152 research outputs found

    Using optically-pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum

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    KEY POINTS: The application of conventional cryogenic magnetoencephalography (MEG) to the study of cerebellar functions is highly limited because typical cryogenic sensor arrays are far away from the cerebellum and naturalistic movement is not allowed in the recording. A new generation of MEG using optically pumped magnetometers (OPMs) that can be worn on the head during movement has opened up an opportunity to image the cerebellar electrophysiological activity non-invasively. We use OPMs to record human cerebellar MEG signals elicited by air-puff stimulation to the eye. We demonstrate robust responses in the cerebellum. OPMs pave the way for studying the neurophysiology of the human cerebellum. ABSTRACT: We test the feasibility of an optically pumped magnetometer-based magnetoencephalographic (OP-MEG) system for the measurement of human cerebellar activity. This is to our knowledge the first study investigating the human cerebellar electrophysiology using optically pumped magnetometers. As a proof of principle, we use an air-puff stimulus to the eyeball in order to elicit cerebellar activity that is well characterized in non-human models. In three subjects, we observe an evoked component at approx. 50 ms post-stimulus, followed by a second component at approx. 85-115 ms post-stimulus. Source inversion localizes both components in the cerebellum, while control experiments exclude potential sources elsewhere. We also assess the induced oscillations, with time-frequency decompositions, and identify additional sources in the occipital lobe, a region expected to be active in our paradigm, and in the neck muscles. Neither of these contributes to the stimulus-evoked responses at 50-115 ms. We conclude that OP-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum

    Blinking and the Brain - Pathways and Pathology

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    Objective Measures of Emotion Related to Brand Attitude: A New Way to Quantify Emotion-Related Aspects Relevant to Marketing

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    With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted

    Blinking and the Brain - Pathways and Pathology

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    An investigation of the integrity of two components of the cerebellar neurocircuitry involved in classical eyeblink conditioning in children prenatally exposed to alcohol: a magnetic resonance spectroscopy and functional magnetic resonance imaging study

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    Includes bibliographical references.Impairment in classical eyeblink conditioning (EBC) has previously been reported in children with fetal alcohol spectrum disorders (FASD) (Jacobson et al., 2008). The deep cerebellar nuclei and cerebellar cortex are critical elements of the cerebellar-brainstem circuitry that mediates EBC (Green et al., 2002a; Yeo and Hardiman, 1992; Perret et al., 1993). In this study, we used magnetic resonance spectroscopy (MRS) and functional MRI (fMRI) to assess the effects of prenatal alcohol exposure on brain metabolism in the cerebellar deep nuclei and brain function in the cerebellar cortex, respectively. We found that higher levels of prenatal alcohol exposure were associated with lower levels of both N-Acetylaspartate (NAA) and choline-containing metabolites, and with higher levels of glutamate plus glutamine (Glx), suggesting a disruption of the glutamate-glutamine cycling involved in glutamatergic excitatory neurotransmission. Since the interpositus nucleus is one of the most crucial structures in the acquisition of the EBC response, abnormal metabolism in this region could be responsible for altered synaptic plasticity in children with FASD. Of the four cerebellar regions that were identified as being activated more by control children during rhythmic vs. non-rhythmic finger tapping, smaller differences in BOLD (blood oxygenation level dependent) activation were observed in children with FASD in two, namely vermis IV-V and right Crus I. Increasing levels of prenatal alcohol exposure were, however, associated with smaller differences in activation in all four regions, all of which have previously been linked to timed responses. In the paced/unpaced finger tapping fMRI study, we found four regions where increased BOLD activation during unpaced tapping compared to rest was associated with improved ability to maintain rhythm as evidenced by lower intertapping variability - right VIIIa and b, left VIIIa and right VI. These regions have previously been implicated in motor control with additional evidence of timing in lobule VI. In three of the regions, all except right VIIIa, increasing alcohol exposure was related to smaller increases in activation during unpaced tapping, with the strongest relations seen in the dosage dependent variable. Interestingly, the location of the activation in right VI is similar to a region that has been implicated in studies of EBC (Blaxton et al., 1996; Cheng et al., 2008). Our results point to altered metabolic levels in the deep nuclei and reduced functioning of several cerebellar cortical regions in children with FASD, highlighting the extensive damage caused by prenatal alcohol exposure. Although we did not find associations of EBC performance with either metabolite levels or activity in these regions, suggesting that damage to these areas are not primarily responsible for the observed EBC deficit, the extent of this damage could play a role in the impaired EBC performance seen in these children

    Eyeblink Conditioning in Schizophrenia: A Critical Review

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    There is accruing evidence of cerebellar abnormalities in schizophrenia. The theory of cognitive dysmetria considers cerebellar dysfunction a key component of schizophrenia. Delay eyeblink conditioning (EBC), a cerebellar-dependent translational probe, is a behavioral index of cerebellar integrity. The circuitry underlying EBC has been well characterized by non-human animal research, revealing the cerebellum as the essential circuitry for the associative learning instantiated by this task. However, there have been persistent inconsistencies in EBC findings in schizophrenia. This article thoroughly reviews published studies investigating EBC in schizophrenia, with an emphasis on possible effects of antipsychotic medication and stimulus and analysis parameters on reports of EBC performance in schizophrenia. Results indicate a consistent finding of impaired EBC performance in schizophrenia, as measured by decreased rates of conditioning, and that medication or study design confounds do not account for this impairment. Results are discussed within the context of theoretical and neurochemical models of schizophrenia

    Functional properties of hippocampal circuitry

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    Programa de Doctorado en NeurocienciasEl aprendizaje es el mecanismo mediante el cual el sistema nervioso se adapta a los cambios en las condiciones ambientales y sociales mediante la generación de nuevos comportamientos y/o actividades mentales. Estas habilidades motoras y cognitivas adquiridas se almacenan en diversas formas de memoria (declarativas, procedimentales, etc.) en función del tipo de aprendizaje adquirido. Los aprendizajes más frecuentemente abordados de forma experimental se suelen clasificar en no asociativos (como la habituación y la sensibilización) y asociativos (principalmente los condicionamientos clásico e instrumental). La participación de las estructuras nerviosas depende del tipo de aprendizaje y memoria que se considere. Uno de los modelos experimentales más utilizados en el estudio de los mecanismos neuronales que subyacen al aprendizaje asociativo es el condicionamiento clásico del reflejo corneal, el cual se ha estudiado en muy diversas especies de mamíferos, incluida la especie humana. El condicionamiento clásico del reflejo corneal se induce habitualmente mediante la presentación de un estímulo neutro (el estímulo incondicionado) incapaz de inducir per se una respuesta palpebral (por ejemplo, un tono de una determinada frecuencia) que se sigue de un soplo de aire aplicado a la córnea (el estímulo incondicionado) que sí es capaz de inducir una respuesta refleja palpebral. La presentación conjunta y repetida de ambos estímulos termina por producir la aparición de una respuesta condicionada cada vez que se presenta el estímulo condicionado (esto es, el tono). Existen dos paradigmas básicos de condicionamiento clásico o pavloviano: el paradigma de demora y el paradigma de traza. En el primer caso, el estímulo condicionado está presente hasta que se aplica el estímulo incondicionado y ambos terminan de forma simultánea. En el segundo caso, el estímulo condicionado termina antes de la presentación del estímulo incondicionado por lo que existe un intervalo de tiempo (la traza) separando ambos estímulos. Es tradicional asumir que ambos tipos de condicionamiento se generan en estructuras cerebrales diferente, el de demora en el cerebelo y el de traza en el hipocampo. Sin embargo estudios previos de nuestro grupo han mostrado que ambas estructuras participan en ambos paradigmas de condicionamiento, así como otras muchas como las cortezas sensorial, motora y prefrontal, determinados núcleos talámicos y otras estructuras subcorticales como el complejo amigdalino y el núcleo rojo. En la propuesta de Tesis Doctoral se estudiarán los cambios funcionales que ocurren en seis sinapsis diferentes del circuito intrínseco del hipocampo y de las vías aferentes al mismo durante el condicionamiento de traza en el conejo despierto. Los animales experimentales se ssometerán a condicionamientos de demora y de traza, pero también se estudiará el efecto sobre dichas sinapsis hipocampales del contexto en el que se sitúa al animal durante la prueba de aprendizaje, así como los cambios que producen la presentación no emparejada de los estímulos condicionado e incondicionado (es decir, durante un pseudocondicionamiento). En una segunda serie experimental se estudiará el efecto sobre este tipo de aprendizaje asociativo de la desconexión funcional transitoria del giro dentado. Esta desconexión funcional transitoria se realizará mediante la inyección local controlada de un adenovirus portador del ADN necesario para la síntesis controlada del fragmento C de la toxina tetánica. La síntesis de esta neurotoxina se activará mediante la inyección de doxiciclina. La expresión del fragmento C de la toxina tetánica en las neuronas del giro dentado produjo su desconexión funcional de sus neuronas blanco, esto es, de las células piramidales de CA3. Con este modelo experimental se espera demostrar que la expresión de respuestas palpebrales condicionadas en conejos disminuye significativamente o, incluso, desaparece durante el periodo en que existe una desconexión funcional entre el giro dentado y las neuronas piramidales de CA3. También se estudiará si las memorias desaparecidas durante el periodo de desconexión funcional reaparecen en el momento en que termine la expresión de la toxina tetánica en las neuronas del giro dentado. De confirmarse estos resultados, se podría sugerir que tal vez las memorias asociadas a este tipo de aprendizaje asociativo no se almacenan, como se ha supuesto hasta el momento presente, en la ultraestructura y composición molecular de los contactos sinápticos dentro del circuito intrínseco del hipocampo.Universidad Pablo de Olavide. Departamento de Fisiología, Anatomía y Biología Celula

    Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task

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    The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework

    Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow

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    An optical flow gradient algorithm was applied to spontaneously forming net- works of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e. a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling pat- terns. We begin by briefly reviewing the mathematics of the optical flow algorithm, and then describe how to solve for the displacement vectors and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the algorithm for capturing different types of spatiotemporal calcium activity. We discuss the imaging requirements, parameter selection and threshold selection for reliable measurements, and offer perspectives on uses of the vector data.Comment: 23 pages, 5 figures. Peer reviewed accepted version in press in Annals of Biomedical Engineerin
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