Staging of brain pathology related to sporadic Parkinson’s disease

The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.

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A Neural Substrate of Prediction and Reward

Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in our concepts of the structural and functional organization of these nuclei. From earlier data it had appeared that the basal ganglia served primarily to integrate diverse inputs from the entire cerebral cortex and to "funnel" these influences, via the ventrolateral thalamus, to the motor cortex (Allen & Tsukahara 1974, Evarts & Thach 1969, Kemp & Powell 1971). In particular, the basal

/pdf/parallel-organization-of-functionally-segregated-circuits-159qr6wgp1.pdf

Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.

https://science.sciencemag.org/content/sci/255/5052/1707.full.pdf

Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system

Nat. Med. 10, 982–986 (2004) Supplementary Video 2 was inadvertently omitted and should have been cited on page 984 together with Supplementary Video 1. Supplementary Video 2 is now provided in supplementary information online. We regret the error.

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Erratum: CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation (Nature Medicine (2004) 10 (982-986))

In a system for unsupervised spike sorting, features/dimensions suitable for clustering of the recorded spike signal data are identified, and the feature space is scaled according to the computed respective importances of the various features/dimensions. Clustering is performed on the scaled feature space.

Systems and methods for spike sorting

Behavioural and cognitive neuroscience.

The invention provides methods and apparatuses for monitoring task engagement by measuring beta frequency oscillations in the brain. Changes in power, frequency, and/or coherency of beta frequency oscillations correlate to an individual's engagement in or disengagement from a task. Accordingly, beta frequency oscillations can be used to determine if an individual prematurely disengages from a task, to diagnose if a person has a disorder affecting task engagement, and to evaluate the efficacy of a treatment for a disorder.

Monitoring task engagement using beta oscillations

Clinical studies have shown that patients with anxiety disorders exhibited coactivation of limbic cortices and basal ganglia, which together form a large-scale brain network. The mechanisms by which such a large-scale network could induce or modulate anxiety-like states are largely unknown. This article reviews our experimental program in macaques demonstrating a causal involvement of local striatal and frontal cortical sites in inducing pessimistic decision-making that underlies anxiety. Where relevant, we related these findings to the wider literature. To identify such sites, we have made a series of methodologic advances, including the combination of causal evidence for behavioral modification of pessimistic decisions with viral tracing methods. Critically, we introduced a version of the classic approach-avoidance (Ap-Av) conflict task, modified for use in non-human primates. We performed microstimulation of limbic-related cortical regions and the striatum, focusing on the pregenual anterior cingulate cortex (pACC), the caudal orbitofrontal cortex (cOFC), and the caudate nucleus (CN). Microstimulation of localized sites within these regions induced pessimistic decision-making by the monkeys, supporting the idea that the focal activation of these regions could induce an anxiety-like state, which subsequently influences decision-making. We further performed combined microstimulation and tract-tracing experiments by injecting anterograde viral tracers into focal regions, at which microstimulation induced increased avoidance. We found that effective stimulation sites in both pACC and cOFC zones projected preferentially to striosomes in the anterior striatum. Experiments in rodents have shown that the striosomes in the anterior striatum project directly to the dopamine-containing cells in the substantia nigra, and we have found evidence for a functional connection between striosomes and the lateral habenular region in which responses to reward are inhibitory. We present here further evidence for network interactions: we show that the pACC and cOFC project to common structures, including not only the anterior parts of the striosome compartment but also the tail of the CN, the subgenual ACC, the amygdala, and the thalamus. Together, our findings suggest that networks having pACC and cOFC as nodes share similar features in their connectivity patterns. We here hypothesize, based on these results, that the brain sites related to pessimistic judgment are mediated by a large-scale brain network that regulates dopaminergic functions and includes striosomes and striosome-projecting cortical regions.

/pdf/causal-evidence-for-induction-of-pessimistic-decision-making-8filno7gib.pdf

Ann M. Graybiel

Papers

Erratum: CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation (Nature Medicine (2004) 10 (982-986))

Systems and methods for spike sorting

Behavioural and cognitive neuroscience.

Monitoring task engagement using beta oscillations

Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes