Aberrant hand movement preparatory and executory neural activation patterns and their temporal dynamics (timing and duration) in schizophrenia spectrum disorder: An fMRI study
Abstract
Abstract
In everyday life, hand and arm movements are typically followed by rich sensorymotor feedback, which supports us in planning, executing, and monitoring
movement. Spatiotemporally, dynamic coordination among cortical, subcortical,
and cerebellar neural systems responsible for cognitive control, movement
planning, and sensory-motor feedback integration are crucial in ensuring a
coherent hand movement preparation and execution. During preparation,
coordinated neural activity and sensory-motor signal integration form corollary
discharge, which generates motor commands and an efference copy used by
internal forward models to predict sensory-motor feedback (e.g., hand
movements). These predictive models, help in distinguishing self-generated from
externally caused sensory-motor feedback, while mismatches between predicted
vs. actual feedback can disrupt the sense of agency (subjective experience of
initiating and controlling movements)—may lead to passivity experiences (feeling
that one’s actions are controlled externally despite being self-initiated). Patients
with schizophrenia spectrum disorders (SSD) exhibit deficits in action planning,
predictive mechanisms, and coordination among brain areas, which contribute to
psychomotor abnormalities, passivity experiences, and impaired sense of
agency. However, no prior functional magnetic resonance imaging (fMRI) study
has separated hand movement preparation from execution; thus, it remains
unclear how, beyond amplitude, timing and duration of blood oxygenation level
dependent (BOLD) responses during distinct phases (entire movement,
preparation, and execution) unfold in patients with SSD.
To address these gaps, we used an MRI- compatible passive movement device
(PMD). During fMRI experiment, participants grasped the handle mounted on
PMD, while hand movement task consisted of an extension from the left end to
the right end (~ 5.5 cm trajectory) and return to the left end. fMRI data were
recorded with a 3 Tesla MRI scanner, while participants performed active and
passive (moved by PMD) hand movements with video feedback either from their
own (self) or other (pre-recorded, gender swapped) hand moving in accordance
with their own hand. Participants have detected temporal delays between hand
movement and feedback. BOLD responses were modelled using the canonical
hemodynamic response function to analyse amplitude, first-order temporal derivatives to assess timing, and second-order derivatives to evaluate duration.
First, we investigated timing and duration of neural responses during entire hand
movements (Article 1). Second, explored neural response amplitude patterns
during preparatory and execution phases (Article 2). Third, examined timing and
duration of neural responses during preparation and execution phases (Article 3).
Across three studies, results revealed widespread spatiotemporal abnormalities
in patients with SSD. Notably, Article 1 has shown delayed BOLD responses
during complete movement, whereas Article 2 has revealed reduced or reversed
preparatory BOLD amplitudes in the lobule VIII of the right cerebellum, basal
ganglia (putamen, caudate nucleus), left insula, left thalamus, and in the frontalparietal-temporal areas. These abnormalities reflect impaired neural responses
across cortical, subcortical, and cerebellar networks, suggesting dysfunctions in
predictive mechanisms and sensory-motor feedback integration, potentially
driving delusions of agency and ego-disturbances (blurred boundaries between
self and external control). Both Article 2 and Article 3 revealed that amplitude,
timing, and duration of neural responses were primarily disrupted during
preparatory phase—not execution. Furthermore, while Article 2 highlighted
preparatory abnormalities in neural activation or suppression (reduced or
increased), Article 3 identified delayed or advanced timing in the right
supplementary motor area, right precentral gyrus, and left middle temporal gyrus.
These regions are closely linked to psychomotor processes, planning, corollary
discharge, efference copy, and inhibitory regulation of unintended movements.
In summary, by applying temporally sensitive analyses to movement phasespecific BOLD responses, this dissertation identified abnormalities in amplitude,
timing, and duration across cortical, subcortical, and cerebellar regions. The most
pronounced dysfunctions emerged during hand movement preparation,
implicating impaired sensory-motor integration, imprecise corollary discharge and
efference copy, and impaired prediction—core neural mechanisms underlying
disrupted sense of agency, passivity experiences, and ego-disturbances in
patients with SSD. Finally, these novel analytical methods and movement phase
specific neural characteristic mechanisms offer a new foundation for future
research across psychiatric, neurodegenerative, and neurological disorders.
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