Intranasal Insulin Boosts Gustatory Sensitivity.

Intranasal insulin has been the subject of attention not only with respect to enhancing memory processes, but also for its anorexic effects, as well as its effects on olfactory sensitivity. In the present study, the influence of intranasal insulin on gustatory sensitivity was investigated using intranasal applications of insulin or placebo in a double-blind manner alongside a control condition without any application. We hypothesised that, because it mediates satiety, intranasal insulin alters gustatory sensitivity, whereas placebo application and the control should not alter gustatory sensitivity. We did not expect the sensitivity to the different taste solutions to differ. Sweet, salty, bitter and sour liquids in four concentrations each were sprayed onto the tongue of healthy male subjects. Additionally, water with no taste was applied to enable calculation of taste sensitivity in terms of parameter d' of signal detection theory. The task of the subject was to identify the quality of the respective tastant. Gustatory sensitivity and blood parameters were evaluated using repeated-measures ANOVAs. Gustatory sensitivity (implying all tastants) improved significantly after intranasal insulin application compared to the application of placebo, although it did not reach significance compared to the control condition. Subjects performed best when detecting the sweet taste and worst when detecting the bitter taste. The blood parameters glucose, insulin, homeostatic model assessment and leptin did not differ with respect to insulin or placebo condition, nor did they differ regarding measurements preceding or following intranasal application, in confirmation of preserved peripheral euglycaemia during the experiment. Thus, it can be concluded that the application of intranasal insulin led to an improved gustatory sensitivity compared to placebo.

Changes of cerebral white matter in patients suffering from Pantothenate Kinase-Associated Neurodegeneration (PKAN): A diffusion tensor imaging (DTI) study.

BACKGROUND: To look for microstructural white matter alterations in patients with dystonia due to Pantothenate Kinase-Associated Neurodegeneration. MATERIAL AND METHODS: We examined 21 genetically confirmed patients and an age-matched group of 21 healthy controls by diffusion tensor imaging. Evaluation of data was performed by tract-based spatial statistics analysis and a voxel-wise comparison of calculated maps of fractional anisotropy. Findings were compared between groups and correlated to the dystonia score of the Burke-Fahn-Marsden Scale (p ≤ 0.05). RESULTS: Patients showed reductions of fractional anisotropy mainly in the periventricular substance surrounding the third ventricle, in the medial part of both putamina and in the frontal white matter including the anterior limbs of the internal capsules and the corpus callosum. Infratentorially, the cerebellar white matter and dorsal parts of the pons and medulla were affected. CONCLUSION: In addition to cortical grey matter changes, we now have a second structural finding pointing to a more widespread affection of cerebral tissue in PKAN dystonia than just the lesion and iron accumulation in the globus pallidus.

Neuronal differences between chronic low back pain and depression regarding long-term habituation to pain.

BACKGROUND: Longitudinal studies of experimental pain are rare and little is known about the differences regarding sensitization and habituation over longer periods in patients with chronic pain or depression compared with controls. METHODS: We used a standardized longitudinal painful heat paradigm that was designed to induce long-term habituation in 19 patients with chronic low back pain (CLBP), 21 patients with depression (DEP) and 21 healthy participants (controls) over a time course of eight consecutive days. We applied functional magnetic resonance imaging on the first and last day of this period and after 3 months. RESULTS: Although the pain paradigm was standardized, patients with DEP exhibited significantly higher pain thresholds and a trend to higher pain ratings and, in functional imaging, showed less activation of the operculum and the secondary somatosensory cortex (S2) as compared to patients with CLBP and controls. Conversely, patients with CLBP showed increased activation in the anterior insula and parietal operculum as compared to patients with DEP and controls. Within session, all participants sensitized to pain, which was associated with higher activation levels in the thalamus, amygdala, midcingulate cortex, and sensory and motor areas. However, patients with depression showed significantly less activation in midbrain and brainstem areas. CONCLUSION: Given that pain and depression potentiate each other clinically, our data suggest that this may involve different cortical pain areas.

Motor activation in patients with Pantothenate-Kinase Associated Neurodegeneration: a functional magnetic resonance imaging study.

BACKGROUND: In a variety of dystonias, functional magnetic resonance imaging has shown deviations of cortical and basal ganglia activations within the motor network, which might cause the movement disturbances. Because these investigations have never been performed in secondary dystonia due to Pantothenate-Kinase Associated Neurodegeneration, we report our results in a small group of such patients from the Dominican Republic. METHODS: Functional magnetic resonance imaging was carried out in 7 patients with a genetically confirmed mutation of the PANK2 gene and a non-affected control group (matched pairs) using an event-related motor activation paradigm (hand movements). RESULTS: Compared to the control group (p ≤ 0.01), patients showed a larger amount of activated voxels starting in the contralateral cerebellum and contralateral premotor cortex 2 s before the actual hand movement. Whereas these "hyperactivations" gradually diminished over time, activations in the contralateral primary motor cortex and the supplementary motor area peaked during the next second and those of the contralateral putamen at the time of the actual hand movement. In a multiple regression analysis, all these areas correlated positively with the degree of dystonia of the contralateral arm as judged by the Burke-Fahn-Marsden-scale (p ≤ 0.001). CONCLUSION: As in other forms of dystonia, the increased activations of the motor system found in our patients could be related to the origin of the dystonic movements. Because in this condition the primary lesion affects the pallidum, a defect of the feed-back control mechanism between basal ganglia and cortex might be the responsible factor.

Within-session sensitization and between-session habituation: a robust physiological response to repetitive painful heat stimulation.

Habituation and sensitization are important behavioural responses to repeated exposure of painful stimuli. Whereas within-session response dynamics to nociceptive stimuli is well characterized, little is known about long-term behaviour due to repetitive nociceptive stimulation. We used a standardized longitudinal heat pain paradigm in 66 healthy participants, 21 patients with chronic low back pain and 22 patients with depression who received daily sessions of 60 suprathreshold heat stimuli (48 °C each) for eight consecutive days. All three groups showed the same response: Repeated painful stimulation over several days resulted in substantially decreased pain ratings to identical painful stimuli. The decreased perception of pain over time was associated with a very robust increase in pain ratings in each single pain session, i.e., all participants sensitized within sessions and habituated between sessions. This uniform pattern was equally present in all examined groups. Chronic pain and depression do not seem to interfere with short-term sensitization and long-term habituation in this model of repetitive phasic heat pain.