RESUMEN
OBJECTIVE: The medial forebrain bundle (MFB) is a novel promising deep brain stimulation (DBS) target in severe affective disorders that courses through the subthalamic region according to tractography studies. Its potential therapeutic role arose in connection with the development of hypomania during stimulation of the subthalamic nucleus (STN) in Parkinson's disease, offering an alternative explanation for the occurrence of this side effect. However, until now its course exclusively described by tractography had not yet been confirmed by any anatomical method. The aim of this study was to fill this gap as well as to provide a detailed description of the fiber tracts surrounding the STN to facilitate a better understanding of the background of side effects occurring during STN DBS. METHODS: Ten human cadaveric brains (20 hemispheres) and 100 healthy subjects (200 hemispheres) from the S500 Release of the Human Connectome Project were involved in this study. Nineteen hemispheres were dissected according to Klingler's method. One additional hemisphere was prepared for histological examinations to validate the macroscopical results and stained with neurofibril silver impregnation according to Krutsay. The authors also aimed to reconstruct the MFB using tractography and correlated the results with their dissections and histological findings. RESULTS: The white matter connections coursing through the subthalamic region were successfully dissected. The ansa lenticularis, lenticular fasciculus, thalamic fasciculus, ipsi- and contralateral cerebellar fibers, and medial lemniscus were revealed as closely related fiber tracts to the STN. However, the existence of a distinct fiber bundle corresponding to the MFB described by tractography could not be identified. Using tractography, the authors showed that the depiction of the streamlines representing the MFB was also strongly dependent on the threshold parameters. CONCLUSIONS: According to this study's findings, the streamlines of the MFB described by tractography arise from the limitations of the diffusion-weighted MRI fiber tracking method and actually correspond to subthalamic fiber bundles, especially the ansa lenticularis and lenticular fasciculus, which erroneously continue in the anterior limb of the internal capsule, toward the prefrontal cortex.
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Haz Prosencefálico Medial , Núcleo Subtalámico , Humanos , Haz Prosencefálico Medial/anatomía & histología , Haz Prosencefálico Medial/diagnóstico por imagen , Núcleo Subtalámico/anatomía & histología , Núcleo Subtalámico/diagnóstico por imagen , Masculino , Femenino , Cadáver , Adulto , Persona de Mediana Edad , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Estimulación Encefálica Profunda/métodos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/diagnóstico por imagen , Anciano , Imagen de Difusión TensoraRESUMEN
The amygdaloid body is a limbic nuclear complex characterized by connections with the thalamus, the brainstem and the neocortex. The recent advances in functional neurosurgery regarding the treatment of refractory epilepsy and several neuropsychiatric disorders renewed the interest in the study of its functional Neuroanatomy. In this scenario, we felt that a morphological study focused on the amygdaloid body and its connections could improve the understanding of the possible implications in functional neurosurgery. With this purpose we performed a morfological study using nine formalin-fixed human hemispheres dissected under microscopic magnification by using the fiber dissection technique originally described by Klingler. In our results the amygdaloid body presents two divergent projection systems named dorsal and ventral amygdalofugal pathways connecting the nuclear complex with the septum and the hypothalamus. Furthermore, the amygdaloid body is connected with the hippocampus through the amygdalo-hippocampal bundle, with the anterolateral temporal cortex through the amygdalo-temporalis fascicle, the anterior commissure and the temporo-pulvinar bundle of Arnold, with the insular cortex through the lateral olfactory stria, with the ambiens gyrus, the para-hippocampal gyrus and the basal forebrain through the cingulum, and with the frontal cortex through the uncinate fascicle. Finally, the amygdaloid body is connected with the brainstem through the medial forebrain bundle. Our description of the topographic anatomy of the amygdaloid body and its connections, hopefully represents a useful tool for clinicians and scientists, both in the scope of application and speculation.
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Amígdala del Cerebelo/anatomía & histología , Cerebro/anatomía & histología , Vías Nerviosas/anatomía & histología , Sustancia Blanca/anatomía & histología , Anciano , Humanos , Hipotálamo/anatomía & histología , Haz Prosencefálico Medial/anatomía & histología , Persona de Mediana EdadRESUMEN
The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05 ± 5.7 years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FAt ), radial diffusivity (RDt ), and axial diffusivity (ADt ). Lower ratings of interindividual pain intensity correlated with higher FAt and lower RDt of the MFB. As changes in FAt and RDt may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.
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Imagen de Difusión Tensora/métodos , Haz Prosencefálico Medial/anatomía & histología , Nocicepción/fisiología , Adulto , Variación Biológica Poblacional , Humanos , Masculino , Haz Prosencefálico Medial/diagnóstico por imagen , Adulto JovenRESUMEN
In humans, sensorimotor cortical areas receive relevant dopaminergic innervation-although an anatomic description of the underlying fiber projections is lacking so far. In general, dopaminergic projections towards the cortex originate within the ventral tegmental area (VTA) and are organized in a meso-cortico-limbic system. Using a DTI-based global tractography approach, we recently characterized the superolateral branch of the medial forebrain bundle (slMFB), a prominent pathway providing dopaminergic (and other transmitters) innervation for the pre-frontal cortex (Coenen et al., NeuroImage Clin 18:770-783, 2018). To define the connections between VTA and sensory-motor cortical fields that should contain dopaminergic fibers, we use the slMFB as a key structure to lead our fiber selection procedure: using a similar tracking-seed and tractography algorithm, we describe a dorsal extension of this slMFB that covers sensorimotor fields that are dorsally appended to pre-frontal cortical areas. This "motorMFB", that connects the VTA to sensorimotor cortical fields, can be further segregated into three sub-bundles with a seed-based fiber-selection strategy: A PFC bundle that is attendant to the pre-frontal cortex, passes the lateral VTA, runs through the border zone between the posterior and lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus. An MB bundle that is attendant to the mammillary bodies runs directly through the medial VTA, passes the lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus as well as the supplementary motor area (SMA) and the dorsal premotor cortex (dPMC). Finally, a BC bundle that is attendant to the brainstem and cerebellum runs through the lateral VTA, passes the anterior ventral thalamic nucleus, and covers the SMA, pre-SMA, and the dPMC. We, furthermore, included a fiber tracking of the well-defined dentato-rubro-thalamic tract (DRT) that is known to lie in close proximity with respect to fiber orientation and projection areas. As expected, the tract is characterized by a decussation at the ponto-mesencephal level and a projection covering the superior-frontal and precentral cortex. In addition to the physiological role of these particular bundles, the physiological and pathophysiological impact of dopaminergic signaling within sensorimotor cortical fields becomes discussed. However, some limitations have to be taken into account in consequence of the method: the transmitter content, the directionality, and the occurrence of interposed synaptic contacts cannot be specified.
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Neuronas Dopaminérgicas , Corteza Sensoriomotora/anatomía & histología , Área Tegmental Ventral/anatomía & histología , Adulto , Encéfalo/anatomía & histología , Conectoma/métodos , Imagen de Difusión por Resonancia Magnética , Humanos , Masculino , Haz Prosencefálico Medial/anatomía & histología , Vías Nerviosas/anatomía & histologíaRESUMEN
Brain micro-electrical stimulation and its applications are among the most important issues in the field of brain science and neurophysiology. Deep brain stimulation techniques have been used in different theraputic or alternative medicine applications including chronic pain control, tremor control, Parkinson's disease control and depression control. Recently, brain electrical stimulation has been used for tele-control and navigation of small animals such as rodents and birds. Electrical stimulation of the medial forebrain bundle (MFB) area has been reported to induce a pleasure sensation in rat which can be used as a virtual reward for rat navigation. In all cases of electrical stimulation, the temporal adaptation may deteriorate the instantaneous effects of the stimulation. Here, we study the adaptation effects of the MFB electrical stimulation in rats. The animals are taught to press a key in an operant conditioning chamber to self-stimulate the MFB region and receive a virtual reward for each key press. Based on the number of key presses, and statistical analyses the effects of adaptation on MFB stimulation is evaluated. The stimulation frequency were changed from 100 to 400 Hz, the amplitude were changed from 50 to 170 µA and the pulse-width were changed from 180 to 2000 µs. In the frequency of 250 Hz the adaptation effect were observed. The amplitude did not show a significant effect on MFB adaptation. For all values of pulse-widths, the adaptation occurred over two consecutive days, meaning that the number of key presses on the second day was less than the first day.
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Adaptación Fisiológica , Estimulación Encefálica Profunda/métodos , Haz Prosencefálico Medial/fisiología , Autoestimulación/fisiología , Animales , Condicionamiento Operante/fisiología , Estimulación Eléctrica , Electrodos Implantados , Masculino , Haz Prosencefálico Medial/anatomía & histología , Ratas , Ratas Wistar , Recompensa , Técnicas Estereotáxicas , Factores de TiempoRESUMEN
Introduction: Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human medial forebrain bundle (MFB) and the connectivity of the ventral tegmental area (VTA). A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB) - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.). This work aims at a normative description of the human MFB (and more detailed the slMFB) anatomy with respect to distant prefrontal connections and microstructural features. Methods and material: Healthy subjects (nâ¯=â¯55; mean age⯱â¯SD, 40⯱â¯10â¯years; 32 females) underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments) of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB. Results: The MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right) and 98% (left) of the total relative fiber counts of the slMFB. Discussion: The anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and cortical prefrontal regions - but not to emotion-related regions on the medial cortical surface - realized via the superolateral branch of the MFB. Local tractography approaches appear to be inferior in showing these far-reaching projections. Since these local approaches are typically used for surgical targeting of DBS procedures, the here established detailed map might - as a normative template - guide future efforts to target deep brain stimulation of the slMFB in depression and other disorders related to dysfunction of reward and reward-associated learning.
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Lóbulo Frontal/anatomía & histología , Haz Prosencefálico Medial/anatomía & histología , Corteza Prefrontal/anatomía & histología , Área Tegmental Ventral/anatomía & histología , Adulto , Estimulación Encefálica Profunda/métodos , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Haz Prosencefálico Medial/fisiología , Persona de Mediana EdadRESUMEN
Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.
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Conectoma/métodos , Sistema Límbico/fisiología , Haz Prosencefálico Medial/fisiología , Adulto , Amígdala del Cerebelo/anatomía & histología , Amígdala del Cerebelo/fisiología , Encéfalo/anatomía & histología , Encéfalo/fisiología , Tronco Encefálico/anatomía & histología , Tronco Encefálico/fisiología , Imagen de Difusión Tensora/métodos , Epilepsia del Lóbulo Temporal/patología , Femenino , Hipocampo/anatomía & histología , Hipocampo/fisiología , Humanos , Sistema Límbico/anatomía & histología , Imagen por Resonancia Magnética , Masculino , Haz Prosencefálico Medial/anatomía & histología , Vías Nerviosas , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/fisiologíaRESUMEN
BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.
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Dolor Crónico/cirugía , Estimulación Encefálica Profunda/métodos , Imagen de Difusión Tensora/métodos , Giro del Cíngulo/anatomía & histología , Giro del Cíngulo/cirugía , Procedimientos Neuroquirúrgicos/métodos , Electrodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Haz Prosencefálico Medial/anatomía & histología , Haz Prosencefálico Medial/cirugía , Persona de Mediana Edad , Dimensión del Dolor , Tálamo/anatomía & histología , Tálamo/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Images obtained through ultra-high-field 7.0-tesla magnetic resonance imaging with track-density imaging provide clear, high-resolution tractograms that have been hitherto unavailable, especially in deep brain areas such as the limbic and thalamic regions. This study is a largely pictorial description of the deep fiber tracts in the brain using track-density images obtained with 7.0-T diffusion-weighted imaging. METHODS: To identify the fiber tracts, we selected 3 sets of tractograms and performed interaxis correlation between them. These tractograms offered an opportunity to extract new information in areas that have previously been difficult to examine using either in vivo or in vitro human brain tractography. RESULTS: With this new technique, we identified 4 fiber tracts that have not previously been directly visualized in vivo: septum pellucidum tract, anterior thalamic radiation, superolateral medial forebrain bundle, and inferomedial forebrain bundle. CONCLUSIONS: We present the high-resolution images as a tool for researchers and clinicians working with neurodegenerative and psychiatric diseases, such as Parkinson disease, Alzheimer disease, and depression, in which the accurate positioning of deep brain stimulation is essential for precise targeting of nuclei and fiber tracts.
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Núcleos Talámicos Anteriores/anatomía & histología , Imagen de Difusión Tensora/métodos , Sistema Límbico/anatomía & histología , Haz Prosencefálico Medial/anatomía & histología , Fibras Nerviosas/ultraestructura , Tabique Pelúcido/anatomía & histología , Tálamo/anatomía & histología , Adulto , Humanos , Procesamiento de Imagen Asistido por Computador , MasculinoAsunto(s)
Núcleos Talámicos Anteriores/anatomía & histología , Imagen de Difusión Tensora/métodos , Sistema Límbico/anatomía & histología , Haz Prosencefálico Medial/anatomía & histología , Fibras Nerviosas/ultraestructura , Tabique Pelúcido/anatomía & histología , Tálamo/anatomía & histología , Humanos , MasculinoRESUMEN
The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.
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Afecto/fisiología , Mapeo Encefálico/psicología , Depresión/fisiopatología , Lóbulo Frontal/fisiología , Cápsula Interna/fisiología , Haz Prosencefálico Medial/anatomía & histología , Haz Prosencefálico Medial/fisiología , Tálamo/anatomía & histología , Adulto , Anciano , Animales , Mapeo Encefálico/métodos , Imagen de Difusión Tensora/métodos , Imagen de Difusión Tensora/psicología , Femenino , Lóbulo Frontal/anatomía & histología , Humanos , Cápsula Interna/anatomía & histología , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Vías Nerviosas/fisiología , Técnicas de Trazados de Vías Neuroanatómicas/métodos , Tálamo/fisiologíaRESUMEN
Major depression (MD) might be conceptualized as pathological under-arousal of positive affective systems as parts of a network of brain regions assessing, reconciling and storing emotional stimuli versus an over-arousal of parts of the same network promoting separation-distress/GRIEF. In this context depression can be explained as an emotional pain state that is the result of a disregulation of several sub-systems that under physiological conditions are concerned with bodily or emotional homeostasis of the human organism in a social context. Physiologically, homeostasis is maintained by influences of the SEEKING system represented - amongst others - by the medial forebrain bundle (MFB). Neuroimaging studies show that the MFB has a proven access to the GRIEF/Sadness system. A functional decoupling of these systems with a dysfunctional GRIEF pathway might result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles as opponents in maintenance of emotional homeostasis. Chronic electrical modulation of the reward SEEKING pathways with deep brain stimulation might show anti-depressive effects in humans suffering from MD by re-initiating an emotional equilibrium (of higher or lower activity) between these opposing systems.
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Afecto/fisiología , Trastorno Depresivo/terapia , Haz Prosencefálico Medial/fisiología , Manejo del Dolor/métodos , Estimulación Encefálica Profunda , Trastorno Depresivo/psicología , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/terapia , Imagen de Difusión Tensora , Campos Electromagnéticos , Pesar , Humanos , Procesamiento de Imagen Asistido por Computador , Haz Prosencefálico Medial/anatomía & histología , Motivación , Núcleo Accumbens/fisiología , Recompensa , Especificidad de la EspecieRESUMEN
The medial prefrontal cortex (MPFC) is involved in cardiovascular control. MPFC electrical stimulation has been reported to cause depressor and bradycardic responses in anesthetized rats. Although the pathway involved is yet unknown, there is evidence indicating the existence of a relay in the lateral hypothalamus (LH). The medial forebrain bundle (MFB) that courses in the lateral portion of the LH carries the vast majority of telencephalic afferent as well efferent projections, including those from the MPFC. To evaluate if the hypotensive pathway originating in the MPFC courses the MFB, we studied the effect of coronal or sagittal knife cuts through the LH and other brain areas on the cardiovascular responses to MPFC electrical stimulation. Knife cuts were performed using blades 1 to 6 mm wide. Results indicate that the neural pathway descending from the MFB decussates early in the vicinity of MPFC, crossing the midline within the corpus callosum and yielding two descending pathways that travel rostro-caudally in the lateral portion of the LH, within the MFB. The decussation was confirmed by histological analysis of brain sections processed after the injection of biotinilated dextran amine in the site of the stimulation in the MPFC. Because knife cuts through the LH ipsilateral had minimal effects on the cardiovascular responses and knife cuts performed contralateral to the stimulated MPFC had no effect on the response to MPFC stimulation, data indicate that the contralateral limb of the pathway may be only activated as an alternative pathway when the ipsilateral pathway is blocked.
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Vías Autónomas/fisiología , Fenómenos Fisiológicos Cardiovasculares , Diencéfalo/fisiología , Haz Prosencefálico Medial/fisiología , Corteza Prefrontal/fisiología , Animales , Vías Autónomas/anatomía & histología , Biotina/análogos & derivados , Mapeo Encefálico , Desnervación , Dextranos , Diencéfalo/anatomía & histología , Vías Eferentes/anatomía & histología , Vías Eferentes/fisiología , Estimulación Eléctrica , Lateralidad Funcional/fisiología , Área Hipotalámica Lateral/anatomía & histología , Área Hipotalámica Lateral/fisiología , Masculino , Haz Prosencefálico Medial/anatomía & histología , Corteza Prefrontal/anatomía & histología , Ratas , Ratas Wistar , Coloración y EtiquetadoRESUMEN
Behavioral adaptations of double-pulse methods--primarily collision and refractory period tests--have been employed to unveil the electrophysiological and anatomical characteristics of neural networks of known function. These paradigms are based on trade-off functions: a determination of different combinations of stimuli that yield the same behavioral output. A detailed explanation of the logic and methodology underlying these techniques is elaborated in this paper. The implementation of such approaches to the study of brain stimulation reward (BSR) has provided a means of discriminating between the neurons underlying this behavior from other cells activated by the stimulating electrode, endowing them with a particularly powerful scientific scope. An increasingly detailed portrait of the BSR substrate, both within and outside the medial forebrain bundle, has been emerging as a result of these investigations and is reviewed in this paper. Finally, the challenges associated with these paradigms are discussed and potential solutions as well as future experimental ventures proposed. Attention is drawn to the major contribution of these methods to our understanding of the neural pathways and characteristics underlying BSR.
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Mapeo Encefálico , Haz Prosencefálico Medial/fisiología , Recompensa , Autoestimulación/fisiología , Adaptación Fisiológica/fisiología , Animales , Conducta Animal , Estimulación Eléctrica/métodos , Haz Prosencefálico Medial/anatomía & histología , Conducción Nerviosa , Tiempo de Reacción , Periodo Refractario ElectrofisiológicoRESUMEN
The terminal arbors of dopaminergic projections in the nucleus accumbens (Acb) core degenerate more rapidly, completely and permanently in a variety of neurotoxic circumstances than do those in the medial shell. It is unknown if this always reflects purely losses of the distal parts of axons from the core (as proposed in methamphetamine intoxication), or whether, in some circumstances, the disproportionate loss of core axons may also stem from an intrinsic vulnerability to degeneration of core-projecting neuronal perikarya. Experiments described here addressed this issue in the following manner. Three days after Fluoro-Gold (FG), a retrogradely transported tracer, had been iontophoresed selectively into the core or medial shell of male Sprague-Dawley rats, each received an infusion of saline vehicle containing or lacking 6-hydroxydopamine (6-OHDA) in the ipsilateral medial forebrain bundle (MFB). Twenty-one days later the brains were processed to exhibit ventral mesencephalic neurons containing FG. Application of an unbiased sampling method revealed substantially greater losses of FG labeled neurons relative to controls in rats that had received 6-OHDA lesions and deposition of FG in the Acb core as compared to the medial shell. Of the few core-projecting neurons that remained in the ventral mesencephalon after these lesions, 54% did not co-localize tyrosine hydroxylase immunoreactivity (TH-ir) and, thus, were not expected to degenerate. The capacity to selectively remove core-projecting dopaminergic neurons may be useful in the determination of molecular correlates of vulnerability and resistance to neurotoxicity and to possibly test the role of the core in reinforcement paradigms.
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Haz Prosencefálico Medial/efectos de los fármacos , Mesencéfalo/efectos de los fármacos , Neuronas/metabolismo , Núcleo Accumbens/efectos de los fármacos , Oxidopamina/toxicidad , Adrenérgicos/toxicidad , Animales , Recuento de Células , Colorantes Fluorescentes/metabolismo , Inmunohistoquímica , Masculino , Haz Prosencefálico Medial/anatomía & histología , Haz Prosencefálico Medial/metabolismo , Mesencéfalo/citología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/metabolismo , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Estilbamidinas/metabolismo , Factores de Tiempo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Previous work with psychophysically-based collision methods and pharmacological manipulation suggests a role in medial forebrain bundle (MFB) self-stimulation for neurons lying along the midline between the cerebral hemispheres, in the mid- and/or hindbrain. Also, recently-proposed models of the anatomical substrate for medial forebrain bundle stimulation reward suggest that at least part of the directly-activated axons of this substrate arise from mid- and/or hindbrain somata, bifurcate, and send bilateral projections to the MFB of each hemisphere. Branches of these axons are thought to cross the midline at some point near the ventral tegmental area. This study examines the effects on MFB stimulation reward of lesioning midbrain structures that lie along the midline between hemispheres. In 13 rats, lesions of the median raphe, the decussation of the superior cerebellar peduncle, or the interpeduncular nucleus were all ineffective in altering the stimulation frequency required to maintain half-maximal levels of operant responding for stimulation reward. These results are discussed in terms of implications for recent models of the anatomical substrate for brain stimulation reward.
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Haz Prosencefálico Medial/fisiología , Mesencéfalo/fisiología , Autoestimulación/fisiología , Animales , Condicionamiento Operante/fisiología , Área Hipotalámica Lateral/fisiología , Masculino , Haz Prosencefálico Medial/anatomía & histología , Mesencéfalo/anatomía & histología , Tractos Piramidales/fisiología , Núcleos del Rafe/fisiología , Ratas , Ratas Long-Evans , Recompensa , Área Tegmental Ventral/fisiologíaRESUMEN
Electrolytic lesions of the anterior medial forebrain bundle (MFB) have been shown to attenuate the rewarding impact of stimulating more caudal MFB sites. In the present study, excitotoxic lesions were employed to determine the relative contribution of somata or fibers of passage contributing to that effect. Changes in reward efficacy were inferred, at three currents, from lateral displacements of the curve relating the rate of responding to the number of stimulation pulses per train. After baseline data were collected from stimulation sites in the lateral hypothalamus (LH) and the ventral tegmental area (VTA), 70 nmol of N-methyl-D-aspartic acid was injected via cannulae aimed at basal forebrain sites. Three subjects were injected with vehicle and served as controls. In 5 out of 15 cases, lesions encompassing the lateral preoptic area, anterior LH, and substantia innominata resulted in long-lasting, large increases (0.2-0.47 log10 units) in the number of pulses required to maintain half-maximal rates of self-stimulation for low currents delivered via the LH electrode; smaller increases (0.08-0.33 log10 units) were noted at moderate and high currents. Seven rats with similar or more dorsally located damage showed moderate or transient increases in the number of pulses required to maintain half-maximal rates of LH or VTA self-stimulation. Vehicle injections did not affect behaviour. Varying degrees of demyelination were seen, mostly removed from the electrode tip, and in locations that varied substantially across subjects manifesting similar changes in self-stimulation. These results support the notion that somata in the basal forebrain give rise to some of the directly activated fibers subserving self-stimulation of the MFB.
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Agonistas de Aminoácidos Excitadores/toxicidad , Haz Prosencefálico Medial/fisiología , N-Metilaspartato/toxicidad , Prosencéfalo/fisiología , Autoestimulación/fisiología , Animales , Axones/fisiología , Condicionamiento Operante/fisiología , Agonistas de Aminoácidos Excitadores/administración & dosificación , Área Hipotalámica Lateral/anatomía & histología , Área Hipotalámica Lateral/fisiología , Inyecciones , Masculino , Haz Prosencefálico Medial/anatomía & histología , N-Metilaspartato/administración & dosificación , Área Preóptica , Prosencéfalo/anatomía & histología , Ratas , Recompensa , Área Tegmental Ventral/anatomía & histología , Área Tegmental Ventral/fisiologíaRESUMEN
Extracellular recordings were obtained, in urethane-anesthetized rats, from 44 neurons in the rostral bed nuclei of the medial forebrain bundle (MFB). These cells were antidromically activated by stimulation of MFB sites that typically support self-stimulation. Recording sites included the magnocellular preoptic nucleus, substantia innominata, ventral pallidum, olfactory tubercle, and horizontal limb of the diagonal band. Refractory period estimates ranged from 0.35 to 1.20 ms (mean +/- SD = 0.72 +/- 0.30 ms, n = 15) for stimulation sites in the lateral hypothalamic and ventral tegmental areas when using currents of twice threshold and procedures designed to estimate excitability at or near the site of stimulation. Interelectrode conduction velocity estimates ranged from 1.48 to 20.0 m/s (mean +/- SD = 9.26 +/- 7.22 m/s, n = 11) and were obtained by dividing the interelectrode distance by the difference in the response latency from the two MFB stimulation sites. The refractory period and conduction velocity estimates for these neurons overlap the psychophysically derived estimates for MFB reward neurons. These data are consistent with the hypothesis that neurons arising in the rostral bed nucleus of the MFB compose at least part of the directly activated substrate for MFB self-stimulation.
Asunto(s)
Axones/fisiología , Haz Prosencefálico Medial/fisiología , Conducción Nerviosa/fisiología , Periodo Refractario Electrofisiológico/fisiología , Recompensa , Animales , Estimulación Eléctrica , Electrodos Implantados , Electrofisiología , Área Hipotalámica Lateral/anatomía & histología , Área Hipotalámica Lateral/citología , Área Hipotalámica Lateral/fisiología , Masculino , Haz Prosencefálico Medial/anatomía & histología , Haz Prosencefálico Medial/citología , Microelectrodos , Ratas , Área Tegmental Ventral/anatomía & histología , Área Tegmental Ventral/citología , Área Tegmental Ventral/fisiologíaRESUMEN
Psychophysical data consistent with rostro-caudal conduction along reward-relevant neurons linking the lateral hypothalamus (LH) and ventral tegmental area (VTA) have lead to the hypothesis that some of the directly activated neurons responsible for medial forebrain bundle (MFB) self-stimulation arise anterior to the level of the LH. This hypothesis has been challenged on the grounds that lesions to the anterior LH (ALH) often fail to degrade the rewarding value of stimulating more posterior MFB sites. The present study was aimed at investigating the effect of lesion location and stimulation current on the efficacy of ALH lesions in an effort to account for the inconsistencies in the earlier data. Self-stimulation thresholds were obtained for LH and VTA sites by estimating the number of pulses per stimulation train required for half-maximal responding at each of 3 currents. Electrolytic lesions (anodal, 1.0 mA for 10 s) were then made to the ALH at varying medial-lateral coordinates. In 7 of the 14 rats with MFB stimulation sites, lesions to the ALH produced increases in threshold which often declined over the next several days to weeks; in 5 cases thresholds remained elevated by 0.1 to 0.25 log10 units above baseline up to end of testing. In all but one case, the effective lesions were centered in the lateral ALH. Increases in threshold were more likely to be detected when stimulating at low currents; at low currents fewer neurons are recruited and the lesion can have a greater proportional effect on threshold. These data support the hypothesis that cell bodies, terminals, or fibers of passage in the ALH contribute to the rewarding effect of stimulating more posterior MFB sites.
Asunto(s)
Hipotálamo Anterior/fisiología , Haz Prosencefálico Medial/fisiología , Autoestimulación/fisiología , Animales , Electrodos Implantados , Hipotálamo Anterior/anatomía & histología , Masculino , Haz Prosencefálico Medial/anatomía & histología , Ratas , Recompensa , Área Tegmental Ventral/anatomía & histología , Área Tegmental Ventral/fisiologíaRESUMEN
Electrical stimulation at a locomotor site can prime (i.e., shorten the latency to initiate) stepping elicited by subsequent stimulation of the same or a different site. We tested for the priming effect in representative sites along the medial forebrain bundle, and determined if its magnitude showed regional differences. Rats (n = 20) were anesthetized with Nembutal and held in a stereotaxic apparatus over a wheel. Stepping was detected by accelerometers attached to the hindlimbs. Priming and test trains of stimulation (0.5-ms cathodal pulses, 50 Hz, 25-75 microA, 7-9-s train duration) separated by 20 s were delivered every 90 s. When the priming and test stimulations were applied to the same site, the priming effects were similar along the entire extent of the medial forebrain bundle. When the priming and test sites were different, the priming effect depended on their relative positions. Anterior stimulation primed posterior sites at magnitude comparable to those produced by stimulating the same posterior site. Posterior stimulation primed anterior sites at a level half of that produced by stimulation of the same anterior site. This pattern was found for priming and test sites that were ipsilateral and contralateral. Priming is a general and robust phenomenon with properties that may be useful for studying locomotor initiation pathways.