RESUMO
Visual perception is abnormal in psychotic disorders such as schizophrenia. In addition to hallucinations, laboratory tests show differences in fundamental visual processes including contrast sensitivity, center-surround interactions, and perceptual organization. A number of hypotheses have been proposed to explain visual dysfunction in psychotic disorders, including an imbalance between excitation and inhibition. However, the precise neural basis of abnormal visual perception in people with psychotic psychopathology (PwPP) remains unknown. Here, we describe the behavioral and 7 tesla MRI methods we used to interrogate visual neurophysiology in PwPP as part of the Psychosis Human Connectome Project (HCP). In addition to PwPP (n = 66) and healthy controls (n = 43), we also recruited first-degree biological relatives (n = 44) in order to examine the role of genetic liability for psychosis in visual perception. Our visual tasks were designed to assess fundamental visual processes in PwPP, whereas MR spectroscopy enabled us to examine neurochemistry, including excitatory and inhibitory markers. We show that it is feasible to collect high-quality data across multiple psychophysical, functional MRI, and MR spectroscopy experiments with a sizable number of participants at a single research site. These data, in addition to those from our previously described 3 tesla experiments, will be made publicly available in order to facilitate further investigations by other research groups. By combining visual neuroscience techniques and HCP brain imaging methods, our experiments offer new opportunities to investigate the neural basis of abnormal visual perception in PwPP.
Assuntos
Transtorno Bipolar , Conectoma , Transtornos Psicóticos , Esquizofrenia , Humanos , Conectoma/métodos , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Intrathecal application of morphine is among the most powerful methods used to treat severe chronic pain. However, this approach commonly produces itch sufficiently severe that patients are forced to choose between relief of pain or itch. The neuronal populations responsible for processing and transmitting information underlying itch caused by intrathecal application of morphine have not been identified and characterized. We describe two populations of antidromically identified trigeminothalamic tract (VTT) neurons in anesthetized rats that are differentially affected by morphine and explain several aspects of opioid-induced itch and analgesia. We found that intrathecal application of morphine increased ongoing activity of itch-responsive VTT neurons. In addition, intrathecal application of morphine increased responses to pruritogens injected into the skin and greatly heightened responses to innocuous mechanical stimuli. In contrast, the ongoing activity and responses to noxious pinches in nociceptive VTT neurons were frequently inhibited by the same dose of morphine. These results reveal that i.t. application of morphine affects specific subpopulations of VTT neurons in ways that may produce itch, hyperknesis, alloknesis, and analgesia.
Assuntos
Analgésicos Opioides/efeitos adversos , Morfina/efeitos adversos , Vias Neurais/efeitos dos fármacos , Dor/tratamento farmacológico , Prurido/induzido quimicamente , Tálamo/citologia , Núcleos do Trigêmeo/citologia , Potenciais de Ação/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Animais , Antirreumáticos/farmacologia , Cloroquina/farmacologia , Estimulação Elétrica , Histamina/farmacologia , Injeções Espinhais/métodos , Masculino , Morfina/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Serotonina/farmacologia , Estimulação Química , Tálamo/lesões , Núcleos do Trigêmeo/lesõesRESUMO
Rodent models of facial itch and pain provide a valuable tool for distinguishing between behaviors related to each sensation. In rats, pruritogens applied to the face elicit scratching using the hindlimb while algogens elicit wiping using the forelimb. We wished to determine the role of trigeminothalamic tract (VTT) neurons in carrying information regarding facial itch and pain to the forebrain. We have characterized responses to facially applied pruritogens (serotonin, BAM8-22, chloroquine, histamine, capsaicin, and cowhage) and noxious stimuli in 104 VTT neurons recorded from anesthetized rats. Each VTT neuron had a mechanically sensitive cutaneous receptive field on the ipsilateral face. All pruriceptive VTT neurons also responded to noxious mechanical and/or thermal stimulation. Over half of VTT neurons responsive to noxious stimuli also responded to at least one pruritogen. Each tested pruritogen, with the exception of cowhage, produced an increase in discharge rate in a subset of VTT neurons. The response to each pruritogen was characterized, including maximum discharge rate, response duration, and spike timing dynamics. Pruriceptive VTT neurons were recorded from throughout superficial and deep layers of the spinal trigeminal nucleus and were shown to project via antidromic mapping to the ventroposterior medial nucleus or posterior thalamic nuclei. These results indicate that pruriceptive VTT neurons are a subset of polymodal nociceptive VTT neurons and characterize a system conducive to future experiments regarding the similarities and differences between facial itch and pain.
Assuntos
Neurônios/fisiologia , Dor/fisiopatologia , Prurido/induzido quimicamente , Tálamo/fisiologia , Núcleo Espinal do Trigêmeo/fisiologia , Animais , Masculino , Vias Neurais/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception has been observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in the visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in the visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels, specifically disorganization, across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.
Assuntos
Transtornos Psicóticos , Córtex Visual , Percepção Visual , Humanos , Masculino , Feminino , Adulto , Transtornos Psicóticos/fisiopatologia , Córtex Visual/fisiopatologia , Percepção Visual/fisiologia , Adulto Jovem , Percepção de Movimento/fisiologia , Espectroscopia de Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
Contour integration, the process of joining spatially separated elements into a single unified line, has consistently been found to be impaired in schizophrenia. Recent work suggests that this deficit could be associated with psychotic symptomatology, rather than a specific diagnosis such as schizophrenia. Examining a transdiagnostic sample of participants with psychotic psychopathology, we obtained quantitative indices of contour perception in a psychophysical behavioral task. We found impaired contour discrimination performance among people with psychotic psychopathology (PwPP, n = 62) compared to healthy controls (n = 34) and biological relatives of PwPP (n = 44). Participants with schizophrenia (n = 31) showed impaired task performance compared to participants with bipolar disorder (n = 18). We also measured responses during an analogous task using ultra-high field (7T) functional MRI and found higher responses in the lateral occipital cortex of PwPP compared to controls. Using task-based functional connectivity analyses, we observed abnormal connectivity between visual brain areas during contour perception among PwPP. These connectivity differences only emerged when participants had to distinguish the contour object from background distractors, suggesting that a failure to suppress noise elements relative to contour elements may underlie impaired contour processing in PwPP. Our results are consistent with impaired contour integration in psychotic psychopathology, and especially schizophrenia, that is related to cognitive dysfunction, and may be linked to impaired functional connectivity across visual regions.
RESUMO
Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception is observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.
RESUMO
Itch of peripheral origin requires information transfer from the spinal cord to the brain for perception. Here, primate spinothalamic tract (STT) neurons from lumbar spinal cord were functionally characterized by in vivo electrophysiology to determine the role of these cells in the transmission of pruriceptive information. One hundred eleven STT neurons were identified by antidromic stimulation and then recorded while histamine and cowhage (a nonhistaminergic pruritogen) were sequentially applied to the cutaneous receptive field of each cell. Twenty percent of STT neurons responded to histamine, 13% responded to cowhage, and 2% responded to both. All pruriceptive STT neurons were mechanically sensitive and additionally responded to heat, intradermal capsaicin, or both. STT neurons located in the superficial dorsal horn responded with greater discharge and longer duration to pruritogens than STT neurons located in the deep dorsal horn. Pruriceptive STT neurons discharged in a bursting pattern in response to the activating pruritogen and to capsaicin. Microantidromic mapping was used to determine the zone of termination for pruriceptive STT axons within the thalamus. Axons from histamine-responsive and cowhage-responsive STT neurons terminated in several thalamic nuclei including the ventral posterior lateral, ventral posterior inferior, and posterior nuclei. Axons from cowhage-responsive neurons were additionally found to terminate in the suprageniculate and medial geniculate nuclei. Histamine-responsive STT neurons were sensitized to gentle stroking of the receptive field after the response to histamine, suggesting a spinal mechanism for alloknesis. The results show that pruriceptive information is encoded by polymodal STT neurons in histaminergic or nonhistaminergic pathways and transmitted to the ventrobasal complex and posterior thalamus in primates.
Assuntos
Axônios/fisiologia , Células do Corno Posterior/fisiopatologia , Prurido/fisiopatologia , Tratos Espinotalâmicos/fisiopatologia , Percepção do Tato/fisiologia , Animais , Mapeamento Encefálico , Capsaicina/farmacologia , Eletroencefalografia , Histamina/farmacologia , Macaca fascicularis , Mucuna/toxicidade , Nociceptividade , Extratos Vegetais/farmacologia , Células do Corno Posterior/citologia , Células do Corno Posterior/efeitos dos fármacos , Prurido/induzido quimicamente , Tratos Espinotalâmicos/citologia , Tratos Espinotalâmicos/efeitos dos fármacos , Núcleos Talâmicos/citologia , Núcleos Talâmicos/fisiopatologia , TatoRESUMO
Previous research has shown that corticostriatal N-methyl-D-aspartate receptor (NMDAR) activation is necessary for operant learning. NMDAR activation induces plasticity-related intracellular signaling processes leading to gene expression, which are hypothesized to be important steps in codifying the content of learning. Operant learning induces immediate early gene (IEG) expression in key corticostriatal structures, namely the dorsomedial striatum (DMS), the orbitofrontal (OFC), and anterior cingulate cortices (ACC). Both the ACC and OFC send glutamatergic projections to the DMS, which is a crucial site for operant behavior. However, the role of NMDAR activation in these corticostriatal regions in operant learning is unknown. To test this hypothesis, the NMDA antagonist AP-5 (1 microg/0.5 microl) or saline was bilaterally microinjected into the ACC, OFC, and DMS of food-deprived rats just prior to operant learning sessions. NMDAR antagonism in the ACC and DMS impaired the acquisition of lever pressing for sucrose pellets but had no effect on lever pressing once learned. NMDAR blockade in OFC did not significantly impair operant learning, suggesting that NMDAR activation in operant learning is site-specific. These data extend our understanding of the role of NMDA receptors in operant learning and behavior throughout an extended corticostriatal network.