Corticostriatal circuitry Haber, Suzanne N.
Dialogues in clinical neuroscience,
03/2016, Letnik:
18, Številka:
1
Journal Article
Odprti dostop
Corticostriatal connections play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. ...The cortex projects to the striatum topographically. Thus, different regions of the striatum have been associated with these different functions: the ventral striatum with reward; the caudate nucleus with cognition; and the putamen with motor control. However, corticostriatal connections are more complex, and interactions between functional territories are extensive. These interactions occur in specific regions in which convergence of terminal fields from different functional cortical regions are found. This article provides an overview of the connections of the cortex to the striatum and their role in integrating information across reward, cognitive, and motor functions. Emphasis is placed on the interface between functional domains within the striatum.
Coupling stimuli and actions with positive or negative outcomes facilitates the selection of appropriate actions. Several brain regions are involved in the development of goal-directed behaviors and ...habit formation during incentive-based learning. This Review focuses on higher cognitive control of decision making and the cortical and subcortical structures and connections that attribute value to stimuli, associate that value with choices, and select an action plan. Delineating the connectivity between these areas is fundamental for understanding how brain regions work together to evaluate stimuli, develop actions plans, and modify behavior, as well as for elucidating the pathophysiology of psychiatric diseases.
Coupling stimuli and actions with positive or negative outcomes facilitates action selection. Haber and Behrens review cognitive control of decision making and the cortical and subcortical structures and connections that attribute value to stimuli, associate that value with choices, and select an action plan.
Continuous high-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson's disease (PD) management. However, the mechanisms underlying DBS effects remain enigmatic and ...are the subject of an ongoing debate. Here, we present and test a closed-loop stimulation strategy for PD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD. Application of pallidal closed-loop stimulation leads to dissociation between changes in basal ganglia (BG) discharge rates and patterns, providing insights into PD pathophysiology. Furthermore, cortico-pallidal closed-loop stimulation has a significantly greater effect on akinesia and on cortical and pallidal discharge patterns than standard open-loop DBS and matched control stimulation paradigms. Thus, closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD. Such strategies have the potential to be effective in additional brain disorders in which a pathological neuronal discharge pattern can be recognized.
► Novel DBS based on neuronal activity (closed-loop, CL-DBS) is superior to standard DBS ► Corticopallidal CL-DBS yields greater alleviation of parkinsonian akinesia ► Corticopallidal CL-DBS yields greater reduction of oscillatory neuronal discharge ► Pallidopallidal CL-DBS leads to dissociation between discharge rate and patterns
Although cells in many brain regions respond to reward, the cortical-basal ganglia circuit is at the heart of the reward system. The key structures in this network are the anterior cingulate cortex, ...the orbital prefrontal cortex, the ventral striatum, the ventral pallidum, and the midbrain dopamine neurons. In addition, other structures, including the dorsal prefrontal cortex, amygdala, hippocampus, thalamus, and lateral habenular nucleus, and specific brainstem structures such as the pedunculopontine nucleus, and the raphe nucleus, are key components in regulating the reward circuit. Connectivity between these areas forms a complex neural network that mediates different aspects of reward processing. Advances in neuroimaging techniques allow better spatial and temporal resolution. These studies now demonstrate that human functional and structural imaging results map increasingly close to primate anatomy.
Deep brain stimulation is a promising therapeutic approach for patients with treatment-resistant obsessive-compulsive disorder, a condition linked to abnormalities in corticobasal ganglia networks. ...Effective targets are placed in one of four subcortical areas with the goal of capturing prefrontal, anterior cingulate, and basal ganglia connections linked to the limbic system. These include the anterior limb of the internal capsule, the ventral striatum, the subthalamic nucleus, and a midbrain target. The goal of this review is to examine these 4 targets with respect to the similarities and differences of their connections. Following a review of the connections for each target based on anatomic studies in nonhuman primates, we examine the accuracy of diffusion magnetic resonance imaging tractography to replicate those connections in nonhuman primates, before evaluating the connections in the human brain based on diffusion magnetic resonance imaging tractography. Results demonstrate that the four targets generally involve similar connections, all of which are part of the internal capsule. Nonetheless, some connections are unique to each site. Delineating the similarities and differences across targets is a critical step for evaluating and comparing the effectiveness of each and how circuits contribute to the therapeutic outcome. It also underscores the importance that the terminology used for each target accurately reflects its position and its anatomic connections, so as to enable comparisons across clinical studies and for basic scientists to probe mechanisms underlying deep brain stimulation.
Anatomic tracing is recognized as a critical source of knowledge on brain circuitry that can be used to assess the accuracy of diffusion MRI (dMRI) tractography. However, most prior studies that have ...performed such assessments have used dMRI and tracer data from different brains and/or have been limited in the scope of dMRI analysis methods allowed by the data. In this work, we perform a quantitative, voxel-wise comparison of dMRI tractography and anatomic tracing data in the same macaque brain. An ex vivo dMRI acquisition with high angular resolution and high maximum b-value allows us to compare a range of q-space sampling, orientation reconstruction, and tractography strategies. The availability of tracing in the same brain allows us to localize the sources of tractography errors and to identify axonal configurations that lead to such errors consistently, across dMRI acquisition and analysis strategies. We find that these common failure modes involve geometries such as branching or turning, which cannot be modeled well by crossing fibers. We also find that the default thresholds that are commonly used in tractography correspond to rather conservative, low-sensitivity operating points. While deterministic tractography tends to have higher sensitivity than probabilistic tractography in that very conservative threshold regime, the latter outperforms the former as the threshold is relaxed to avoid missing true anatomical connections. On the other hand, the q-space sampling scheme and maximum b-value have less of an impact on accuracy. Finally, using scans from a set of additional macaque brains, we show that there is enough inter-individual variability to warrant caution when dMRI and tracer data come from different animals, as is often the case in the tractography validation literature. Taken together, our results provide insights on the limitations of current tractography methods and on the critical role that anatomic tracing can play in identifying potential avenues for improvement.
Abstract The thalamus is a critical component of the frontal cortical-basal ganglia–thalamic circuits that mediate motivation and emotional drive, planning and cognition for the development and ...expression of goal-directed behaviors. Each functional region of the frontal cortex is connected with specific areas of each basal ganglia (BG) structure and of the thalamus. In addition, the thalamus sends a massive, topographically organized projection directly to the striatum. Tract-tracing and physiological experiments have indicated a general topographic organization of the cortical-BG–thalamic loops and supported a model of BG function based on parallel and segregated pathways. However, the learning and execution of appropriate behavioral responses require integration of inputs related to emotional, cognitive, and motor cortical functions. Our recent data indicate that integration may occur via non-reciprocal connections between the striatum and substantia nigra and within “hot spots” of convergence between corticostriatal projections from different functional regions. Similarly, integration may exist in the thalamus. There are non-reciprocal connections between the thalamus and cortex via thalamocortical projections that terminate in the superficial and deep cortical layers. These terminals can influence different functional cortical areas that, in turn, project to the striatum and back to the thalamus. In addition, a non-reciprocal corticothalamic projection terminates in thalamic regions that are parts of other circuits. Finally, ‘hot spots’ of convergence between terminals from different cortical regions may also occur in the thalamus as is seen in the striatum. Thus, via several different pathways, the thalamus may serve as an important center of integration of networks that underlie the ability to modulate behaviors.
The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown ...primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurologic and psychiatric disorders. Our experiments were designed to demonstrate the existence and organization of prefrontal-STN projections, help delineate the "limbic" STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate, and dorsal prefrontal cortices of Macaca nemestrina and Macaca fascicularis to analyze the organization of terminals and passing fibers in the STN. Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior.
The fundamental importance of prefrontal cortical connectivity to information processing and, therefore, disorders of cognition, emotion, and behavior has been recognized for decades. Anatomic ...tracing studies in animals have formed the basis for delineating the direct monosynaptic connectivity, from cells of origin, through axon trajectories, to synaptic terminals. Advances in neuroimaging combined with network science have taken the lead in developing complex wiring diagrams or connectomes of the human brain. A key question is how well these magnetic resonance imaging (MRI)-derived networks and hubs reflect the anatomic "hard wiring" first proposed to underlie the distribution of information for large-scale network interactions. In this review, we address this challenge by focusing on what is known about monosynaptic prefrontal cortical connections in non-human primates and how this compares to MRI-derived measurements of network organization in humans. First, we outline the anatomic cortical connections and pathways for each prefrontal cortex (PFC) region. We then review the available MRI-based techniques for indirectly measuring structural and functional connectivity, and introduce graph theoretical methods for analysis of hubs, modules, and topologically integrative features of the connectome. Finally, we bring these two approaches together, using specific examples, to demonstrate how monosynaptic connections, demonstrated by tract-tracing studies, can directly inform understanding of the composition of PFC nodes and hubs, and the edges or pathways that connect PFC to cortical and subcortical areas.
ABSTRACT Background Understanding the neural mechanisms of psychiatric disorders requires the use of rodent models; however, frontal-striatal homologies between rodents and primates are unclear. In ...contrast, within the striatum, the shell of the nucleus accumbens, the hippocampal projection zone, and the amygdala projection zone (referred to as the striatal emotion processing network EPN) are conserved across species. We used the relationship between the EPN and projections from the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) to assess network similarities across rats and monkeys. Methods We first compared the location and extent of each major component of the EPN in rats and macaques. Next, we used anatomic cases with anterograde injections in ACC/OFC to determine the extent to which corticostriatal terminal fields overlapped with these components and with each other. Results The location and size of each component of the EPN were similar across species, containing projections primarily from infralimbic cortex in rats and area 25 in monkeys. Other ACC/OFC terminals overlapped extensively with infralimbic cortex/area 25 projections, supporting cross-species similarities in OFC topography. However, dorsal ACC had different connectivity profiles across species. These results were used to segment the monkey and rat striata according to ACC/OFC inputs. Conclusions Based on connectivity with the EPN, and consistent with prior literature, the infralimbic cortex and area 25 are likely homologues. We also see evidence of OFC homologies. Along with segmenting the striatum and identifying striatal hubs of overlapping inputs, these results help to translate findings between rodent models and human pathology.
PDF
