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Functional Imaging of the Human Brainstem during Somatosensory Input and Autonomic Output.

Henderson LA, Macefield VG - Front Hum Neurosci (2013)

Bottom Line: We and others have begun to explore changes in brainstem activity in humans during a number of challenges, including cutaneous and muscle pain, as well as during maneuvers that evoke increases in sympathetic nerve activity.More recently we have successfully recorded sympathetic nerve activity concurrently with functional magnetic resonance imaging of the brainstem, which will allow us, for the first time to explore brainstem sites directly responsible for conditions such as hypertension.Since many pathophysiological conditions no doubt involve changes in brainstem function and structure, defining these changes will likely result in a greater ability to develop more effective treatment regimens.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Histology, University of Sydney , Sydney, NSW , Australia.

ABSTRACT
Over the past half a century, many investigations in experimental animal have explored the functional roles of specific regions in the brainstem. Despite the accumulation of a considerable body of knowledge in, primarily, anesthetized preparations, relatively few studies have explored brainstem function in awake humans. It is important that human brainstem function is explored given that many neurological conditions, from obstructive sleep apnea, chronic pain, and hypertension, likely involve significant changes in the processing of information within the brainstem. Recent advances in the collection and processing of magnetic resonance images have resulted in the possibility of exploring brainstem activity changes in awake healthy individuals and in those with various clinical conditions. We and others have begun to explore changes in brainstem activity in humans during a number of challenges, including cutaneous and muscle pain, as well as during maneuvers that evoke increases in sympathetic nerve activity. More recently we have successfully recorded sympathetic nerve activity concurrently with functional magnetic resonance imaging of the brainstem, which will allow us, for the first time to explore brainstem sites directly responsible for conditions such as hypertension. Since many pathophysiological conditions no doubt involve changes in brainstem function and structure, defining these changes will likely result in a greater ability to develop more effective treatment regimens.

No MeSH data available.


Related in: MedlinePlus

Medullary activation during repeated innocuous brushing of the thumb and big toe in five subjects. Note that thumb brushing activates a region of the ipsilateral dorsal medulla that is lateral and marginally rostral to that region activated by brushing of the big toe. These activation patterns are consistent with the well-described termination patterns of non-noxious somatosensory afferent neurons, i.e., the cuneate and gracile nuclei. Note that during each of the six brushing period (vertical gray bars), the mean (±SEM) percentage change in signal intensity increases. The slice locations in Montreal Neurological Institute space are shown at the lower left of each section.
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Figure 2: Medullary activation during repeated innocuous brushing of the thumb and big toe in five subjects. Note that thumb brushing activates a region of the ipsilateral dorsal medulla that is lateral and marginally rostral to that region activated by brushing of the big toe. These activation patterns are consistent with the well-described termination patterns of non-noxious somatosensory afferent neurons, i.e., the cuneate and gracile nuclei. Note that during each of the six brushing period (vertical gray bars), the mean (±SEM) percentage change in signal intensity increases. The slice locations in Montreal Neurological Institute space are shown at the lower left of each section.

Mentions: With this in mind, we and others have begun to use fMRI to explore neural activation patterns during acute noxious and non-noxious somatosensory stimulation in healthy individuals. In a recent series of investigations, we measured brain activity using a 3 T MRI scanner during non-noxious somatosensory activation evoked by lightly brushing various parts of the body in healthy individuals (Wrigley et al., 2009; Henderson et al., 2011; Gustin et al., 2012). Using Blood Oxygen Level Dependant (BOLD) imaging, we collected 130 fMRI volumes covering the entire brain, during which we brushed the big toe or thumb using a repeated “On-Off” paradigm (seven Off, six On periods). Although the aim of this investigation was to explore changes within the primary somatosensory cortex, in five individuals our fMRI scans also encompassed the caudal medulla, including the level at which non-noxious somatosensory afferents from the body terminate. In a preliminary investigation we explored medullary signal changes during thumb and toe brushing to determine if we could identify activation of the cuneate and gracile nuclei, respectively. Using brainstem-specific software (SUIT toolbox in SPM8) (Diedrichsen et al., 2011) we isolated and normalized the brainstem, applied global signal detrending (Macey et al., 2004) and then determined significant patterns of signal intensity increases during each brushing period using a repeated box-car model. A second-level conjunction analysis (p < 0.005, uncorrected for multiple comparisons) revealed the well-described somatotopic organization of non-noxious somatosensory termination patterns within the brainstem. That is, innocuous brushing of the big toe resulted in activation of the region of the ipsilateral gracile nucleus, whereas brushing of the thumb activated the region of the ipsilateral cuneate nucleus (Figure 2). It can be seen in Figure 2 that signal intensity increased during each brushing period and subsequently returned toward baseline levels during the rest periods. A similar activation pattern during innocuous stimulation of the upper limb has been shown previously (Ghazni et al., 2010). We also found signal intensity increases during both brushing paradigms in the region of the lateral reticular nucleus. It is known from experimental animal investigations that lateral reticular nucleus neurons receive ascending inputs from the dorsal horn and respond to noxious and non-noxious somatosensory stimulation (Kitai et al., 1967). Although the precise role of this region remains unknown, it projects to the cerebellar vermis and may play a role in co-ordinating movement, although a role for this region in cardiovascular regulation has also been described (Thomas et al., 1977). In addition to a somatotopic representation within the lower brainstem, we have previously shown a similar organization within the relevant recipient region of the thalamus and primary somatosensory cortex (Wrigley et al., 2009; Gustin et al., 2012).


Functional Imaging of the Human Brainstem during Somatosensory Input and Autonomic Output.

Henderson LA, Macefield VG - Front Hum Neurosci (2013)

Medullary activation during repeated innocuous brushing of the thumb and big toe in five subjects. Note that thumb brushing activates a region of the ipsilateral dorsal medulla that is lateral and marginally rostral to that region activated by brushing of the big toe. These activation patterns are consistent with the well-described termination patterns of non-noxious somatosensory afferent neurons, i.e., the cuneate and gracile nuclei. Note that during each of the six brushing period (vertical gray bars), the mean (±SEM) percentage change in signal intensity increases. The slice locations in Montreal Neurological Institute space are shown at the lower left of each section.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3775150&req=5

Figure 2: Medullary activation during repeated innocuous brushing of the thumb and big toe in five subjects. Note that thumb brushing activates a region of the ipsilateral dorsal medulla that is lateral and marginally rostral to that region activated by brushing of the big toe. These activation patterns are consistent with the well-described termination patterns of non-noxious somatosensory afferent neurons, i.e., the cuneate and gracile nuclei. Note that during each of the six brushing period (vertical gray bars), the mean (±SEM) percentage change in signal intensity increases. The slice locations in Montreal Neurological Institute space are shown at the lower left of each section.
Mentions: With this in mind, we and others have begun to use fMRI to explore neural activation patterns during acute noxious and non-noxious somatosensory stimulation in healthy individuals. In a recent series of investigations, we measured brain activity using a 3 T MRI scanner during non-noxious somatosensory activation evoked by lightly brushing various parts of the body in healthy individuals (Wrigley et al., 2009; Henderson et al., 2011; Gustin et al., 2012). Using Blood Oxygen Level Dependant (BOLD) imaging, we collected 130 fMRI volumes covering the entire brain, during which we brushed the big toe or thumb using a repeated “On-Off” paradigm (seven Off, six On periods). Although the aim of this investigation was to explore changes within the primary somatosensory cortex, in five individuals our fMRI scans also encompassed the caudal medulla, including the level at which non-noxious somatosensory afferents from the body terminate. In a preliminary investigation we explored medullary signal changes during thumb and toe brushing to determine if we could identify activation of the cuneate and gracile nuclei, respectively. Using brainstem-specific software (SUIT toolbox in SPM8) (Diedrichsen et al., 2011) we isolated and normalized the brainstem, applied global signal detrending (Macey et al., 2004) and then determined significant patterns of signal intensity increases during each brushing period using a repeated box-car model. A second-level conjunction analysis (p < 0.005, uncorrected for multiple comparisons) revealed the well-described somatotopic organization of non-noxious somatosensory termination patterns within the brainstem. That is, innocuous brushing of the big toe resulted in activation of the region of the ipsilateral gracile nucleus, whereas brushing of the thumb activated the region of the ipsilateral cuneate nucleus (Figure 2). It can be seen in Figure 2 that signal intensity increased during each brushing period and subsequently returned toward baseline levels during the rest periods. A similar activation pattern during innocuous stimulation of the upper limb has been shown previously (Ghazni et al., 2010). We also found signal intensity increases during both brushing paradigms in the region of the lateral reticular nucleus. It is known from experimental animal investigations that lateral reticular nucleus neurons receive ascending inputs from the dorsal horn and respond to noxious and non-noxious somatosensory stimulation (Kitai et al., 1967). Although the precise role of this region remains unknown, it projects to the cerebellar vermis and may play a role in co-ordinating movement, although a role for this region in cardiovascular regulation has also been described (Thomas et al., 1977). In addition to a somatotopic representation within the lower brainstem, we have previously shown a similar organization within the relevant recipient region of the thalamus and primary somatosensory cortex (Wrigley et al., 2009; Gustin et al., 2012).

Bottom Line: We and others have begun to explore changes in brainstem activity in humans during a number of challenges, including cutaneous and muscle pain, as well as during maneuvers that evoke increases in sympathetic nerve activity.More recently we have successfully recorded sympathetic nerve activity concurrently with functional magnetic resonance imaging of the brainstem, which will allow us, for the first time to explore brainstem sites directly responsible for conditions such as hypertension.Since many pathophysiological conditions no doubt involve changes in brainstem function and structure, defining these changes will likely result in a greater ability to develop more effective treatment regimens.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Histology, University of Sydney , Sydney, NSW , Australia.

ABSTRACT
Over the past half a century, many investigations in experimental animal have explored the functional roles of specific regions in the brainstem. Despite the accumulation of a considerable body of knowledge in, primarily, anesthetized preparations, relatively few studies have explored brainstem function in awake humans. It is important that human brainstem function is explored given that many neurological conditions, from obstructive sleep apnea, chronic pain, and hypertension, likely involve significant changes in the processing of information within the brainstem. Recent advances in the collection and processing of magnetic resonance images have resulted in the possibility of exploring brainstem activity changes in awake healthy individuals and in those with various clinical conditions. We and others have begun to explore changes in brainstem activity in humans during a number of challenges, including cutaneous and muscle pain, as well as during maneuvers that evoke increases in sympathetic nerve activity. More recently we have successfully recorded sympathetic nerve activity concurrently with functional magnetic resonance imaging of the brainstem, which will allow us, for the first time to explore brainstem sites directly responsible for conditions such as hypertension. Since many pathophysiological conditions no doubt involve changes in brainstem function and structure, defining these changes will likely result in a greater ability to develop more effective treatment regimens.

No MeSH data available.


Related in: MedlinePlus