Decreased cortical somatosensory finger representation in X-linked recessive bulbospinal neuronopathy (Kennedy disease): a magnetoencephalographic study.

BACKGROUND: Kennedy disease (KD) clinically presents as progressive lower motor neuron disease with minimal or no sensory impairment. However, electrophysiological studies found abnormal somatosensory-evoked potentials even in absence of clinical deficits. Little is known about possible influences of this sensory neuropathy on the central somatosensory processing. METHODS: In this study, the cortical topography of index finger representation was studied in 7 patients with genetically proven KD compared to healthy control subjects by means of magnetoencephalography using an established stimulation paradigm. Data analysis was carried out with synthetic aperture magnetometry (SAM). Additionally, the latency and source amplitude of the earliest cortical somatosensory-evoked field (SEF) component were determined based on traditional single dipole source analysis. RESULTS: In KD patients the latency of the SEF was prolonged (48.6 vs. 37.4 ms, P < .005). There was no significant difference in dipole source amplitude, but stimulus-related SAM activation of the contralateral sensorimotor cortex (pseudo-t-values -.107 vs. -.199, P < .05), including maximum activity (53.5%), was reduced. CONCLUSIONS: These results implicate that even subclinical sensory neuropathy leads to possible functional reorganization of the sensorimotor cortex in KD patients and reinforces the view that in KD the somatosensory system is extensively involved.

Age-related changes in cortical swallowing processing.

The cortical organization of swallowing has been mainly studied in young and healthy subjects. Aging effects on human deglutition have been found in several behavioral studies and are known to affect both the oral and pharyngeal phases of swallowing. The aim of this study was to evaluate a potential cortical compensation of age-related swallowing impairment. Whole-head MEG was employed in 9 healthy elderly subjects (mean age 71.6 years) and compared to 9 healthy young participants (mean age 23.8 years). Data were analyzed by means of time-frequency plots and synthetic aperture magnetometry (SAM). Group analysis of individual SAM data was performed using a permutation test. The main finding of this study was an increase of somatosensory cortical activation during swallowing execution in elderly subjects compared to the young control group. This effect was present in both hemispheres. These results point to adaptive cerebral changes in response to aging effects on the complex process of swallowing. Our finding underlines the relevance of age matched control groups in neuroimaging studies related to deglutition or other complex sensorimotor processes.

Measurement of pharyngeal sensory cortical processing: technique and physiologic implications.

BACKGROUND: Dysphagia is a major complication of different diseases affecting both the central and peripheral nervous system. Pharyngeal sensory impairment is one of the main features of neurogenic dysphagia. Therefore an objective technique to examine the cortical processing of pharyngeal sensory input would be a helpful diagnostic tool in this context. We developed a simple paradigm to perform pneumatic stimulation to both sides of the pharyngeal wall. Whole-head MEG was employed to study changes in cortical activation during this pharyngeal stimulation in nine healthy subjects. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test. RESULTS: Our results revealed bilateral activation of the caudolateral primary somatosensory cortex following sensory pharyngeal stimulation with a slight lateralization to the side of stimulation. CONCLUSION: The method introduced here is simple and easy to perform and might be applicable in the clinical setting. The results are in keeping with previous findings showing bihemispheric involvement in the complex task of sensory pharyngeal processing. They might also explain changes in deglutition after hemispheric strokes. The ipsilaterally lateralized processing is surprising and needs further investigation.

Time-dependent hemispheric shift of the cortical control of volitional swallowing.

An important part of the cortical processing of swallowing takes place in the sensorimotor cortex, predominantly in the left hemisphere. However, until now, only deglutition related brain activation with low time resolution exceeding a time interval of 1 s has been reported. In this study, we have examined the chronological sequence of cortical swallowing processing in humans by means of high temporal resolution magnetoencephalography (MEG). The cortical MEG activity was recorded during self-paced volitional swallowing in 10 healthy subjects. Data were analyzed using synthetic aperture magnetometry and the group analysis was performed using a permutation test. Swallowing-related muscle activity was recorded by electromyography. Within the time interval of 1 s of the most pronounced muscular swallowing execution, the MEG analysis revealed neural activation in the primary sensorimotor cortex. During the first 600 ms, only left hemispheric activation was found, bihemispheric activation during the next 200 ms and a right hemispheric activation during the last 200 ms. Thus, our results demonstrate a time-dependent shift of neural activation from left to right sensorimotor cortex during deglutition with left hemispheric dominance in the early stage of volitional swallowing and right hemispheric dominance during its later part.

Cortical compensation associated with dysphagia caused by selective degeneration of bulbar motor neurons.

According to recent neuroimaging studies, swallowing is processed within multiple regions of the human brain. In contrast to this, little is known about the cortical contribution and compensatory mechanisms produced by impaired swallowing. In the present study, we therefore investigated the cortical topography of volitional swallowing in patients with X-linked bulbospinal neuronopathy (Kennedy disease, KD). Eight dysphagic patients with genetically proven KD and an age-matched healthy control group were studied by means of whole-head magnetoencephalography using a previously established swallowing paradigm. Analysis of data was carried out with synthetic aperture magnetometry (SAM). The group analysis of individual SAM results was performed using a permutation test. KD patients showed significantly larger swallow-related activation of the bilateral primary sensorimotor cortex than healthy controls. In contrast to the control group, in KD patients the maximum activity was located in the right sensorimotor cortex. Furthermore, while in nondysphagic subjects a previously described time-dependent shift from the left to the right hemisphere was found during the one second of most pronounced swallow-related muscle activity, KD patients showed a strong right hemispheric activation in each time segment analyzed. Since the right hemisphere has an established role in the coordination of the pharyngeal phase of swallowing, the stronger right hemispheric activation observed in KD patients indicates cortical compensation of pharyngeal phase dysphagia.

Cortical recovery of swallowing function in wound botulism.

BACKGROUND: Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. METHODS: In this study, we applied whole-head magnetoencephalography (MEG) in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM). RESULTS: The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC). In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. CONCLUSION: These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.

Functional oropharyngeal sensory disruption interferes with the cortical control of swallowing.

BACKGROUND: Sensory input is crucial to the initiation and modulation of swallowing. From a clinical point of view, oropharyngeal sensory deficits have been shown to be an important cause of dysphagia and aspiration in stroke patients. In the present study we therefore investigated effects of functional oropharyngeal disruption on the cortical control of swallowing. We employed whole-head MEG to study cortical activity during self-paced volitional swallowing with and without topical oropharyngeal anesthesia in ten healthy subjects. A simple swallowing screening-test confirmed that anesthesia caused swallowing difficulties with decreased swallowing speed and reduced volume per swallow in all subjects investigated. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of the individual SAM data was performed using a permutation test. RESULTS: The analysis of normal swallowing revealed bilateral activation of the mid-lateral primary sensorimotor cortex. Oropharyngeal anesthesia led to a pronounced decrease of both sensory and motor activation. CONCLUSION: Our results suggest that a short-term decrease in oropharyngeal sensory input impedes the cortical control of swallowing. Apart from diminished sensory activity, a reduced activation of the primary motor cortex was found. These findings facilitate our understanding of the pathophysiology of dysphagia.