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Biomedical subjects

Antoni Valero-Cabré

Publications and source records attributed to Antoni Valero-Cabré.

14 recordsLinked to original sources

Disruption of primary motor cortex before learning impairs memory of movement dynamics.

Although multiple lines of evidence implicate the primary motor cortex (M1) in motor learning, the precise role of M1 in the adaptation to novel movement dynamics and in the subsequent consolidation of a memory of those dynamics remains unclear. Here we used repetitive transcranial magnetic stimulation (rTMS) to dissociate the contribution of M1 to these distinct aspects of motor learning. Subjects performed reaching movements in velocity-dependent force fields over three epochs: a null-field baseline epoch, a clockwise-field learning epoch (15 min after the baseline epoch), and a clockwise-field retest epoch (24 h after the learning epoch). Half of the subjects received 15 min of 1 Hz rTMS to M1 between the baseline and learning epochs. Subjects given rTMS performed identically to control subjects during the learning epoch. However, control subjects performed with significantly less error than rTMS subjects in the retest epoch on the following day. These results suggest that M1 is not critical to the network supporting motor adaptation per se but that, within this network, M1 may be important for initiating the development of long-term motor memories.

Adaptation, Physiological↗

Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex.

Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating human cortical excitability beyond the duration of the stimulation train. However, the basis and extent of this "off-line" modulation remains unknown. In a group of anesthetized cats, we applied patterns of real or sham focal rTMS to the visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain glucose uptake during (on-line), immediately after (off-line), or 1 h after (late) stimulation. During the on-line period LF and HF rTMS induced a significant relative reduction of (14)C-2DG uptake in the stimulated VP cortex and tightly linked cortical and subcortical structures (e.g. the superficial superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue areas in the unstimulated hemisphere. During the off-line period HF rTMS induced a significant relative increase in (14)C-2DG uptake in the targeted VP cortex, whereas LF rTMS generated the opposite effect, with only mild network impact. Moderate distributed effects were only recorded after LF rTMS in the posterior thalamic structures. No long lasting cortical or subcortical effects were detected during the late period. Our findings demonstrate opposite modulation of rTMS on local and distant effects along a specific network, depending on the pattern of stimulation. Such effects are demonstrated in the anesthetized animal, ruling out behavioral and non-specific reasons for the differential impact of the stimulation. The findings are consistent with previous differential electrophysiological and behavioral effects of low and high frequency rTMS patterns and provide support to uses of rTMS in neuromodulation.

Animals↗

Differential motor and electrophysiological outcome in rats with mid-thoracic or high lumbar incomplete spinal cord injuries.

We have investigated the motor changes in rats subjected to a moderate photochemical injury on mid-thoracic (T8) or high lumbar (L2) spinal cord segments. Fourteen days after surgery, L2 injured animals presented gross locomotor deficits (scored 10+/-2.8 in the BBB scale), decreased amplitude of motor-evoked potentials (MEPs) recorded on tibialis anterior (TA) and plantar (PL) muscles (24% and 6% of the preoperative mean values, respectively), reduced M wave amplitudes (75%, 62%), and also facilitated monosynaptic reflexes evidenced by an increase of the H/M amplitude ratio (158% and 563%). On the other hand, T8 injured animals had only slight deficits in locomotion (18+/-0.6 in the BBB scale), a minimal reduction in MEP amplitudes (78% and 71% in TA and PL muscles), normal M wave amplitudes, and a milder increase of the H/M ratio in the TA muscle (191%) but less pronounced in the PL muscle (172%). The percentage of spared tissue at the site of injury was similar in both experimental groups (L2: 79% and T8: 82%). Taken together, these results indicate that lumbar spinal injuries have more severe consequences on hindlimb motor output than injuries exerted on thoracic segments. The causes of this anatomical difference may be attributed to damage inflicted on the central pattern generator of locomotion resulting in dysfunction of lumbar motoneurons and altered spinal reflexes modulation.

Animals↗

Effects of postweaning social isolation and re-socialization on the expression of vasoactive intestinal peptide (VIP) and dendritic development in the medial prefrontal cortex of the rat.

In the present study we evaluated the effects of early social isolation and re-socialization on dendritic development and the expression of the vasoactive intestinal peptide (VIP) in the medial prefrontal cortex (mPFC) of the rat. Sprague-Dawley male rats were reared either in isolation (IC) or social (SC) conditions from postnatal day 18 to 32. Rats were then behaviorally evaluated in the open field test, and approximately half of the animals were sacrificed. Their brains were processed either for immunocytochemical labeling against VIP or for the Golgi-Cox-Sholl staining. The remaining IC rats were re-socialized during 30 additional days. The results demonstrated that early social isolation impair neuronal dendritic arborization and increase the number of VIP-immunoreactive neurons. Furthermore, animals displayed hyperlocomotion in the open-field test. According to our structural, immunocytochemical and open-field data, the resocialization experience was unable to reverse neuronal and behavioral abnormalities.

Age Factors↗

Impact of repetitive transcranial magnetic stimulation of the parietal cortex on metabolic brain activity: a 14C-2DG tracing study in the cat.

Transcranial magnetic stimulation (TMS) is increasingly utilized in clinical neurology and neuroscience. However, detailed knowledge of the impact and specificity of the effects of TMS on brain activity remains unresolved. We have used 14C-labeled deoxyglucose (14C-2DG) mapping during repetitive TMS (rTMS) of the posterior and inferior parietal cortex in anesthetized cats to study, with exquisite spatial resolution, the local and distant effects of rTMS on brain activity. High-frequency rTMS decreases metabolic activity at the primary site of stimulation with respect to homologue areas in the unstimulated hemisphere. In addition, rTMS induces specific distant effects on cortical and subcortical regions known to receive substantial efferent projections from the stimulated cortex. The magnitude of this distal impact is correlated with the strength of the anatomical projections. Thus, in the anesthetized animal, the impact of rTMS is upon a distributed network of structures connected to the primary site of application.

Anesthesia↗

Reorganization of reflex responses mediated by different afferent sensory fibers after spinal cord transection.

Adult rats were submitted to a complete spinal cord transection at T9 level to address peripheral and spinal reflex changes in the caudal lumbar segments. Compound muscle and nerve action potentials decreased in amplitude and increased their duration between 14 and 30 days but recovered to near to normal values thereafter. The H wave amplitude increased during follow-up, resulting in significantly higher H/M ratio in tibialis anterior (223%), gastrocnemius (160%), and plantar (304%) muscles with respect to preoperatory values (P < 0.01). Sixty minutes after spinal cord transection, component C1 (conveyed by Aalphabeta afferents) disappeared in the crossed but not in the ipsilateral withdrawal reflex. Components C2 (Adelta) and C3 (C afferents) were abolished on both. C1 and C3 reappeared for both reflexes in all injured animals, while C2 reappeared in a few cases. C1 ipsilateral component became highly facilitated (209% of presurgery values, P < 0.01), whereas C3 (82%) and C2 (24%) recovered partially. Crossed reflex component C1 attained in all animals similar to normal values (85%) but with longer duration. C3 increased with time although it remained significantly lower than the original (67%) whereas C2 reappeared in only 2/8 animals. In conclusion, spinal cord injury induces a transient disability of caudal spinal cord segments that progressively reverts along time. Ipsilateral reflex components mediated by thick Aalphabeta fibers (H reflex and C1) but not those mediated by thin fibers (C2 and C3) remained present after injury showing long-lasting facilitation whereas contralateral reflex components were abolished after injury and showed limited recovery.

Afferent Pathways↗

Peripheral and spinal motor reorganization after nerve injury and repair.

Functional recovery after peripheral nerve injury depends on the amount as well as on the accuracy of reinnervation by regenerative axons. In this study, the rat sciatic nerve was subjected to crush injury or complete transection repaired by either (1) straight nerve suture, (2) crossed nerve suture of tibial and peroneal fascicles, or (3) silicone tubulization leaving a gap of 4 mm. The compound muscle action potentials (CMAP) of gastrocnemius, tibialis anterior and plantar muscles were recorded 90 days post operation to assess functional reinnervation and Fast Blue, Fluoro Gold and DiI were applied to the nerve branches projecting into these muscles to quantify morphological reinnervation. The CMAP amplitude achieved in gastrocnemius, tibialis anterior and plantar muscles was higher after nerve crush (86%, 82%, 65% of control) than after any surgical nerve repair (straight suture: 49%, 53%, 32%; crossed suture: 56%, 50%, 31%; silicone tube: 42%, 44%, 25%). The total number of labeled motoneurons, however, did not significantly differ between groups (control: 1238 +/- 82, crush: 1048 +/- 49, straight suture: 1175 +/- 106, crossed suture: 1085 +/- 84, silicone tube: 1250 +/- 182). The volume occupied by labeled motoneurons within the spinal cord was larger after surgical nerve repair than in crush or normal control animals, and fewer neurons showed abnormal multiple projections after crush (2.5%) or straight suture (2.2%) than following crossed suture (5%) or silicone tube (6%). In conclusion, nerve repair with a silicone tube leaving a short gap does not increase accuracy of reinnervation.

Action Potentials↗

Morphologic and functional evaluation of peripheral nerve fibers regenerated through polyimide sieve electrodes over long-term implantation.

We evaluated by morphologic and functional analysis the regeneration of peripheral nerve fibers through polyimide regenerative-type electrodes over long-term implantation. Polyimide sieve electrodes were placed in silicone chambers and implanted between the severed ends of the sciatic nerve in rats. The sieve part had 281 round via holes of 40 microm in diameter, with nine integrated recording-stimulating electrodes arranged around the via holes. The degree of axonal regeneration was examined at 2, 7, and 12 months postimplantation (mpi). Regeneration was successful in 12 of the 13 animals implanted. Reinnervation of distal muscle and nerves increased with time, reaching a plateau about 7 mpi. The number of myelinated fibers increased from 2 to 7 months, at which time it was similar to control values. With time the myelinated fibers matured, with significant increases in axon diameter and myelin thickness. Only 0.6% of the regenerated axons showed evidence of compression near the implanted electrode. The majority of the myelinated fibers that crossed the via holes and had been regenerated through the distal nerve had a normal appearance. Sieve electrodes were useful for nerve stimulation at postimplantation. Stimulation through different active electrodes excited nerve bundles, evoking compound muscle action potentials of varying shape and amplitude, indicative of selective axonal stimulation.

Action Potentials↗

On the use of fast blue, fluoro-gold and diamidino yellow for retrograde tracing after peripheral nerve injury: uptake, fading, dye interactions, and toxicity.

The usefulness of three retrograde fluorescent dyes for tracing injured peripheral axons was investigated. The rat sciatic was transected bilaterally and the proximal end briefly exposed to either Fast Blue (FB), Fluoro-Gold (FG) or to Diamidino Yellow (DY) on the right side, and to saline on the left side, respectively. The nerves were then resutured and allowed to regenerate. Electrophysiological tests 3 months later showed similar latencies and amplitudes of evoked muscle and nerve action potentials between tracer groups. The nerves were then cut distal to the original injury and exposed to a second (different) dye. Five days later, retrogradely labelled neurones were counted in the dorsal root ganglia (DRGs) and spinal cord ventral horn. The number of neurones labelled by the first tracer was similar for all three dyes in the DRG and ventral horn except for FG, which labelled fewer motoneurones. When used as second tracer, DY labelled fewer neurones than FG and FB in some experimental situations. The total number of neurones labelled by the first and/or second tracer was reduced by about 30% compared with controls. The contributions of cell death as well as different optional tracer combinations for studies of nerve regeneration are discussed.

Amidines↗

Modulation of input-output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex.

OBJECTIVES: Exploring the modulatory effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on the excitability of the motor cortex as measured by the input-output curve technique (I-O curve). METHODS: Sixteen healthy subjects participated in this experiment. On two different sessions, conducted 1 week apart, rTMS was applied either at a frequency of 20 or 1 Hz at 90% of individual motor threshold (MT) for a total of 1600 pulses each. Before and after rTMS, the cortical excitability was assessed by measuring MT and the size of motor evoked potentials (MEPs) collected at different intensities of stimulation. RESULTS: The analysis on the whole population showed a significant decrease of cortical excitability after 1 Hz rTMS and an increase after 20 Hz rTMS. A subsequent cluster analysis pointed out the presence of two distinct groups of subjects with opposite responses at the same frequency of stimulation. Significant variations on MT were found for both groups only for the facilitatory effect irrespective of the frequency of stimulation. CONCLUSIONS: The results provide further insight into interindividual differences in the effects of rTMS and suggest the existence of subpopulations with specific patterns of response to rTMS.

Adult↗

Functional impact of axonal misdirection after peripheral nerve injuries followed by graft or tube repair.

Accuracy of reinnervation is one of the main factors conditioning functional recovery after brain, spinal, or peripheral axonal damage. Using the peripheral nerve as an experimental model, we studied the amount of inaccurate muscle reinnervation and its consequences on walking. Adult rats were submitted to an 8-mm resection of the sciatic nerve repaired by autograft (AG, n = 9), silicone (SIL, n = 13) or poly-L-lactate-epsilon-caprolactone (PLC, n = 11) single guides, and fascicular tubulization of peroneal and tibial branches with a dual silicone tube (FSIL, n = 9). At the end of follow-up, the sciatic nerve and its tibial and peroneal fascicles were dissected and stimulated by means of a suction electrode. In control rats, gastrocnemius and plantar muscles are fully innervated by the tibial fascicle and the tibialis anterior muscle by the peroneal nerve. None of the groups had noticeable recovery of locomotion assessed by the walking track index (SFI around -70 in all groups). After resection, all animals of groups AG, SIL, and PLC showed aberrant muscle reinnervation by axons from a non-corresponding fascicle, whereas in group FSIL only one of six regenerated animals showed misdirected activity. The proportion of inaccurate muscle activation was similar in group AG (47% for gastrocnemius, 54% for tibialis anterior, and 44% for plantar muscles) and in group SIL (42%, 42%, and 42%), and reduced in group PLC (26%, 38%, and 27%). In conclusion, fascicular silicone tubulization allowed the highest degree of accuracy but the lowest recovery, whereas resorbable PLC guides provided for the best balance between amount and accuracy of reinnervation after nerve resection.

Action Potentials↗

Changes in crossed spinal reflexes after peripheral nerve injury and repair.

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300-400%) and C2 (150-350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

Action Potentials↗