Cingulum NeuroSciences Institute

Manlius, NY, United States

Cingulum NeuroSciences Institute

Manlius, NY, United States
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Palomero-Gallagher N.,Jülich Research Center | Eickhoff S.B.,Jülich Research Center | Eickhoff S.B.,Heinrich Heine University Düsseldorf | Hoffstaedter F.,Jülich Research Center | And 12 more authors.
NeuroImage | Year: 2015

Human subgenual anterior cingulate cortex (sACC) is involved in affective experiences and fear processing. Functional neuroimaging studies view it as a homogeneous cortical entity. However, sACC comprises several distinct cyto- and receptorarchitectonical areas: 25, s24, s32, and the ventral portion of area 33. Thus, we hypothesized that the areas may also be connectionally and functionally distinct. We performed structural post mortem and functional in vivo analyses. We computed probabilistic maps of each area based on cytoarchitectonical analysis of ten post mortem brains. Maps, publicly available via the JuBrain atlas and the Anatomy Toolbox, were used to define seed regions of task-dependent functional connectivity profiles and quantitative functional decoding. sACC areas presented distinct co-activation patterns within widespread networks encompassing cortical and subcortical regions. They shared common functional domains related to emotion, perception and cognition. A more specific analysis of these domains revealed an association of s24 with sadness, and of s32 with fear processing. Both areas were activated during taste evaluation, and co-activated with the amygdala, a key node of the affective network. s32 co-activated with areas of the executive control network, and was associated with tasks probing cognition in which stimuli did not have an emotional component. Area 33 was activated by painful stimuli, and co-activated with areas of the sensorimotor network. These results support the concept of a connectional and functional specificity of the cyto- and receptorarchitectonically defined areas within the sACC, which can no longer be seen as a structurally and functionally homogeneous brain region. © 2015 Elsevier Inc.


Palomero-Gallagher N.,Jülich Research Center | Palomero-Gallagher N.,Cingulum Neurosciences Institute | Palomero-Gallagher N.,Julich Aachen Research Alliance | Zilles K.,Jülich Research Center | And 6 more authors.
Journal of Comparative Neurology | Year: 2013

Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B, BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains. © 2013 Wiley Periodicals, Inc.


Vogt B.A.,Boston University | Vogt B.A.,Cingulum Neurosciences Institute | Vogt B.A.,Jülich Research Center | Hof P.R.,Mount Sinai School of Medicine | And 9 more authors.
Journal of Comparative Neurology | Year: 2013

Homologizing between human and nonhuman area 32 has been impaired since Brodmann said he could not homologize with certainty human area 32 to a specific cortical domain in other species. Human area 32 has four divisions, however, and two can be structurally homologized to nonhuman species with cytoarchitecture and receptor architecture: pregenual (p32) and subgenual (s32) in human and macaque monkey and areas d32 and v32 in rat and mouse. Cytoarchitecture showed that areas d32/p32 have a dysgranular layer IV in all species and that areas v32/s32 have large and dense neurons in layer V, whereas a layer IV is not present in area v32. Areas v32/s32 have the largest neurons in layer Va. Features unique to humans include large layer IIIc pyramids in both divisions, sparse layer Vb in area p32, and elongated neurons in layer VI, with area s32 having the largest layer Va neurons. Receptor fingerprints of both subdivisions of area 32 differed between species in size and shape, although AMPA/GABAA and NMDA/GABAA ratios were comparable among humans, monkeys, and rats and were significantly lower than in mice. Layers I-III of primate and rodent area 32 subdivisions share more similarities in their receptor densities than layers IV-VI. Monkey and human subdivisions of area 32 are more similar to each other than to rat and mouse subdivisions. In combination with intracingulate connections, the location, cytoarchitecture, and ligand binding studies demonstrate critical homologies among the four species. © 2013 Wiley Periodicals, Inc.


Shyu B.-C.,Academia Sinica, Taiwan | Sikes R.W.,Northeastern University | Vogt L.J.,Cingulum NeuroSciences Institute | Vogt L.J.,New York University | And 2 more authors.
Journal of Neurophysiology | Year: 2010

Although the cingulate cortex is frequently activated in acute human pain studies, postsynaptic responses are not known nor are links between nociceptive afferents, neuronal responses, and outputs to other structures. Intracellular potentials were recorded from neurobiotin-injected, pyramidal neurons in anterior cingulate area 24b following noxious stimulation of the sciatic nerve in anesthetized rabbits. Layer IIIc pyramids had extensive and horizontally oriented basal dendrites in layer IIIc where nociceptive afferents terminate. They had the longest excitatory postsynaptic potentials (EPSPs; 545 ms) that were modulated with hyperpolarizing currents. Pyramids in layer V had an intermediate tuft of oblique apical dendrites in layer IIIc that were 150-350 μm from somata in layer Va and 351-550 μm in layer Vb. Although average EPSP durations were short in layers II-IIIab (222 ± 31), Va (267 ± 65), and Vb (159 ± 31), there were five neurons in layers IIIab-Va that had EPSP durations lasting >300 ms (548 ± 63 ms). Neurons in layers IIIc, Va, and Vb had the highest amplitude EPSPs (6.25, 6.84 ± 0.58, and 6.4 ± 0.47 mV, respectively), whereas those in layers II-IIIab were 5 ± 0.56 mV. Nociceptive responses in layer Vb were complex and some had initial inhibitory postsynaptic potentials with shorter-duration EPSPs. Layers II-IIIab had dye-coupled pyramids and EPSPs in these layers had short durations (167 ± 33 ms) compared with those in layers IIIc-Va (487 ± 28 ms). In conclusion there are two populations of anterior cingulate cortex pyramids with EPSPs of significantly different durations, although their dendritic morphologies do not predict EPSP duration. Short-duration EPSPs are thalamic-mediated, nociceptive responses lasting ≤200 ms. Longer, "integrative" EPSPs are >350 ms and are likely modulated by intracortical axon collateral discharges. These findings suggest that links between nociception and projections to cortical and motor systems are instantaneous because nociceptive responses are generated directly by pyramidal projection neurons in all layers. Copyright © 2010 The American Physiological Society.


Vogt B.A.,Cingulum Neurosciences Institute | Vogt B.A.,Boston University | Paxinos G.,University of New South Wales
Brain Structure and Function | Year: 2014

A gulf exists between cingulate area designations in human neurocytology and those used in rodent brain atlases with a major underpinning of the former being midcingulate cortex (MCC). The present study used images extracted from the Franklin and Paxinos mouse atlas and Paxinos and Watson rat atlas to demonstrate areas comprising MCC and modifications of anterior cingulate (ACC) and retrosplenial cortices. The laminar architecture not available in the atlases is also provided for each cingulate area. Both mouse and rat have a MCC with neurons in all layers that are larger than in ACC and layer Va has particularly prominent neurons and reduced neuron densities. An undifferentiated ACC area 33 lies along the rostral callosal sulcus in rat but not in mouse and area 32 has dorsal and ventral subdivisions with the former having particularly large pyramidal neurons in layer Vb. Both mouse and rat have anterior and posterior divisions of retrosplenial areas 29c and 30, although their cytology is different in rat and mouse. Maps of the rodent cingulate cortices provide for direct comparisons with each region in the human including MCC and it is significant that rodents do not have a posterior cingulate region composed of areas 23 and 31 like the human. It is concluded that rodents and primates, including humans, possess a MCC and this homology along with those in ACC and retrosplenial cortices permit scientists inspired by human considerations to test hypotheses on rodent models of human diseases. © 2012 Springer-Verlag Berlin Heidelberg.


Vogt B.A.,Cingulum Neurosciences Institute | Vogt B.A.,Boston University | Vogt B.A.,Jülich Research Center
Neurogastroenterology and Motility | Year: 2013

The article by Agostini et al. (2013) in this issue of Neurogastroenterology and Motility evaluated patients with Crohn's disease (CD) for volumetric changes throughout the brain. They observed decreased gray matter volumes in dorsolateral prefrontal cortex and anterior midcingulate cortex (aMCC) and disease duration was negatively correlated with volumes in subgenual anterior cingulate (sACC), posterior MCC (pMCC), ventral posterior cingulate (vPCC), and parahippocampal cortices. As all patients were in remission and suffered from ongoing abdominal pain, this study provides a critical link between forebrain changes and abdominal pain experience independent of active disease and drug treatment. The aMCC has a role in feedback-mediated decision making and there are specific cognitive tasks that differentiate aMCC and pMCC that can be used to evaluate defects in CD. The sACC is an important area as it has impaired functions in major depression. As depressive symptoms are a feature in a subset of patients with active inflammatory diseases including IBD, treatment targeting this subregion should prove efficacious. Finally, vPCC has a role in ongoing self-monitoring of the personal relevance of sensory stimuli including visceral signals via sACC. This pathway may be interrupted by vPCC atrophy in CD. Cingulate atrophy in CD leads to targeting chronic pain and psychiatric symptoms via cingulate-mediated therapies. These include psychotherapy, guided imagery and relaxation training, analgesic dosages of morphine or antidepressants, and hypnosis. Thus, a new generation of novel treatments may emerge from drug and non-traditional therapies for CD in this formative area of research. © 2013 Blackwell Publishing Ltd.


Chang W.-P.,A-Life Medical | Wu J.-S.,National Taiwan University | Lee C.-M.,Academia Sinica, Taiwan | Vogt B.A.,Cingulum NeuroSciences Institute | And 2 more authors.
Epilepsia | Year: 2011

Purpose: Seizure-like activities generated in anterior cingulate cortex (ACC) are usually classified as simple partial and are associated with changes in autonomic function, motivation, and thought. Previous studies have shown that thalamic inputs can modulate ACC seizure, but the exact mechanisms have not been studied thoroughly. Therefore, we investigated the role of thalamic inputs in modulating ACC seizure-like activities. In addition, seizure onset and propagation are difficult to determine in vivo in ACC. We studied the spatiotemporal changes in epileptiform activity in this cortex in a thalamic-ACC slice to clearly determine seizure onset. Methods: We used multielectrode array (MEA) recording and calcium imaging to investigate the modulatory effect of thalamic inputs in a thalamic-ACC slice preparation. Key Findings: Seizure-like activities induced with 4-aminopyridine (4-AP; 250 μm) and bicuculline (5-50 μm) in ACC were attenuated by glutamate receptor antagonists, and the degree of disinhibition varied with the dose of bicuculline. Seizure-like activities were decreased with 1 Hz thalamic stimulation, whereas corpus callosum stimulation could increase ictal discharges. Amplitude and duration of cingulate seizure-like activities were augmented after removing thalamic inputs, and this effect was not observed with those induced with elevated bicuculline (50 μm). Seizure-like activities were initiated in layers II/III and, after thalamic lesions, they occurred mainly in layers V/VI. Two-dimensional current-source density analyses revealed sink signals more frequently in layers V/VI after thalamic lesions, indicating that these layers produce larger excitatory synchronization. Calcium transients were synchronized after thalamic lesions suggesting that ACC seizure-like activities are subjected to desynchronizing modulation by thalamic inputs. Therefore, ACC seizure-like activities are subject to desynchronizing modulation from medial thalamic inputs to deep layer pyramidal neurons. Significance: Cingulate seizure-like activities were modulated significantly by thalamic inputs. Repeated stimulation of the thalamus efficiently inhibited epileptiform activity, demonstrating that the desynchronization was pathway-specific. The clinical implications of deep thalamic stimulation in the modulation of cingulate epileptic activity require further investigation. © 2011 International League Against Epilepsy.


Vogt B.A.,Cingulum Neurosciences Institute | Vogt B.A.,Boston University
Brain Structure and Function | Year: 2015

The rabbit cingulate cortex is highly differentiated in contrast to rodents and numerous recent advances suggest the rabbit area map needs revision. Immunohistochemistry was used to assess cytoarchitecture with neuron-specific nuclear binding protein (NeuN) and neurocytology with intermediate neurofilament proteins, parvalbumin and glutamic acid decarboxylase. Key findings include: (1) Anterior cingulate cortex (ACC) area 32 has dorsal and ventral divisions. (2) Area 33 is part of ACC. (3) Midcingulate cortex (MCC) has anterior and posterior divisions and this was verified with extensive quantitative analysis and a horizontal series of sections. (4) NeuN, also known as Fox-3, is not limited to somata and formed nodules, granular clusters and striations in the apical dendrites of pyramidal neurons. (5) Area 30 forms a complex of anterior and posterior parts with further medial and lateral divisions. (6) Area 29b has two divisions and occupies substantially more volume than in rat. (7) Area 29a begins with a subsplenial component and extends relatively further caudal than in rat. As similar areal designations are often used among species, direct comparisons were made of rabbit areas with those in rat and monkey. The dichotomy of MCC is of particular interest to studies of pain as anterior MCC is most frequently activated in human acute pain studies and the rabbit can be used to study this subregion. Finally, the area 30 complex is not primarily dysgranular as in rat and is more differentiated than in any other mammal including human. The large and highly differentiated rabbit cingulate cortex provides a unique model for assessing cingulate cortex, pain processing and RNA splicing functions. © 2015 Springer-Verlag Berlin Heidelberg


Varlinskaya E.I.,Binghamton University State University of New York | Vogt B.A.,Developmental Exposure Alcohol Research Center | Vogt B.A.,Cingulum Neurosciences Institute | Spear L.P.,Binghamton University State University of New York
Developmental Psychobiology | Year: 2013

The study assessed possible age differences in brain activation patterns to low dose ethanol (5g/kg intraperitoneally) and the influence of social context on this activation. Early adolescent or young adult male Sprague-Dawley rats were placed either alone or with an unfamiliar partner of the same age and sex following saline or ethanol administration. c-Fos protein immunoreactivity was used to index neuronal activation in 15 regions of interest. Ethanol had little effect on c-Fos activation. In adolescents, social context activated an "autonomic" network including the basolateral and central amygdala, bed nucleus of the stria terminalis, lateral hypothalamus, and lateral septum. In contrast, when adult rats were alone, activation was evident in a "reward" network that included the substantia nigra, nucleus accumbens, anterior cingulate and orbitofrontal cortices, lateral parabrachial nucleus, and locus coeruleus. © 2012 Wiley Periodicals, Inc.


PubMed | Cingulum Neurosciences Institute
Type: Journal Article | Journal: Brain structure & function | Year: 2016

The rabbit cingulate cortex is highly differentiated in contrast to rodents and numerous recent advances suggest the rabbit area map needs revision. Immunohistochemistry was used to assess cytoarchitecture with neuron-specific nuclear binding protein (NeuN) and neurocytology with intermediate neurofilament proteins, parvalbumin and glutamic acid decarboxylase. Key findings include: (1) Anterior cingulate cortex (ACC) area 32 has dorsal and ventral divisions. (2) Area 33 is part of ACC. (3) Midcingulate cortex (MCC) has anterior and posterior divisions and this was verified with extensive quantitative analysis and a horizontal series of sections. (4) NeuN, also known as Fox-3, is not limited to somata and formed nodules, granular clusters and striations in the apical dendrites of pyramidal neurons. (5) Area 30 forms a complex of anterior and posterior parts with further medial and lateral divisions. (6) Area 29b has two divisions and occupies substantially more volume than in rat. (7) Area 29a begins with a subsplenial component and extends relatively further caudal than in rat. As similar areal designations are often used among species, direct comparisons were made of rabbit areas with those in rat and monkey. The dichotomy of MCC is of particular interest to studies of pain as anterior MCC is most frequently activated in human acute pain studies and the rabbit can be used to study this subregion. Finally, the area 30 complex is not primarily dysgranular as in rat and is more differentiated than in any other mammal including human. The large and highly differentiated rabbit cingulate cortex provides a unique model for assessing cingulate cortex, pain processing and RNA splicing functions.

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