Maladaptive Cortical Plasticity Research Articles

P 84 Altered sensorimotor integration of afferent inhibition in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition which frequently results in sensorimotor dysfunction of the affected limb. With respect to pathophysiology an impaired interaction in sensorimotor cortex has been hypothesized 1 . Sensorimotor interactions can be assessed through transcranial magnetic stimulation (TMS) that is preceded by an electrical stimulation of peripheral motor or sensory nerves (short/ long afferent inhibition; SAI/LAI). Previous studies revealed only minor alterations of LAI using peripheral motor stimulation in CRPS 2 . This study uses a more comprehensive assessment of SAI and LAI, induced by motor and sensory peripheral stimulation, to assess interaction of the sensorimotor system in CRPS. Methods : 13 unilateral upper limb affected patients with CRPS (9 females, 54 ± 17.8 years) and 11 controls (HCs; 8 females, 52± 18.3 years) received TMS on either hemisphere. SAI and LAI were induced by a motor (m_) or sensory (s_) median nerve stimulation preceded by TMS with 20ms (m_SAI) and 200ms (m_LAI) or 23ms (s_SAI) and 203ms (s_LAI), respectively 3 . Twenty paired and single TMS stimuli were randomly applied for each condition. Results: Pain levels were 5.1±1.5/10 at rest and 7.4±2.1/10 during movements. ANOVA revealed a significant group effect for patients vs. HCs on the affected side (F=2.2, p=0.048). Post hoc tests were corrected for multiple comparisons and showed reduced inhibition in patients after sensory stimulation (s_SAI: t=-2.51, p=0.04; s_LAI: t=-2.53 p=0.038) and motor stimulation with ISI 200ms (m_LAI: t=-2.62, p=0.032). Afferent sensorimotor inhibition was lower in patients with longer disease duration (r=-0.66, p=0.014). Discussion: We demonstrate altered sensorimotor integration of afferent inhibition in CRPS. Since afferent inhibition after sensory stimulation is thought to be mediated via interconnections especially between Brodmann area 3b of somatosensory and the motor cortex, our results complement existing literature about maladaptive cortical plasticity of these regions in CRPS 4,5 . Impairment in LAI, that is thought to involve higher-order somatosensory cortical areas and the posterior parietal cortex is in line with existing literature on chronic pain 2,4 . Future longitudinal investigation should evaluate intra- and intercortical sensorimotor integration systematically in CRPS to better understand their impact in development of sensorimotor symptoms. Literature: 1 Harris AJ. Cortical origins of pathological pain. Lancet 1999. 2 Morgante et al. Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand. Mov Disord. 2017. 3 Sailer A, et al. Brain. 2003. 4 Chen et al. Modulation of motor cortex excitability by median nerve and digit stimulation. Exp Brain Res. 1999. 5 Pfannmöller et al. Investigations on maladaptive plasticity in the sensorimotor cortex of unilateral upper limb CRPS I patients. RNN. 2019.

BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury

Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1CreER;Bdnfflox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury-induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.

Modulation of Corticospinal Excitability by Two Different Somatosensory Stimulation Patterns; A Pilot Study.

Following amputation, almost two-thirds of amputees experience unpleasant to painful sensations in the area of the missing limb. Whereas the mechanism of phantom limb pain (PLP) remains unknown, it has been shown that maladaptive cortical plasticity plays a major role in PLP. Transcutaneous electrical nerve stimulation (TENS) generating sensory input is believed to be beneficial for PLP relief. TENS effect may be caused by possible reversing reorganization at the cortical level that can be evaluated by changes in the excitability of the corticospinal (CS) pathway. Excitability changes are dependent on the chosen stimulation patterns and parameters. The aim of this study was to investigate the effect of two TENS patterns on the excitability of the CS tract among healthy subjects. We compared a non-modulated TENS as a conventional pattern with pulse width modulated TENS pattern. Motor evoked potentials (MEPs) from APB muscles of stimulated arm (TENS-APB) and contralateral arm (Control-APB) were recorded. We applied single TMS pulses on two subjects for each TENS pattern. The results showed that both patterns increase the CS excitability, while the effects of the conventional TENS is stronger. However, the amplitude of MEPs from control-APB after TENS delivery remained almost the same.Clinical Relevance- The primary results revealed changes in the activity of CS pathway for both patterns. A future study on a larger population is needed to provide strong evidence on the changes in CS excitability. The evaluation part with more factors such as changes in intracortical inhibition (ICI) may be beneficial to find an optimal modulated TENS pattern to enhance pain alleviation process in PLP.

Impaired motor cortical plasticity associated with cannabis use disorder in young adults.

Maladaptive cortical plasticity has been described in individuals with heroin and methamphetamine addiction and may mediate other substance abuse disorders. It is unknown whether cannabis dependence in humans alters the capacity for induction of cortical plasticity. The aim of this study was to non-invasively investigate cortical plasticity with transcranial magnetic stimulation in young adults who meet DSM-5 criteria for cannabis use disorder (CUD). Thirty men (ages 20- 30) who used cannabis daily over the previous 6 months (15 diagnosed of CUD) and 15 demographically matched non-users were enrolled in this study. All participants underwent two sessions of theta burst stimulation (TBS) in which either continuous TBS (cTBS; 600 pulses, 80% active motor threshold) or intermittent TBS (iTBS; 2-s train of cTBS repeated every 10 s for a total of 190 s, 600 pulses) was applied over the primary motor cortex. The effects of these protocols were assessed by analysing the contralateral motor evoked potentials (MEPs). The relationships between cortical plasticity and problematic cannabis use, degree of dependence, and nicotine addiction were also investigated. Significant MEP inhibition after cTBS was observed in both cannabis users without CUD and non-users, while this inhibition was not seen in cannabis users with CUD. Strikingly, less motor cortical plasticity was observed in subjects with severe problematic cannabis use. No significant differences between users and non-users were found in the iTBS-induced cortical plasticity measures. Our study provides the first evidence of maladaptive cortical plasticity associated with cannabis use disorder and problematic cannabis use in humans.

Patterns of cortical reorganization in facial synkinesis: a task functional magnetic resonance imaging study.

Facial synkinesis, a sequela of peripheral facial nerve palsy, is characterized by simultaneous involuntary facial movement during a voluntary desired one. Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles. This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis, using the task functional magnetic resonance imaging. Facial motor tasks, including blinking and smiling, were performed by 16 patients (aged 30.6 ± 4.5 years, 14 females/2 males) and 24 age- and sex-matched healthy controls (aged 29.1 ± 4.2 years, 19 females/5 males). Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls. Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face, than those on the unaffected side. Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area. This study was registered in Chinese Clinical Trial Registry (registration number: ChiCTR1800014630).

Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation.

Neuroprosthetics research in amputee patients aims at developing new prostheses that move and feel like real limbs. Targeted muscle and sensory reinnervation (TMSR) is such an approach and consists of rerouting motor and sensory nerves from the residual limb towards intact muscles and skin regions. Movement of the myoelectric prosthesis is enabled via decoded electromyography activity from reinnervated muscles and touch sensation on the missing limb is enabled by stimulation of the reinnervated skin areas. Here we ask whether and how motor control and redirected somatosensory stimulation provided via TMSR affected the maps of the upper limb in primary motor (M1) and primary somatosensory (S1) cortex, as well as their functional connections. To this aim, we tested three TMSR patients and investigated the extent, strength, and topographical organization of the missing limb and several control body regions in M1 and S1 at ultra high-field (7 T) functional magnetic resonance imaging. Additionally, we analysed the functional connectivity between M1 and S1 and of both these regions with fronto-parietal regions, known to be important for multisensory upper limb processing. These data were compared with those of control amputee patients (n = 6) and healthy controls (n = 12). We found that M1 maps of the amputated limb in TMSR patients were similar in terms of extent, strength, and topography to healthy controls and different from non-TMSR patients. S1 maps of TMSR patients were also more similar to normal conditions in terms of topographical organization and extent, as compared to non-targeted muscle and sensory reinnervation patients, but weaker in activation strength compared to healthy controls. Functional connectivity in TMSR patients between upper limb maps in M1 and S1 was comparable with healthy controls, while being reduced in non-TMSR patients. However, connectivity was reduced between S1 and fronto-parietal regions, in both the TMSR and non-TMSR patients with respect to healthy controls. This was associated with the absence of a well-established multisensory effect (visual enhancement of touch) in TMSR patients. Collectively, these results show how M1 and S1 process signals related to movement and touch are enabled by targeted muscle and sensory reinnervation. Moreover, they suggest that TMSR may counteract maladaptive cortical plasticity typically found after limb loss, in M1, partially in S1, and in their mutual connectivity. The lack of multisensory interaction in the present data suggests that further engineering advances are necessary (e.g. the integration of somatosensory feedback into current prostheses) to enable prostheses that move and feel as real limbs.

Auditory and Visual Electrophysiology of Deaf Children with Cochlear Implants: Implications for Cross-modal Plasticity.

Deaf children who receive a cochlear implant early in life and engage in intensive oral/aural therapy often make great strides in spoken language acquisition. However, despite clinicians’ best efforts, there is a great deal of variability in language outcomes. One concern is that cortical regions which normally support auditory processing may become reorganized for visual function, leaving fewer available resources for auditory language acquisition. The conditions under which these changes occur are not well understood, but we may begin investigating this phenomenon by looking for interactions between auditory and visual evoked cortical potentials in deaf children. If children with abnormal auditory responses show increased sensitivity to visual stimuli, this may indicate the presence of maladaptive cortical plasticity. We recorded evoked potentials, using both auditory and visual paradigms, from 25 typical hearing children and 26 deaf children (ages 2–8 years) with cochlear implants. An auditory oddball paradigm was used (85% /ba/ syllables vs. 15% frequency modulated tone sweeps) to elicit an auditory P1 component. Visual evoked potentials (VEPs) were recorded during presentation of an intermittent peripheral radial checkerboard while children watched a silent cartoon, eliciting a P1–N1 response. We observed reduced auditory P1 amplitudes and a lack of latency shift associated with normative aging in our deaf sample. We also observed shorter latencies in N1 VEPs to visual stimulus offset in deaf participants. While these data demonstrate cortical changes associated with auditory deprivation, we did not find evidence for a relationship between cortical auditory evoked potentials and the VEPs. This is consistent with descriptions of intra-modal plasticity within visual systems of deaf children, but do not provide evidence for cross-modal plasticity. In addition, we note that sign language experience had no effect on deaf children’s early auditory and visual ERP responses.

Chronic sensory stroke with and without central pain is associated with bilaterally distributed sensory abnormalities as detected by quantitative sensory testing.

Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P < 0.01). Patients with sensory stroke but without CPSP (non-pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P < 0.05). In patients with CPSP, changes in CDT, PHS, dynamic mechanical allodynia, and temporal pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

Sustained Effect of Botulinum Neurotoxin in Myoclonus Owing to Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is defined as continuous myoclonic jerking of a body part of cortical origin and often resembles a movement disorder. Unfortunately, anti-epileptic therapy is frequently ineffective. Currently, the effect of botulinum neurotoxin (BoNT) therapy in EPC is controversial. We analyzed case histories, treatment protocols, and video documentation of 5 patients with EPC, who received BoNT therapy in our movement disorders unit. The Unified Myoclonus Rating Scale was used to document treatment effects. In all patients, BoNT treatment significantly reduced severity and frequency of myoclonus and led to pronounced improvement of speech and arm utilization, regardless of etiology or duration of EPC. BoNT represents a safe, effective treatment in EPC, offering long-term abatement of myoclonus. The substantial functional profit may hint at mechanisms beyond local impairment of neuromuscular transmission, such as modulation of maladaptive cortical plasticity, as observed in dystonia and poststroke spasticity.

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study

ObjectiveTo better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. Methods17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6±9.8y.o, disease duration 22±35months) underwent a 29-channel resting-state electroencephalography (EEG – 5min opened-eyes, 5min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs – N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7±15.1y.o). ResultsEyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers’ clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. ConclusionsWe showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. SignificanceThis might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach.

Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings.

BackgroundMechanisms underlying the development of phantom limb pain and neuropathic pain after limb amputation and spinal cord injury, respectively, are poorly understood. The goal of this systematic review was to assess the robustness of evidence in support of “maladaptive plasticity” emerging from applications of advanced functional magnetic resonance imaging (MRI).MethodsUsing MeSH heading search terms in PubMed and SCOPUS, a systematic review was performed querying published manuscripts.ResultsFrom 146 candidate publications, 10 were identified as meeting the inclusion criteria. Results from fMRI investigations provided some level of support for maladaptive cortical plasticity, including longitudinal studies that demonstrated a change in functional organization related to decreases in pain. However, a number of studies have reported no relationship between reorganization, pain and deafferentation, and emerging evidence has also suggested the opposite — that is, chronic pain is associated with preserved cortical function.ConclusionBased solely on advanced functional neuroimaging results, there is only limited evidence for a relationship between chronic pain intensity and reorganization after deafferentation. The review demonstrates the need for additional neuroimaging studies to clarify the relationship between chronic pain and reorganization.

Sensory abnormalities in focal hand dystonia and non-invasive brain stimulation.

It has been proposed that synchronous and convergent afferent input arising from repetitive motor tasks may play an important role in driving the maladaptive cortical plasticity seen in focal hand dystonia (FHD). This hypothesis receives support from several sources. First, it has been reported that in subjects with FHD, paired associative stimulation produces an abnormal increase in corticospinal excitability, which was not confined to stimulated muscles. These findings provide support for the role of excessive plasticity in FHD. Second, the genetic contribution to the dystonias is increasingly recognized indicating that repetitive, stereotyped afferent inputs may lead to late-onset dystonia, such as FHD, more rapidly in genetically susceptible individuals. It can be postulated, according to the two factor hypothesis that dystonia is triggered and maintained by the concurrence of environmental factors such as repetitive training and subtle abnormal mechanisms of plasticity within somatosensory loop. In the present review, we examine the contribution of sensory-motor integration in the pathophysiology of primary dystonia. In addition, we will discuss the role of non-invasive brain stimulation as therapeutic approach in FHD.

Peripheral nervous system origin of phantom limb pain

Nearly all amputees continue to feel their missing limb as if it still existed, and many experience chronic phantom limb pain (PLP). What is the origin of these sensations? There is currently a broad consensus among investigators that PLP is a top-down phenomenon, triggered by loss of sensory input and caused by maladaptive cortical plasticity. We tested the alternative hypothesis that PLP is primarily a bottom-up process, due not to the loss of input but rather to exaggerated input, generated ectopically in axotomized primary afferent neurons in the dorsal root ganglia (DRGs) that used to innervate the limb. In 31 amputees, the local anesthetic lidocaine was applied intrathecally and/or to the DRG surface (intraforaminal epidural block). This rapidly and reversibly extinguished PLP and also nonpainful phantom limb sensation (npPLS). Control injections were ineffective. For intraforaminal block, the effect was topographically appropriate. The suppression of PLP and npPLS could also be demonstrated using dilute lidocaine concentrations that are sufficient to suppress DRG ectopia but not to block the propagation of impulses generated further distally in the nerve. PLP is driven primarily by activity generated within the DRG. We recommend the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain.

Can maladaptive cortical plasticity form new sensory experiences? Revisiting phantom pain

Phantom pain has become an influential example of maladaptive cortical plasticity. According to this model, sensory deprivation following limb amputation allows for intra-regional invasion of neighbouring cortical representations into the former hand area of the primary sensorimotor cortex, which gives rise to pain sensations. Over the years, this model was extended to explain other disorders of pain, motor control and tinnitus, and has inspired rehabilitation strategies. Yet, other research, demonstrating that phantom hand representation is maintained in the sensorimotor system, and that phantom pain can be triggered by bottom-up aberrant inputs, may call this model to question. Using fMRI, we identified the cortical area representing the missing hand in a group of 18 arm amputees. This allowed us to directly study changes in the ‘phantom’ cortex associated with chronic phantom pain, using functional connectivity and voxel-based morphometry. We show that, while loss of sensory input is generally characterized by structural degeneration of the deprived sensorimotor cortex, the experience of persistent pain was associated with preserved intra-regional structure and functional organization. Furthermore, consistent with the dissociative nature of phantom sensations from other sensory experiences, phantom pain is also associated with reduced long-range inter-regional functional connectivity. We propose that this disrupted inter-regional connectivity may be consequential, rather than causal, of the retained yet isolated local representation of phantom pain. We therefore propose that, contrary to the maladaptive model, cortical plasticity occurs when powerful and long-lasting subjective sensory experience, most likely due to peripheral inputs, is decoupled from the external sensory environment.

Les nouvelles approches des dystonies (clinique, génétique et hypothèses physio-pathologiques)

Dystonia is defined by the occurrence of abnormal twisting movements and posture, and may be generalized or focal. Many subtypes of dystonias have been described, including monogenic forms (eg. DYT1 and DYT6), secondary dystonias related to metabolic disorders, forms due to brain lesions (including post-anoxic brain injury), and tardive dystonia. Dystonia may also be associated with myoclonus (myoclonus-dystonia, DYT11) or parkinsonism (rapid-onset dystonia parkinsonism DYT1). Paroxystic dystonias are a subgroup of paroxysmal dyskinesias. Diagnosis is based mainly on clinical features, age at onset, outcome, associated neurological signs, and brain MRI. Until recently, basal ganglia dysfunction and alterations of the sensory-motor network with maladaptive cortical plasticity were the core pathophysiological features of dystonia. Cerebellar and cerebello-thalamic anatomic-functional abnormalities may also play a role. The main objectives of this review are to highlight the principal characteristics of dystonias and to provide an overview of known culprit genes and environmental factors. Current pathophysiological knowledge, including anatomic-functional abnormalities, is summarized.

Functional imaging in hereditary dystonia

Impaired cortical inhibiton and maladaptive cortical plasticity are functional hallmarks of sporadic focal dystonias. Whether or not these mechanisms translate to generalized dystonias and whether these features reflect state or trait characteristics are topics of research in hereditary dystonias. We present a series of studies using a multitracer approach with positron emission tomography (PET) and diffusion tensor MRI (DTI) in the DYT1 and the DYT6 genotype. In these hereditary dystonias functional and microstructural abnormalities were found in cortico-striatal-pallido-thalamocortical (CSPTC) and cerebellar-thalamo-cortical circuits. Genotype-specific abnormalities were localized to the basal ganglia, SMA and cerebellum. Functional changes, as potential correlates of maladaptive sensorimotor plasticity were found throughout the sensorimotor system and were more pronounced in affected mutation carriers than in their non-manifesting counterparts. In both genotypes, striatal metabolic abnormalities were paralleled by genotype-specific reductions in D(2) receptor availability. However, these reductions failed to show a clear association with clinical or functional markers of the disease. By contrast, microstructural changes of cerebellar pathways clearly related to penetrance and may thus represent the main intrinsic abnormality underlying cortical downstream effects, such as increased sensorimotor responsivity. These studies are consistent with the view of primary torsion dystonia as a neurodevelopmental circuit disorder involving CSPTC and related cerebellar pathways.

Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first through fourth digits. We hypothesize that aberrant afferent input from CTS will lead to maladaptive cortical plasticity, which may be corrected by appropriate therapy. Functional MRI (fMRI) scanning and clinical testing was performed on CTS patients at baseline and after 5 weeks of acupuncture treatment. As a control, healthy adults were also tested 5 weeks apart. During fMRI, sensory stimulation was performed for median nerve innervated digit 2 (D2) and digit 3 (D3), and ulnar nerve innervated digit 5 (D5). Surface-based and region of interest (ROI)-based analyses demonstrated that while the extent of fMRI activity in contralateral Brodmann Area 1 (BA 1) and BA 4 was increased in CTS compared to healthy adults, after acupuncture there was a significant decrease in contralateral BA 1 (P < 0.005) and BA 4 (P < 0.05) activity during D3 sensory stimulation. Healthy adults demonstrated no significant test-retest differences for any digit tested. While D3/D2 separation was contracted or blurred in CTS patients compared to healthy adults, the D2 SI representation shifted laterally after acupuncture treatment, leading to increased D3/D2 separation. Increasing D3/D2 separation correlated with decreasing paresthesias in CTS patients (P < 0.05). As CTS-induced paresthesias constitute diffuse, synchronized, multidigit symptomatology, our results for maladaptive change and correction are consistent with Hebbian plasticity mechanisms. Acupuncture, a somatosensory conditioning stimulus, shows promise in inducing beneficial cortical plasticity manifested by more focused digital representations.

Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome

Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI-4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HC). CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short-term brain response to acupuncture stimulation, as well as the influence of longer-term acupuncture therapy effects on this short-term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non-specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala – the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter-digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala.