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1.  Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain 
PLoS ONE  2014;9(10):e109664.
It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality.
PMCID: PMC4188621  PMID: 25291361
2.  Functional and structural changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea 
NeuroImage : Clinical  2014;6:275-283.
Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnoea (OSA) during daytime wakefulness, leading to hypertension, but the underlying mechanisms are poorly understood. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI) of the brain we aimed to identify the central processes responsible for the sympathoexcitation. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted percutaneously into the common peroneal nerve in 17 OSA patients and 15 healthy controls lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. Fluctuations in BOLD signal intensity covaried with the intensity of the concurrently recorded bursts of MSNA. In both groups there was a positive correlation between MSNA and signal intensity in the left and right insulae, dorsolateral prefrontal cortex (dlPFC), dorsal precuneus, sensorimotor cortex and posterior temporal cortex, and the right mid-cingulate cortex and hypothalamus. In OSA the left and right dlPFC, medial PFC (mPFC), dorsal precuneus, anterior cingulate cortex, retrosplenial cortex and caudate nucleus showed augmented signal changes compared with controls, while the right hippocampus/parahippocampus signal intensity decreased in controls but did not change in the OSA subjects. In addition, there were significant increases in grey matter volume in the left mid-insula, the right insula, left and right primary motor cortices, left premotor cortex, left hippocampus and within the brainstem and cerebellum, and significant decreases in the mPFC, occipital lobe, right posterior cingulate cortex, left cerebellar cortex and the left and right amygdala in OSA, but there was no overlap between these structural changes and the functional changes in OSA. These data suggest that the elevated muscle vasoconstrictor drive in OSA may result from functional changes within these brain regions, which are known to be directly or indirectly involved in the modulation of sympathetic outflow via the brainstem. That there was no overlap in the structural and functional changes suggests that asphyxic damage due to repeated episodes of nocturnal obstructive apnoea is not the main cause of the sympathoexcitation.
•Obstructive sleep apnea increases muscle sympathetic nerve activity (MSNA).•fMRI was used to identify brain sites temporally coupled to the increase in MSNA.•Augmented BOLD signal intensity occurred in several cortical and subcortical sites.•The elevated MSNA in OSA may result from functional changes within these sites.
PMCID: PMC4215471  PMID: 25379440
fMRI; Microneurography; Muscle sympathetic nerve activity; Obstructive sleep apnoea
3.  3-Benzhydryl-1,3,4-thia­diazole-2(3H)-thione 
In the title compound, C15H12N2S2, the two phenyl rings and the planar (r.m.s. deviation = 0.002 Å) thia­diazole ring adopt a propeller conformation about the central C—H axis with H—C—C—C(phen­yl) torsion angles of 44 and 42° and an H—C—N—C(thia­diazole) torsion angle of 28°. Intra­molecular C—H⋯S and C—H⋯N contacts are observed. In the crystal, centrosymmetrically related mol­ecules associate through C—H⋯π inter­actions. These are connected into a supra­molecular chain along [101] by C—H⋯N inter­actions.
PMCID: PMC3884419  PMID: 24427045
4.  Functional Imaging of the Human Brainstem during Somatosensory Input and Autonomic Output 
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.
PMCID: PMC3775150  PMID: 24062670
trigeminal nuclei; dorsal column nuclei; pain; sympathetic nerve activity; rostral ventrolateral medulla
5.  1-[4-Chloro-3-(trifluoro­meth­yl)phen­yl]-4-phenyl-1H-1,2,3-triazole 
In the title compound, C15H9ClF3N3, the phenyl and chloro-trifluoro­methyl benzene rings are twisted with respect to the planar triazole group, making dihedral angles of 21.29 (12) and 32.19 (11)°, respectively. In the crystal, the mol­ecules pack in a head-to-tail arrangement along the a axis with closest inter-centroid distances between the triazole rings of 3.7372 (12) Å.
PMCID: PMC3515254  PMID: 23284474
6.  Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images 
The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.
PMCID: PMC3461643  PMID: 23060818
skin sympathetic nerve activity; emotionally charged images; microneurography; sweat release; skin blood flow
7.  Methyl 3-[4-(4-nitro­benz­yloxy)phen­yl]propano­ate 
The title compound, C17H17NO5, crystallizes with two mol­ecules (A and B) in the asymmetric unit. The conformational structures of the two mol­ecules show small but significant differences in the dihedral angles between the two aryl rings with values of 18.8 (1)° for mol­ecule A and 7.5 (1)° for mol­ecule B. In mol­ecule A, the propano­ate group is twisted out of the plane of the benzene group [Car—Car—C—C torsion angle = −44.9 (2)°], while for mol­ecule B, this group lies closer to the plane [Car—Car—C—C torsion angle = 8.6 (3)°]. C—H⋯O inter­actions characterize the crystal-packing inter­actions in this compound.
PMCID: PMC3393271  PMID: 22807828
8.  Investigating Ionic Effects Applied to Water Based Organocatalysed Aldol Reactions 
Saturated aqueous solutions of various common salts were examined for their effect on aqueous aldol reactions catalysted by a highly active C2-symmetric diprolinamide organocatalyst developed in our laboratory. With respect to the aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, deionised water was always a superior medium to salt solutions though some correlation to increasing anion size and depression in enantiomeric excess could be observed. Additionally, the complete inhibition of catalyst activity observed when employing tap water could be alleviated by the inclusion of ethylenediaminetetraacetate (EDTA) into the aqueous media prior to reaction initiation. Extension of these reaction conditions demonstrated that these ionic effects vary on a case-to-case basis depending on the ketone/aldehyde combination.
PMCID: PMC3257117  PMID: 22272120
ionic solution; organocatalysis; aldol; water

Results 1-8 (8)