Operant Conditioning of H-Reflex Can Correct a Locomotor Abnormality after Spinal Cord Injury in Rats

Operant Conditioning of H-Reflex Can Correct a Locomotor Abnormality after Spinal Cord Injury in Rats Yi Chen Xiang Yang Chen Lyn B. Jakeman Lu Chen Bradford T. Stokes Jonathan R. Wolpaw

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Operant Conditioning of H-Reflex Can Correct a Locomotor Abnormality after Spinal Cord Injury in Rats 2006 Journal of Neuroscience 10.1523/jneurosci.2198-06.2006 chen2006-operant-conditioning-of-h-reflex-c chen2006-operant-conditioning-of-h-reflex-c.txt, the project's staged copy e5b66ad4dd719c87ac492ed2af2527b1a2d823d3 open-access neuroscience

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them whether operant conditioning of a spinal reflex can change locomotion after spinal cord injury Quotation withheld because this record is not cleared for redistribution. whether descending input shaped by reflex conditioning can improve motor function in the injured spinal cord Quotation withheld because this record is not cleared for redistribution. shows a targeted reflex conditioning protocol removes a lesion-induced locomotor asymmetry, establishing the principle that descending-input conditioning can change a complex motor behaviour Quotation withheld because this record is not cleared for redistribution. existence Quotation withheld because this record is not cleared for redistribution. H-reflex operant conditioning after spinal cord injury Quotation withheld because this record is not cleared for redistribution. electrophysiology electrophysiology Quotation withheld because this record is not cleared for redistribution. mechanisms Up-conditioning strengthens the motoneuron response to primary afferent input, recruiting more motoneurons into the locomotor burst (and making each fire more), which enlarges and broadens the soleus burst and thereby lengthens right stance until symmetry is restored Quotation withheld because this record is not cleared for redistribution. mechanisms The enlarged locomotor burst produced by up-conditioning is the proposed origin of the restored right/left symmetry Quotation withheld because this record is not cleared for redistribution. mechanisms In normal animals compensatory adjustments by other muscles cancel the conditioning-induced change; in lesioned animals those compensatory adjustments are impaired or absent, so the conditioning effect is allowed to alter locomotion Quotation withheld because this record is not cleared for redistribution. up-conditioning raises the locomotor burst, probably by recruiting more motoneurons to primary afferent input, and the burst also broadens Quotation withheld because this record is not cleared for redistribution. the lesion spares the corticospinal tract, which is the only descending path known to be essential for H-reflex conditioning - so the protocol can still work Quotation withheld because this record is not cleared for redistribution. in intact animals other muscles compensate and symmetry is preserved; after injury that compensation is impaired, so the same conditioning changes locomotion Quotation withheld because this record is not cleared for redistribution. conditioning is delivered continuously in the home cage, 3000-9000 stimulus trials per day over 50 days Quotation withheld because this record is not cleared for redistribution. H-reflex size is expressed in units of background EMG rather than peak-to-peak, because the rat H-reflex form is too variable for a peak measure Quotation withheld because this record is not cleared for redistribution. The study only establishes the principle; the functional and clinical significance of the effect is not yet assessed. what this limits: what the study establishes, stated by the authors as principle only: THE PRESENT RESULTS MERELY VALIDATE THE PRINCIPLE THAT SPINAL REFLEX CONDITIONING CAN AFFECT A COMPLEX MOTOR FUNCTION AFTER SPINAL CORD INJURY Quotation withheld because this record is not cleared for redistribution. Whether treadmill results in quadrupedal rats transfer to over-ground walking in bipedal humans is unknown. what this limits: transfer to human walking: THE EXTENT TO WHICH THE EFFECTS OF CONDITIONING ON TREADMILL LOCOMOTION IN THE QUADRIPEDAL RAT PREDICT ITS EFFECTS ON OVER-GROUND LOCOMOTION IN THE BIPEDAL HUMAN REMAINS TO BE DETERMINED Quotation withheld because this record is not cleared for redistribution. How long the conditioning effects last is not established. what this limits: any claim about how long the effect lasts: THE LONG-TERM PERSISTENCE OF THE EFFECTS OF H-REFLEX CONDITIONING IS NOT YET WELL DEFINED Quotation withheld because this record is not cleared for redistribution. Large between-rat variability in absolute EMG measures limits the power to detect group differences. what this limits: between-group comparisons on absolute measures: THIS WIDE INTER-RAT VARIABILITY MEANS THAT VERY LARGE GROUPS OF LC AND NORMAL RATS WOULD BE NEEDED FOR INTERGROUP DIFFERENCES TO BECOME SIGNIFICANT Quotation withheld because this record is not cleared for redistribution. the measured asymmetry is an EMG proxy, and whether it corresponds to an actual limp is stated to be unknown what this limits: the step from the EMG measure to the behaviour: IT IS NOT AS YET CLEAR WHETHER THE SOLEUS EMG ASYMMETRY CREATED BY THE LC LESION IS ASSOCIATED WITH AN ACTUAL LIMP IN WALKING Quotation withheld because this record is not cleared for redistribution. the results are said to merely validate a principle, with clinical significance unassessed what this limits: the same scope as limitations[0] - the principle, not the clinical application: MUCH REMAINS TO BE LEARNED BEFORE THE POTENTIAL of the method is known Quotation withheld because this record is not cleared for redistribution. only soleus bursts were measured; stance and swing need direct measurement and other muscles are untested what this limits: the soleus-burst proxy for stance and swing: THE DATA PRESENTED HERE RELY ON THE RIGHT AND LEFT SOLEUS LOCOMOTOR BURSTS TO ASSESS SPECIFIC ASPECTS OF LOCOMOTION, and these measures only APPEAR TO PARALLEL THE RIGHT AND LEFT STANCE PHASES OF LOCOMOTION Quotation withheld because this record is not cleared for redistribution. whether quadrupedal treadmill results predict bipedal over-ground human locomotion is undetermined duplicate of: limitations[1] · what this limits: the same scope as limitations[1] - prediction from quadrupedal treadmill work to BIPEDAL HUMAN over-ground locomotion Quotation withheld because this record is not cleared for redistribution. the long-term persistence of the effect is not well defined, and up-conditioning decays faster than down-conditioning in monkeys what this limits: the same scope as limitations[2] - persistence, where the human comparison is that THE EFFECTS OF DOWN-CONDITIONING ARE STILL EVIDENT 4 MONTHS LATER Quotation withheld because this record is not cleared for redistribution. inter-rat variability in absolute EMG measures is so wide that very large groups would be needed for group differences to reach significance what this limits: absolute measures specifically: ABSOLUTE MEASURES SUCH AS SOLEUS BURST AMPLITUDE DIFFER WIDELY ACROSS NORMAL RATS AND EVEN BETWEEN THE RIGHT AND LEFT LEGS OF INDIVIDUAL RATS Quotation withheld because this record is not cleared for redistribution. the locomotor analysis uses only the seven rats in which conditioning succeeded what this limits: the up-conditioning locomotion analysis, which used only the animals in which conditioning worked: THE SEVEN SUCCESSFUL RATS CONSTITUTED THE EXPERIMENTAL GROUP OF HRup RATS FOR EVALUATION OF THE EFFECTS OF UP-CONDITIONING ON TREADMILL LOCOMOTION Quotation withheld because this record is not cleared for redistribution. 13 female rats only what this limits: any sex-general reading: SUBJECTS WERE 13 FEMALE SPRAGUE DAWLEY RATS Quotation withheld because this record is not cleared for redistribution. reward-contingent shaping, applied to a spinal reflex rather than to a voluntary action Quotation withheld because this record is not cleared for redistribution. evidence that far fewer trials suffice in people, used to argue the rat protocol's intensity is not a barrier Quotation withheld because this record is not cleared for redistribution. five rats that were never exposed to up-conditioning, run through the same two sessions as the conditioned animals eliminates: the passage of time and repeated testing as the explanation of the change - if the unconditioned rats changed too, the effect would not be the conditioning · outcome: held Quotation withheld because this record is not cleared for redistribution. locomotor abnormality here means an EMG burst-onset asymmetry, not an observed gait defect - the paper says whether there is a limp at all is unknown Quotation withheld because this record is not cleared for redistribution. successful conditioning is stipulated as a change of at least 20% in the intended direction, a criterion carried over from earlier papers Quotation withheld because this record is not cleared for redistribution. the abnormality is PHYSIOLOGICALLY defined and the lesion ANATOMICALLY defined - the paper states the two bases separately Quotation withheld because this record is not cleared for redistribution. symmetry is an index constructed so that 0.5 means symmetric, built from burst-onset times rather than from limb kinematics Quotation withheld because this record is not cleared for redistribution. claim_type: mechanism a second reading DIFFERING from the recorded value. Recorded: existence — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: right lateral column transection, then 50 days of H-reflex up-conditioning by nerve-cuff stimulation and food reward in the freely moving rat, with treadmill locomotion measured before and after a second reading DIFFERING from the recorded value. Recorded: electrophysiology — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. phenomenon: activity-dependent spinal cord plasticity a second reading DIFFERING from the recorded value. Recorded: H-reflex operant conditioning after spinal cord injury — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. extends → Chen et al., 2005 (H-reflex conditioning in normal rats) Quotation withheld because this record is not cleared for redistribution. builds-on → Chen et al., 2001a and Chen et al., 2005 Quotation withheld because this record is not cleared for redistribution. extends → work showing that patterned sensory input from locomotor training induces spinal plasticity, by adding a descending-input route Quotation withheld because this record is not cleared for redistribution. supports → the feasibility of reflex conditioning in people with partial spinal cord injuries who retain a functioning CST Quotation withheld because this record is not cleared for redistribution. qualifies → its own translational claim, by stating the rat-to-human locomotion question is undetermined status: the paper's own words: remains to be determined Quotation withheld because this record is not cleared for redistribution. distinguishes-from → the same conditioning in normal rats, where it does not change locomotor symmetry at all differs in: THE AXIS IS WHETHER THE ANIMAL IS INJURED. 'Quotation withheld' The same conditioning does nothing in an intact animal and changes locomotion in an injured one - so the effect is a property of the DAMAGED system, and a therapy claim depends entirely on that. Quotation withheld because this record is not cleared for redistribution. H-reflex —causes→ locomotor asymmetry H-reflex locomotor asymmetry strength of the relation: 0.85 · note: SCOPE: this holds in lesioned rats and explicitly does NOT hold in normal rats, where the same conditioning leaves symmetry unchanged Quotation withheld because this record is not cleared for redistribution. lateral column —distinct-from→ corticospinal tract lateral column corticospinal tract strength of the relation: 1 · note: the whole design rests on this separation - the lesion removes one and spares the other Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the procedure transected the LC and left the CST intact; distinct-from is loose. Quotation withheld because this record is not cleared for redistribution. locomotor asymmetry —operationalised-as→ step-cycle symmetry locomotor asymmetry step-cycle symmetry strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span defines step-cycle symmetry; 'locomotor asymmetry' is not named. Quotation withheld because this record is not cleared for redistribution. EVIDENCE CORRECTED (RE-GROUNDED) · H-reflex —operationalised-as→ background EMG H-reflex background EMG EVIDENCE CORRECTED: RE-GROUNDED. The old span explained why the measure is used. This sentence IS THE OPERATIONALISATION, as a formula: '…and was expressed in units of average background EMG…'. The second endpoint appears twice - as the subtrahend and as the unit. — strength of the relation: 0.9 · note: the measurement unit was chosen because the animal's reflex form is too variable for the obvious measure Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but endpoint by anaphora: 'in this manner' = measured relative to average background EMG amplitude (previous sentence). Quotation withheld because this record is not cleared for redistribution. H-reflex —operationalised-as→ background EMG H-reflex background EMG strength of the relation: 0.9 · note: RE-GROUNDS another row of this record: the old span named ONE endpoint. Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but H-reflex size is expressed IN UNITS of background EMG; operationalised-as is loose. Quotation withheld because this record is not cleared for redistribution. ANOVA ANOVA Quotation withheld because this record is not cleared for redistribution. post hoc multiple comparison (Tukey's test) post hoc multiple comparison (Tukey's test) Quotation withheld because this record is not cleared for redistribution. t-test t-test Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. standard deviation standard deviation Quotation withheld because this record is not cleared for redistribution. coefficient of variation coefficient of variation Quotation withheld because this record is not cleared for redistribution. one-way repeated-measures ANOVA with Tukey's test one-way repeated-measures ANOVA with Tukey's test Quotation withheld because this record is not cleared for redistribution. coefficient of variation across step cycles coefficient of variation across step cycles Quotation withheld because this record is not cleared for redistribution. Up-conditioning the soleus H-reflex enlarged the right soleus burst and corrected the locomotor asymmetry. Quotation withheld because this record is not cleared for redistribution. Right lateral-column transection shortened the right stance phase: right-to-left burst-onset time was only 77% of left-to-right. Quotation withheld because this record is not cleared for redistribution. The conditioning protocol roughly doubled the size of the conditioning H-reflex while leaving background EMG and the direct muscle (M) response unchanged, showing the change was reflex-specific rather than a general increase in muscle activation. Quotation withheld because this record is not cleared for redistribution. In up-conditioned rats the locomotor H-reflexes and right soleus burst amplitude and width grew significantly between the first and second sessions. Quotation withheld because this record is not cleared for redistribution. Step-cycle duration did not change in either the up-conditioned or the control group. Quotation withheld because this record is not cleared for redistribution. In normal rats neither up- nor down-conditioning affects right/left step symmetry. Quotation withheld because this record is not cleared for redistribution. Up-conditioning succeeded in 7 of 8 lesioned rats (87.5%). Quotation withheld because this record is not cleared for redistribution. lateral column transection left a persistent burst-onset asymmetry: right-to-left time was 0.43 of the cycle against 0.50 in normal rats Quotation withheld because this record is not cleared for redistribution. the right stance phase was shortened to 77% of the opposite interval Quotation withheld because this record is not cleared for redistribution. up-conditioning succeeded in 7 of 8 rats Quotation withheld because this record is not cleared for redistribution. locomotor H-reflexes and right soleus burst amplitude and width all increased in the conditioned group Quotation withheld because this record is not cleared for redistribution. the asymmetry disappeared in the up-conditioned group Quotation withheld because this record is not cleared for redistribution. a stance H-reflex increase came with a burst amplitude increase 0.32 times as large Quotation withheld because this record is not cleared for redistribution. the same conditioning does not change locomotor symmetry in normal rats Quotation withheld because this record is not cleared for redistribution. 72% of the right lateral column was destroyed, with other structures mostly intact Quotation withheld because this record is not cleared for redistribution. conditioning H-reflex conditioning H-reflex Quotation withheld because this record is not cleared for redistribution. step-cycle symmetry step-cycle symmetry Quotation withheld because this record is not cleared for redistribution. successful conditioning successful conditioning Quotation withheld because this record is not cleared for redistribution. step-cycle symmetry step-cycle symmetry Quotation withheld because this record is not cleared for redistribution. successful conditioning successful conditioning Quotation withheld because this record is not cleared for redistribution. burst onset burst onset Quotation withheld because this record is not cleared for redistribution. burst offset burst offset Quotation withheld because this record is not cleared for redistribution. H-reflex up-conditioning H-reflex up-conditioning Quotation withheld because this record is not cleared for redistribution. step-cycle symmetry step-cycle symmetry Quotation withheld because this record is not cleared for redistribution. treadmill speed treadmill speed Quotation withheld because this record is not cleared for redistribution. M-response size M-response size Quotation withheld because this record is not cleared for redistribution. H-reflex size H-reflex size Quotation withheld because this record is not cleared for redistribution. burst amplitude burst amplitude Quotation withheld because this record is not cleared for redistribution. burst width burst width Quotation withheld because this record is not cleared for redistribution. 212 ± 49% — final size of the conditioning H-reflex in successfully up-conditioned rats, as a percentage of its pre-conditioning control size Quotation withheld because this record is not cleared for redistribution. 87.5% — proportion of rats (7 of 8) in which up-conditioning met the success criterion Quotation withheld because this record is not cleared for redistribution. 0.43 ± 0.02 — right-to-left burst-onset interval as a fraction of the whole step cycle in lesioned rats, versus the 0.50 of symmetrical locomotion Quotation withheld because this record is not cleared for redistribution. 280 ± 38% — increase in the stance-phase locomotor H-reflex after up-conditioning, as a percentage of its first-session value Quotation withheld because this record is not cleared for redistribution. 158 ± 22% — increase in right soleus locomotor burst amplitude after up-conditioning, as a percentage of its first-session value Quotation withheld because this record is not cleared for redistribution. 72 ± 18% — proportion of the right lateral column destroyed by the transection, verified histologically Quotation withheld because this record is not cleared for redistribution. p = 0.008 — significance of the disappearance of the right/left step-cycle asymmetry in the up-conditioned group Quotation withheld because this record is not cleared for redistribution. 13 — number of rats used in the study Quotation withheld because this record is not cleared for redistribution. 13 female Sprague Dawley rats — the sample Quotation withheld because this record is not cleared for redistribution. 10% of peak — the stipulated threshold defining burst onset and offset Quotation withheld because this record is not cleared for redistribution. at least 20% change — the stipulated criterion for successful conditioning Quotation withheld because this record is not cleared for redistribution. 0.43 versus 0.50 of the step cycle, p = 0.009 — the lesion-induced asymmetry against normal Quotation withheld because this record is not cleared for redistribution. 212% of control, 7 of 8 rats, 87.5% success — the conditioning effect and its success rate Quotation withheld because this record is not cleared for redistribution. 0.32 times as large, r = 0.60, p = 0.04 — burst amplitude change per unit H-reflex change Quotation withheld because this record is not cleared for redistribution. 72 plus or minus 18% of the right lateral column destroyed — verified lesion extent Quotation withheld because this record is not cleared for redistribution.

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