Restorative Neurology and Neuroscience

Purpose: Prelingual deafness has been shown to lead to brain reorganization as demonstrated by functional parameters, but anatomical evidences still remain controversial. The present study investigated hemispheric asymmetry changes in deaf subjects using MRI, hypothesizing auditory-, language- or visual-related regions after early deafness. Methods: Prelingually deaf adolescents (n = 16) and age- and gender-matched normal controls (n = 16) were recruited and hemispheric asymmetry was evaluated with voxel-based morphometry (VBM) from MRI combined with analysis of cortical thickness (CTh). Results: Deaf adolescents showed more rightward asymmetries (L < R) of grey matter volume (GMV) in the cerebellum and more leftward CTh asymmetries (L > R) in the posterior cingulate gyrus and gyrus rectus. More rightward CTh asymmetries were observed in the precuneus, middle and superior frontal gyri, and middle occipital gyrus. The duration of hearing aid use was correlated with asymmetry of GMV in the cerebellum and CTh in the gyrus rectus. Interestingly, the asymmetry of the auditory cortex was preserved in deaf subjects. Conclusions: When the brain is deprived of auditory input early in life there are signs of both irreversible morphological asymmetry changes in different brain regions but also signs of reorganization and plasticity which are dependent on hearing aid use, i.e. use-dependent.

Neglect and related phenomena, as anosognosia for hemiplegia and somatoparaphrenia, are often associated to right-hemisphere lesions. These deficits can be alleviated by caloric vestibular stimulation, but little is known about the efficacy of this physiological intervention on neglect following left-hemisphere lesions. Here we report the case of an ambidextrous left brain-damaged patient with severe right personal and extrapersonal neglect, anosognosia for right hemiplegia and somatoparaphrenia. These symptoms co-occurred with more typical manifestations of left-brain damage, such as aphasia and apraxia. Neurological examination revealed right hemiplegia, hemianesthesia and hemianopia. Visuo-spatial tests for personal and extrapersonal neglect, as well as an anosognosia questionnaire, were submitted before and after caloric vestibular stimulation. Results showed a dramatic improvement of anosognosia for hemiplegia and neglect; no change was observed for the remaining deficits. The results confirm the notion of the selectivity of vestibular stimulation for neglect and related disorders and extend this notion by showing that similar effects can be obtained after lesion of the left hemisphere, suggesting that similar mechanisms are responsible for left- and right-sided neglect. Such a peculiar association of language and visuo-spatial disorders jointly present after a left-sided lesion opens the question of the link between handedness and lateralization of cognitive functions.

The locked-in syndrome (LiS) is typically characterized by a paralysis of almost all body muscles combined with intact cognitive functions. In practice, there are often additional brain damages besides the one directly causing LiS. These damages can lead to cognitive impairment, which substantially complicates the diagnosis of LiS. At the level of behavior, therefore, the disease can be confused with akinetic mutism, vegetative state (syn. unresponsive wakefulness state) and some other conditions. Using instrumental methods in addition to behavioral diagnostics helps to avoid diagnostic errors and to improve prognosis of rehabilitation of such patients. These methods, which include measurements of brain electric or magnetic fields, electrical potential of muscles, blood flow and oxygen consumption in the brain, are reviewed in this paper.

Purpose: To investigate the mRNA and protein alterations of α-synuclein in the brain of Alzheimer's disease-like mouse model at the different ages, and to evaluate the effects of 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) on α-synuclein expression. Methods: TSG (120 or 240 μmol kg⁻¹d⁻¹) was intragastrically administered to APPV717I transgenic (Tg) mice at 4- or 10-month-old for 6 months. Results: mRNA expression of α-synuclein increased in hippocampus in 4 month to 16 month old Tg mice compared with age-matched control. α-synuclein protein expression in hippocampus also increased in 4 month to 16 month old Tg mice significantly. Significant down-regulation of α-synuclein mRNA and protein expression in hippocampus was found after treatment of TSG for 6 months in both 10- and 16-month-old Tg mice. Production of dimer and tetramer of α-synuclein protein in Tg mice was inhibited after treatment with TSG. Conclusions: The expression and aggregation of α-synuclein was age-dependently increased in Tg mice. TSG not only prevents over-expression of α-synuclein at an early stage, but also reverses the increased expression of α-synuclein and inhibits the aggregation at the late stage of Tg mice. TSG may have potential to the prevention and treatment of Alzheimer's diseases.

Purpose: Learning a skilled movement is associated with more efficient use of subcortical motor circuits which can coordinate features of the movements such as the timing and patterns of activation of different muscles. Learning a motor skill could strengthen spinal interneuron circuits that facilitate the movement. We hypothesized that learning a simple, alternating movement would produce changes in spinal circuits that mediate reciprocal inhibition between antagonist muscles. Methods: Sixteen healthy adult subjects were trained to perform a wrist flexion and extension task to control the movement of a cursor between targets appearing on a computer display. The goal of the task was to hit the targets. Subjects practiced for 15 minutes daily until reaching the acquisition criterion. Surface EMG recordings from wrist flexor and extensor muscles showed reduced co-contraction during acquisition of the task. Results: Compared to the initial session, in the final session short-latency reciprocal inhibition was enhanced during the late-extension phase in the final session. This phase-dependent increase in short-latency reciprocal inhibition is likely to facilitate switching activation between wrist antagonistic muscles. Conclusions: Learning a motor skill can produce alterations in spinal reflex circuits that facilitate the desired movement.

Purpose: In aphasic patients, some studies have already emphasized the efficacy of transcranial direct current stimulation (tDCS) during the treatment of noun retrieval deficits. To date, in the same population, there are have been no studies addressing tDCS effects in the recovery of verb retrieval deficits. In this study, we wanted to test the potential of tDCS to improve verb production in a group of aphasic patients. Methods: Seven chronic subjects participated in an intensive language training for their difficulties in action naming. Each subject was treated with tDCS (20 min., 1 mA) over the left hemisphere in three different conditions: anodic tDCS over Wernicke's area, anodic tDCS and sham stimulation over Broca's area. Each experimental condition was performed in five consecutive daily sessions over three weeks with 6 days of intersession interval. Results: In all patients, results showed a significantly better response accuracy during the anodic tDCS over Broca's area with respect to the other two conditions which still persisted at one month after the end of the treatment suggesting a long-term effect on the recovery of their verb retrieval deficits. Conclusion: These findings further confirm that tDCS represents a useful new therapeutic interventions for the rehabilitation of lexical deficits in aphasic patients.

Purpose: Recovery is limited following traumatic brain injury (TBI) since injured axons regenerate poorly and replacement of lost cells is minimal. Behavioral improvements could instead be due to plasticity of uninjured brain regions. We hypothesized that plasticity of the uninjured hemisphere occurs contralateral to a focal TBI in the adult rat. Thus, we performed cortical mapping of the cortex contralateral to the TBI using intracortical microstimulation (ICMS). Methods: A focal TBI was induced using the weight-drop technique (n = 5) and sham-injured animals were used as controls (n = 4). At five weeks post-injury, ICMS was used to map the motor area contralateral to the injury. Motor responses were detected by visual inspection and electromyography (EMG). Results: In sham- and brain-injured animals, numerous fore- and hindlimb motor responses contralateral to the stimulation (ipsilateral to the injury) were obtained. Compared to sham-injured controls, there was a markedly increased (p < 0.05) number of fore- and hindlimb responses ipsilateral to the stimulation after TBI. Conclusion: Following focal TBI in the rat, our data suggest reorganization of cortical and/or subcortical regions in the uninjured hemisphere contralateral to a focal TBI leading to an altered responsiveness to ICMS. Although we cannot exclude that these changes are maladaptive, it is plausible that this plasticity process positively influences motor recovery after TBI.

Purpose: Ceftriaxone, a β-lactam antibiotic, can selectively enhance the expression of glutamate transporter 1 (GLT1), the most abundant astrocytic glutamate transporter expressed in the cortex. It has been found to have neuroprotective effects when administered prior to brain ischemic damage or during the acute phase post-stroke, but its effects in chronic period have not been examined. Methods: We examined the effects of ceftriaxone on the acquisition of motor skill and the functional outcome after focal ischemic cortical lesions. In adult male rats, ceftriaxone (200 mg/kg) or vehicle was intraperitoneally injected daily for 5 days, a treatment regime previously established to upregulate GLT-1. This preceded 28 days of skilled reach training in intact animals or began 3 days following lesions, followed by 5 weeks of rehabilitative reach training. Results: In intact rats, ceftriaxone did not affect skill learning rate or final performance. Following ischemic lesions, though there was no significant difference in lesion sizes between groups, ceftriaxone exacerbated initial deficits in reaching performance. Conclusion: These findings of detrimental effects on motor functional outcome suggest that ceftriaxone may be more useful for neuroprotection during the acute phase of ischemia than for functional recovery in the post-acute period after ischemic damage.