Is there an optimal age for recovery from motor cortex lesions? II. behavioural and anatomical consequences of unilateral motor cortex lesions in perinatal, infant, and adult rats

Purpose: The purpose of this study was to compare the behavioural and anatomical effects of unilateral motor cortex ablation in neonatal, infant, and adult rats. Methods: Rats were given unilateral lesions of the motor cortex on the day of birth (P1), at ten days of age (P10), or in adulthood. They were trained on several motor tasks (skilled forelimb reaching, beam traversing, tongue extension), general motor activity, and a test of spatial learning (Morris water task). Results: Although all lesion groups were equally impaired at skilled reaching with the forelimb contralateral to the lesion, rats with P1 lesions also were impaired at traversing a narrow beam and at learning the Morris task. Gross anatomical analyses revealed that the P1 rats had smaller brains than the other groups, a result that may account for the larger behavioural deficits in the P1 group. Analysis of Golgi-Cox stained neurons showed that relative to control groups, all lesion groups showed an increase in dendritic length in the basilar dendrites of layer III pyramidal cells and, paradoxically a decrease in length of the apical dendrites of the same cells. Conclusions: The bilateral alterations in dendritic organization following the motor cortex lesions suggest that there has been a bilateral reor-ganization of intrinsic cortical connectivity following motor cortex lesions at any age. These alterations in connectivity are likely not identical in the young and adult animals, however, because relative to controls, both the young operated groups, but not the adult group, showed a bilat-eral drop in spine density in the basilar dendrites of layer V pyramidal cells. These findings are discussed with respect to the idea that there may be critical ages in development in which animals can use anatomical modifications to compensate for deficits produced by cortical injury.     

Is there an optimal age for recovery from motor cortex lesions? I. Behavioral and anatomical sequelae of bilateral motor cortex lesions in rats on postnatal days 1, 10, and in adulthood

Rats were given bilateral lesions of the motor cortex on the day of birth (P1), tenth day of life (P10), or in adulthood. They were trained on several motor tasks (skilled forelimb reaching, beam traversing, tongue extension), general motor activity, and a test of spatial learning (Morris water task). Although all lesion groups were impaired at skilled reaching, the P10 group was less impaired than either of the other two lesion groups. Furthermore, on the other motor tests the P10 group did not differ from controls whereas both P1 and adult groups were impaired. Only the P1 lesion group was impaired at the acquisition of the Morris water task. Anatomical analyses revealed that the P1 and P10 rats had smaller brains than the other two groups as well as having a generalized decrease in cortical thickness. Dendritic analysis of layer III pyramidal cells in the parietal cortex revealed a decrease in apical arbor in the lesion groups and an increase in the basilar arbor of the P1 and adult lesion animals. The P1 and adult operated groups showed an increase in spine density in the basilar dendrites of layer V pyramidal cells. Finally, analysis of the pattern of corticospinal projections revealed that the P1 animals had a markedly wider field of corticospinal projection neurons than any of the other groups. The widespread anatomical changes in all lesion groups versus the relatively better behavioral recovery after P10 lesions suggests that day 10 represents an optimal period for adapting to brain damage and subsequent brain reorganization.     

Can lesions to the motor cortex induce amyotrophic lateral sclerosis?

A recent staging effort for amyotrophic lateral sclerosis (ALS) has demonstrated that the TDP-43 neuropathology may initiate focally in the motor cortex in the majority of patients. We searched our data bank for patients with lesions of the motor cortex which preceded disease onset. We performed a search of our patient- and MRI-data bank and screened 1,835 patients with amyotrophic lateral sclerosis for frontal lobe/motor cortex lesions. We found 18 patients with definite ALS who had documented and defined lesions of the motor cortex, which preceded the initial ALS symptoms by 8–42 years. In the vast majority (15/18) of the patients, the onset of ALS was closely related to the focal lesion since it started in a body region reflecting the damaged cortical area. The findings suggest that initial lesions to the motor cortex may be a contributing initiating factor in some patients with ALS or determine the site of onset in individuals pre-disposed to ALS.     

Association between the fMRI manifestations of activated brain areas and muscle strength in patients with space-occupying lesions in motor cortex

INTRODUCTIONThe functional magnetic resonance imaging (fMRI) study of centralnervous system (CNS) tumor around motor area has disclosed thechanges of motor function in the motor cortexes of ipsilateral andcontralateral hemispheres. This study was to obser…     

Is the human primary motor cortex involved in motor imagery?

Participation of the primary motor cortex (M1) in motor imagery was addressed using functional magnetic resonance imaging at 2.0 T and 2 x 2 x 4 mm3 resolution in six right-handed subjects. Paradigms comprised visually cued execution and imagination of a sequential finger-to-thumb opposition task (12 s) contrasted with motor rest and visual imagery (18 s), respectively. Motor execution activated M1 as well as other parts of the motor system including supplementary motor area (SMA) and premotor areas (PM). In contrast, motor imagery did not lead to activations in M1 except for 1/6 subjects but involved SMA and PM bilaterally as well as the anterior intraparietal cortex. Moreover, a region-of-interest analysis revealed a weak initial MRI signal increase in M1 in 4/6 subjects. This novel finding of a transient response reflecting the onset of imagination which does not lead to sustained M1 activation may explain previous contradictory reports.     

An unavoidable modulation? Sensory attention and human primary motor cortex excitability

The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task‐specific dystonia, widely lack laboratory‐based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation‐induced GABA‐related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use‐dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition.     

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

PRIMARY OBJECTIVE: To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. RESEARCH DESIGN: We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. METHODS AND PROCEDURES: In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. MAIN OUTCOMES AND RESULTS: In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. CONCLUSION: The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model.     

Does the recruitment of excitation and inhibition in the motor cortex differ?

The level of excitability within the motor cortex can be described as a balance between excitation and inhibition, but it is unknown how well both processes correlate. To address this question, the authors measured motor cortical excitability and inhibition in healthy human subjects, comparing the recruitment of motor evoked potentials (MEPs) and the duration of the cortical silent period (CSP) after transcranial magnetic stimulation (TMS). Single-pulse "focal" TMS was applied at intensities varying between 90% and 200% of motor thresholds to the right motor cortex of 15 healthy volunteers. The peak-to peak size of MEP responses and the duration of the CSP were measured in small hand muscles. Stimulus-response (S-R) curves were constructed by plotting the MEP size and CSP duration against stimulus intensities. The absolute duration of CSP and the size MEPs correlated significantly and to a similar extent with stimulus intensity (r = 0.60 and 0.53, respectively). The slope of the MEP-S-R was steeper compared with CSP-S-R, particularly at low stimulation intensities. CSP duration saturated earlier and CSP-S-Rs were shifted upwards at a given stimulus intensity compared with MEP-S-Rs. The findings suggest that recruitment of inhibition and excitation within the sensorimotor cortex correlate. However, inhibitory effects are recruited at lower intensities and saturate earlier than excitation.     

Plasticity of motor threshold and motor-evoked potential amplitude – A model of intrinsic and synaptic plasticity in human motor cortex?

BackgroundNeuronal plasticity is the physiological correlate of learning and memory. In animal experiments, synaptic (i.e. long-term potentiation (LTP) and depression (LTD)) and intrinsic plasticity are distinguished. In human motor cortex, cortical plasticity can be demonstrated using transcranial magnetic stimulation (TMS). Changes in motor-evoked potential (MEP) amplitudes most likely represent synaptic plasticity and are thus termed LTP-like and LTD-like plasticity.Objective/hypothesisWe investigated the role of changes of motor threshold and their relation to changes of MEP amplitudes.MethodsWe induced plasticity by paired associative stimulation (PAS) with 25 ms or 10 ms inter-stimulus interval or by motor practice (MP) in 64 healthy subjects aged 18–31 years (median 24.0).ResultsWe observed changes of MEP amplitudes and motor threshold after PAS[25], PAS[10] and MP. In all three protocols, long-term individual changes in MEP amplitude were inversely correlated to changes in motor threshold (PAS[25]: P = .003, n = 36; PAS[10]: P = .038, n = 19; MP: P = .041, n = 19).ConclusionWe conclude that changes of MEP amplitudes and MT represent two indices of motor cortex plasticity. Whereas increases and decreases in MEP amplitude are assumed to represent LTP-like or LTD-like synaptic plasticity of motor cortex output neurons, changes of MT may be considered as a correlate of intrinsic plasticity.     

Is one motor cortex enough for two hands?

We report on a patient with mirror movements sustained by a mono‐hemispheric fast control of bilateral hand muscles and normal hand function. Transcranial magnetic stimulation of the right motor cortex evoked contractions of muscles in both hands while no responses were observed from the left hemisphere. Somatosensory‐evoked potentials, functional magnetic resonance, and diffusion tractography showed evidence of sensorimotor dissociation and asymmetry of corticospinal projections, suggestive of reorganization after early unilateral left brain lesion. This is the first evidence that, in certain rare conditions, good hand function is possible with ipsilateral corticospinal reorganization, supporting the role of unexplored mechanisms of motor recovery.     

Primary motor cortex hyperexcitability in Fabry’s disease

ObjectiveInvolvement of pyramidal cells and/or changes in excitability of brain areas remote from an ischemic stroke has been demonstrated. Since in Fabry disease (FD), specific cerebrovascular lesions are present, we thought to investigate motor cortex excitability, using transcranial magnetic stimulation.MethodsResting (RMT) and active (AMT) motor threshold, input–output curve (IN–OUT), central motor conduction time (CMCT), cortical silent period (cSP), short and long interval intracortical inhibition (SICI and LICI), intracortical facilitation (ICF), short interval intracortical facilitation (SICF) and short afferent inhibition (SAI) were measured in the cortical representation of the right first dorsal interosseous muscle in 11 patients with FD and 11 sex- and age matched healthy subjects.ResultsFD patients showed a significant increase of steepness in IN–OUT, ICF and SICF curves. RMT, AMT, CMCT, SICI, LICI and SAI were normal.ConclusionsOur data documented an increased activity of motor cortex glutamatergic excitatory circuits in FD, evident also in patients without brain MRI lesions. Following enzyme replacement treatment, this abnormality was partly reversed.SignificanceWe suggest that our findings are expression of subtle “biochemical brain lesions”, due to an early involvement of neurons and/or astrocytes by the cascade of pathologic events leading to brain damage in FD.     

Neuronal injury in the motor cortex after chronic stroke and lower limb motor impairment: a voxelbased lesion symptom mapping study

Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro- nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.     

Impairment–oriented training and adaptive motor cortex reorganisation after stroke: a fTMS study

In a sample of 28 subacute anterior circulation ischemic stroke patients with severe arm paresis, reduced motor cortex excitability (increased motor thresholds, reduced MEP amplitudes, reduced number of active points) and a reduced conduction velocity in the corticospinal system were found in the affected hemisphere. At the same time motor cortex topology for the abductor pollicis brevis (APB) representation was comparable for the affected and non–affected hemisphere. Considerable arm motor recovery (Fugl–Meyer test) was observed when assessed four weeks later after a period of rehabilitation intervention. Motor cortex excitability and conduction velocity in the corticospinal system improved in the affected hemisphere. In addition, APB representation showed a medial shift in patients with such a representation at pre test (n = 14). Multiple stepwise regression indicated that of all transcranial magnetic stimulation (TMS) parameters only the medial shift of the motor cortex map predicted motor recovery. Assessing the effect of training time (nonintensified vs. intensified therapy) and type of arm training (Bobath approach vs. Arm BASIS training) with a randomised controlled design revealed that the impairment–oriented Arm BASIS training improved motor control more than the control conditions. In addition, patients of the group receiving the Arm BASIS training with an APB representation at pre test showed a medial shift of the motor cortex map and improved conduction times. In conclusion, changes in motor cortex topology were likely to be relevant for motor recovery and might have been induced by the impairment–oriented training.     

Does post-movement beta synchronization reflect an idling motor cortex?

After the completion of a voluntary movement, a synchronization of cortical beta rhythms is recorded over the contralateral central region, which is assumed to reflect the termination of the motor command. In order to test this hypothesis, we compared in eight healthy subjects the synchronization of EEG beta rhythms following active and passive index extension. The passive movement was also performed after deafferentation by ischaemic nerve block in three subjects. Beta synchronization was present in all subjects after both active and passive movements, and disappeared under ischaemia in all three subjects. Post-movement beta synchronization can not solely be explained by an idling motor cortex. It may also, at least in part, reflect a movement-related somatosensory processing.     

Goal or movement? Action representation within the primary motor cortex

Although facilitation of the cortico‐spinal system during action observation is widely accepted, it remains controversial whether this facilitation reflects a replica of the observed movements or the goal of the observed motor acts. In the present transcranial magnetic stimulation study, we recorded motor evoked potentials from two hand muscles (first dorsal interosseous and abductor digiti minimi) while 22 healthy participants observed a hand reaching towards and grasping a bottle. To test for alternative coding levels (goal vs. movement), three relevant aspects were systematically manipulated: the type of observed movement (precision grip or whole hand grasping), situational context (bottle positioned in front of or behind a wall‐like barrier), and processing stage (transcranial magnetic stimulation pulse delivered at the onset of the movement or at the moment of contact between the fingers and the object). At movement onset, motor evoked potential responses reflected the program necessary to achieve the action goal within the situational context. During movement observation, however, the type of observed movement was taken into account and a transition towards a movement‐related modulation was observed. These results suggest that, rather than being exclusive alternatives, goal coding and movement coding may relate to different processing stages.     

TMS: a navigator for NIRS of the primary motor cortex?

Near-infrared spectroscopy (NIRS) is a non-invasive optical imaging technique, which is increasingly used to measure hemodynamic responses in the motor cortex. The location at which the NIRS optodes are placed on the skull is a major factor in measuring the hemodynamic responses optimally. In this study, the validity of using transcranial magnetic stimulation (TMS) in combination with a 3D motion analysis system to relocate the TMS derived position was tested. In addition, the main goal was to quantify the advantage of using TMS to locate the optimal position in relation to the most commonly used EEG C3 position. Markers were placed on the TMS coil and on the head of the subject. In eleven subjects, a TMS measurement was performed to determine the individual motor-evoked potential center-of-gravity (MEP-CoG). This procedure was repeated in nine subjects to test the validity. Subsequently, hemodynamic responses were measured at the MEP-CoG position and at the C3 position during a thumb abduction and adduction task. On average, the MEP-CoG location was located 19.2 mm away from the C3 position. The reproducibility study on the MEP-CoG relocation procedure revealed no systematic relocations. No differences in early and delayed hemodynamic responses were found between the C3 and MEP-CoG position. These results indicate that using TMS for NIRS optodes positioning on the motor cortex does not result in higher hemodynamic response amplitudes. This could be explained if NIRS and TMS assess slightly different functions.