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There has been considerable interest in the role of anterior cingulate and lateral frontal cortex in normal cognition, and particularly its role in cognitive control. It has also been suggested that dysfunction of this frontal brain circuit is responsible for many of the cognitive deficits observed after head injury. Several recent PET and SPECT studies of head injury have lent support to this idea, and suggest that the hypothesis is worth further examination. The paper presents a selective overview of evidence that this specific frontal lobe circuit is impaired after head injury.

Aging comprises many physiological modifications, including structural and metabolic changes, yet little is known about how aging affects the way in which neurons process and integrate sensory information from the environments. Here the framework of “modified use” as a determinant of cortical reorganization was applied for the investigation of age-related modifications of cortical maps and processing, and of associated changes of behavior. The age-related changes of walking behavior in rats were contrasted with the parallel changes of sensorimotor processing developing at the cortical level. Based on the regional specificity of these changes attempts are made to separate age-related changes arising as a consequence of degeneration from a result of adaptable processes following reduced use at high age. Finally, findings from long-term treatment with the Ca^2+-blocker nimodipine, or from housing animals under enriched environmental conditions to ameliorate aging effects were described. Combined, these results show the general treatability of age-related changes. The data imply that age-related changes can be reversed by short periods of training and stimulation schedules even if they have developed. Clearly, the development of specific measures to delay aging processes and to rehabilitate aged brains depends on future progress in understanding mechanisms and effects of aging.

Background Our understanding of brainstem swallowing centers is mainly based on experimental animals. In order to solve this problem also in humans, a clinical-anatomical study on dysphagic patients with different lesion patterns was performed. Patients and methods We studied 43 consecutively admitted dysphagic patients with unilateral paresis of the vagal nerve (PVN), Avellis’ syndrome (AS), Wallenberg’s syndrome (WS), posterior fossa tumour (PFT) or cerebellar hemorrhage (CH) with regard to clinical and anatomical aspects. Findings There was a continuum with regard to functional outcome from neurogenic dysphagia (ND): Patients with PFT or CH had a significantly worse outcome than patients with WS; the outcome of WS patients was significantly worse than that of patients with PVN or AS. In AS only the Nucleus ambiguus (NA) and its surrounding reticular formation (RF) were affected. In all patients with WS, the infarctions of the dorsolateral medulla were situated in the rostral third of the medulla and affected the NA and the Nucleus tractus solitarii (NTS) with their surrounding RF. In patients with PFT and CH, the NTS and its surrounding RF were affected on both sides. The overlap area of WS and PFT lesions is situated in the NTS and the surrounding RF, especially in its Nucleus parvocellularis. Interpretation Our results point to the fact, that in humans the dorsomedial central pattern generators (CPGs) for swallowing are situated in the rostral part of the dorsal medulla oblongata near the NTS/surrounding RF (especially Nucleus parvocellularis) and that the dorsomedial CPGs are superior to the ventrolateral CPGs (near the NA/surrounding RF) with regard to their swallowing-relevance. Furthermore, we hypothesize that — due to the individual asymmetry of the swallowing-dominant forebrain hemisphere — the outcome from ND in WS depends on the side of the medullary infarction.

Injury to the mammalian auditory nerve is associated with a lack of long-distance elongation and leads to definitive loss of the hearing function. To overcome this central nervous system typical lack of functional regeneration, a combined neurotrophic and antiinhibitory treatment is applied. After complete unilateral sectioning of the auditory nerve in adult rats a combination of the Nogo-A inhibitor IN-1 and the neurotrophic factor NT-3 is administrated intrathecally into the cerebellopontine angle for one week. Functional regeneration is evaluated by measuring auditory brainstem evoked potentials for a follow-up period of up to three months. After treatment, up to forty percent of the animals showed a second vertex-positive wave in the auditory brainstem evoked potentials which occurred between three to four weeks after sectioning and remained stable during the follow-up period. A limited degree of functional regeneration of the axotomized auditory nerve is possible after application of IN-1 and NT-3. For additional improvement of functional results further investigations on combined treatments with scar reducing agents, neurotrophic factors and neuroprotective drugs remain necessary.

Perceptional benefits and potential risks of electrical stimulation of the central auditory system are constantly changing due to ongoing developments and technical modifications. Therefore, we would like to introduce current treatment protocols and strategies that might have an impact on functional results of auditory brainstem implants (ABI) in profoundly deaf patients. Patients with bilateral tumours as a result of neurofibromatosis type 2 with complete dysfunction of the eighth cranial nerves are the most frequent candidates for auditory brainstem implants. Worldwide, about 300 patients have already received an ABI through a translabyrinthine or suboccipital approach supported by multimodality electrophysiological monitoring. Patient selection is based on disease course, clinical signs, audiological, radiological and psycho-social criteria. The ABI provides the patients with access to auditory information such as environmental sound awareness together with distinct hearing cues in speech. In addition, this device markedly improves speech reception in combination with lip-reading. Nonetheless, there is only limited open-set speech understanding. Results of hearing function are correlated with electrode design, number of activated electrodes, speech processing strategies, duration of pre-existing deafness and extent of brainstem deformation. Functional neurostimulation of the central auditory system by a brainstem implant is a safe and beneficial procedure, which may considerably improve the quality of life in patients suffering from deafness due to bilateral retrocochlear lesions. The auditory outcome may be improved by a new generation of microelectrodes capable of penetrating the surface of the brainstem to access more directly the auditory neurons.

Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson’s disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al. , Brain 126: 2153–2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significant 70 Hz activity was observed in only 2 of 11 nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the presence of 300 Hz oscillations. The two rhythms probably arise from different mechanisms, reflecting different functional and/or spatial aspects of subthalamic pathophysiology. Fast subthalamic oscillations could be exploited for intra-operative electrophysiological monitoring of the subthalamic nucleus, post-operative confirmation of electrode placement and patient-specific ‘reglage’ of the electrical parameters for chronic deep brain stimulation.

Twenty-one cases of a vegetative state (VS) and 5 cases of a minimally conscious state (MCS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically at 3 months after brain injury. These cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The mesencephalic reticular formation was selected as a target in 2 cases of VS, and the CM-pf complex was selected as a target in the other 19 cases of VS and 5 cases of MCS. Eight of the 21 patients emerged from the VS, and became able to obey verbal commands. However, they remained in a bedridden state except for 1 case. Four of the 5 MCS patients emerged from the bedridden state, and were able to enjoy their life in their own home. DBS therapy may be useful for allowing patients to emerge from the VS, if the candidates are selected according to appropriate neurophysiological criteria. Also, a special neurorehabilitation system may be necessary for emergence from the bedridden state in the treatment of VS patients. Further, DBS therapy is useful in MCS patients to achieve consistent discernible behavioral evidence of consciousness, and emergence from the bedridden state.

Deep brain stimulation has gained increasing interest in the treatment of movement disorders. Presenting our clinical series of 179 patients operated upon since 1999, the indications, risks and benefits for the patients are discussed in order to further imporve the techniques and their applications.

The preliminary results obtained by the Study Group for Treatment of Involuntary Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian Neurosurgical Society, are reported. The series includes 16 cases of very advanced Parkinson’s Disease (PD), aged 46–81; 15 of them were not eligible for Deep Brain Stimulation. Ten cases have been evaluated at 3–30 months after implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2–8 Volt, 100–400 μsec., 20–120 Hz) by chronically implanted electrodes, relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia are reduced. Standing, gait, motor performance, speech and swallowing are improved. Benefit is marked as far as axial symptoms is concerned. Also the symptoms of Long Term Dopa Syndrome — dyskinesias, motor fluctuations — and other secondary effect of levodopa administration — psychiatric symptoms — are improved. Levodopa dosage may be reduced by 50%. The effect seems persistent and does not fade away with time. Improvement ranged, on the basis of the UPDRS scale, from <25% to 75%. There was only one case of complete failure. Quality of life is markedly improved in patients who were absolutely incapable of walking and unable arise out of chair. After stimulation they could walk, even if assistance was necessary. Improvement was observed also in those with disabling motor fluctuation and dyskinesias which could be abolished.

Despite growing recognition among those who provide care for traumatic brain injury patients, endocrine dysfunction following brain injury is an often under-recognized phenomenon. From historical reports one would conclude that endocrine dysfunctions hardly ever occurs following trauma to the head. However, recent studies suggest that a significant proportion of patients suffer some degree of hypopituitarism. To date, there are no clear predicting factors identifying patients at risk for developing hormonal disturbances and thus no parameters exist for screening. Several retrospective analyses and literature reviews, and more recently, a few longitudinal studies of brain injured patients have been performed.