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Taking Sides with Pain – Lateralization aspects Related to Cerebral Processing of Dental Pain  [PDF]
Mike Brügger,Dominik A. Ettlin,Michael Meier,Thierry Keller,Roger Luechinger,Ashley Barlow,Sandro Palla,Lutz J?ncke,Kai Lutz
Frontiers in Human Neuroscience , 2011, DOI: 10.3389/fnhum.2011.00012
Abstract: The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding.
On Functional Lateralization of Amygdala Involved in Emotion

Wang Cuiyan,Liu Chang,

心理科学进展 , 2007,
Abstract: Functional lateralization of amygdala involved in emotion is reviewed from three aspects:conscious level,sex,emotional type.Indeed,the function of amygdala is asymmetry,and left amygdala shows more active than right amygdala.Right amygdala is responsible for early stage,basic,backstage emotion activities which is not easy to be tested,and left amygdala involves followed,concrete,sustained,proscenium emotion activities which is easy to be tested.It is not very clear about its mechanism of functional lateralization.The hypothesis and prospects on future studies about lateralization of amygdala are also reviewed in the paper.
Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization
Biological Research , 2003, DOI: 10.4067/S0716-97602003000100007
Abstract: analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. in order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.
Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization  [cached]
Biological Research , 2003,
Abstract: Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.
Homer1a signaling in the amygdala counteracts pain-related synaptic plasticity, mGluR1 function and pain behaviors
Anke Tappe-Theodor, Yu Fu, Rohini Kuner, Volker Neugebauer
Molecular Pain , 2011, DOI: 10.1186/1744-8069-7-38
Abstract: In contrast to wild-type mice, H1a-mice mice did not develop increased pain behaviors (spinal reflexes and audible and ultrasonic vocalizations) after induction of arthritis in the knee joint. Whole-cell patch-clamp recordings in brain slices showed that excitatory synaptic transmission from the BLA to the central nucleus (CeA) did not change in arthritic H1a-mice but increased in arthritic wild-type mice. A selective mGluR1 antagonist (CPCCOEt) had no effect on enhanced synaptic transmission in slices from H1a-BLA mice with arthritis but inhibited transmission in wild-type mice with arthritis as in our previous studies in rats.The results show that Homer1a expressed in forebrain neurons, prevents the development of pain hypersensitivity in arthritis and disrupts pain-related plasticity at synapses in amygdaloid nuclei. Furthermore, Homer1a eliminates the effect of an mGluR1 antagonist, which is consistent with the well-documented disruption of mGluR1 signaling by Homer1a. These findings emphasize the important role of mGluR1 in pain-related amygdala plasticity and provide evidence for the involvement of Homer1 proteins in the forebrain in the modulation of pain hypersensitivity.Neuroplasticity in the amygdala plays an important role in emotional-affective aspects of pain [1,2]. A growing body of literature is addressing pain-related functions of different amygdala nuclei and signaling mechanisms in these areas [3-16]. Neurotransmission from the lateral amygdala (LA) to the basolateral amygdala (BLA) and further to the central nucleus of the amygdala (CeA) regulates input and output functions of the amygdala. The designation of the latero-capsular division of the central nucleus of the amygdala (CeLC) as the "nociceptive amygdala" emphasizes its role in pain processing and modulation [1,2]. CeLC neurons receive excitatory glutamatergic input directly from neurons in the BLA and inhibitory input via glutamatergic activation of GABAergic neurons in the intercalated ce
Gaussian Mixture Modeling of Hemispheric Lateralization for Language in a Large Sample of Healthy Individuals Balanced for Handedness  [PDF]
Bernard Mazoyer, Laure Zago, Ga?l Jobard, Fabrice Crivello, Marc Joliot, Guy Perchey, Emmanuel Mellet, Laurent Petit, Nathalie Tzourio-Mazoyer
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101165
Abstract: Hemispheric lateralization for language production and its relationships with manual preference and manual preference strength were studied in a sample of 297 subjects, including 153 left-handers (LH). A hemispheric functional lateralization index (HFLI) for language was derived from fMRI acquired during a covert sentence generation task as compared with a covert word list recitation. The multimodal HFLI distribution was optimally modeled using a mixture of 3 and 4 Gaussian functions in right-handers (RH) and LH, respectively. Gaussian function parameters helped to define 3 types of language hemispheric lateralization, namely “Typical” (left hemisphere dominance with clear positive HFLI values, 88% of RH, 78% of LH), “Ambilateral” (no dominant hemisphere with HFLI values close to 0, 12% of RH, 15% of LH) and “Strongly-atypical” (right-hemisphere dominance with clear negative HFLI values, 7% of LH). Concordance between dominant hemispheres for hand and for language did not exceed chance level, and most of the association between handedness and language lateralization was explained by the fact that all Strongly-atypical individuals were left-handed. Similarly, most of the relationship between language lateralization and manual preference strength was explained by the fact that Strongly-atypical individuals exhibited a strong preference for their left hand. These results indicate that concordance of hemispheric dominance for hand and for language occurs barely above the chance level, except in a group of rare individuals (less than 1% in the general population) who exhibit strong right hemisphere dominance for both language and their preferred hand. They call for a revisit of models hypothesizing common determinants for handedness and for language dominance.
Basolateral Amygdala Lesion Inhibits the Development of Pain Chronicity in Neuropathic Pain Rats  [PDF]
Zheng Li, Jing Wang, Lin Chen, Meng Zhang, You Wan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070921
Abstract: Background Chronicity of pain is one of the most interesting questions in chronic pain study. Clinical and experimental data suggest that supraspinal areas responsible for negative emotions such as depression and anxiety contribute to the chronicity of pain. The amygdala is suspected to be a potential structure for the pain chronicity due to its critical role in processing negative emotions and pain information. Objective This study aimed to investigate whether amygdala or its subregions, the basolateral amygdala (BLA) and the central medial amygdala (CeA), contributes to the pain chronicity in the spared nerve injury (SNI)-induced neuropathic pain model of rats. Methodology/Principal Findings (1) Before the establishment of the SNI-induced neuropathic pain model of rats, lesion of the amygdaloid complex with stereotaxic injection of ibotenic acid (IBO) alleviated mechanical allodynia significantly at days 7 and 14, even no mechanical allodynia at day 28 after SNI; Lesion of the BLA, but not the CeA had similar effects; (2) however, 7 days after SNI when the neuropathic pain model was established, lesion of the amygdala complex or the BLA or the CeA, mechanical allodynia was not affected. Conclusion These results suggest that BLA activities in the early stage after nerve injury might be crucial to the development of pain chronicity, and amygdala-related negative emotions and pain-related memories could promote pain chronicity.
Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1
Wenjie Ren, Volker Neugebauer
Molecular Pain , 2010, DOI: 10.1186/1744-8069-6-93
Abstract: Pain has a strong emotional component and is significantly associated with anxiety and depression. The amygdala plays a key role in emotional learning and memory as well as in affective disorders [1-4] and is also important for the emotional-affective dimension of pain and pain modulation [5-8]. Pharmacologic inhibition of amygdala hyperactivity has been shown to decrease nocifensive and affective responses in animal pain models [5,8-13]. Conversely, pharmacologic activation can produce pain behavior even in the absence of tissue injury [14-17].The amygdala consists of several anatomically and functionally distinct nuclei [2,18]. The laterocapsular division of the central nucleus (CeLC) has been termed the "nociceptive amygdala" because it receives nociceptive-specific information from the spinal cord and brainstem (external parabrachial area, PB) and the vast majority of CeLC neurons respond exclusively or preferentially to noxious stimuli [5,8,19]. Synaptic plasticity of PB inputs to the CeLC has been shown in models of arthritic pain [20-23], visceral pain [24] and chronic neuropathic pain [25] and is associated with pain-related central sensitization of CeLC neurons [21,26-31]. Highly processed multimodal, including nociceptive, information reaches the CeLC from thalamus and cortex through the lateral-basolateral (LA-BLA) network [5,8]. The LA-BLA circuitry is critical for the emotional evaluation of sensory stimuli and for acquisition and consolidation of aversive associations [2,3,32,33]. Our previous studies showed pain-related synaptic plasticity of excitatory transmission at the LA-BLA and BLA-CeLC synapses [10,20,23]. The BLA can influence CeA processes via direct glutamatergic projections and through indirect disynaptic routes involving GABAergic neurons in the intercalated cell masses (ITC) that project to the CeA [2,32,34]. Activation of inhibitory ITC neurons and subsequent inhibition of CeA neurons has been suggested to play an important role in fear
Hemispheric Asymmetry for Affective Stimulus Processing in Healthy Subjects–A fMRI Study  [PDF]
Esther Beraha, Jonathan Eggers, Catherine Hindi Attar, Stefan Gutwinski, Florian Schlagenhauf, Meline Stoy, Philipp Sterzer, Thorsten Kienast, Andreas Heinz, Felix Bermpohl
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046931
Abstract: Background While hemispheric specialization of language processing is well established, lateralization of emotion processing is still under debate. Several conflicting hypotheses have been proposed, including right hemisphere hypothesis, valence asymmetry hypothesis and region-specific lateralization hypothesis. However, experimental evidence for these hypotheses remains inconclusive, partly because direct comparisons between hemispheres are scarce. Methods The present fMRI study systematically investigated functional lateralization during affective stimulus processing in 36 healthy participants. We normalized our functional data on a symmetrical template to avoid confounding effects of anatomical asymmetries. Direct comparison of BOLD responses between hemispheres was accomplished taking two approaches: a hypothesis-driven region of interest analysis focusing on brain areas most frequently reported in earlier neuroimaging studies of emotion; and an exploratory whole volume analysis contrasting non-flipped with flipped functional data using paired t-test. Results The region of interest analysis revealed lateralization towards the left in the medial prefrontal cortex (BA 10) during positive stimulus processing; while negative stimulus processing was lateralized towards the right in the dorsolateral prefrontal cortex (BA 9 & 46) and towards the left in the amygdala and uncus. The whole brain analysis yielded similar results and, in addition, revealed lateralization towards the right in the premotor cortex (BA 6) and the temporo-occipital junction (BA 19 & 37) during positive stimulus processing; while negative stimulus processing showed lateralization towards the right in the temporo-parietal junction (BA 37,39,42) and towards the left in the middle temporal gyrus (BA 21). Conclusion Our data suggests region-specific functional lateralization of emotion processing. Findings show valence asymmetry for prefrontal cortical areas and left-lateralized negative stimulus processing in subcortical areas, in particular, amygdala and uncus.
Circadian Modulation of Anxiety: A Role for Somatostatin in the Amygdala  [PDF]
Anne Albrecht, Marlen Thiere, Jorge Ricardo Bergado-Acosta, Janine Poranzke, Bettina Müller, Oliver Stork
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0084668
Abstract: Pharmacological evidence suggests that the neuropeptide somatostatin (SST) exerts anxiolytic action via the amygdala, but findings concerning the putative role of endogenous SST in the regulation of emotional responses are contradictory. We hypothesized that an endogenous regulation of SST expression over the course of the day may determine its function and tested both SST gene expression and the behavior of SST knock out (SST-/-) mice in different aversive tests in relation to circadian rhythm. In an open field and a light/dark avoidance test, SST-/- mice showed significant hyperactivity and anxiety-like behavior during the second, but not during the first half of the active phase, failing to show the circadian modulation of behavior that was evident in their wild type littermates. Behavioral differences occurred independently of changes of intrinsically motivated activity in the home cage. A circadian regulation of SST mRNA and protein expression that was evident in the basolateral complex of the amygdala of wild type mice may provide a neuronal substrate for the observed behavior. However, fear memory towards auditory cue or the conditioning context displayed neither a time- nor genotype-dependent modulation. Together this indicates that SST, in a circadian manner and putatively via its regulation of expression in the amygdala, modulates behavior responding to mildly aversive conditions in mice.
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