Search

In analogy to the appreciation of humor, that of tickling is based upon the re-interpretation of an anticipated emotional situation. Hence, the anticipation of tickling contributes to the final outburst of ticklish laughter. To localize the neuronal substrates of this process, functional magnetic resonance imaging (fMRI) was conducted on 31 healthy volunteers. The state of anticipation was simulated by generating an uncertainty respecting the onset of manual foot tickling. Anticipation was characterized by an augmented fMRI signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area, as well as by an attenuated one in the internal globus pallidus. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling. These findings are consistent with an encoding of the expected emotional consequences of tickling and suggest that early regulatory mechanisms influence, automatically, the laughter circuitry at the level of affective and sensory processing. Tickling activated not only those regions of the brain that were involved during anticipation, but also the posterior insula, the anterior cingulate cortex and the periaqueductal gray matter. Sequential or combined anticipatory and tickling-related neuronal activities may adjust emotional and sensorimotor pathways in preparation for the impending laughter response.

Early acquisition of a second language influences the development of language abilities and cognitive functions. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the impact of early bilingualism on the organization of the cortical language network during sentence production. Two groups of adult multilinguals, proficient in three languages, were tested on a narrative task; early multilinguals acquired the second language before the age of three years, late multilinguals after the age of nine. All participants learned a third language after nine years of age. Comparison of the two groups revealed substantial differences in language-related brain activity for early as well as late acquired languages. Most importantly, early multilinguals preferentially activated a fronto-striatal network in the left hemisphere, whereas the left posterior superior temporal gyrus (pSTG) was activated to a lesser degree than in late multilinguals. The same brain regions were highlighted in previous studies when a non-target language had to be controlled. Hence the engagement of language control in adult early multilinguals appears to be influenced by the specific learning and acquisition conditions during early childhood. Remarkably, our results reveal that the functional control of early and subsequently later acquired languages is similarly affected, suggesting that language experience has a pervasive influence into adulthood. As such, our findings extend the current understanding of control functions in multilinguals.

The insular cortex is fundamentally involved in the processing of interoceptive information. It has been postulated that the integrative monitoring of the bodily responses to environmental stimuli is crucial for the recognition and experience of emotions. Because emotional arousal is known to be closely coupled to functions of the anterior insula, we suspected laughter to be associated primarily with neuronal activity in this region. An anatomically constrained re-analysis of our imaging data pertaining to ticklish laughter, to inhibited ticklish laughter, and to voluntary laughter revealed regional differences in the levels of neuronal activity in the posterior and mid-/anterior portions of the insula. Ticklish laughter was associated specifically with right ventral anterior insular activity, which was not detected under the other two conditions. Hence, apparently, only laughter that is evoked as an emotional response bears the signature of autonomic arousal in the insular cortex.

The burst of laughter that is evoked by tickling is a primitive form of vocalization. It evolves during an early phase of postnatal life and appears to be independent of higher cortical circuits. Clinicopathological observations have led to suspicions that the hypothalamus is directly involved in the production of laughter. In this functional magnetic resonance imaging investigation, healthy participants were 1) tickled on the sole of the right foot with permission to laugh, 2) tickled but asked to stifle laughter, and 3) requested to laugh voluntarily. Tickling that was accompanied by involuntary laughter activated regions in the lateral hypothalamus, parietal operculum, amygdala, and right cerebellum to a consistently greater degree than did the 2 other conditions. Activation of the periaqueductal gray matter was observed during voluntary and involuntary laughter but not when laughter was inhibited. The present findings indicate that hypothalamic activity plays a crucial role in evoking ticklish laughter in healthy individuals. The hypothalamus promotes innate behavioral reactions to stimuli and sends projections to the periaqueductal gray matter, which is itself an important integrative center for the control of vocalization. A comparison of our findings with published data relating to humorous laughter revealed the involvement of a common set of subcortical centers.

Olfactory dysfunction is a frequent nonmotor symptom in idiopathic Parkinson's disease (PD) and may be considered as an early clinical feature of the disease preceding motor symptoms by years. According to recent neuropathological staging concepts, impaired olfaction is assumed to indicate an early pathological process and might be associated with structural changes in the brain. A morphometric analysis of magnetic resonance images [voxel-based morphometry (VBM)] was used to investigate gray matter atrophy related to psychophysically measured scores of olfactory function in early PD patients (n= 15, median Hoehn and Yahr stage 1.5), moderately advanced PD patients (n= 12, median Hoehn and Yahr stage 2.5), and age-matched healthy controls (n= 17). In PD patients, but not in controls, cortical atrophy in olfactory-related brain regions correlated specifically with olfactory dysfunction. Positive correlations between olfactory performance and gray matter volume were observed in the right piriform cortex in early PD patients and in the right amygdala in moderately advanced patients. The results provided first evidence that olfactory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex. In addition, olfactory-correlated atrophy in these brain regions is consistent with the assumption that olfactory impairment as an early symptom of PD is likely to be associated with extranigral pathology.

Is it the age of second language acquisition (AoA) that primarily determines the manner of cerebral representation of multiple languages in the brain, or is it proficiency? Here, we review recent neuroimaging studies that aimed at investigating AoA effects by comparing early with late (usually with L2 acquisition onset after 6 years of age) bilinguals during a variety of language tasks on a number of languages. Most studies did indeed report AoA effects. Of particular interest is that the region mainly found to functionally differ between early and late bilinguals is the left inferior frontal gyrus, which was modulated during syntactic processing, word generation, and sentence generation. Additionally, differences were observed in gray-matter density of the posterior parietal cortex as well as in right-hemisphere involvement. Interestingly, despite some convergence of findings from a localizational point of view, underlying causes of organizational and functional differences for the effect of AoA on bilingual language processing still remain to be uncovered. Hypotheses currently used for explaining activation differences are described (notably cortical efficiency, executive control, neuroanatomical changes, and right-hemisphere involvement) in relation to AoA and language proficiency.

The insular cortex is fundamentally involved in the processing of interoceptive information. It has been postulated that the integrative monitoring of the bodily responses to environmental stimuli is crucial for the recognition and experience of emotions. Because emotional arousal is known to be closely coupled to functions of the anterior insula, we suspected laughter to be associated primarily with neuronal activity in this region. An anatomically constrained re-analysis of our imaging data pertaining to ticklish laughter, to inhibited ticklish laughter, and to voluntary laughter revealed regional differences in the levels of neuronal activity in the posterior and mid-/anterior portions of the insula. Ticklish laughter was associated specifically with right ventral anterior insular activity, which was not detected under the other two conditions. Hence, apparently, only laughter that is evoked as an emotional response bears the signature of autonomic arousal in the insular cortex.

Olfactory dysfunction is a frequent nonmotor symptom in idiopathic Parkinson's disease (PD) and may be considered as an early clinical feature of the disease preceding motor symptoms by years. According to recent neuropathological staging concepts, impaired olfaction is assumed to indicate an early pathological process and might be associated with structural changes in the brain. A morphometric analysis of magnetic resonance images [voxel-based morphometry (VBM)] was used to investigate gray matter atrophy related to psychophysically measured scores of olfactory function in early PD patients (n = 15, median Hoehn and Yahr stage 1.5), moderately advanced PD patients (n = 12, median Hoehn and Yahr stage 2.5), and age-matched healthy controls (n = 17). In PD patients, but not in controls, cortical atrophy in olfactory-related brain regions correlated specifically with olfactory dysfunction. Positive correlations between olfactory performance and gray matter volume were observed in the right piriform cortex in early PD patients and in the right amygdala in moderately advanced patients. The results provided first evidence that olfactory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex. In addition, olfactory-correlated atrophy in these brain regions is consistent with the assumption that olfactory impairment as an early symptom of PD is likely to be associated with extranigral pathology.

Olfactory disorders are common in patients with idiopathic Parkinson's disease (IPD). In IPD patients with hyposmia olfactory event-related potentials (ERPs) are typically found to be delayed or absent. Altered ERPs in IPD patients may also be consistent with reduced neuronal activity in the medial temporal lobe following olfactory stimulation, as demonstrated by functional magnetic resonance imaging (fMRI). We analyzed ERPs and fMRI scans of hyposmic IPD patients (n=18) to gain further insight about the brain regions involved in generation of olfactory ERPs. Patients were separated into two groups (n=9 per group), based on the detectability (+) or non-detectability (-) of ERPs. Central activation during olfactory stimulation was examined using fMRI. Both ERP+ and ERP- patients showed activity in brain areas relevant to olfactory processing, such as the amygdala, parahippocampal regions, and temporal regions (BA 37, 21/22). Comparison of both groups revealed higher activation in ERP+ patients, especially in the amygdala, parahippocampal cortex, inferior frontal gyrus (BA 47), insula, cingulate gyrus, striatum, and inferior temporal gyrus. The relationship between the expression of olfactory ERPs and cortical activation patterns seen during olfactory stimulation in fMRI in IPD patients supports the idea that ERPs are a sensitive marker of neurodegeneration in olfactory regions. In accordance with current neuropathological staging concepts, olfactory ERPs may be reflecting pathological changes in olfactory regions, independent of the typically observed nigro-striatal degeneration in IPD. Reduced activation of primary olfactory areas in the ERP-group may reflect a severe disruption of olfactory processing in these patients.

Background: Olfactory dysfunction is a frequent non-motor symptom in Parkinson’s disease (PD) and is considered to be an early manifestation of the disease. Objective: To establish the cortical basis of olfactory function in patients with PD. Method: Functional magnetic resonance imaging (fMRI) was used to investigate brain activity related to olfactory processing in patients with hyposmic PD at mild to moderate stages of the disease (n = 12, median Hoehn and Yahr stage 2.0) and in healthy, age-matched controls (n = 16) while passively perceiving a positively valenced (rose-like) odorant. Results: In both patients with PD and healthy controls, olfactory stimulation activated brain regions relevant for olfactory processing (ie the amygdaloid complex, lateral orbitofrontal cortex, striatum, thalamus, midbrain and the hippocampal formation). In controls, a bilateral activation of the amygdala and hippocampus was observed, whereas patients with PD involved these structures in the left hemisphere only. Group comparison showed that regions of higher activation in patients with PD were located bilaterally in the inferior frontal gyrus (BA 44/45) and anterior cingulate gyrus (BA 24/32), and the left dorsal and right ventral striatum. Conclusions: In patients with PD, results obtained under the specific conditions used suggest that neuronal activity in the amygdala and hippocampus is reduced. Assuming an impact on olfactory-related regions early in PD, our findings support the idea that selective impairment of these brain regions contributes to olfactory dysfunction. Furthermore, neuronal activity in components of the dopaminergic, cortico-striatal loops appears to be upregulated, indicating that compensatory processes are involved. This mechanism has not yet been demonstrated during olfactory processing in PD.

Tumors escape immune-mediated rejection by a variety of mechanisms during tumor progression. The elucidation of these mechanisms in vivo suffers from a lack of suitable models of spontaneous tumor formation escaping active specific immunotherapy (ASI). In a rat neu transgenic (rNeu-TG) mouse model of spontaneous breast tumor formation, we showed that rNeu-TG mice developed late escape tumors despite the presence of a persistent rNeu-specific immune response after ASI. Cell suspensions derived from these escape tumors grew in vaccinated tumor-free mice, whereas injected spontaneous tumor cells were rejected. Escape tumors retained rNeu or MHC class I expression but significantly upregulated Fas (CD95, Apo-1) ligand. We further demonstrated that Fas-L on escape tumor cells correlated with apoptosis of infiltrating T lymphocytes. Thus, our results provide evidence that spontaneous breast tumors upregulate Fas-L expression after vaccination that may promote tumor escape in vivo after ASI.