map exists, however, that quantifiably details the location of the different language modalities for pediatric patients with epilepsy. METHODS A series of 41 consecutive pediatric patients underwent cortical language mapping (24 female; range 5.2-18.5 yr; mean age 13.8 yr), either extraoperative (n = 34) or intraoperative (n = 7), prior to epileptic focus resection. The exact location of where an error occurred was recorded and transposed on a cortical parcellation system. Statistical analysis used a binomial one sided exact test with a cut off set at 60%. RESULTS Results show an increased range of sites for both visual and auditory naming as compared to adults. Cortical stimulation language testing was conducted 2102 times; 1201 visual and 901 auditory. Visual naming sites extended into the anterior temporal lobe. Auditory naming sites extended from the anterior temporal lobe to the middle temporal and posterior temporal gyrus. CONCLUSION The anterior temporal lobe is a commonly resected region, often felt to be of minimal risk. Knowledge of how these 2 language modalities extend into the temporal lobe in addition to how they differ from adults provides insight into which areas are safe to resect and which areas to spare during pediatric epilepsy surgery.

A preliminary study of association between adolescent estradiol level and dorsolateral prefrontal cortex activity during emotion regulation

Non-human primate models have been useful in clarifying estradiol’s role in cognitive processing. These animal studies indicate estradiol impacts cognitive processes supported by regions within dorsolateral prefrontal cortex (DLPFC). Although human functional neuroimaging studies have begun to find similar relationships between estradiol in women for some forms of ‘cold’ cognitive control, to date no studies have examined the relationship between estradiol and DLPFC function in the context of active attempts to regulate one’s emotions. Here, we asked whether peripheral 17-beta estradiol levels in adolescent girls in different pubertal developmental stages (age = 14.9 years ± 1.74) were related to engagement of DLPFC regions during the use of a cognitive strategy for regulating emotion known as reappraisal using functional Magnetic Resonance Imaging. Findings indicated that higher estradiol levels predicted greater DLPFC activity during the down-regulation of negative emotion using reappraisal. This is the first report of an association between estradiol level and DLPFC activity during cognitive reappraisal of negative emotion. The study suggests a possibility that estradiol might positively contribute to regulatory function of a cortical system important for emotional experiences.

Plasticity versus stability across the human cortical visual connectome

Whether and how the balance between plasticity and stability varies across the brain is an important open question. Within a processing hierarchy, it is thought that plasticity is increased at higher levels of cortical processing, but direct quantitative comparisons between low- and high-level plasticity have not been made so far. Here, we address this issue for the human cortical visual system. We quantify plasticity as the complement of the heritability of resting-state functional connectivity and thereby demonstrate a non-monotonic relationship between plasticity and hierarchical level, such that plasticity decreases from early to mid-level cortex, and then increases further of the visual hierarchy. This non-monotonic relationship argues against recent theory that the balance between plasticity and stability is governed by the costs of the “coding-catastrophe”, and can be explained by a concurrent decline of short-term adaptation and rise of long-term plasticity up the visual processing hierarchy.

Hebbian associative plasticity in the visuo-tactile domain: A cross-modal paired associative stimulation protocol

We developed and assessed the effects of a novel cross-modal protocol aimed at inducing associative (Hebbian-like) plasticity in the somatosensory cortical system through vision. Associative long-term potentiation can be induced in the primary somatosensory cortex (S1) by means of paired associative stimulation (PAS), in which a peripheral electrical stimulation of the median nerve is repeatedly paired with a transcranial magnetic stimulation (TMS) pulse over S1. Considering the mirror proprieties of S1, the cross-modal PAS (cm-PAS) consists of repetitive observation of bodily tactile stimulations, paired with TMS pulses over the contralateral S1. Through three experiments in healthy participants, we demonstrate that the cm-PAS is able to induce excitatory plastic effects with functional significance in S1, improving somatosensory processing at both behavioral (tactile acuity) and neurophysiological (somatosensory-evoked potentials) levels. The plastic effects induced by cm-PAS depend on the interval (20 ms) between the visual stimulus and the magnetic pulse, the targeted cortical site (S1), and the tactile content of the visual stimulus, which must represent a touch event. Such specificity implies the involvement of cross-modal, mirror-like, mechanisms in S1, which are able to visually promote associative synaptic plasticity in S1 likely through the recruitment of predictive coding processes.

Structural and Diffusion MRI Analyses With Histological Observations in Patients With Lissencephaly.

The development of cortical convolutions, gyri and sulci, is a complex process that takes place during prenatal development. Lissencephaly, a rare genetic condition characterized by the lack of cortical convolutions, offers a model to look into biological processes that lead to the development of convolutions. Retrospective, qualitative, and quantitative analyses of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed in patients with lissencephaly (N = 10) and age-/sex-matched controls (N = 10). In order to identify microstructural correlates of structural MRI and DTI findings, postmortem brains of patients with lissencephaly (N = 4) and age-matched controls (N = 4) were also examined with histology. Patients with lissencephaly had significantly smaller gyrification index and volumes of hemispheric white and gray matter, compared to the age-/sex-matched control group. However, there was no significant difference between groups in the subcortical gray matter volumes. Although the majority of patients with lissencephaly had a preserved normal-like appearance of major fissures and primary sulci, the spatial distribution of agyric cortical regions was different in patients with lissencephaly-1 (LIS1) and doublecortin (DCX) mutations. Lastly, in patients with lissencephaly, the spatiotemporal distribution of projection pathways was preserved while short- to medium-range cortico-cortical pathways were absent or fewer in number. Our results indicate that in the patients with lissencephaly cortical system is affected more than the subcortical one.

Bereitschaftspotential and lateralized readiness potential in children with attention deficit hyperactivity disorder: altered motor system activation and effects of methylphenidate

Attention deficit hyperactivity disorder (ADHD) has been linked to abnormal functioning of cortical motor areas such as the supplementary motor area, the premotor cortex and primary motor cortex (MI). The Bereitschaftspotential (BP) and lateralized readiness potential (LRP) are movement-related potentials generated by cortical motor areas. We hypothesized that the BP and LRP would be altered in children with ADHD. A group of 17 children with ADHD (mean age: 11.5 ± 1.9 years) and a control group of 16 typically developing children (mean age: 12.2 ± 2.0 years) performed movements at self-chosen irregular intervals while a 64-channel DC-EEG was registered. BP and LRP were calculated from the EEG. The ADHD group had significantly lower and on average positive BP amplitudes at Cz. In agreement with age-dependent maturation effects the LRP had a positive polarity in both groups, but lower amplitudes were found in the ADHD group without medication. The control group showed a mid-central negativity and a positivity over motor areas contra-lateral to the side of movement, whereas no negativity over Cz and a more diffuse positivity was found in the ADHD group. LRP group differences diminished after MPH administration as indicated by an interaction between group and time of measurement/medication. The cortical motor system shows altered functioning during movement preparation and initiation in children affected by ADHD. Positive Bereitschaftspotential polarities may represent delayed cortical maturation. Group differences of LRP were pharmacologically modulated by the catecholaminergic agent MPH.

Impact of increasing age on functioning free muscle transplantation for facial palsy reconstruction.

Management of facial paralysis in older patients is controversial. The purpose of this study is to evaluate the impact of increasing age on functioning free muscle transplantation (FFMT). Twenty-nine facial paralysis patients over 50 years old received FFMT. A separate group of patients aged 41-50 years old were included as control. Outcome assessments included use of the SMILE evaluation system for excursion, a cortical adaptation scoring system for brain plasticity, and a subjective satisfaction assessment score. Meta-analysis of literature over the past 50 years was also performed to examine the impact of older age. The mean change in excursion movement was 13.39 ± 5.49 mm. Weakest excursion was found in the oldest age group (11.74 ± 4.84 mm, p = .097), in concordance with the meta-analysis. There was significant difference between the three different neurotizers (p = .036). Excursion and satisfaction score were significantly worse in the older cohort with the cross face-nerve graft FFMT. FFMT is a viable option in the elderly patient group but performs weaker in excursion. The choice of neurotizer is dependent on the patient's goals and the suitable age at which the benefits outweigh the risks.

Impaired Motor Skill Acquisition Using Mirror Visual Feedback Improved by Transcranial Direct Current Stimulation (tDCS) in Patients With Parkinson's Disease.

Recent non-invasive brain stimulation techniques in combination with motor training can enhance neuroplasticity and learning. It is reasonable to assume that such neuroplasticity-based interventions constitute a useful rehabilitative tool for patients with Parkinson’s Disease (PD). Regarding motor skill training, many kinds of tasks that do not involve real motor movements have been applied to PD patients. The purpose of this study is to elucidate whether motor skill training using mirror visual feedback (MVF) is useful to patients with PD in order to improve untrained hand performance dependent on the time course of training; and whether MVF combined with anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) causes an additional effect based on increased motor cortical excitability. Eighteen right-handed patients with PD in the off-medication state and 10 age-matched healthy subjects (HS) performed four sessions of right-hand ball rotation using MVF (intervention) on two separate days, 1 week apart (day 1 and day 2). HS subjects received only sham stimulation. The intervention included four sessions of motor-skill training using MVF for 20 min comprised of four sets of training for 30 s each. PD patients were randomly divided into two intervention groups without or with anodal tDCS over the right M1 contralateral to the untrained hand. As the behavior evaluation, the number of ball rotations of the left hand was counted before (pre) and immediately after (post) intervention on both days (pre day 1, post day 1, pre day 2, and post day 2). Motor evoked potential (MEP), input-output function, and cortical silent period were recorded to evaluate the motor cortical excitatory and inhibitory system in M1 pre day 1 and post day 2. The number of ball rotations of the left hand and the facilitation of MEP by intervention were significantly impaired in patients with PD compared to HS. In contrast, if anodal tDCS was applied to right M1 of patients with PD, the number of ball rotations in accordance with I-O function at 150% intensity was significantly increased after day 1 and retained until day 2. This finding may help provide a new strategy for neurorehabilitation improving task-specific motor memory without real motor movements in PD.

Quantitative ultrasound (QUS) axial transmission method reflects anisotropy in micro-arrangement of apatite crystallites in human long bones: A study with 3-MHz-frequency ultrasound

Anisotropic arrangement of apatite crystallites, i.e., preferential orientation of the apatite c-axis, is known to be an important bone quality parameter that governs the mechanical properties. However, noninvasive evaluation of apatite orientation has not been achieved to date. The present paper reports the potential of quantitative ultrasound (QUS) for noninvasive evaluation of the degree of apatite orientation in human bone for the first time. A novel QUS instrument for implementation of the axial transmission (AT) method is developed, so as to achieve precise measurement of the speed of sound (SOS) in the cortex (cSOS) of human long bone. The advantages of our QUS instrument are the following: (i) it is equipped with a cortical bone surface-morphology detection system to correct the ultrasound transmission distance, which should be necessary for AT measurement of long bone covered by soft tissue of non-uniform thickness; and (ii) ultrasound with a relatively high frequency of 3 MHz is employed, enabling thickness-independent cSOS measurement even for the thin cortex by preventing guide wave generation. The reliability of the proposed AT measurement system is confirmed through comparison with the well-established direct transmission (DT) method. The cSOS in human long bone is found to exhibit considerable direction-dependent anisotropy; the axial cSOS (3870 ± 66 m/s) is the highest, followed by the tangential (3411 ± 94 m/s) and radial (3320 ± 85 m/s) cSOSs. The degree of apatite orientation exhibits the same order, despite the unchanged bone mineral density. Multiple regression analysis reveals that the cSOS of human long bone strongly reflects the apatite orientation. The cSOS determined by the AT method is positively correlated with that determined by the DT method and sensitively reflects the apatite orientation variation, indicating the validity of the AT instrument developed in this study. Our instrument will be beneficial for noninvasive evaluation of the material integrity of the human long-bone cortex, as determined by apatite c-axis orientation along the axial direction.

Effortful verb retrieval from semantic memory drives beta suppression in mesial frontal regions involved in action initiation

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15-30 Hz) as an index of cortical activation, we performed a whole-brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb-related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.

Altered Cortico-Striatal Functional Connectivity During Resting State in Obsessive-Compulsive Disorder.

Background: Neuroimaging studies show that obsessive–compulsive disorder (OCD) is characterized by an alteration of the cortico–striato–thalamo–cortical (CSTC) system in terms of an imbalance of activity between the direct and the indirect loop of the CSTC. As resting-state functional connectivity (FC) studies investigated only specific parts of the CSTC in patients with OCD up to now, the present study aimed at exploring FC in the CSTC as a whole. Methods: We investigated potential alterations in resting-state FC within the CSTC system in 44 OCD patients and 40 healthy controls by taking into consideration all relevant nodes of the direct and indirect CSTC loop. Results: Compared to healthy controls, OCD patients showed an increased FC between the left subthalamic nucleus (STN) and the left external globus pallidus (GPe), as well as an increased FC between the left GPe and the left internal globus pallidus (GPi). Conclusion: These findings may contribute to a better understanding of the OCD pathophysiology by providing further information on the connectivity alterations within specific regions of the CSTC system. In particular, increased FC between the STN and the left GPe may play a major role in OCD pathology. This assumption is consistent with the fact that these regions are also the main target sites of therapeutic deep brain stimulation in OCD.

Radiographic Humerus Union Measurement (RHUM) Demonstrates High Inter- and Intraobserver Reliability in Assessing Humeral Shaft Fracture Healing.

Orthopedic surgeons use radiographs to determine degrees of fracture healing, guide progression of clinical care, and assist in determining weight bearing and removal of immobilization. However, no gold standard exists to determine the progression of healing of humeral shaft fractures treated non-operatively. The purpose of this study was to determine whether a scale comparable to the modified Radiographic Union Score for Tibial (RUST) fractures applied to non-operatively treated humeral shaft fractures can increase interobserver reliability in determining fracture healing. A retrospective review was undertaken by three orthopedic traumatologists and one musculoskeletal radiologist, who evaluated 50 sets of anteroposterior and lateral radiographs, presented at random, of non-operatively treated humeral shaft fractures at various stages of healing from 17 patients. The radiographs were scored using a modified RUST scale called the Radiographic Humerus Union Measurement (RHUM). Observers were blinded to the time from injury. After a 4-week washout period, observers again scored the same radiographs. Observers classified each fracture as either healed or not healed based on the combination of radiographs. Inter- and intraobserver reliability of the RHUM were determined using an intraclass correlation coefficient(ICC). Interobserver reliability of determining a healed fracture was calculated using Cohen's kappa (κ) statistics. A receiver operator characteristic curve was conducted to determine the RHUM score predictive of a fracture being considered healed. ICC demonstrated almost perfect interobserver reliability (ICC, 0.838; ICC 95% CI, 0.765 to 0.896) and intraobserver reliability (ICC range, 0.822 to 0.948) of the RHUM. κ demonstrated substantial agreement between observers in considering a fracture healed (κ = 0.647). Receiver operating characteristic (ROC) curve demonstrated that a RHUM of 10 or higher is an excellent predictor of the observer considering the fracture healed (area under the ROC curve = 0.946, specificity = 0.957, 95% CI specificity, 0.916 to 0.979). This cortical scoring system has excellent interobserver reliability in humeral shaft fractures treated non-operatively. Consistent with previous cortical scoring systems, a RHUM score of 10 or above can be considered radiographically healed.

A 2-year follow-up of isolated Medial Patellofemoral Ligament Reconstruction by using soft suture anchor and adjustable cortical fixation system

PurposeNumerous surgical techniques and fixation methods have been described in medial patellofemoral ligament (MPFL) reconstruction such as choice of graft, graft fixation method of patella/femur and initial tension. We describe short term clinical results of MPFL reconstruction by using soft suture anchor and adjustable cortical fixation system. MethodsTwenty-four patients who underwent isolated MPFL reconstruction by using soft suture anchor and adjustable cortical fixation system were included in this study. All patients were followed up for at least 2 years, and pre-operative and 2 years post-operative Kujala score, IKDC score and Knee Injury and Osteoarthritis Outcome Score were used to assess clinical outcome. Radiographic evaluation included the Q angle, congruence angle and patellar tilt angle. Pre- and post-operative changes were evaluated by Mann–Whitney U test. ResultsThere were no complications including re-dislocation, patella fracture, infection, and joint contracture. The apprehension test was positive in 4.2% post-operatively. A statistically significant improvement in clinical scores and radiographic evaluation were evident after surgery. ConclusionsIsolated MPFL Reconstruction using soft suture anchor and adjustable cortical fixation system led good restoration of patellar stability and significant improvement of knee function in short-term results. This surgical technique can reduce complications such as patella fractures, and can be done safely. Clinical relevanceThis technique may be a treatment option with little associated complications in the treatment for patellar instability. Level of EvidenceCase series, Level IV.

Cerebellar repetitive transcranial magnetic stimulation restores pharyngeal brain activity and swallowing behaviour after disruption by a cortical virtual lesion.

Key points Despite evidence that the human cerebellum has an important role in swallowing neurophysiology, the effects of cerebellar stimulation on swallowing in the disrupted brain have not been explored.In this study, for the first time, the application of cerebellar neurostimulation is characterized in a human model of disrupted swallowing (using a cortical virtual lesion).It is demonstrated that cerebellar stimulation can reverse the suppressed activity in the cortical swallowing system and restore swallowing function in a challenging behavioural task, suggesting the findings may have important therapeutic implications. Repetitive transcranial magnetic stimulation (rTMS) can alter neuronal activity within the brain with therapeutic potential. Low frequency stimulation to the ‘dominant’ cortical swallowing projection induces a ‘virtual‐lesion’ transiently suppressing cortical excitability and disrupting swallowing behaviour. Here, we compared the ability of ipsi‐lesional, contra‐lesional and sham cerebellar rTMS to reverse the effects of a ‘virtual‐lesion’ in health. Two groups of healthy participants (n = 15/group) were intubated with pharyngeal catheters. Baseline pharyngeal motor evoked potentials (PMEPs) and swallowing performance (reaction task) were measured. Participants received 10 min of 1 Hz rTMS to the pharyngeal motor cortex which elicited the largest PMEPs to suppress cortical activity and disrupt swallowing behaviour. Over six visits, participants were randomized to receive 250 pulses of 10 Hz cerebellar rTMS to the ipsi‐lesional side, contra‐lesional side or sham while assessing PMEP amplitude or swallowing performance for an hour afterwards. Compared to sham, active cerebellar rTMS, whether administered ipsi‐lesionally (P = 0.011) or contra‐lesionally (P = 0.005), reversed the inhibitory effects of the cortical ‘virtual‐lesion’ on PMEPs and swallowing accuracy (ipsi‐lesional, P < 0.001, contra‐lesional, P < 0.001). Cerebellar rTMS was able to reverse the disruptive effects of a ‘virtual lesion’. These findings provide evidence for developing cerebellar rTMS into a treatment for post‐stroke dysphagia.

Neural correlates of sound-learning experiences in the auditory system: Translational candidates for hearing rehabilitation

A major disconnect between traditional auditory perception research and recent neuroscience is the high propensity in the auditory system for neuroplasticity. Altered processing of reward-associated sound stimuli can contribute to adaptive behavior, such as hearing, listening, and attending appropriately to sound cues. I will the present work from animal models of learning-induced neuroplasticity in the cortical and subcortical auditory system. The data show how receptive fields and tonotopic maps in primary auditory cortex (A1) as well as the auditory brainstem response (ABR) can change when adult animals trained by pairing a tone with the availability to obtain reward alters sound coding in the auditory system. Over the course of conditioning, increases and reductions, respectively, in ABR amplitude and peak latencies predict how well animals can pick out the learned sound-frequency acoustic cue from other frequencies following conditioning. Furthermore, receptive fields in A1 have narrower tuning for a remembered sound frequency—and only in animals who successfully remember that frequency over others assessed by behavioral test. Therefore, learned sounds are preferentially processed over novel and distractor sounds following conditioning. Significant behavioral preferences for learned tones may be due, in part, to the observed changes in auditory processing across the auditory system.