Long-latency Responses Research Articles

Changes in intra- and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

In quadrupeds, such as cats, cutaneous afferents from the forepaw dorsum signal external perturbations and send inputs to spinal circuits to co-ordinate the activity in muscles of all four limbs. How these cutaneous reflex pathways from forelimb afferents are reorganized after an incomplete spinal cord injury is not clear. Using a staggered thoracic lateral hemisections paradigm, we investigated changes in intralimb and interlimb reflex pathways by electrically stimulating the left and right superficial radial nerves in seven adult cats and recording reflex responses in five forelimb and ten hindlimb muscles. After the first (right T5-T6) and second (left T10-T11) hemisections, forelimb-hindlimb co-ordination was altered and weakened. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-, mid- and long-latency homonymous and crossed reflex responses in forelimb muscles and their phase modulation remained largely unaffected after staggered hemisections. The occurrence of homolateral and diagonal mid- and long-latency responses in hindlimb muscles evoked with left and right superficial radial nerve stimulation was significantly reduced at the first time point after the first hemisection, but partially recovered at the second time point with left superficial radial nerve stimulation. These responses were lost or reduced after the second hemisection. When present, all reflex responses, including homolateral and diagonal, maintained their phase-dependent modulation. Therefore, our results show a considerable loss in cutaneous reflex transmission from cervical to lumbar levels after incomplete spinal cord injury, albeit with preservation of phase modulation, probably affecting functional responses to external perturbations. KEY POINTS: Cutaneous afferent inputs co-ordinate muscle activity in the four limbs during locomotion when the forepaw dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb co-ordination. We investigated cutaneous reflexes from forelimb afferents during quadrupedal locomotion by electrically stimulating the superficial radial nerve bilaterally, before and after staggered lateral thoracic hemisections in cats. We showed a loss/reduction of mid- and long-latency homolateral and diagonal reflex responses in hindlimb muscles early after the first hemisection that partially recovered with left superficial radial nerve stimulation, before being reduced after the second hemisection. Targeting cutaneous reflex pathways from forelimb afferents projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.

Forelimb movements contribute to hindlimb cutaneous reflexes during locomotion in cats.

During quadrupedal locomotion, interactions between spinal and supraspinal circuits and somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine whether forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two cats with a low spinal transection (T12-T13) during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion, whereas short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, whereas mid- or longer-latency excitatory responses were reduced or abolished. Our results in intact cats and the comparison with spinal-transected cats suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.NEW & NOTEWORTHY During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.

Detecting lies in investigative interviews through the analysis of response latencies and error rates to unexpected questions

In this study, we propose an approach to detect deception during investigative interviews by integrating response latency and error analysis with the unexpected question technique. Sixty participants were assigned to an honest (n = 30) or deceptive group (n = 30). The deceptive group was instructed to memorize the false biographical details of a fictitious identity. Throughout the interviews, participants were presented with a randomized sequence of control, expected, and unexpected open-ended questions about identity. Responses were audio recorded for detailed examination. Our findings indicate that deceptive participants showed markedly longer latencies and higher error rates when answering expected (requiring deception) and unexpected questions (for which premeditated deception was not possible). Longer response latencies were also observed in participants attempting deception when answering control questions (which necessitated truthful answers). Moreover, a within-subject analysis highlighted that responding to unexpected questions significantly impaired individuals’ performance compared to answering control and expected questions. Leveraging machine-learning algorithms, our approach attained a classification accuracy of 98% in distinguishing deceptive and honest participants. Additionally, a classification analysis on single response levels was conducted. Our findings underscore the effectiveness of merging response latency metrics and error rates with unexpected questioning as a robust method for identity deception detection in investigative interviews. We also discuss significant implications for enhancing interview strategies.

Erroneous Compensation for Long-Latency Feedback Delays as Origin of Essential Tremor.

Essential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with 24 ET patients (14 female; 10 male) and 28 neurologically intact (NI) human volunteers (17 female; 11 male) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients' early muscular responses (short and long-latency responses, 20-50 and 50-100 ms, respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.

Changes in intra- and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9- to 13-week interval in seven adult cats (4males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery. KEY POINTS: Cutaneous afferent inputs coordinate muscle activity in the four limbs during locomotion when the foot dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb coordination. We investigated cutaneous reflexes during quadrupedal locomotion by electrically stimulating the superficial peroneal nerve bilaterally, before and after staggered lateral thoracic hemisections of the spinal cord in cats. We showed a loss/reduction of mid- and long-latency responses in all four limbs after staggered hemisections, which correlated with altered coordination of the fore- and hindlimbs and impaired balance. Targeting cutaneous reflex pathways projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.

Bilateral neuromuscular control in patients one year after unilateral ACL rupture or reconstruction. A cross-sectional study

ObjectivesTo compare bilateral neuromuscular control in patients one year after anterior cruciate ligament reconstruction (ACL-R) or conservative treatment (ACL-C) to healthy controls (ACL-I). DesignCross-sectional study. SettingElectromyography of vastus medialis (VM) and lateralis (VL), biceps femoris (BF) and semitendinosus (ST) was recorded during stair descent and anterior tibial translation. Each step of stair descent was divided into pre-activity, weight-acceptance and push-off phase. Pre-activation, short, medium (MLR) and long latency responses (LLR) were defined for reflex activity. ParticipantsN = 38 patients one year after ACL reconstruction (ACL-R), N = 26 participants with conservative treatment one year after ACL rupture (ACL-C), N = 38 healthy controls with an intact ACL (ACL-I). Main outcome measuresNormalized root mean squares per muscle and phase (α = 0.05). ResultsDuring stair descent, within-group leg differences were found for the quadriceps in ACL-R during all phases and for the BF in ACL-C during weight-acceptance. Between-group leg differences were found for BF in both patient groups compared to ACL-I during push-off.Between-group differences in pre-activation for VM between ACL-R and ACL-C, and between ACL-C and ACL-I were found, and as LLR between patients and ACL-R versus ACL-I. Pre-activation of BF and MLR of ST differed for each patient group compared to ACL-I. ConclusionsBilateral neuromuscular alterations are still present one year after ACL rupture or reconstruction.

Word frequency and reading demands modulate brain activation in the inferior frontal gyrus

Processing efficiency differs between high- and low-frequency words, with less frequent words resulting in longer response latencies in several linguistic behavioral tasks. Nevertheless, studies using functional MRI to investigate the word frequency effect have employed diverse methodologies and produced heterogeneous results. In this study, we examine the effect of word frequency through complementary analytical approaches and functional connectivity analyses. Furthermore, we examine whether reading demands, which have been shown to influence reading-related activation, modulate the effects of word frequency. We conducted MRI scanning on 54 healthy participants who performed two versions of a single-word reading task involving high- and low-frequency words: a low-level perceptual reading task and a high-level semantic reading task. The results indicate that word frequency influenced the activation of the pars orbitalis and pars triangularis of the inferior frontal gyrus, but only in the semantic reading task. Additionally, the ventral occipitotemporal cortex exhibited stronger regional activation during the semantic reading task compared to the perceptual reading task, with no effects of word frequency. Functional connectivity analyses demonstrated significant coupling among regions within both the dorsal and ventral reading networks, without any observable effects of word frequency or task. These findings were consistent across group- and individual-level analytical approaches. Overall, our results provide further support for the involvement of the inferior frontal gyrus in semantic processing during reading, as indicated by the effect of word frequency and the influence of reading demands, highlighting the role of the ventral reading network. These findings are discussed in line with their implications for lexical and pre-lexical reading processing.

A thalamo-parietal cortex circuit is critical for place-action coordination.

The anterior and lateral thalamus (ALT) contains head direction cells that signal the directional orientation of an individual within the environment. ALT has direct and indirect connections with the parietal cortex (PC), an area hypothesized to play a role in coordinating viewer-dependent and viewer-independent spatial reference frames. This coordination between reference frames would allow an individual to translate movements toward a desired location from memory. Thus, ALT-PC functional connectivity would be critical for moving toward remembered allocentric locations. This hypothesis was tested in rats with a place-action task that requires associating an appropriate action (left or right turn) with a spatial location. There are four arms, each offset by 90°, positioned around a central starting point. A trial begins in the central starting point. After exiting a pseudorandomly selected arm, the rat had to displace the correct object covering one of two (left versus right) feeding stations to receive a reward. For a pair of arms facing opposite directions, the reward was located on the left, and for the other pair, the reward was located on the right. Thus, each reward location had a different combination of allocentric location and egocentric action. Removal of an object was scored as correct or incorrect. Trials in which the rat did not displace any objects were scored as "no selection" trials. After an object was removed, the rat returned to the center starting position and the maze was reset for the next trial. To investigate the role of the ALT-PC network, muscimol inactivation infusions targeted bilateral PC, bilateral ALT, or the ALT-PC network. Muscimol sessions were counterbalanced and compared to saline sessions within the same animal. All inactivations resulted in decreased accuracy, but only bilateral PC inactivations resulted in increased non selecting, increased errors, and longer latency responses on the remaining trials. Thus, the ALT-PC circuit is critical for linking an action with a spatial location for successful navigation.

Neuromuscular control in males and females 1 year after an anterior cruciate ligament rupture or reconstruction during stair descent and artificial tibial translation

Neuromuscular alterations are reported in patients with anterior cruciate ligament reconstruction (ACL-R) and conservative treatment (copers with ACL deficiency, ACL-C). However, it is unclear whether sex influences neuromuscular control. The objective was to investigate differences in neuromuscular control regarding sex and treatment type one year after ACL rupture in comparison to a group with an intact ACL (ACL-I). Electromyography of vastus medialis (VM) and lateralis, biceps femoris (BF) and semitendinosus (ST) was recorded in ACL-R (N = 38), ACL-C (N = 26), and ACL-I (N = 38) during stair descent and reflex activity by anterior tibial translation while standing. The movements of stair descent were divided into pre-activity, weight-acceptance and push-off phases, reflex activity in pre-activation, short, medium (MLR), and long latency responses (LLR). Normalized root mean squares for each muscle of involved and matched control limb per phase were calculated and analyzed with two-way ANOVA (α = 0.05). During stair descent, neuromuscular differences of BF were significant during push-off only (p = 0.001). Males of ACL-R and ACL-C had higher BF activity compared to ACL-I (p = 0.009, 0.007 respectively). During reflex activity, VM and BF were significantly different between treatment groups for pre-activation (p = 0.013, 0.035 respectively). VM pre-activation of females was higher in ACL-R compared to ACL-C (p = 0.018), and lower in ACL-C compared to ACL-I (p = 0.034). Males of ACL-R showed higher VM and less BF pre-activation (p = 0.025, p = 0.003 respectively) compared to ACL-I. Males of ACL-C had less BF pre-activation compared to ACL-I (p = 0.019). During MLR, intra-group differences in ST were found for treatment (p = 0.011) and females of ACL-R compared to ACL-I (p = 0.015). During LLR, overall intra-group differences in VM were present for treatment (p = 0.034) and in females (ACL-R versus ACL-C (p = 0.015), ACL-I (p = 0.049), respectively). One year after an ACL rupture, neuromuscular alterations persist regardless of treatment and sex. Standard rehabilitation protocols may not be able to restore neuromuscular control. Future research should include long-term follow up and focus on exercises targeting neuromuscular function.

Speed of Information Processing and Verbal Working Memory in Children and Adolescents With Cochlear Implants.

Verbal working memory delays are found in many deaf children with cochlear implants compared with normal-hearing peers, but the factors contributing to these delays are not well understood. This study investigated differences between cochlear implant users and normal-hearing peers in memory scanning speed during a challenging verbal working memory task. To better understand variability in verbal working memory capacity within each sample, associations between memory scanning speed, speech recognition, and language were also investigated. Twenty-five prelingually deaf, early implanted children (age, 8-17 yr) with cochlear implants and 25 normal-hearing peers completed the Wechsler Intelligence Scale for Children, Fifth Edition, Letter-Number Sequencing (LNS) working memory task. Timing measures were made for response latency and average pause duration between letters/numbers recalled during the task. Participants also completed measures of speech recognition, vocabulary, and language comprehension. Children with cochlear implants had longer pause durations than normal-hearing peers during three-span LNS sequences, but the groups did not differ in response latencies or in pause durations during two-span LNS sequences. In the sample of cochlear implant users, poorer speech recognition was correlated with longer pause durations during two-span sequences, whereas poorer vocabulary and weaker language comprehension were correlated with longer response latencies during two-span sequences. Response latencies and pause durations were unrelated to language in the normal-hearing sample. Children with cochlear implants have slower verbal working memory scanning speed than children with normal hearing. More robust phonological-lexical representations of language in memory may facilitate faster memory scanning speed and better working memory in cochlear implant users.

The Gender Incongruency Effect in L3 Swedish due to Imperfect Gender Acquisition in L2 German

Abstract The study examines gender incongruency effects during gender retrieval in L3 Swedish learners, which are due to gender misassignment in L2 German. Twenty learners of L3 Swedish who had previously acquired two gender systems; one in their L1 Polish and the other in their L2 German, completed a speeded Gender Decision Task in Swedish and an untimed Gender Assignment Task in German. All noun stimuli were congruent in gender across the three languages (neuter → neuter, masculine and feminine → uter). Learners who erroneously assigned neuter gender to feminine but not to masculine nouns in L2 German showed higher error rates and longer response latencies in their attempts to retrieve uter gender in L3 Swedish. No interference was observed for neuter nouns. The present study thus demonstrates that incorrect gender representations in L2 German compete for selection with the target gender representations in L3 Swedish and that this cross-language interference is not always successfully resolved. Based on these findings, it is suggested that in the multilingual lexicon the connection of the uter gender node to the feminine gender node is weaker than to the masculine gender node.

Joint, distributed and hierarchically organized encoding of linguistic features in the human auditory cortex.

The precise role of the human auditory cortex in representing speech sounds and transforming them to meaning is not yet fully understood. Here we used intracranial recordings from the auditory cortex of neurosurgical patients as they listened to natural speech. We found an explicit, temporally ordered and anatomically distributed neural encoding of multiple linguistic features, including phonetic, prelexical phonotactics, word frequency, and lexical-phonological and lexical-semantic information. Grouping neural sites on the basis of their encoded linguistic features revealed a hierarchical pattern, with distinct representations of prelexical and postlexical features distributed across various auditory areas. While sites with longer response latencies and greater distance from the primary auditory cortex encoded higher-level linguistic features, the encoding of lower-level features was preserved and not discarded. Our study reveals a cumulative mapping of sound to meaning and provides empirical evidence for validating neurolinguistic and psycholinguistic models of spoken word recognition that preserve the acoustic variations in speech.

Effect of galvanic vestibular stimulation applied at the onset of stance on muscular activity and gait cycle duration in healthy individuals.

Locomotion requires the complex involvement of the spinal and supraspinal systems. So far, the role of vestibular input in gait has been assessed mainly with respect to gait stability. The noninvasive technique of galvanic vestibular stimulation (GVS) has been reported to decrease gait variability and increase gait speed, but the extent of its effect on spatiotemporal gait parameters is not fully known. Objective: Characterize vestibular responses during gait and determine the influence of GVS on cycle duration in healthy young participants. Methods: Fifteen right-handed individuals participated in the study. Electromyography (EMG) recordings of the bilateral soleus (SOL) and tibialis anterior muscles (TA) were performed. First, to determine stimulation intensity, an accelerometer placed on the vertex recorded the amplitude of the head tilts evoked by the GVS (1-4 mA, 200 ms) to establish a motor threshold (T). Second, while participants walked on a treadmill, GVS was applied at the onset of the stance phase during the treadmill gait with an intensity of 1 and 1.5 T with the cathode behind the right (RCathode) or left ear (LCathode). EMG traces were rectified, averaged (n = 30 stimuli), and analyzed. Latency, duration, and amplitude of vestibular responses as well as the mean duration of the gait cycles were measured. Results: GVS mainly induced long-latency responses in the right SOL, right TA and left TA. Only short-latency responses were triggered in the left SOL. Responses in the right SOL, left SOL and left TA were polarity dependent, being facilitatory with RCathode and inhibitory with LCathode, whereas responses in the right TA remained facilitatory regardless of the polarity. With the RCathode configuration, the stimulated cycle was prolonged compared with the control cycle at both 1 and 1.5 T, due to prolonged left SOL and TA EMG bursts, but no change was observed in right SOL and TA. With LCathode, GVS did not modify the cycle duration. Conclusion: During gait, a brief, low-intensity GVS pulse delivered at the right stance onset induced mainly long-latency polarity-dependent responses. Furthermore, a RCathode configuration increased the duration of the stimulated gait cycle by prolonging EMG activity on the anodic side. A similar approach could be explored to influence gait symmetry in individuals with neurological impairment.

Morphological and sensorimotor phenotypes in a zebrafish CHARGE syndrome model are domain-dependent.

CHARGE syndrome is a heterogeneous disorder characterized by a spectrum of defects affecting multiple tissues and behavioral difficulties such as autism, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and sensory deficits. Most CHARGE cases arise from de novo, loss-of-function mutations in chromodomain-helicase-DNA-binding-protein-7 (CHD7). CHD7 is required for processes such as neuronal differentiation and neural crest cell migration, but how CHD7 affects neural circuit function to regulate behavior is unclear. To investigate the pathophysiology of behavioral symptoms in CHARGE, we established a mutant chd7 zebrafish line that recapitulates multiple CHARGE phenotypes including ear, cardiac, and craniofacial defects. Using a panel of behavioral assays, we found that chd7 mutants have specific auditory and visual behavior deficits that are independent of defects in sensory structures. Mauthner cell-dependent short-latency acoustic startle responses are normal in chd7 mutants, while Mauthner-independent long-latency responses are reduced. Responses to sudden decreases in light are also reduced in mutants, while responses to sudden increases in light are normal, suggesting that the retinal OFF pathway may be affected. Furthermore, by analyzing multiple chd7 alleles we observed that the penetrance of morphological and behavioral phenotypes is influenced by genetic background but that it also depends on the mutation location, with a chromodomain mutation causing the highest penetrance. This pattern is consistent with analysis of a CHARGE patient dataset in which symptom penetrance was highest in subjects with mutations in the CHD7 chromodomains. These results provide new insight into the heterogeneity of CHARGE and will inform future work to define CHD7-dependent neurobehavioral mechanisms.

Intensity and inter-stimulus-interval effects on human middle- and long-latency auditory evoked potentials in an unpredictable auditory context.

It is not known how Auditory-Evoked Responses (AERs) comprising Middle Latency Responses (MLRs) and Long Latency Responses (LLRs) are modulated by stimulus intensity and inter-stimulus interval (ISI) in an unpredictable auditory context. Further, intensity and ISI effects on MLR and LLR have never been assessed simultaneously in the same humans. To address this important question, thirty participants passively listened to a random sequence of auditory clicks of three possible intensities (65, 75, and 85 dB) at five possible ISI ranges (0.25 to 0.5s, 0.5 to 1s, 1 to 2s, 2 to 4s, 4 to 8s) over four to seven one-hour sessions while EEG was recorded. P0, Na, Pa, Nb, and Pb MLR peaks and N1 and P2 LLR peaks were measured. MLRs P0 (p=.005), Pa (p=.021), and Pb (p=<.001) were modulated by intensity, while only MLR Pb (p=<.001) was modulated by ISI. LLR N1 and P2 were modulated by both intensity and ISI (all p values < .001). Intensity and ISI interacted at Pb, N1, and P2 (all p values < .001), with greater intensity effects at longer ISIs and greater ISI effects at louder intensities. Together, these results provide a comprehensive picture of intensity and ISI effects on AER across the entire thalamocortical auditory pathway, while controlling for stimulus predictability. Moreover, they highlight P0 as the earliest MLR response sensitive to stimulus intensity and Pb (~50 ms) as the earliest cortical response coding for ISIs above 250 ms and showing an interdependence between intensity and ISI effects.

Reliability of transcranial magnetic stimulation and H-reflex measurement during balance perturbation tasks.

Following ankle movement, posterior balance perturbation evokes short- (SLR ∼30–50 ms), medium- (MLR ∼50–60 ms), and long-latency responses (LLR ∼70–90 ms) in soleus muscle before voluntary muscle contraction. Transcranial magnetic stimulation (TMS) and Hoffmann-reflex (H-reflex) measurements can provide insight into the contributions of corticospinal and spinal mechanisms to each response. Motor evoked potential (MEP) and H-reflex responses have shown good reliability in some dynamic muscle contraction tasks. However, it is still unclear how reliable these methods are in dynamic balance perturbation and corticospinal modulation during long amplitude balance perturbation tasks. 14 subjects completed two test sessions in this study to evaluate the reliability of MEPs, H-reflex, and corticospinal modulation during balance perturbation. In each session, the balance perturbation system operated at 0.25 m/s, accelerating at 2.5 m/s2 over 0.3 m displacement. MEPs and H-reflexes were elicited in the right leg soleus muscle at four delays after ankle movement (10 ms, 40 ms, 80 ms, and 140 ms), respectively. Test-retest reliability of MEP and H-reflex amplitudes were assessed via intraclass correlation coefficients (ICC) both between- and within-session. Between-session test-retest reliability for MEPs was excellent (ICC = 0.928–0.947), while H-reflex demonstrated moderate-to-good reliability (ICC = 0.626–0.887). Within-session reliability for both MEPs and H-reflex was excellent (ICC = 0.927–0.983). TMS and H-reflex measurements were reliable at different delays after perturbation between- and within-sessions, which indicated that these methods can be used to measure corticospinal excitability during balance perturbation.

Using Accuracy and Response Times to Assess Inhibitory Control in Kindergarten Children: An Analysis with Explanatory Item Response Models

ABSTRACT Inhibitory control is a core executive function that develops during childhood and is measured with tasks that require the inhibition of a dominant response. The current study examined the diagnostic value of using response accuracy and latency in a simple inhibitory control test, the computerized Pointing-Stroop Task (cPST), for kindergarten children. The cPST was completed by 135 children, ages 3 through 6 years with diverse national and cultural backgrounds. In explanatory response models, item difficulties and time intensities could be predicted very reliably by congruency and item position, with incongruent responses causing more errors and longer response latency. Moreover, the prediction of fluid intelligence (a close correlate of inhibitory control) from children’s performance in the cPST was enhanced by using response accuracy and response latency, which had a multiplicative effect, indicating that efficient (accurate and fast) inhibitory control is related to fluid intelligence. These results suggest that measuring the efficiency of inhibitory control in young children is a more appropriate assessment than using either response accuracy or response latency.

Characterizing subcutaneous cortical auditory evoked potentials in mice

Auditory Brainstem Responses (ABRs) are a reliably robust measure of auditory thresholds in the mammalian hearing system and can be used to determine deficits in the auditory periphery. However, because these measures are limited to the lower stages of the auditory pathway, they are insensitive to changes or deficits that occur in the thalamic and cortical regions. Cortical Auditory Evoked Potentials (CAEPs), as longer latency responses, capture information from these regions. However they are less frequently used as a diagnostic tool, particularly in rodent models, due to their inherent variability and subsequent difficult interpretation.The purpose of this study was to develop a consistent measure of subcutaneous CAEPs to auditory stimuli in mice and to determine their origin. To this end, we investigated the effect on the CAEPs recorded in response to different stimuli (noise, click, and tone (16 kHz) bursts), stimulus presentation rates (2/s, 6/s, 10/s) and electrode placements. Recordings were examined for robust CAEP components to determine the optimal experimental paradigm. We argue that CAEPs can measure robust and replicable cortical responses. Furthermore, by deactivating the auditory cortex with lidocaine we demonstrated that the contralateral cortex is the main contributor to the CAEP. Thus CAEP measurements could prove to be of value diagnostically in future for deficits in higher auditory areas.

Cognitive deficits and altered cholinergic innervation in young adult male mice carrying a Parkinson's disease Lrrk2G2019S knockin mutation

Impaired executive function is a common and debilitating non-motor symptom of idiopathic and hereditary Parkinson's disease (PD), but there is little understanding of the underlying pathophysiological mechanisms and circuits. The G2019S mutation in the kinase domain of leucine-rich repeat kinase 2 (LRRK2) greatly increases risk for late-onset PD, and non-manifesting LRRK2G2019S carriers can also exhibit early and significant cognitive impairment. Here, we subjected young adult male mice carrying a Lrrk2G2019S knockin mutation to touchscreen-based operant tasks that measure attention, goal-directed learning and cognitive flexibility, all of which rely on frontal-striatal connectivity and are strongly modulated by cholinergic innervation. In a visuospatial attention task, mutant mice exhibited significantly more omissions and longer response latencies than controls that could not be attributed to deficits in motivation, visual sensory perception per se or locomotion, thereby suggesting impairments in divided attention and/or action-selection as well as generally slower information processing speed. Pretreating mice with the acetylcholinesterase inhibitor donepezil normalized both higher omission rates and longer response latencies in the mutants, but did not affect any performance metric in controls. Strikingly, cholinergic fiber density in cortical areas PL/IL and DMS (dorsomedial striatum) was significantly sparser in mutants than in controls, while further behavioral interrogation of the mutants revealed significant impairments in action-outcome associations but preserved cognitive flexibility. These data suggest that the Lrrk2G2019S mutation negatively impacts cholinergic innervation anatomically and functionally by young adulthood, impairing corticostriatal network function in ways that may contribute to early PD-associated executive function deficits.

Transcranial electrical stimulation elicits short and long latency responses in the tongue muscles

ObjectiveIntraoperative transcranial electrical stimulation evokes a motor response at short latency (SLR) of a few milliseconds in cranial nerves innervated muscles. In addition, a long latency response (LLR) is known for the laryngeal nerve. We present here the LLR in the tongue muscles. MethodsIn 22 neurosurgical interventions we have applied electrical stimulation pulses transcranially over the motor cortex of fully anesthetized patients. Stimulation sites were lateral (C3/C4 – Cz) or medial (C1–C2). We recorded motor evoked potentials from the tongue as the target muscle of the hypoglossal nerve. ResultsStimulation evoked a SLR of the tongue with a median (IQR) latency of 14 (13, 19) ms. In addition, a LLR appeared at 58 (54, 66) ms. Median (IQR) response amplitudes were 60 (32, 185) μV for SLR and 30 (20, 47) μV for LLR. While stimulation by C3/C4 – Cz evoked both the SLR and the LLR, stimulation by C1–C2 evoked preferably the LLR with a success rate of 16/18 (89%) surgeries (p =.0007). ConclusionsTranscranial electrical stimulation robustly elicits a LLR in the tongue muscles of anesthetized patients. SignificanceWe corroborated preliminary findings on the LLR of the tongue muscles in more patients.