Changes in event-related brain responses and habituation during child development – A systematic literature review

ObjectiveThis systematic review highlights the influence of developmental changes of the central nervous system on habituation assessment during child development. Therefore, studies on age dependant changes in event-related brain responses as well as studies on behavioural and neurophysiological habituation during child development are compiled and discussed.MethodsTwo PubMed searches with terms “(development evoked brain response (fetus OR neonate OR children) (electroencephalography OR magnetoencephalography))” and with terms “(psychology habituation (fetal OR neonate OR children) (human brain))” were performed to identify studies on developmental changes in event-related brain responses as well as habituation studies during child development.ResultsBoth search results showed a wide diversity of subjects’ ages, stimulation protocols and examined behaviour or components of event-related brain responses as well as a demand for more longitudinal study designs.ConclusionsA conclusive statement about clear developmental trends in event-related brain responses or in neurophysiological habituation studies is difficult to draw. Future studies should implement longitudinal designs, combination of behavioural and neurophysiological habituation measurement and more complex habituation paradigms to assess several habituation criteria.SignificanceThis review emphasizes that event-related brain responses underlie certain changes during child development which should be more considered in the context of neurophysiological habituation studies.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI

ObjectiveSpinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI.MethodsWe used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation).ResultsSomatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants.ConclusionsOur results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI.SignificanceIdentifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity.     

Neurophysiological adaptations to spaceflight and simulated microgravity

Changes in physiological functions after spaceflight and simulated spaceflight involve several mechanisms. Microgravity is one of them and it can be partially reproduced with models, such as head down bed rest (HDBR). Yet, only a few studies have investigated in detail the complexity of neurophysiological systems and their integration to maintain homeostasis. Central nervous system changes have been studied both in their structural and functional component with advanced techniques, such as functional magnetic resonance (fMRI), showing the main involvement of the cerebellum, cortical sensorimotor, and somatosensory areas, as well as vestibular-related pathways. Analysis of electroencephalography (EEG) led to contrasting results, mainly due to the different factors affecting brain activity. The study of corticospinal excitability may enable a deeper understanding of countermeasures' effect, since greater excitability has been shown being correlated with better preservation of functions. Less is known about somatosensory evoked potentials and peripheral nerve function, yet they may be involved in a homeostatic mechanism fundamental to thermoregulation. Extending the knowledge of such alterations during simulated microgravity may be useful not only for space exploration, but for its application in clinical conditions and for life on Earth, as well.     

Early nociceptive evoked potentials (NEPs) recorded from the scalp

ObjectiveNeurophysiological investigation of nociceptive pathway has so far been limited to late cortical responses. We sought to detect early components of the cortical evoked potentials possibly reflecting primary sensory activity.MethodsThe 150 IDE micropatterned electrode was used to selectively activate Aδ intraepidermic fibres of the right hand dorsum in 25 healthy subjects and 3 patients suffering from trigeminal neuralgia. Neurographic recordings were performed to assess type of stimulated fibres and check selectivity. Cortical evoked potentials were recorded from C3′-Fz and Cz-Au1.ResultsNeurographic recordings confirmed selective activation of Aδ fibres. Early components were detected after repetitive stimulation (0.83/s rate and 250–500 averages); the first negative component occured at 40 ms (N40) on the contralateral scalp.ConclusionsThe provided data support the hypothesis that N40 could be the cortical primary response conducted by fast Aδ fibres.SignificanceThis is the first report of early, possibly primary, cortical responses in humans by nociceptive peripheral stimulation. Although not perfected yet to allow widespread diagnostic use, this is probably the only method to allow fully objective evaluation of the nociceptive system, with important future implications in experimental and clinical neurophysiology.     

Engagement of cortico-cortical and cortico-subcortical networks in a patient with epileptic spasms: An integrated neurophysiological study

ObjectiveWe aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques.MethodsSeventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks.ResultsIctal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain.ConclusionsIn this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient.SignificanceCortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.     

A new potential specifically marks the sensory thalamus in anaesthetised patients

ObjectiveDuring deep brain stimulation (DBS) surgery, we analysed somatosensory evoked potentials (SSEPs) using microelectrode recordings (MERs) in patients under general anaesthesia.MethodsWe obtained MERs from 5 patients with refractory epilepsy. Off-line analysis isolated local field potentials (LFPs, 2–200 Hz) and high frequency components (HFCs, 0.5–5 kHz). Trajectories were reconstructed off-line.ResultsThe ventral caudate (V.c.) nucleus was most frequently recorded from (171 mm). Very high frequency oscillations (VHFOs) were recorded up to 8 mm in length from all 4 electrodes but were most frequently recorded from the V.c. The properties of VHFOs were similar among all nuclei (frequency >1500 Hz, amplitude ∼3 µV, starting time ∼14 ms, duration 8–9 ms). Consecutive recordings did not show any synchronization or propagation, but a new kind of potential (high frequency oscillation, HFO) appeared abruptly inside the V.c. (frequency = 848 ± 66 Hz, amplitude = 5.2 ± 1.8 µV starting at 17.7 ± 0.5 ms, spanning 3.4 ± 0.3 ms).ConclusionsVHFOs are widely extending and cannot be ascribed to the V.c. HFOs in patients under general anaesthesia can serve as a landmark to identify the V.c. in thalamic DBS surgery.SignificanceThalamic processing involves nuclei other than the V.c, and HFO can be used to improve DBS surgery.     

Median somatosensory evoked potential as a predictor of clinical outcome after urgent surgical extracranial internal carotid artery recanalization

ObjectiveChanges in the N20/P25 amplitude of somatosensory evoked potentials (SEP) of the median nerve have been found to correlate with those in cortical regional cerebral blood flow (rCBF). Our study presents the use of median nerve SEP amplitude in predicting the clinical outcome of urgent surgical internal carotid artery (ICA) recanalization.MethodsA total of 27 patients suffering an acute ischemic stroke (AIS) with extracranial ICA occlusion within 24 h were prospectively recruited. The primary preoperative endpoints included the SEP amplitude absolute value (SEP-amp) and the SEP amplitude side-to-side ratio (SEP-ratio).Clinical outcome at 3 months postoperatively was assessed using the modified Rankin scale (mRS-3M).ResultsThe positive predictive values (PPVs) for SEP-amp and SEP-ratio were 95.5% and 100%, respectively, with the negative predictive values (NPVs) being 60.0% and 100%, respectively. The SEP-ratio correlated fully with mRS-3M.ConclusionThe median SEP side-to-side N20/P25 amplitude ratio seems to be a very strong positive and negative predictor of the clinical outcome of urgent recanalization of an extracranial ICA occlusion.SignificanceThe results suggest that cortical evoked activity may help in selection patient for surgical recanalization and predict clinical recovery after an acute ischemic stroke.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.     

Long-term effects of concussion on relevancy-based modulation of somatosensory-evoked potentials

ObjectiveThe purpose of this investigation was to better understand the effects of concussions on the ability to selectively up or down-regulate incoming somatosensory information based on relevance.MethodsMedian nerve somatosensory-evoked potentials (SEPs) were elicited from electrical stimulation and recorded from scalp electrodes while participants completed tasks that altered the relevance of specific somatosensory information being conveyed along the stimulated nerve.ResultsWithin the control group, SEP amplitudes for task-relevant somatosensory information were significantly greater than for non-relevant somatosensory information at the earliest cortical processing potentials (N20-P27). Alternatively, the concussion history group showed similar SEP amplitudes for all conditions at early processing potentials, however a pattern similar to controls emerged later in the processing stream (P100) where both movement-related gating and facilitation of task-relevant information were present.ConclusionsPreviously concussed participants demonstrated impairments in the ability to up-regulate relevant somatosensory information at early processing stages. These effects appear to be chronic, as this pattern was observed on average several years after participants’ most recent concussion.SignificanceGiven the role of the prefrontal cortex in relevancy-based facilitation during movement-related gating, these findings lend support to the notion that this brain area may be particularly vulnerable to concussive forces.     

Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia

ObjectiveWe examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia.MethodsWe prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement.ResultsCCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts.ConclusionFor the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus.SignificanceThis intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.     

Bedside neurophysiological tests can identify neonates with stroke leading to cerebral palsy

ObjectiveThe unspecific symptoms of neonatal stroke still challenge its bedside diagnosis. We studied the accuracy of routine electroencephalography (EEG) and simultaneously recorded somatosensory evoked potentials (EEG-SEP) for diagnosis and outcome prediction of neonatal stroke.MethodsWe evaluated EEG and EEG-SEPs from a hospital cohort of 174 near-term neonates with suspected seizures or encephalopathy, 32 of whom were diagnosed with acute ischemic or hemorrhagic stroke in MRI. EEG was scored for background activity and seizures. SEPs were classified as present or absent. Developmental outcome of stroke survivors was evaluated from medical records at 8- to 18-months age.ResultsThe combination of continuous EEG and uni- or bilaterally absent SEP (n = 10) was exclusively seen in neonates with a middle cerebral artery (MCA) stroke (specificity 100%). Moreover, 80% of the neonates with this finding developed with cerebral palsy. Bilaterally present SEPs did not exclude stroke, but predicted favorable neuromotor outcome in stroke survivors (positive predictive value 95%).ConclusionsAbsent SEP combined with continuous EEG background in near-term neonates indicates an MCA stroke and a high risk for cerebral palsy.SignificanceEEG-SEP offers a bedside method for diagnostic screening and a reliable prediction of neuromotor outcome in neonates suspected of having a stroke.     

Fixation-related potentials in naming speed: A combined EEG and eye-tracking study on children with dyslexia

ObjectiveWe combined electroencephalography (EEG) and eye-tracking recordings to examine the underlying factors elicited during the serial Rapid-Automatized Naming (RAN) task that may differentiate between children with dyslexia (DYS) and chronological age controls (CAC).MethodsThirty children with DYS and 30 CAC (M_age = 9.79 years; age range 7.6 through 12.1 years) performed a set of serial RAN tasks. We extracted fixation-related potentials (FRPs) under phonologically similar (rime-confound) or visually similar (resembling lowercase letters) and dissimilar (non-confounding and discrete uppercase letters, respectively) control tasks.ResultsResults revealed significant differences in FRP amplitudes between DYS and CAC groups under the phonologically similar and phonologically non-confounding conditions. No differences were observed in the case of the visual conditions. Moreover, regression analysis showed that the average amplitude of the extracted components significantly predicted RAN performance.ConclusionFRPs capture neural components during the serial RAN task informative of differences between DYS and CAC and establish a relationship between neurocognitive processes during serial RAN and dyslexia.SignificanceWe suggest our approach as a methodological model for the concurrent analysis of neurophysiological and eye-gaze data to decipher the role of RAN in reading.     

Effects of stimulation intensity on intracranial cortico-cortical evoked potentials: A titration study

ObjectiveThe aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks.MethodsWe studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5–10 mA, median 6 mA).ResultsWe found that with a biphasic 0.15 ms/phase pulse at least 2–4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6–7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology.ConclusionsWe determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate.SignificanceThis titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.     

Sleep modulates effective connectivity: A study using intracranial stimulation and recording

ObjectiveSleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks’ organization.MethodsWe analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM – N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach.ResultsSleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity.In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep.ConclusionsSleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity.SignificanceWe found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study

ObjectiveTo test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).MethodsIn a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.ResultsThe facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.ConclusionsThe results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.SignificanceThese observations can be used to optimize iTBS investigational and therapeutic applications.     

Bradykinesia in Alzheimer’s disease and its neurophysiological substrates

ObjectiveAlzheimer’s disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer’s disease.MethodsTwenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation.ResultsPatients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer’s disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery.ConclusionThis study provides new information on the pathophysiology of altered voluntary movements in Alzheimer’s disease.SignificanceThe study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer’s disease.