Deformation Rate-Adaptive Conducting Polymers and Composites.

Materials are more easily damaged during accidents that involve rapid deformation. Here, a design strategy is described for electronic materials comprised of conducting polymers that defies this orthodox property, making their extensibility and toughness dynamically adaptive to deformation rates. This counterintuitive property is achieved through a morphology of interconnected nanoscopic core-shell micelles, where the chemical interactions are stronger within the shells than the cores. As a result, the interlinked shells retain material integrity under strain, while the rate of dissociation of the cores controls the extent of micelle elongation, which is a process that adapts to deformation rates. A prototype based on polyaniline shows a 7.5-fold increase in ultimate elongation and a 163-fold increase in toughness when deformed at increasing rates from 2.5 to 10 000% min-1 . This concept can be generalized to other conducting polymers and highly conductive composites to create "self-protective" soft electronic materials with enhanced durability under dynamic movement or deformation.

Coupling of single cutaneous afferents in the hand with ankle muscles, and their response to rapid light touch displacements.

Light touch reduces sway during standing. Unexpected displacement of a light touch reference at the finger can produce rapid responses in ankle muscles when standing, suggesting cutaneous receptors in the hand are functionally coupled with ankle muscles. Using microneurography in the median nerve, we tested the hypotheses: 1) that cutaneous afferent activity of mechanoreceptors of the hand would modulate electromyographic (EMG) activity of ankle muscles, and 2) that displacement of a light touch contact across a receptor's sensory territory would be encoded in the afferent activity. Spike-triggered averaging of EMG activity of tibialis anterior (TA) and soleus (SOL) demonstrated that 34 of 42 (81%) cutaneous afferents recorded modulated activity of ankle muscles with latencies between 40 and 119 ms. Cutaneous afferents of all types (slow and fast adapting, types I and II) demonstrated responses in TA and SOL, in both the ipsilateral and contralateral leg. Activity from 11 cutaneous afferents was recorded while a light touch contact was displaced across their receptive fields. Afferent activity increased with stimulus onset and remained elevated for the stimulus duration for all afferents recorded. These results suggest that cutaneous afferents from the hand consistently form connections with motor pools of the leg at latencies implicating spinal pathways. In addition, the same population of afferents is readily excited by the displacement of a light touch contact. Therefore, cutaneous receptors of the hand can be recruited and used to alter motoneuron pool excitability in muscles important to balance control, at latencies relevant for rapid balance responses.NEW & NOTEWORTHY Light touch provides cutaneous feedback argued to contribute to balance control and shown to reduce postural sway. We demonstrate that activity of cutaneous afferents in the median nerve modulates motor pool excitability of ankle muscles at short latencies and that these afferents respond when a light touch contact is displaced. These findings suggest that cutaneous receptors of the hand can contribute to rapid regulation of muscle activity important to standing balance.

Lung volume recruitment improves volitional airway clearance in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: In this study we evaluated the effects of lung volume recruitment treatment (LVR), a low-tech, low-cost, manual "breath-stacking" technique used to help people cough with enough force to clear their airways, thereby reducing the risk of aspiration and choking, on five volitional airway clearance and protection behaviors used by people living with amyotrophic lateral sclerosis (PwALS). METHODS: Using a repeated-measures cross-over design, 29 PwALS performed five volitional airway clearance and protection behaviors in LVR treatment and in no-treatment, control conditions. Peak cough flow (PCF) was used to measure maximum expiratory rate during forced expiration, throat clearing, hawking, post-swallow coughing, and the supraglottic swallowing maneuver. Comparisons were made as a function of condition (treatment or control) and three time-points (pretreatment, and 15 and 30 minutes posttreatment). RESULTS: LVR treatment had a significant positive effect on maximum expiratory rates during all tested airway clearance and protection behaviors. Increased PCF values lasted for up to 30 minutes post-LVR for all tested behaviors in the treatment condition. DISCUSSION: We found that LVR treatment could increase control over airway clearance in PwALS, as well as provide improved airway protection for up to 30 minutes, the duration of a typical meal. This study has implications for patient care. These include offering patients control over some of the most feared symptoms of ALS, particularly choking during activities of daily living, and enhanced ALS respiratory care in low-resource settings. Findings may have implications for other neurodegenerative disorders in which dysphagia occurs with retained sensory function.

Influence of a light touch reference on cutaneous reflexes from the hand during standing.

Light touch of a stable reference reduces sway during standing. However, unexpected displacement of a light touch reference leads to short-latency reactions in ankle muscles consistent with a balance reaction, that are replaced by responses in arm muscles on subsequent trials. We anticipated that the excitability of sensorimotor pathways arising from finger cutaneous afferents would reflect these changes in behavior. We hypothesized that (1) interlimb cutaneous reflexes in muscles of the ipsilateral leg, derived from median nerve (MED) stimulation would be facilitated when touch was stable, but reduced when touch was unreliable, (2) intralimb MED reflexes in muscles of the homonymous arm would be facilitated when touch was unreliable and participants tracked the touch reference with arm movements, and (3) radial nerve (RAD) evoked reflexes would be unaffected, given that the RAD innervation territory is not involved in the light touch task. Cutaneous reflexes were evoked using a transcutaneous train of pulses (5 × 1.0 ms square-wave pulses; 300 Hz) and recorded using electromyography of muscles of the ipsilateral arm and leg. As hypothesized, interlimb MED reflexes recorded in soleus (SOL) were larger when touching the stable reference (mean ± SD % MVC; 4.78 ± 1.57) than when not touching a reference (1.00 ± 1.05) or when touching an unstable reference (1.07 ± 1.16). In addition, intralimb MED reflexes in anterior deltoid (AD) were larger when touching an unstable reference (4.50 ± 1.31), compared to touching a stable reference (1.34 ± 1.01) or not touching (1.50 ± 1.00). In contrast, interlimb RAD reflexes in SOL were larger when not touching (4.29 ± 4.34), compared with touching a stable (1.14 ± 1.84) or unstable reference (3.11 ± 4.15). These findings indicate that cutaneous reflexes from the hand are scaled with a rapid change in motor behavior when a touch reference becomes unstable, suggesting that spinal sensorimotor pathways are functionally reweighted based in part upon the reliability of tactile inputs.

The effect of light touch on standing sway when the stability of the external touch reference becomes unreliable.

Lightly touching a stable reference is associated with sway reduction during standing. Unexpected displacement of the touch reference results in a false-positive balance reaction in some participants, but only with the first such disturbance. This study investigated whether light touch reduces standing sway (1) after the touch reference becomes unreliable, and (2) when participants are aware the touch reference is unreliable. 40 healthy adults, 20 that were naïve to the possibility of a touch reference displacement and 20 that were made aware prior to testing, were asked to stand while lightly touching (< 1 N) a reference with normal vision or vision occluded. Motion of the center of pressure was used to estimate standing sway before and after a single displacement, and then multiple displacements, of a touch reference. Sway area was always reduced while touching the reference, compared to standing with vision occluded without touch, even when the reference was known to be unreliable. In addition, sway area was further reduced following a single touch displacement in Naïve participants when vision was occluded. These results suggest that tactile cues from the finger interact with postural control in a complex manner, depending upon the expectation and experience of the characteristics of the touched object. Taken together, light touch can (1) be used as a spatial reference that assists in sway stabilization, (2) be a source of movement variability that impacts the performance of a skilled task, or (3) introduce noise in the sensory channels impacting fidelity.

Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity.

BACKGROUND: Powered exoskeletons provide a way to stand and walk for people with severe spinal cord injury. Here, we used the ReWalk exoskeleton to determine the training dosage required for walking proficiency, the sensory and motor changes in the nervous system with training, and the functionality of the device in a home-like environment. METHODS: Participants with chronic (> 1 yr) motor complete or incomplete spinal cord injury, who were primarily wheelchair users, were trained to walk in the ReWalk for 12 weeks. Measures were taken before, during, immediately after, and 2-3 months after training. Measures included walking progression, sitting balance, skin sensation, spasticity, and strength of the corticospinal tracts. RESULTS: Twelve participants were enrolled with 10 completing training. Training progression and walking ability: The progression in training indicated about 45 sessions to reach 80% of final performance in training. By the end of training, participants walked at speeds of 0.28-0.60 m/s, and distances of 0.74-1.97 km in 1 h. The effort of walking was about 3.3 times that for manual wheelchair propulsion. One non-walker with an incomplete injury became a walker without the ReWalk after training. Sensory and motor measures: Sitting balance was improved in some, as seen from the limits of stability and sway speed. Neuropathic pain showed no long term changes. Change in spasticity was mixed with suggestion of differences between those with high versus low spasticity prior to training. The strength of motor pathways from the brain to back extensor muscles remained unchanged. Adverse events: Minor adverse events were encountered by the participants and trainer (skin abrasions, non-injurious falls). Field testing: The majority of participants could walk on uneven surfaces outdoors. Some limitations were encountered in home-like environments. CONCLUSION: For individuals with severe SCI, walking proficiency in the ReWalk requires about 45 sessions of training. The training was accompanied by functional improvements in some, especially in people with incomplete injuries. TRIAL REGISTRATION: NCT02322125 Registered 22 December 2014.

Activation of ankle muscles following rapid displacement of a light touch contact during treadmill walking.

The first exposure of a rapid displacement of a light touch reference induces an inappropriate balance corrective response during standing in a proportion of participants that is extinguished with repeated exposures. We hypothesized that if the spatial touch reference was critical to performing of a task the evoked response would be more consistently expressed across participants and observed with repeated exposures to the disturbance. To test this, 20 participants received either forward (N = 10) or backward right-touch displacements at right-heel strike during motorized treadmill walking without visual feedback. Electromyographic recordings from four arm, four leg and one neck muscle were sampled along with joint kinematic and step cycle data. Rapid displacement of the touch surface elicited responses in all 20 participants. However, the frequency of first trial responses was not different from what was observed during standing. In contrast, responses were observed in all participants with subsequent trials. None of the participants tripped or stumbled as a result of the touch perturbations; however, the step cycle duration was consistently shorter following the first forward-touch displacement. A post-experiment questionnaire revealed that many participants often perceived the touch plate displacement as a disturbance to the treadmill belt speed, suggesting the disturbance was occasionally misinterpreted. The activation of ankle muscles following the unexpected slip of a touch reference during walking suggests that tactile information from the finger is a relevant sensory cue for the regulation and control of stepping and stability.

The amplitude of interlimb cutaneous reflexes in the leg is influenced by fingertip touch and vision during treadmill locomotion.

Light touch at the fingertip has been shown to influence postural control during standing and walking. Interlimb cutaneous reflexes have been proposed to provide a neural link between the upper and lower limbs to assist in interlimb coordination during activities such as walking. In this study, we tested the hypothesis that cutaneous sensory pathways linking the arm and leg will be facilitated if subjects use light touch to assist with postural control during treadmill walking. To test this, interlimb cutaneous reflexes from the median nerve, serving the skin contact region, and radial nerve, serving an irrelevant sensory territory, were tested in the legs of subjects walking on treadmill in an unstable environment. Interlimb cutaneous reflexes were tested while subjects (a) touched or (b) did not touch a stable contact with their fingertip, and while the eyes were either (c) open or (d) closed. Reflexes arising from both nerves were facilitated when vision was removed that was then ameliorated when touch was provided. These changes in reflex amplitude during the eyes closed conditions were mirrored by changes in background muscle activity. We suggest that this facilitation of interlimb reflexes from both nerves arises from a generalized increase in excitability related to the postural anxiety of walking on a treadmill with the eyes closed, which is then restored by the provision of light touch. However, the influence of touch when the eyes were open differed depending upon the nerve stimulated. Radial nerve reflexes in the legs were suppressed when touch was provided, mirroring a suppression in the background muscle activity. In contrast, median nerve reflexes in the leg were larger when touch was provided with the eyes open, despite a suppression of background muscle activity. This nerve-specific effect of touch on the amplitude of the interlimb cutaneous reflexes suggests that touch sensory information from the median nerve was facilitated when that input was functionally relevant.

Balance-corrective responses to unexpected perturbations at the arms during treadmill walking.

The arms have been shown to be involved in the regulation of balance during walking. The use of a walking aid enhances balance by increasing the base of support and reducing the load on the legs by partly transferring it to the arms. However, when actively engaged during a balance task, perturbations to the arms can destabilize balance. Previous studies have investigated postural adjustments associated with focal arm movements during standing and walking. However, balance-corrective reactions to unexpected perturbations to the arms during walking have not been well studied. In the present study, subjects walked on a treadmill while grasping a pair of handles when sudden perturbations were delivered by displacing the handles in the forward or backward direction. Instructing subjects to oppose the displacement of the handles resulted in strong responses in the arms that were accompanied by activation of muscles in the legs, comparable to those observed in other balance disturbance studies. Conversely, when subjects were instructed to allow the handles to move when displaced, no responses were observed in the arms. However, similar responses were observed in the legs whether subjects opposed the displacement of the handles or not when perturbations were applied at heel strike. The results from this study show that balance reactions can be elicited in the legs in response to perturbations applied at the arms, and that the expression of these responses is affected by the task engaged in by the arms.

The effect of light touch on the amplitude of cutaneous reflexes in the arms during treadmill walking.

Light touch contact of the tip of one finger can influence the postural control of subjects standing or walking on a treadmill. It is suggested that haptic cues from the finger provide an important sensory cue for the control of posture. In the current study, we used intra-limb cutaneous reflexes in the arms to test the hypothesis that transmission in sensory pathways relevant to the light touch contact would be modulated when light touch is used to increase stability during walking in an unstable environment. Subjects walked on a treadmill and received periodic pulls to the waist. Cutaneous reflexes were evoked from stimulation of the median and radial nerves while the subjects either (a) lightly touched or (b) did not touch a stable contact with the tip of their index finger, while the eyes were either (c) open or (d) closed. The results showed that cutaneous reflexes were modulated by both touch and vision. The effect of touch depended on the nerve being stimulated. The provision of touch in the absence of vision resulted in facilitation of median nerve reflexes evoked in the posterior deltoid and the triceps brachii, but resulted in the suppression of radial nerve reflexes. The nerve-specific influence of touch observed in the responses suggests that cutaneous afferent pathways are facilitated in the presence of touch if they transport sensory information from functionally relevant sensory cues.

The contribution of light touch sensory cues to corrective reactions during treadmill locomotion.

The arms play an important role in balance regulation during walking. In general, perturbations delivered during walking trigger whole-body corrective responses. For instance, holding to stable handles can largely attenuate and even suppress responses in the leg muscles to perturbations during walking. Particular attention has been given to the influence of light touch on postural control. During standing, lightly touching a stable contact greatly reduces body sway and enhances corrective responses to postural perturbations, whereas light touch during walking allows subjects to continue to walk on a treadmill with the eyes closed. We hypothesized that in the absence of mechanical support from the arms, sensory cues from the hands would modulate responses in the legs to balance disturbing perturbations delivered at the torso during walking. To test this, subjects walked on a treadmill while periodically being pulled backwards at the waist while walking. The amplitude of the responses evoked in tibialis anterior to these perturbations was compared across 4 test conditions, in a 2 × 2 design. Subjects either (a) lightly touched or (b) did not touch a stable contact, while the eyes were (c) open or (d) closed. Allowing the subjects to touch a stable contact resulted in a reduction in the amount of fore-aft oscillation of the body on the treadmill, which was accompanied by a reduction in the ongoing electromyographic activity in both tibialis anterior and soleus during undisturbed walking. In contrast, the provision of touch resulted in an increase in the amplitude of the evoked responses in tibialis anterior to the backward perturbations that was more evident when subjects walked with the eyes closed. These results indicate that light touch provides a sensory cue that can be used to assist in stabilizing the body while walking. In addition, the sensory information provided by light touch contributes to the regulation of corrective reactions initiated by balance disturbances encountered during walking.

Self-directed rehabilitation training intensity thresholds for efficient recovery of skilled forelimb function in rats with cervical spinal cord injury.

Task specific rehabilitation training is commonly used to treat motor dysfunction after neurological injures such as spinal cord injury (SCI), yet the use of task specific training in preclinical animal studies of SCI is not common. This is due in part to the difficulty in training animals to perform specific motor tasks, but also due to the lack of knowledge about optimal rehabilitation training parameters to maximize recovery. The single pellet reaching, grasping and retrieval (SPRGR) task (a.k.a. single pellet reaching task or Whishaw task) is a skilled forelimb motor task used to provide rehabilitation training and test motor recovery in rodents with cervical SCI. However, the relationships between the amount, duration, intensity, and timing of training remain poorly understood. In this study, using automated robots that allow rats with cervical SCI ad libitum access to self-directed SPRGR rehabilitation training, we show clear relationships between the total amount of rehabilitation training, the intensity of training (i.e., number of attempts/h), and performance in the task. Specifically, we found that rats naturally segregate into High and Low performance groups based on training strategy and performance in the task. Analysis of the different training strategies showed that more training (i.e., increased number of attempts in the SPRGR task throughout rehabilitation training) at higher intensities (i.e., number of attempts per hour) increased performance in the task, and that improved performance in the SPRGR task was linked to differences in corticospinal tract axon collateral densities in the injured spinal cords. Importantly, however, our data also indicate that rehabilitation training becomes progressively less efficient (i.e., less recovery for each attempt) as both the amount and intensity of rehabilitation training increases. Finally, we found that Low performing animals could increase their training intensity and transition to High performing animals in chronic SCI. These results highlight the rehabilitation training strategies that are most effective to regain skilled forelimb motor function after SCI, which will facilitate pre-clinical rehabilitation studies using animal models and could be beneficial in the development of more efficient clinical rehabilitation training strategies.

Whole-body responses: neural control and implications for rehabilitation and fall prevention.

Humans are one of the unique species that utilize bipedal gait to ambulate in our environment. Despite this fact, coordination of the arms with the legs and the rest of body is essential for many daily activities. As such, whole-body responses have emerged as the preferred strategy following perturbations to balance during both standing and walking. Complex neural circuitry may allow for this coordination through the use of propriospinal pathways linking lumbar and cervical pattern generators in the spinal cord, with supraspinal centers altering this control depending on the context of the situation. Based on these findings, we argue that whole-body reactions may be exploited for rehabilitation purposes. Preliminary results have indicated training programs designed to elicit whole-body responses are effective in reducing falls and improving functional mobility in older adults with and without neurological impairment.

Balance reactions to light touch displacements when standing on foam.

We hypothesized that standing on an unstable surface would increase the relevance of light touch to standing balance, such that unexpected displacement of a touch reference would result in more consistent expression of balance corrections, compared to standing on a firm surface. Ten healthy participants stood on a foam block atop a force plate without vision, while lightly touching a reference. The touch plate was unexpectedly displaced forwards 10 times. Responses in tibialis anterior (TA) were observed more frequently across the 10 trials compared with standing on a firm surface. However, the responses evoked in trials 2-10 were functionally distinct from those following the first trial. We suggest the first trial responses represent balance corrective responses induced by the slip of the finger relative to the reference. In contrast, the subsequent responses in TA are likely related to an arm-tracking reaction that emerges, indicating a rapid repurposing of the tactile feedback.

Adaptations in the walking pattern of spinal cord injured rats.

Walking ability is a measure of recovery used in many studies that test experimental strategies to treat injuries or diseases of the central nervous system (CNS) in animal models. A common measure in the rat animal model of thoracic spinal cord injury (SCI) is visual inspection and scoring of hind limb activity, which allows the documentation of movements associated with the recovery of locomotor function. In this study, we expand on previously documented visible changes in the locomotor pattern following SCI. The spontaneous recovery of locomotion in rats with thoracic SCIs of variable extent was evaluated using electromyographic (EMG) and kinematic analysis while rats walked on an elevated runway. Comparisons with pre-lesion walking sequences revealed changes in the kinematics and in the muscle activation pattern of various muscles, including enhanced fore limb extensor activity, possibly reflecting an increased contribution to propulsion, altered recruitment of back muscles inserting into the hip (possibly to support stepping movements), and elevated posture during stance, which may compensate for deficits in weight support. These changes were noted in spinal cord injured rats with varying degrees of impairment, including animals with no visually detectable deficit in open-field walking. In summary, the presented results demonstrate that spinal cord injured rats develop alternative locomotor patterns following SCI that cannot be discriminated by the use of qualitative visually based analysis, thus urging the use of quantitative outcome measures in assessing motor function after SCI.

Task specific adaptations in rat locomotion: runway versus horizontal ladder.

In walking quadrupeds the alternating activity pattern of antagonistic leg muscles and the coordination between legs is orchestrated by central pattern generating networks within the spinal cord. These networks are activated by tonic input from the reticular formation in the brainstem. Under more challenging conditions, such as walking on a horizontal ladder, successful locomotion relies upon additional context dependent input from pathways such as the cortico- and rubro-spinal tracts. In this study we used electromyographic and kinematic approaches to characterize the adaptations in the walking pattern in adult uninjured rats crossing a horizontal ladder. We found that the placement of a hind limb on a rung precisely followed the placement of the ipsilateral fore limb. This is different to normal walking where the hind limb is placed behind the position of the ipsilateral fore limb. The increased reach of the hind limbs is achieved by increased flexion of the hip and rotation of the pelvis during the swing phase. Electromyographic observations showed decreased burst duration in Tibialis anterior an ankle flexor muscle. Further changes in the muscle activity pattern were likely due to the reduced stepping frequency during ladder walking. Following a lesion of the dorsal column, containing major parts of the corticospinal tract, we found an increased number of stepping errors and changes in the stepping strategy. The step length of the fore limbs was reduced and the hind limbs were frequently positioned on rungs other than those occupied by the fore limb.

Postural uncertainty leads to dynamic control of cutaneous reflexes from the foot during human walking.

Cutaneous reflexes evoked by stimulation of nerves innervating the foot are modulated in a phase-dependent manner during locomotion. The pattern of modulation of these reflexes has been suggested to indicate a functional role of cutaneous reflexes in assisting to maintain stability during walking. We hypothesized that if cutaneous reflexes assist in maintaining stability during gait, then these reflexes should be modulated in a context-dependent manner when subjects are asked to walk in an environment in which stability is challenged. To do this, we asked subjects to walk on a treadmill under five conditions: (1) normally, (2) with the arms crossed, (3) while receiving unpredictable anterior-posterior (AP) perturbations, (4) with the arms crossed while receiving unpredictable AP perturbations, and (5) with the hands holding onto fixed handles. Cutaneous reflexes arising from electrical stimulation of the superficial peroneal (SP; relevant to stumbling) or distal tibial (TIB; relevant to ground contact sensation) nerves were recorded bilaterally, at four points in the step cycle. Reflexes evoked with SP nerve stimulation showed marked facilitation during the most unstable walking condition in 4 of the 7 muscles tested. SP nerve-evoked reflexes in the muscles of the contralateral leg also showed suppression during the most stable walking condition. Reflexes evoked with TIB nerve stimulation were less affected by changes in the walking task. We argue that the specific adaptation of cutaneous reflexes observed with SP nerve stimulation supports the hypothesis that cutaneous reflexes from the foot contribute to the maintenance of stability during walking.

The effects of lung volume recruitment on coughing and pulmonary function in patients with ALS.

Our objective was to study the intensity and duration of the effects of lung volume recruitment, a manual breath stacking technique, on pulmonary function and coughing in individuals with amyotrophic lateral sclerosis (ALS). Twenty-nine individuals with ALS participated in this study. A cross-over research design was used to compare effects of lung volume recruitment to a control condition. Treatment outcome measures included forced vital capacity (FVC), sniff nasal pressure (SnP) and peak cough flow (PCF). Results demonstrated that LVR had a significantly positive effect on FVC for up to 15 min following treatment but did not have a facilitative effect on SnP at any time-point. LVR had a significantly positive effect on PCF during unassisted coughing at both 15 min and 30 min following treatment, and there was no significant decrease in flow rates from baseline to 30 min later. In conclusion, lung volume recruitment may be an effective treatment for improving coughing and pulmonary function in individuals with ALS. Future research should be focused on determining patient characteristics that contribute to response to treatment, as well as randomized controlled trials of the technique.

Weighted vests, stereotyped behaviors and arousal in children with autism.

The homeostatic theory of stereotyped behaviors assumes that these behaviors modulate arousal. Weighted vests are used to decrease stereotyped behaviors in persons with autism because the input they provide is thought to serve the same homeostatic function. This small-n, randomized and blinded study measured the effects of wearing a weighted vest on stereotyped behaviors and heart rate for six children with autism in the classroom. Weighted vests did not decrease motoric stereotyped behaviors in any participant. Verbal stereotyped behaviors decreased in one participant. Weighted vests did not decrease heart rate. Heart rate increased in one participant. Based on this protocol, the use of weighted vests to decrease stereotyped behaviors or arousal in children with autism in the classroom was not supported.

CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls.

The purpose of this study was to examine the differential effects of acute tryptophan (TRP) depletion vs. sham condition on plasma, cerebrospinal fluid (CSF) biochemical parameters, and mood in the following three subject groups: (1) nine antidepressant-free individuals with remitted depression, (2) eight paroxetine-treated individuals with recently remitted depression, and (3) seven healthy controls. Plasma TRP decreased during TRP depletion and increased during sham condition (p<.01). CSF TRP and 5-hydroxyindoleacetic acid were lower during TRP depletion than sham condition (p<.01 each). During TRP depletion, CSF TRP correlated significantly with the plasma sum of large neutral amino acids (SigmaLNAA) (R=-.52, p=.01), but did not significantly correlate with plasma TRP (R=.15, p=.52). The correlation between CSF TRP and ratio of TRP to SigmaLNAA was R=.41 and p=.06 during TRP depletion, and R=-.44 and p=.04 during sham condition. A negative correlation trend was observed between CSF-TRP levels and peak Hamilton Depression Rating Scale scores during TRP depletion in patients recovered from depression (R=-.45, p=.07), but not in healthy controls (R=-.01, p=.98). CSF neuropeptide Y was higher during TRP depletion than sham condition (t=1.75, p<.10). These results illustrate the importance of assessing plasma SigmaLNAA when using the TRP depletion paradigm. The use of a single CSF sampling technique although practical may result in data acquisition limitations.