Donald Doherty's blog

Author: Donald Doherty

  • A Unified Anatomically Based Model for Speech Production and Perception

    You might expect that the auditory system in the brain is critical for hearing and perceiving speech and that the motor system is critical for the production of speech. And this is the case. However, research in sensorimotor integration has shown that the reverse is also true. The auditory system is involved in speech production and the motor system can be involved in the perception of speech.

    Figure 1. Illustration of the dual stream model of speech processing. In this model, early stages of speech processing occur bilaterally in auditory regions on the dorsal superior temporal gyrus (spectrotemporal analysis; green) and superior temporal sulcus (phonological access/representation; yellow). From there the signals diverge into two broad streams. The temporal lobe ventral stream supports speech comprehension (lexical access and combinatorial processes; pink) whereas a strongly left dominant dorsal stream supports sensory-motor integration and involves structures at the parietal-temporal junction (Sylvian parietal-temporal) and frontal lobe. Figure 3 from “Sensorimotor Integration in Speech Processing: Computational Basis and Neural Organization” by Gregory Hickok, John Houde and Feng Rong. Neuron, February 10, 2011.

    Research scientists studying speech production have shown that a goal of speech production is to generate a target sound. On the other hand, researchers studying speech perception have shown that a goal of speech perception is to recover the motor gesture that generated a perceptual speech event. The authors of a new paper “Sensorimotor Integration in Speech Processing: Computational Basis and Neural Organization” (published February 10, 2011 in Neuron) point out that “there is virtually no theoretical interaction between them.” This paper is an attempt to bring speech production and speech perception research findings together into a single framework to address sensorimotor interaction in speech.

    In this paper, the authors review the evidence for:

    • The role of the auditory system in speech production.
    • Evidence for the role of the motor system in speech perception.
    • Recent progress in mapping an auditory-motor integration circuit for speech and related functions (summarized in Figure 1 above).
    Figure 2. An integrated state feedback control model of speech production. Articulatory control localized to primary motor cortex generates motor commands to the vocal tract and sends a corollary discharge to an internal model which makes forward predictions about both the dynamic state of the vocal tract and about the sensory consequences of those states. Deviations between predicted auditory states and the intended targets or actual sensory feedback generate error signals that are used to correct and update the internal model of the vocal tract. The motor phonological system embodies an internal model of the vocal tract and is localized to premotor cortex. The auditory phonological system encodes auditory targets and forward predictions of sensory consequences and is localized to the superior temporal gyrus and superior temporal sulcus. Motor and auditory phonological systems are linked via an auditory-motor translation system, localized to the Sylvian parietal-temporal area. Figure 4 from “Sensorimotor Integration in Speech Processing: Computational Basis and Neural Organization” by Gregory Hickok, John Houde and Feng Rong. Neuron, February 10, 2011.

    They then go on to consider a unified framework based on a state feedback control architecture (summarized in Figure 2 above), in which sensorimotor integration functions primarily in support of speech production. These include the capacity to learn how to articulate the sounds of one’s language, keep motor control processes tuned, and support online error detection and correction. The system can provide some top-down motor modulation perceptual processes.

  • Neurotrophic Factors and Parkinson’s Disease: Need for a Common Database and Systems Biology Models

    The death of dopaminergic neurons in the substantia nigra is a major pathology underlying Parkinson’s disease. Therefore it makes a lot of sense to look to neurotrophic factors, the most potent mediators of neuronal survival identified to date, as promising therapeutic agents for saving these neurons. A new review paper “Repairing the parkinsonian brain with neurotrophic factors” (published February 2011 in Trends in Neurosciences) states that, so far, clinical trials of neurotrophic factors to treat Parkinson’s disease have been disappointing. Why?

    Figure 1. An overview of glial cell line-derived neurotrophic factor (GDNF) signaling. Figure 1 from “Repairing the parkinsonian brain with neurotrophic factors” by Liviu Aron and Rudiger Klein. Trends in Neurosciences, February 2011.

    Details of molecular signal pathways are known for some neurotrophic factors. For example, one can follow the glial cell line-derived neurotrophic factor (GDNF) signal step-by-step (see Figure 1 above; for text describing the figure please see the review paper). Nevertheless, even for GDNF, the outcomes of the interactions are poorly understood and it remains to be determined what interactions actually promote survival of dopaminergic neurons. The authors of the review conclude that we simply do not know enough yet about how neurotrophic factors work.

    The authors state that “the experimental evidence that neurotrophic factor disturbances alone cause Parkinson’s disease is currently weak.” Nevertheless, they cite the following to encourage continued research in this area:

    • Parkinson’s disease-associated genes require an intact neurotrophic factor network to promote substantia nigra neuron survival during aging.
    • Changes induced by mutations in Parkinson’s disease-associated genes decrease the efficacy of neurotrophic factor signaling.
    • Shared substrates between neurotrophic factors and Parkinson’s disease-associated proteins might represent new targets for drug development in Parkinson’s disease.

    Certainly research in neurotrophic factors and Parkinson’s disease must continue to move forward. Interestingly there were two sentences in the review’s conclusion that seemed tacked on and were not discussed:

    • The creation of a common database with results from standardized experiments could result in a systems biology approach in experimental Parkinson’s disease.
    • Mathematical models of neurotrophic factor action could then be used to predict and test new cellular targets.

    Creating a common database and associated systems biology models may accelerate the field by enabling a broad set of scientists to understand the complex signaling pathways underlying neurotrophic factor function and the way they may be applied to helping Parkinson’s disease patients.

  • Action Potentials Modified by Transmitters Applied to Brain Cell Axons

    Theoretical work and research on large invertebrate axons has suggested since at least the 1970s that axon geometry contributes to signal processing in the nervous system. The fact that the distal ends of axons are of much smaller diameter than near the neuron cell body suggests that action potentials become wider and decrease in amplitude as they move towards an axon’s synaptic bouton. This is a direct consequence of cable theory. As a cable’s diameter decreases its surface to volume ratio increases.

    Figure 1. The branch point of this simulated mylenated axon filters some action potentials. Intermittent conduction failures are apparent by comparing the responses of the parent branch to those of the daughter branches. Figure 4 from “Computer Model for Action Potential Propagation Through Branch Point in Myelinated Nerves” by Stefanie Hampel, Phuong Chung, Claire E McKellar, Donald Hall, Loren L Looger and Julie H Simpson. Journal of Neurophysiology, January 2001.

    At axon branch points the cross sectional area of the two daughter branches together generally present more area than the cross sectional area of the parent axon resulting in the presentation of greater electrical resistance by the daughter branches. This slows down or even stops action potentials and increases their amplitude at the branch point. This can result in filtering of action potentials or even their saltatory conduction along the axon’s branch points depending on the particular biophysical properties of the axon involved.

    The authors of a new paper “Action-Potential Modulation During Axonal Conduction” (published February 4, 2011 in Science) hypothesized that signal processing in the axon may involve more than process geometry. They hypothesized that action potentials are subject to waveform modulation while they travel down axons due to local alterations in the ion conductance from the interaction of neurotransmitters or even gliotransmitters. The research team recorded action potentials from axon branches of hippocampal CA3 pyramidal neurons from slice cultures.

    They found that waveforms of axonal action potentials increased in width in response to the local application of glutamate and an adenosine A1 receptor antagonist to the axon shafts, but not to other unrelated axon branches. Glutamate appeared to modulate action potentials by depolarizing axons through AMPA receptor activation. Next, they showed that activated astrocytes broadened action potentials in adjacent axons. The broadened action potentials resulted in larger excitatory postsynaptic currents on the target neurons.

    Other related blog posts:

    Axon Segments May Form Distinct Processing Units