The Neuroplastic Outcomes from Impaired Sensory Expectations (NOISE) Hypothesis: How ACL Dysfunction Impacts Sensory Perception and Knee Stability

Abstract

Background:

The anterior cruciate ligament (ACL) is integral to maintaining knee joint stability but is susceptible to rupture during physical activity. Despite surgical restoration of passive or mechanical stability, patients struggle to regain strength and prior level of function. Recent efforts have focused on understanding how ACL-related changes in the nervous system contribute to deficits in sensorimotor control following injury and reconstruction. We hypothesize that these challenges are partially due to an increase in sensorimotor uncertainty, a state that reduces the precision of movement control.

Objectives:

This review proposes the ACL NOISE (Neuroplastic Outcomes from Impaired Sensory Expectations) hypothesis, reframing current literature to provide a case that increased sensory noise following ACL injury and reconstruction disrupts sensory predictions, which are anticipations of immediate sensory outcomes or motor commands. This disruption in sensory predictions may contribute to altered neurophysiology, such as cross-modal brain activity, and other persistent clinical deficits.

Design:

Narrative review

Results/findings:

Following injury and reconstruction, the knee and nervous system experience various neurophysiological alterations to overcome elevated sensory uncertainty and inaccurate sensory predictions, contributing to persistent motor deficits.

Conclusions:

We provide a theoretical case based on compelling evidence that suggests prolonged impairment after ACL injury may be secondary to uncertainty in knee sensory perception. Future research should consider testing the NOISE hypothesis by creating a paradigm that examines dynamic joint stability in response to unexpected perturbations. This approach would help assess motor coordination errors and drive the development of clinical strategies aimed at reducing sensory uncertainty following ACL reconstruction.

INTRODCUTION

Coordinating movements like walking, running, and jumping requires joint stability, which depends on muscular control guided by proprioceptive input from muscles and joints.^1,2 Passive joint stability, or the mechanical resistance provided by the bones, ligaments, joint capsule, and other non-contractile tissues surrounding a joint is insufficient to prevent excessive movement or instability alone.¹ Dynamic joint stability is vital and refers to the coordinated contraction of muscles that surround a joint for active stabilization during movement.¹ A key element of both control systems is proprioception, the afferent signal arising from peripheral body parts that contributes to postural control and joint stability.¹ When proprioceptors are stimulated during movement or joint perturbations, they send afferent signals to spinal and supraspinal areas of the central nervous system (CNS) that process sensory inputs.^1,3 These inputs then inform primary and secondary motor regions to generate appropriate efferent signals to the involved muscles, ensuring joint stability.^1,3

The knee joint is a prime example of the importance of both passive and dynamic joint stability for human movement. Passive knee joint stability is maintained by collateral and cruciate ligaments, including the anterior cruciate ligament (ACL), which prevents excessive anterior translation and rotation of the tibia relative to the femur.⁴ However, the ACL also contributes to dynamic joint stability through mechanoreceptors that provide proprioceptive feedback to the nervous system to calibrate muscle activity that ensures dynamic joint stability.^5,6 Unfortunately, the ACL is susceptible to injury, particularly in recreational activities or sports. Epidemiological data in collegiate athletes determined that over 50% of injuries sustained were to the lower extremity, with the ankle and knee accounting for a majority of these injuries.⁷ Although ankle sprains were reported as the most common injury, ACL injuries were particularly debilitating, with 88% resulting in 10 or more days of time loss.⁷ In addition, between 1988 to 2004, the rate of ACL injuries increased each year by 1.3%.⁷ Following an ACL injury, only 55% of individuals return to competitive sports.⁸ Those who do not return experience lower levels of physical activity and report lower levels of general health related quality of life.^9,10

Following failure of the ligament, the current standard of care in the United States involves surgical intervention, ACL reconstruction (ACLR). Each year, approximately 200,000 ACL reconstructions take place in the United States.¹¹ Patients choose between autografts and allografts, with autografts preferred due to lower rupture rates in younger, more active patients.¹² Among autografts, options include quadriceps tendon (QT), bone-patellar-tendon-bone (BPTB), and hamstring tendon (HT), with similar knee function outcomes reported.¹³ One of the most significant challenges in surgical reconstruction is the graft’s inability to fully replicate the native ligament’s proprioceptive properties.¹⁴ A new procedure, bridge-enhanced ACL repair (BEAR), uses a scaffold to facilitate ACL regrowth to restore function of the native ligament.^15,16 However, BEAR's overall outcomes are comparable to ACLR, with no differences in quadriceps strength LSI or psychological readiness to return to sports at 12 months or 2 years post-operative between BEAR and ACLR groups.^16,17 In addition, the time to return to sport between the BEAR and ACLR procedures has been shown to be similar with no significant differences in timeframe,¹⁸ however re-rupture rates for the BEAR procedure range from 0 to 14% relative to 0 to 6% for ACLR.¹⁹ Collectively, these data indicate that advances in surgical procedure and graft optimization may not improve dynamic knee stability or reduce the rate of secondary injury, eluding to a deeper issue that is not resolved by even novel surgical methods.¹⁹

Historically, an ACL injury was viewed as primarily a “structural” or “mechanical” injury that could be fixed by restoring passive joint stability.²⁰ However, despite surgical intervention and focused rehabilitation, individuals with ACLR often experience ongoing motor control deficits, quadriceps muscle weakness, functional limitations, and a high rate of secondary ACL injury when returning to sport.^21-25 Although passive stability of the knee joint can be restored, the persistent difficulty in regaining dynamic stability points to an underappreciated role of the nervous system in ACL injury recovery. We further contend that changes within the nervous system resulting from ACLR, such as disruptions in afferent signaling and integration, lead to sensorimotor uncertainty—a state where variability in sensory inputs and motor outputs reduces the precision of movement control—and inaccurate sensory predictions—anticipations of the immediate sensory outcomes of motor commands. When sensory predictions are incorrect, it can lead to delays or errors in motor responses, ultimately contributing to prolonged neuromuscular dysfunction or aberrant joint mechanics. The following sections review the ACL’s sensory role and contributions to knee joint stability, providing the foundational groundwork for the proposal of the ACL NOISE hypothesis: Neuroplastic Outcomes from Impaired Sensory Expectations (Figure 1). Table 1 provides a list of key terms and definitions that will be used through the review.

Figure 1. Illustrated model of the ACL NOISE Hypothesis: Neuroplastic Outcomes from Impaired Sensory Expectations.

A) ACL injury induces pain, inflammation, peripheral deafferentation, and joint laxity, contributing to sensory noise and impairing the precision of incoming sensory signals. B) Heightened sensory noise leads to sensorimotor uncertainty, challenging the brain’s ability to predict body movement accurately. C) This sensorimotor uncertainty may lead to neurophysiological consequences as the nervous systems compensates for impaired sensory predictions. This relationship (B and C) may be cyclical, with neurophysiological changes further affecting sensory predictions in a feedback loop. D) These neurophysiological changes contribute to clinically relevant outcomes such as quadriceps weakness, altered gait mechanics, and kinesiophobia, further hindering recovery and motor performance. (Figure created with BioRender.com).

*Note: Although the arrows reflect the theoretical process, the actual process is likely more complex than portrayed.

Table 1.

Interpretive Definitions of Key Terms Related to Sensorimotor Control

Term	Definition	Supporting Literature
Noise	Irrelevant or extraneous signals that interfere with the accurate detection of sensory inputs (i.e. proprioception, somatosensation), making it difficult for the nervous system to distinguish salient or useful information from inconsequential information during movement and sensation.	Faisal et al., 2008 26 Wolpert et al., 2011 27
Sensorimotor Uncertainty	A state where variability in sensory inputs and motor outputs reduces the precision of movement control.	Orbán & Wolpert., 2011 28
Sensory Predictions	Anticipations of the immediate sensory outcomes of motor commands, generated by internal models, to guide motor behavior and enable realtime error correction.	Shadmehr et al., 2010 29
Internal Model	Neural mechanisms that simulate movement outcomes or generate motor commands, supporting adaptive motor control and error correction.	Wolpert et al., 1995 30 Kawato, 1999 31
Sensory Expectations	Broader anticipations, built from previous experiences, that help the nervous system predict and process sensory feedback throughout movement.	Shadmehr et al., 2010 29 de Lange., 2018 32

Note: The definitions provided here are interpretive summaries based on the supporting literature and are not exact quotations.

SENSORY NOISE

The integration of sensory information for motor control is a highly intricate and dynamic process. Proprioceptive signals, which inform the brain about the position and movement of the body, are not delivered as precise, clean inputs. Instead, these signals are composed of a series of biochemical and electrical processes that contain a certain level of “noise” or variability.²⁶ This sensory noise arises from both external environmental and internal fluctuations within the sensory and neural systems, as depicted in Figure 2. Despite the presence of noise, the nervous system has evolved sophisticated mechanisms to filter and manage this uncertainty, ensuring efficient motor control. Two key strategies that the brain employs to manage sensorimotor uncertainty are averaging across multiple sensory inputs and relying on prior knowledge or learned expectations (see also “Sensory Expectations” Table 1).^26,32

Figure 2. Signal to Noise Variations.

The figure displays a theoretical time-series plot of neural signals under three different noise conditions: low noise (top), moderate noise (middle), and high noise (bottom). In the low noise condition, three distinct signal spikes (red boxes) are easily discernible from the background noise. In contrast, the moderate noise condition shows increased variability and more frequent fluctuations, making it harder to distinguish signal from noise. In the high noise condition, the signal is highly erratic, masking any detectible signal spikes.

While the nervous system has evolved to compensate for noisy signaling to maintain motor control, these strategies rely on accurate sensory input from peripheral structures (i.e. muscle and joint proprioceptors).^26,33 Damage or dysfunction of these peripheral structures, like after ACL injury or reconstruction, introduces greater noise into sensory signaling (Figure 1A and Figure 2, moderate to high noise variations). The following section outlines the critical role of mechanoreceptors within the ACL in providing proprioceptive feedback and explores how ACL injury and reconstruction further disrupts sensory signaling, contributing to increased sensory noise and sensorimotor uncertainty.

Mechanoreceptors, sensory representation, and gamma loop dysfunction

Early work by Kennedy et al. identified free nerve endings in the synovium of the ACL, suggesting a sensory role for the ligament.⁵ Schultz et al. later found Golgi tendon organ-like mechanoreceptors (ligament tension) near the femoral attachment sites of the ACL, which were thought to contribute to proprioception and muscular reflexes aimed at preventing injurious knee movements.⁶ Further investigations revealed three mechanoreceptor types within the ACL: free nerve endings, which serve as pain receptors; Ruffini end organs, which are slowly adapting and sensitive to capsular stretching and pressure changes within the joint; and Pacinian corpuscles, which are rapidly adapting and respond to vibration and deep pressure.³⁴ These mechanoreceptors are connected to the tibial nerve,⁵ which transmits signals to the dorsal root ganglion of the spinal cord. From there, proprioceptive information about the knee’s condition travels to supraspinal centers. Thus, injury or removal of these mechanoreceptors via surgical means disrupts critical afferent pathways from the knee to the brain, which impairs the nervous system’s ability to process sensory feedback and coordinate appropriate motor responses, ultimately compromising motor control and knee joint stability.³⁵

The ACL’s mechanoreceptors contribute to cortical sensory input that was discovered using somatosensory evoked potentials (SEP).³⁶ In a study by Valeriani et al., SEP responses in ACL deficient (ACLD) patients revealed a diminished cortical P27 response post-stimulation.³⁷ This implies that the loss of the native ACL contributes to cortical reorganization, a phenomenon supported by similar research in limb loss/amputation, low back pain, and patellofemoral pain syndrome.^38-43 Recent work has further confirmed organizational differences in those with ACLR relative to uninjured control subjects.⁴⁴ Other studies employing SEPs stimulated remnants of the ACL in ACLD patients and found detectable SEP responses in 46% to 58% of ACLD patients, contrasting with 100% detection for the intact ligament in uninjured controls.^45,46 Collectively, these findings point to the intricate role of the ACL not only as a mechanical structure, but also as a crucial contributor to cortical sensory input.

In addition to the mechanoreceptors within the ligament, the ACL has also been linked to quadriceps gamma loop dysfunction.^47-50 The gamma loop is crucial for understanding alterations to muscle function and knee joint stability following ACLR, as it is a spinal reflex circuit that regulates the sensitivity and responsiveness of muscle spindles.⁵¹ Muscle spindles are sensory receptors that provide proprioceptive information to the CNS via group Ia afferents, the fastest and most myelinated neurons within the nervous system.^51,52

Early research by Johansson et al. studied the responses of muscle spindle afferents in anaesthetized cats after stretching the ACL.⁵³ They found that ACL afferents regulate muscle stiffness around the knee through gamma motor neuron activity, contributing to knee joint stability.⁵³ Building on the animal model, Konishi et al. used infrapatellar vibration to discover ACLR-associated dysfunction within the gamma loop,⁴⁷ which was also observed in the uninjured limb.^48,49 Although gamma loop dysfunction appeared to recover in the uninjured limb approximately 18 months after ACLR, this dysfunction persisted in the injured limb past 18 months.^41,42

Disruption of ligament mechanosensation and gamma loop function modifies afferent signaling from knee joint proprioceptors and surrounding muscles, increasing sensory noise and heightening sensorimotor uncertainty about the knee’s condition, including joint position and sensory perception.

DISRUPTED SENSORY PREDICTIONS

One of the key mechanisms the nervous system uses to manage signal noise and delays in sensory signaling is theorized to be sensory predictions. Sensory predictions are internal models or expectations that are generated based on prior experiences or sensory inputs (Table 1).²⁹ These internal models allow the brain to anticipate and preemptively adjust motor commands before sensory feedback is fully processed.^29,54 A critical region in this process is the cerebellum, which plays a vital role in generating and updating sensory predictions.²⁹

The cerebellum receives proprioceptive input from muscles, tendons, and joints,^1,3,55 constructing internal models to predict the sensory consequences of the outgoing motor commands. This continuous monitoring allows the cerebellum to compare predicted versus actual sensory feedback, sending corrective signals to the motor cortex to optimize movement accuracy.^29,54 Several studies have assayed the cerebellum’s ability to correct for sensory prediction inaccuracy via a split-belt treadmill walking task, whereby one belt accelerates at twice the speed of the other. Healthy individuals adjust quickly to compensate for the difference in belt speeds, increasing the time spent on the slower leg and reducing the time spent on the faster leg, while also storing this locomotor adaptation when the belts are returned to the same speeds.⁵⁶ Individuals with cerebellar damage (ataxia) show reactive changes to the different belt speeds but do not seem to store the locomotor adaption suggesting that the cerebellum is key to updating these internal models for future action.⁵⁷

The cerebellum and ACL injury

The timing and regulation of motor coordination responses is largely controlled by the cerebellum’s communication with the sensorimotor cortex.^29,58 In a prospective neuroimaging study, Diekfuss et al. found that individuals who later sustained a non-contact ACL injury had lesser sensory-cerebellar connectivity relative to those who were uninjured,⁵⁹ potentially identifying a neural mechanism underlying non-contact ACL injury. This finding suggests ACL injury may be a motor coordination error resulting from inaccurate sensory predictions, leading to inadequate dynamic joint stability and ligament failure. Other evidence indicates that cerebellar activity is depressed in patients with ACLD as well as post ACLR.^60,61 Further, a recent conjunction analysis determined that individuals with ACLR activated fewer unique subregions of the cerebellum relative to uninjured controls, indicating a loss of cerebellar automaticity for involved limb movement.⁴⁴ Taken together, it is possible that an element of the sensorimotor uncertainty after injury is present to a degree before the injury and is a predisposing risk factor.

Unanticipated perturbations

The role of the cerebellum is readily apparent with the compiling of recent data showing ACL injury events occurring in response to unexpected perturbations and a failure to either update the sensory prediction or generate appropriate motor corrections. Observation from video studies of ACL injuries in basketball and soccer athletes indicate that non-contact injuries occur in situations demanding high attention or involving collisions with opponents prior to the time of injury.^62-64 A study by Yom et al. further supports this, revealing that unexpected in-flight lateral perturbations during drop landings can lead to deviations in lower extremity kinematics and kinetics.⁶⁵ Perturbation trials displayed greater ground reaction forces and knee extensor moments, both which affect ACL loading, suggesting unanticipated perturbations during flight can increase ACL injury risk.^66,67

Although not directly comparable to ACL injury or reconstruction, prior research studying reflex responses to unanticipated perturbations using a sudden ankle inversion, or trapdoor mechanism, can provide insights into the variability in updating and correcting for inaccurate sensory prediction. Landing on an inverting platform results in reflexive muscle responses too slow to resist sudden ankle inversion in uninjured subjects.⁶⁸ A similar result was also found using a trapdoor walkway in individuals with and without functional ankle instability (FAI), wherein those with FAI displayed a delayed reflex of the fibularis muscles relative to control subjects.⁶⁹ As the ligaments of the ankle are also dense in mechanoreceptors,⁷⁰ reflexive responses to perturbations or sudden ligament stretch/load may provide some insight into the reactions and compensatory mechanism that individuals with ACL injury or reconstruction might exhibit. Specifically, the delayed muscular response even in healthy ligaments suggests that there is a time lag between the perturbation and the activation of the appropriate muscle groups to maintain dynamic stability with sudden ankle inversion. The time lag between perturbation and muscular response has also been seen at the knee, as ACL injury is thought to occur during the first ~50 ms of initial contact while the hamstring latency response does not occur until ~100 ms.^71,72 Also supporting this notion, Morris et al. found that delayed reactive postural responses to unanticipated tasks were associated with a 36% increase in injury risk,⁷³ stressing the importance for appropriate timing and coordination of muscle activation when faced with uncertainty. These data point to the importance of high-quality sensory feedback for generating accurate sensory predictions, reducing reliance on slower reflexive mechanisms to prevent injury.

A potential strategy to reduce the reliance on a reflexive correction would be to increase preparatory muscle activity to provide stability against such perturbations. For example, Wikstrom et al. compared successful and failed single-leg jump landings in healthy individuals and found that successful jump landing trials had earlier activation and higher preparatory and reactive electromyography (EMG) amplitudes.⁷⁴ Furthermore, Courtney et al. studied individuals with ACLD during an inclined walking task and found that the coper group had greater and earlier hamstring activation relative to non-copers and adapters.⁷⁵ Taken together, these studies highlight the importance of accurate sensory predictions to generate timely anticipatory muscular responses for dynamic knee joint stability.

NEUROPHYSIOLOGICAL CONSEQUENCES

Sensorimotor uncertainty following ACL injury plays a critical role in driving neurophysiological changes that alter motor control and function (Figure 1B and 1C). Impaired sensory perception of the injured limb results in sensorimotor uncertainty, which arises from sensory noise (Table 1).^26,28 In the context of ACL injury and reconstruction, sensory noise may manifest in various forms, including pain, which can alter proprioceptive signaling,⁷⁶ inflammation, which is present in the joint up to 5 years post ACLR,⁷⁷ joint laxity, which can affect muscle activation timing,³⁵ or the loss of mechanosensation as described above.^37,46 These impairments affect afferent signals, rendering them unreliable and effectively disrupting sensory predictions (Table 1).²⁹

In response to this uncertainty, the nervous system undergoes neuroplastic changes, wherein it recalibrates and reorganizes neural pathways to compensate for the loss of reliable proprioceptive input. Specifically, the brain may up-weight more reliable sources of sensory information, like vision or even proprioception from other muscles and joints, to maintain effective motor control.^61,78-82 This neural reorganization reflects a form of neuroplasticity that can have both adaptive and maladaptive outcomes. On one hand, these compensatory mechanisms allow individuals to function despite sensory deficits. On the other hand, we propose this neuroplasticity may lead to long-term alterations in motor control strategies, including prolonged muscle inhibition and changes in corticospinal excitability,⁸³ as the nervous system attempts to recalibrate with less reliable afference to maintain function.

The ACL and quadriceps muscle activation

Following injury to the ACL, patients commonly experience difficulty fully contracting their quadriceps muscle, often due to pain or joint effusion (i.e. sensory noise), which are both sufficient to trigger reflexive quadriceps muscle inhibition.⁸⁴ This phenomenon, commonly known as arthrogenic muscle inhibition (AMI), is thought to be mediated by neurophysiological factors such as alterations in afferent information from the injured joint, impairments in reflexive muscle activation, changes in cortical processing of knee joint information, and decreased corticospinal excitability.⁸³ Sensorimotor uncertainty of the knee joint following ACL injury and reconstruction is one component of the proposed ACL NOISE hypothesis (Figure 1B).

Cortical and spinal excitability

Several studies have investigated quadriceps motor cortex and spinal excitability in individuals with ACL injury and reconstruction. In a longitudinal TMS study by Lepley et al., it was observed that individuals undergoing ACLR exhibited bilateral reductions in spinal-reflexive excitability compared to controls before surgery, as well as higher active motor threshold (AMT) at 6 months post-surgery for both limbs.⁸⁵ A recent systematic review and meta-analysis indicated moderate evidence of reduced corticospinal excitability in both the involved and uninvolved limbs of those with ACLR relative to matched, uninjured control subjects.⁸⁶ Interestingly, microstructural alterations of white matter within corticospinal tract have been identified using diffusor tensor imaging (DTI) in those with ACLR years after surgery. Specifically, the hemisphere of the ACLR limb demonstrated lower volume, lower fractional anisotropy (FA), and higher mean diffusivity (MD) when compared to the uninvolved limb.⁸⁷ These corticospinal tract changes may reflect an adaptive response by the CNS to cope with the sensorimotor uncertainty caused by the injury. While the aforementioned studies highlight changes to the primary motor cortex and the corticospinal tract resulting from injury, previous research in the neurophysiology of motor learning indicates that these motor changes occur after and likely due to changes within the somatosensory cortex.^88-91 Taken together, we suggest that the abrupt disruption in proprioceptive and somatosensory feedback that resulting from ACL injury, and further influenced by the ACLR procedure, contributes to prolonged sensorimotor uncertainty. This uncertainty seemingly leads to chronic decreased motor cortex excitability, which we propose eventually causes structural changes to the corticospinal tract, reinforcing quadriceps inhibition and other reflexive activity.

Spinal-reflex excitability, which is influenced by both presynaptic and postsynaptic pathways, is commonly measured using the Hoffman reflex, or H-reflex.⁹² Spinal-reflex excitability has been shown to decrease bilaterally pre-surgery as well as two weeks following ACLR,⁸⁵ indicating at least in the short term, that altered joint afference from sensory “noise” leads to sensorimotor uncertainty. Within two years after ACLR, no differences in H-reflex were found between limbs or compared to a control group,⁸⁶ but beyond two years, the affected limb showed a greater H-reflex compared to controls.⁸⁶ This increase in spinal-reflex excitability may be an adaptive mechanism to overcome cortical alterations secondary to sensorimotor uncertainty.

The ACL and reflexive muscle activity

Pioneering work by Solomonow et al. demonstrated the connection between sensory input from the ACL and its influence on reflexive muscle activity in a feline model.⁹³ Results indicated that direct stress of the ACL had a moderate inhibitory effect on the quadriceps and a simultaneous excitatory effect on the hamstring muscles.⁹³ In humans, Dyhre-Poulsen and Krogsgaard conducted experiments wherein they stimulated sensory nerve fibers within the ACL of patients with intact ligaments, revealing a reflexive muscle contraction of the semitendinosus muscle.⁷¹ This observed hamstring contraction aligns with the anticipated biomechanical response to ACL failure, characterized by anterior tibial translation. The mediation of this hamstring-reflex arc appears to involve both group Ia and group II afferents.⁹⁴ Disruption of the hamstring-reflex arc via ligament injury likely further contributes to sensorimotor uncertainty, as supraspinal centers must now develop alternative strategies to maintain dynamic knee stability as the previously predicted hamstring reflex is dampened or absent.

The intricate relationship between the ACL and the hamstring-reflex arc has been investigated in prior studies involving patients with ACL rupture by Melnyk et al.³⁵ These patients were categorized into two groups based on subjective measures of knee instability or “giving way” symptoms: copers and non-copers. Muscle activity of the hamstrings was measured using surface EMG following tibial translation during a single-leg weight-bearing task, revealing a significantly longer medium-latency response (MLR) in non-copers compared to copers, while short-latency response (SLR) remained unchanged.³⁵ These findings suggest that altered stretch reflex excitability post-ACL rupture may contribute to “giving way” symptoms or bouts of instability. Courtney et al. found an earlier and greater activation of the hamstring muscles of the ACL deficient limb as well as a loss of the P27 potential in copers,^75,95 indicating central changes in sensory processing that potentially enabled a motor control strategy to increase dynamic knee stability.

Madhaven and Shields conducted a study to assess long latency reflexes (LLR) of the quadriceps and hamstrings muscles in individuals both with and without ACLR while performing a single-leg squat task.⁹⁶ During the task, participants were instructed to follow a sinusoidal wave, and sudden perturbations were introduced at the onset of knee flexion, leading to "overshoot errors". The findings revealed that individuals with ACLR exhibited a greater degree of overshoot error and increased LLR responses compared to those without ACLR, suggesting an impaired ability to respond to unexpected perturbations.⁹⁶ These findings suggest that alterations in muscle function, corticospinal, and spinal-reflexive excitability reflect elevated uncertainty with regard to sensory perception of the knee, further emphasizing the need for accurate sensory information in effective sensorimotor control.

Disruption of sensorimotor processing and attempted neural compensation

ACL injury and reconstruction disrupts neural processing associated with sensory integration, leading to compensatory brain activity strategies to maintain function. Functional magnetic resonance imaging (fMRI) has detected sensory reorganization, resulting in elevated multimodal brain activation among individuals with ACLD and ACLR, relative to uninjured controls.^{44,60,61,78,97} Chaput et al. found that visual cognition was associated with increased brain activity in the precuneus and posterior cingulate gyrus in those with ACLR but not in control subjects.⁷⁹ These regions have a key role in the mapping of visual and proprioceptive information for spatial awareness, limb positioning, and movement perception.^98-100 These findings suggest that individuals with ACLR may rely more on multimodal processing to maintain involved limb motor control, a notion supported by the sensory-reweighting hypothesis. Sensory-reweighting refers to the process by which the brain adjusts its reliance on different sensory inputs to compensate for deficits in one sensory modality.^80,81 Complementing the fMRI data, electroencephalography studies by Baumeister et al. revealed heightened brain activity in regions associated with focused attention and sensory processing in the affected limb of individuals with ACLR.^101,102

CLINICAL CONSEQUENCES

The neurophysiological and neuroplastic changes following ACL injury and reconstruction have profound clinical implications, often reinforcing maladaptive motor patterns and contributing to long-term functional impairments (Figure 1D). Sensorimotor uncertainty, driven by unreliable sensory feedback, has been shown to contribute to muscular co-contraction or limb stiffness,^103,104 which may offer protection but ultimately reduce movement efficiency. These compensatory strategies can alter joint biomechanics, increasing the risk of knee osteoarthritis.¹⁰⁵ Notably, a recent systematic review found that nearly 80% of individuals with a history of ACLR exhibited increased levels of co-contraction magnitude in the affected limb during functional tasks.¹⁰⁶

In addition to motor impairments, sensorimotor uncertainty may also contribute to significant cognitive and emotional consequences. Altered sensory perception can manifest as fear of movement (kinesiophobia) or fear of re-injury, which are common psychological barriers during rehabilitation.¹⁰⁷ This fear may stem from the patient’s diminished confidence in the sensory feedback from their injured or reconstructed limb due to the knee’s ongoing “noisiness” and impaired sensory perception. Psychological factors have been shown to impede return to sport, alter movement patterns and muscle activity, and increase the risk of re-injury.^108,109

Until robust randomized-controlled trials are completed, preliminary evidence exists for a variety of potential neuro-targeted therapy options to enhance sensory feedback and reduce reliance on compensatory sensory modalities.^110-112 Such strategies might include the use of virtual reality, stroboscopic glasses, and dual-task paradigms, which may help to recalibrate proprioceptive control by perturbating vision and/or cognition.^110-112 Chaput et al. recently introduced a visual-cognitive rehabilitation progression for patients recovering from ACLR to promote sensorimotor adaptation.¹¹² Additionally, transcutaneous electrical nerve stimulation may be employed to leverage stochastic resonance, which amplifies relevant sensory signals, reducing sensorimotor uncertainty.¹¹³ By integrating these approaches with traditional rehabilitation, patients may achieve improved motor control by enhancing sensory feedback and reducing sensorimotor uncertainty, ultimately optimizing sensory predictions for more efficient movement and better preparing them for return to sport or their prior level of function.

AREAS FOR FUTURE RESEARCH

A major limitation of current ACL injury risk research is the lack of paradigms that systematically investigate the ability to dynamically stabilize the knee joint in reaction to unanticipated perturbations. Traditional assessments primarily focus on discrete tasks, such as jump landings or cutting maneuvers, which may not fully capture the complex nature of sensorimotor coordination or the ability to respond to unexpected challenges. While tasks like the tuck jump being to approach a more serial nature,¹¹⁴ they still fall short of mimicking the continuous, rhythmic demands of activities like walking or running.

Much can be learned from prior gait sensorimotor adaptation studies, which have demonstrated that individuals can quickly adapt and modify their motor behaviors based on perturbations induced by treadmill belt accelerations or decelerations. However, a limitation of these split belt treadmill paradigms is the inability to force participants to stabilize under different directional perturbations, which is more akin to athletic maneuvers. Other treadmill or moving platform paradigms have introduced medio-lateral perturbations to study reactive balance and gait stability under different directions. Recent studies have found that healthy subjects increase their base of support in response to small perturbations, with higher lateral perturbation intensities eliciting a greater knee joint response, and that lateral perturbations are the most challenging, resulting in wider, shorter, and faster steps.^115-117 These simple gait adaptations are likely a behavioral response secondary to perturbation-induced sensorimotor uncertainty, making treadmill perturbations a desirable paradigm to test the ACL NOISE hypothesis.

CONCLUSION

The ACL NOISE hypothesis reframes how ACL injury disrupts sensorimotor processing, leading to increased sensorimotor uncertainty and compromised dynamic knee stability. The ACL plays a vital role in proprioceptive signaling and reflexive muscle activity essential for joint stability, but injury and sensory noise impairs these functions, resulting in reliance on compensatory neural strategies. In addition, the cerebellum’s involvement in sensory prediction and motor correction emphasizes the importance of accurate sensory feedback for effective motor control. Future research should consider testing the NOISE hypothesis by creating a paradigm that examines dynamic joint stability in response to unexpected perturbations. This approach would help assess motor coordination errors and drive the development of clinical strategies aimed at reducing sensorimotor uncertainty following ACLR.

HIGHLIGHTS.

• ACL injury-related noise affects sensorimotor control and movement precision.

• Sensorimotor uncertainty post-ACL injury may drive neuroplastic changes.

• The cerebellum may play a key role in adapting to unexpected perturbations.

• Neuro-targeted therapies like VR and TENS may enhance sensory feedback post-ACLR.