The Basal Ganglia ThalamicCortical System as Nested Nonlinear Reentrant Oscillators in a Loosely Coupled Network Oscillator Theory

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One could view the basal ganglia-thalamic-cortical system as a set of nested oscillators, as shown in Figure 3. The dynamics of such a configuration and the alternations associated with PD comprise an alternative theory termed the oscillatory theory (7). This theory posits the basal ganglia-thalamic-cortical system to be organized as a large set of nested oscillators loosely coupled in a network. Within each set of nested oscillators, individual oscillators are made up of different combinations of neurons within the anatomical nuclei. Because different oscillators have different numbers of nodes, neuronal activities within these oscillators have different fundamental frequencies. Given combined conduction velocities and synaptic delays on the order of 3 to 4 ms, the oscillator frequencies can range from up to approximately 130 Hz. However, no neuron in the basal ganglia-thalamic-cortical system has a sustained frequency of 130 Hz. To explain this, the oscillator theory holds that each neuron within a node does not discharge with each cycle of the oscillation but rather at some fraction of cycles.

Thus, individual neurons in a node act as rate dividers. The combined activities of all neurons in a node are sufficient to ensure that oscillations continue.

According to the oscillator theory, physiological function is represented within specific basal ganglia-thalamic-cortical circuits and not within specific structures. For example, neurons that respond preferentially to the appearance of a go signal can be found in all the structures within the basal ganglia-thalamic-cortical circuit and, further, the timing of activity for these neurons is approximately the same (within the 10 ms time resolution of the studies) in the MC and putamen (47). The parallel and distributed nature of physiological function within the basal ganglia-thalamic-cortical system also explains why lesions in multiple structures within the basal ganglia-thalamic-cortical system, including the GPe, SMA, VL, and putamen, can produce parkinsonism (48-52) and why DBS of the GPi (4), MC (53), VL (54), GPe (55), and STN (4) can all improve the symptoms of PD.

The oscillator theory's corollary of parallel and distributed processing should not be misinterpreted to suggest that there is no correlation with specific constellations of symptoms and signs with lesions of specific structures. There is a correlation between anatomical locations of lesions and symptomotology, although some studies would suggest that there is not a strong correlation (48). Specific structures occupy unique nodes within different nested oscillators that make up the basal ganglia-thalamic-cortical system, as shown in Figure 3. For example, the putamen is common to at least two reentrant circuits (MC ^ putamen ^ GPe ^ STN ^ GPi ^ VL ^ MC and MC ^ putamen ^ GPi ^ VL ^ MC), whereas the STN is involved in different circuits (MC ^ STN ^ GPi ^ VL ^ MC). Consequently, lesions of different structures are likely to have very different consequences on function within the basal ganglia-thalamic-cortical system.

One consequence of the oscillator theory is that physiological function is modular and localized but not within any particular structure and not in any particular

FIGURE 3 The architecture of the basal ganglia-thalamic-cortical system as nested oscillators of different lengths. There are a number of potential closed loops or circuits with different nodes, corresponding to anatomical structures. Different numbers of nodes cause different fundamental reentrant frequencies.

FIGURE 3 The architecture of the basal ganglia-thalamic-cortical system as nested oscillators of different lengths. There are a number of potential closed loops or circuits with different nodes, corresponding to anatomical structures. Different numbers of nodes cause different fundamental reentrant frequencies.

set of neurons. Rather, there are sets of oscillators that differ in physiological function, and these different oscillators interact to orchestrate behavior. The modularity and localization is fixed to some degree. That is, oscillator circuits particularly related to responding to go signals tend to be more localized in those circuits containing the anterior putamen and anterior globus pallidus, whereas circuits related to execution involve more posterior putamen and globus pallidus (41). However, even within this scheme, representation of physiologic function is dynamic or fluid. Montgomery et al. (39) demonstrated that individual neurons are multipotential in that they can encode different physiological functions depending on the behavioral context. For example, a neuron that preferentially responds to the go signal in one task may change its preference to the onset of a muscle force change. Further, these changes do not require learning or repetition of the task within a consistent block of tasks. These changes do not appear to require any lead time and they seem to be inherent in the physiological architecture.

At this juncture, a discussion of the mechanisms of action of DBS would be helpful. DBS played a central role in reconsideration of basal ganglia physiology and pathophysiology. DBS has proven to be effective, and patients failing in pharmacological manipulations and even brain cell transplants have benefited from DBS (5). Therefore, DBS must be addressing important neuronal pathophysiological mechanisms and, by extension, important physiological mechanisms. DBS has been a useful probe in studying the dynamics of the basal ganglia-thalamic-cortical system.

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