A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation

Thevathasan, Wesley; Pogosyan, Alek; Hyam, Jonathan A.; Jenkinson, Ned; Bogdanovič, Marko; Coyne, Terry; Silburn, Peter A.; Aziz, Tipu Z.; Brown, Peter

doi:10.1093/brain/awr131

Cited by 64 publications

(74 citation statements)

References 52 publications

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“…The hypothesis that deep brain stimulation of the PPTg relieves a block to execute a pre-prepared movement [188] fits well with our data because gait may speedily proceed if freezing of gait is removed. Under these circumstances, we hypothesize that if arousal is increased under PPTg stimulation, patients may be more attentive to what they are doing or in what they are about to do, which would result in an improvement in the success of their actions.…”

Section: Resultssupporting

confidence: 86%

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

Vitale¹,

Capozzo²,

Mazzone³

et al. 2017

Transl Brain Rhythmicity

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The pedunculopontine tegmental nucleus (PPTg) is part of the locomotor mesencephalic region and the reticular activating system (RAS). As such, it is involved in regulating some aspects of the motor control and the wake/sleep cycle, but the way in which it operates is unclear. PPTg neurons respond to a variety of sensory stimuli and to cues that trigger the execution of goal-directed motor acts. In this paper, we discuss data that suggest that in addition to operating via thalamic nuclei, the PPTg may also operate by activating cerebellar nuclei, especially the dentate nucleus. In such a way, an intense and diffuse activation of the cerebral cortex may be achieved. In arousal-demanding reward-related tasks, separate populations of PPTg neurons modulate their discharge pattern to encode, in particular, expectancy and magnitude of reward. These neuronal responses, which should reach thalamic, basal ganglia, and cerebellar nuclei through ascending PPTg fibers are essential for the formation of stimuli-reward associations and action selection. In parallel, PPTg neurons, via descending fibers directed to lower brainstem and spinal motor structures, may automatically influence motor mechanisms and muscle tone in order to cause movements that are executed in a smooth and timely manner. In patients affected by Parkinson's disease, PPTg deep brain stimulation may increase arousal, thus making patients more attentive to behavioral stimuli that trigger motor act, while simultaneously facilitating movement.

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Section: Resultssupporting

confidence: 86%

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

Vitale¹,

Capozzo²,

Mazzone³

et al. 2017

Transl Brain Rhythmicity

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show abstract

“…Data analysis. Auditory startle reflexes were defined as the presence of a short latency response in the sternocleidomastoid muscle within 100 ms after the SAS (Brown et al, 1991b;Thevathasan et al, 2011). The response had to exceed, for at least 20 ms, a threshold of 2 SD above mean background activity, as calculated over a 500 ms period just before the SAS.…”

Section: Methodsmentioning

confidence: 99%

“…As such, the reticulospinal system may be responsible for some of the functional recovery observed after acute corticospinal lesions (Baker, 2011). Recent experiments tested this idea by making focal unilateral pyramidal tract lesions in macaque monkeys (Zaaimi et al, 2012).…”

Section: Role Of Subcortical Structures In Motor Preparationmentioning

confidence: 99%

StartReact Restores Reaction Time in HSP: Evidence for Subcortical Release of a Motor Program

et al. 2013

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Startling acoustic stimuli (SAS) can accelerate reaction times ("StartReact" effect), but the underlying mechanism remains unclear. Both direct release of a subcortically stored motor program and a subcortically mediated trigger for a cortically stored motor program have been hypothesized. To distinguish between these hypotheses, we examined the StartReact effect in humans with pure hereditary spastic paraplegia (HSP). Delayed reaction times in HSP patients in trials both with and without a SAS would argue in favor of a cortically stored response.We instructed 12 HSP patients and 12 matched controls to respond as rapidly as possible to a visual imperative stimulus, in two different conditions: dorsiflexion of the dominant ankle; or flexion of the dominant wrist. In 25% of trials, a SAS was delivered simultaneously with the imperative stimulus. Before these tests, subjects received five SAS while standing to verify normal function of the reticulospinal tract in HSP.Latencies of startle responses in sternocleidomastoid and tibialis anterior muscles were comparable between patients and controls. During the ankle dorsiflexion task, HSP patients had an average 19 ms delay in reaction times compared with controls. Administration of a SAS accelerated ankle dorsiflexion in both groups, but more so in the patients, which completely normalized their latencies. The wrist flexion task yielded no differences in onset latencies between HSP patients and controls.The reticulospinal tract seems unaffected in HSP patients, because startle reflex onsets were normal. The corticospinal tract was affected, as reflected by delayed ankle dorsiflexion reaction times. These delayed onsets in HSP were normalized when the imperative stimulus was combined with a SAS, presumably through release of a subcortically stored motor program conveyed by the preserved reticulospinal tract.

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“…C 2 : side preference during the outcome epoch for all neurons that preferred ipsilateral movement during the movement epoch. model may be useful for informing PPTg deep brain stimulation therapies for movement disorders (Benarroch 2013;Fasano et al 2012;Gradinaru et al 2009;Insola et al 2012;Khan et al 2012;Lourens et al 2011;Nandi et al 2008;Peppe et al 2010;Thevathasan et al 2010Thevathasan et al , 2011aThevathasan et al , 2011bThevathasan et al , 2012aThevathasan et al , 2012bWilcox et al 2011).…”

Section: Pptg Function Across Speciesmentioning

confidence: 99%

Activity in mouse pedunculopontine tegmental nucleus reflects action and outcome in a decision-making task

Thompson

Felsen

2013

Journal of Neurophysiology

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Recent studies across several mammalian species have revealed a distributed network of cortical and subcortical brain regions responsible for sensorimotor decision making. Many of these regions have been shown to be interconnected with the pedunculopontine tegmental nucleus (PPTg), a brain stem structure characterized by neuronal heterogeneity and thought to be involved in several cognitive and behavioral functions. However, whether this structure plays a general functional role in sensorimotor decision making is unclear. We hypothesized that, in the context of a sensorimotor task, activity in the PPTg would reflect task-related variables in a similar manner as do the cortical and subcortical regions with which it is anatomically associated. To examine this hypothesis, we recorded PPTg activity in mice performing an odor-cued spatial choice task requiring a stereotyped leftward or rightward orienting movement to obtain a reward. We studied single-neuron activity during epochs of the task related to movement preparation, execution, and outcome (i.e., whether or not the movement was rewarded). We found that a substantial proportion of neurons in the PPTg exhibited direction-selective activity during one or more of these epochs. In addition, an overlapping population of neurons reflected movement direction and reward outcome. These results suggest that the PPTg should be considered within the network of brain areas responsible for sensorimotor decision making and lay the foundation for future experiments to examine how the PPTg interacts with other regions to control sensory-guided motor output.

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A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation

Cited by 64 publications

References 52 publications

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

StartReact Restores Reaction Time in HSP: Evidence for Subcortical Release of a Motor Program

Activity in mouse pedunculopontine tegmental nucleus reflects action and outcome in a decision-making task

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