Motor cortical functional geometry in cerebral palsy and its relationship to disability.

OBJECTIVE: To investigate motor cortical map patterns in children with diplegic and hemiplegic cerebral palsy (CP), and the relationships between motor cortical geometry and motor function in CP. METHODS: Transcranial magnetic stimulation (TMS) was used to map motor cortical representations of the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles in 13 children with CP (age 9-16 years, 6 males.) The Gross Motor Function Measure (GMFM) and Melbourne upper extremity function were used to quantify motor ability. RESULTS: In the hemiplegic participants (N = 7), the affected (right) FDI cortical representation was mapped on the ipsilateral (N = 4), contralateral (N = 2), or bilateral (N = 1) cortex. Participants with diplegia (N = 6) showed either bilateral (N = 2) or contralateral (N = 4) cortical hand maps. The FDI and TA motor map center-of-gravity mediolateral location ranged from 2-8 cm and 3-6 cm from the midline, respectively. Among diplegics, more lateral FDI representation locations were associated with lower Melbourne scores, i.e. worse hand motor function (Spearman's rho = -0.841, p = 0.036). CONCLUSIONS: Abnormalities in TMS-derived motor maps cut across the clinical classifications of hemiplegic and diplegic CP. The lateralization of the upper and lower extremity motor representation demonstrates reorganization after insults to the affected hemispheres of both diplegic and hemiplegic children. SIGNIFICANCE: The current study is a step towards defining the relationship between changes in motor maps and functional impairments in CP. These results suggest the need for further work to develop improved classification schemes that integrate clinical, radiologic, and neurophysiologic measures in CP.

Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training.

Recovery of motor function elicited by motor training after cortical lesions in rats is enhanced by norepinephrine (neurotransmitter mediating alpha(1)-adrenergic function) and downregulated by alpha(1)-adrenergic antagonists. In spite of this, alpha(1)-adrenergic antagonists are used to treat elderly patients with hypertension and prostate hyperplasia in stroke settings. The purpose of this study was to determine the effects of a single oral dose of the alpha(1)-adrenergic antagonist prazosin on training-dependent plasticity in intact humans, a function thought to contribute to recovery of motor function after cortical lesions. We report that prazosin decreased the ability of motor training to elicit training-dependent plasticity relative to a drug-free condition. These data suggest caution when using alpha(1)-adrenergic blockers in rehabilitative clinical settings following brain lesions.

Modulation of excitability of human motor cortex (M1) by 1 Hz transcranial magnetic stimulation of the contralateral M1.

OBJECTIVE: Previous studies demonstrated that single-pulse transcranial magnetic stimulation (TMS) of one motor cortex (M1) exerts a brief inhibitory effect on the contralateral M1. The purpose of this study was to test the hypothesis that 30min of 1Hz TMS of M1 will result in a lasting increase in excitability in the contralateral M1. METHODS: Healthy volunteers were tested on 2 separate days, before (baseline) and after one of two interventions: (a) stimulation of M1 with 1Hz TMS for 30min at 115% of resting motor threshold, and (b) sham stimulation. Recruitment curves to TMS, pinch force, and simple reaction time were assessed in the hand contralateral to the unstimulated motor cortex. RESULTS: The main finding of this study was that 30min of 1Hz significantly increased recruitment curves in the contralateral motor cortex in the real stimulation condition relative to sham (P<0.005, factorial analysis of variance (ANOVA)). This change outlasted the stimulation period for at least 15min and occurred in the absence of changes in pinch force or reaction time. CONCLUSIONS: These results raise the potential for inducing lasting modulation of excitability in M1 by 1Hz TMS of the other M1, a phenomenon possibly reflecting modulation of interhemispheric interactions. SIGNIFICANCE: It is conceivable that 1Hz TMS applied to M1 may be used to modulate excitability in the opposite motor cortex for therapeutic purposes.

Enhancement of use-dependent plasticity by D-amphetamine.

In healthy individuals, motor training can elicit use-dependent plasticity. Here the authors studied six subjects in whom training alone failed to elicit this effect. Administration of a single dose of 10 mg of D-amphetamine preceding training led to use-dependent plasticity in a subgroup of these subjects. Using pharmacologic interventions to enhance the effects of motor training might help rehabilitative efforts in patients in whom training alone fails.

Cholinergic influences on use-dependent plasticity.

Motor practice elicits use-dependent plasticity in humans as well as in animals. Given the influence of cholinergic neurotransmission on learning and memory processes, we evaluated the effects of scopolamine (a muscarinic receptor antagonist) on use-dependent plasticity and corticomotor excitability in a double-blind placebo-controlled randomized design study. Use-dependent plasticity was substantially attenuated by scopolamine in the absence of global changes in corticomotor excitability. These results identify a facilitatory role for cholinergic influences in use-dependent plasticity in the human motor system.

Mechanisms of use-dependent plasticity in the human motor cortex.

Practicing movements results in improvement in performance and in plasticity of the motor cortex. To identify the underlying mechanisms, we studied use-dependent plasticity in human subjects premedicated with drugs that influence synaptic plasticity. Use-dependent plasticity was reduced substantially by dextromethorphan (an N-methyl-d-aspartate receptor blocker) and by lorazepam [a gamma-aminobutyric acid (GABA) type A receptor-positive allosteric modulator]. These results identify N-methyl-d-aspartate receptor activation and GABAergic inhibition as mechanisms operating in use-dependent plasticity in intact human motor cortex and point to similarities in the mechanisms underlying this form of plasticity and long-term potentiation.

Specific and non-specific effects of transcranial magnetic stimulation on simple and go/no-go reaction time.

The effects of subthreshold transcranial magnetic stimulation (TMS) on simple and go/no-go reaction time (RT) tasks were studied in seven healthy volunteers. Subjects were asked to respond by abducting the thumb in a warning-imperative signal paradigm. TMS was randomly delivered at variable delays to the imperative signal (IS). Simple RT was significantly shortened when TMS was delivered to the left motor cortex and parietal regions simultaneously with IS. In the go/no-go paradigm, a similar trend to shorter RT was seen at a delay of 0 ms. Additionally, a significant shortening was observed at a delay of 90 ms with TMS over the contralateral motor cortex only. Movement-related potentials (MRPs) in the two paradigms showed a predominantly contralateral negativity approximately 80 ms preceding EMG onset. Our findings support the existence of two differentiated effects of TMS on RT: (1) one non-specific effect, evidenced in both the simple and go/no-go paradigms at a 0 ms delay, which can be at least partially explained by intersensory facilitation; and (2) a motor-specific effect of TMS, unveiled in the go/no-go paradigm at a 90 ms delay.

Effects of subthreshold transcranial magnetic stimulation on choice reaction time and correlation with motor cortical activation.

To study the effect of subthreshold transcranial magnetic stimulation (TMS), we measured choice reaction time (RT), with or without TMS, in 7 healthy participants. TMS over the hand motor area was randomly delivered at variable delays after the imperative signal, while participants performed right or left abduction of the thumb. Lateralized movement-related potentials (MRPs) were recorded in a separate session to link the TMS effect with the motor cortical circuitry. For the right hand, the coexistence of a motor specific and non-specific effects of TMS was clearly evidenced, by the RT shortening at delays of 0 and 150 ms. The response dependency of the specific TMS effect was also demonstrated through the response-locked analysis, showing a maximal shortening at 120-ms bin before EMG onset. Furthermore, the lateralized MRP commenced at about 80 ms before EMG onset, indicating that TMS influences the cortical motor circuitry around 30-40 ms before the activation of the primary motor cortex. In contrast, for the left hand, we were faced with some uncertain concepts as human handedness and hemisphere asymmetries in both measures of RT and MRP, and thus it was not possible to substantiate about the motor specific effect of subthreshold TMS.

Anthropometric nutritional assessment of critically ill hospitalized children.

In a prospective study, the nutritional status was evaluated in 46 consecutive admissions to a Pediatric Intensive Care Unit, using anthropometric parameters. About 65% of the patients presented malnutrition on admission, with predominance of the chronic form. The mortality rate was greater in the malnourished (20 versus 12.5%) and chronic malnutrition was associated with a higher incidence of infection (42%). There was a fall in channel of percentile for weight-for-height in 36% of the patients evaluated at the final follow up. These results suggest that a significant number of patients are at nutritional risk at the time of hospital admission, and there is an association between nutritional status and hospital course. The anthropometric nutritional evaluation is a simple an reproducible method, and a valuable parameter for an objective nutritional assessment of the critically ill child. Therefore, it should be performed on admission and follow up of hospitalized children.