Short-latency Afferent Inhibition Research Articles

Human brain cortical correlates of short-latency afferent inhibition: a combined EEG–TMS study

When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensory-evoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico-cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition.

Impairment of sensory-motor plasticity in mild Alzheimer’s disease

BackgroundPrimary motor cortex (M1) is relatively spared in the early stages of Alzheimer’s disease (AD). ObjectiveAim of the present study was to investigate whether abnormal M1 synaptic plasticity is present at an early stage of AD. We employed an electrophysiological protocol, named rapid paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies corticospinal excitability and short latency afferent inhibition (SAI). MethodsWe studied 10 patients with a diagnosis of probable mild AD according to the Mini Mental State Examination score (minimum 21) and 14 age-matched control subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus interval of 25 ms. ResultsBaseline SAI was significantly reduced in AD patients. In the control subjects rPAS induced a significant increase in MEP amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h. Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and SAI in mild AD patients. ConclusionsSensory-motor plasticity is impaired in the motor cortex of AD at an early stage of the disease.

Reduced interhemispheric inhibition in mild cognitive impairment

In mild cognitive impairment (MCI), the corpus callosum is known to be affected structurally. We evaluated callosal function by interhemispheric inhibition (IHI) using transcranial magnetic stimulation (TMS) in MCI patients. We investigated 12 amnestic MCI patients and 16 healthy age-matched control subjects. The IHI was studied with a paired-pulse TMS technique. The conditioning TMS was given over the right primary motor cortex (M1) and the test TMS over the left M1. Motor evoked potentials were recorded from the relaxed first dorsal interosseous muscle. We also studied other motor cortical circuit functions; short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Both the amount of IHI and SAI were significantly reduced in MCI patients as compared with control subjects, whereas SICI or ICF did not differ between them. The degree of IHI significantly correlated with neither the mini-mental state examination score nor the degree of SAI. Our results suggest that transcallosal connection between bilateral M1 is primarily involved in MCI, regardless of SAI dysfunction.

10. Sensorimotor interaction and motor learning in facial muscles

Background and aim : Integration of sensory information with motor output is thought to be important in motor learning. In limb muscles, this is studied using the short afferent inhibition (SAI) paradigm, to assess sensorimotor interaction, and paired associative stimulation (PAS), to evaluate LTP-like plasticity. As far as we know, SAI and PAS paradigms have never been used in the territory of the cranial nerves. The present study was aimed at testing in normal subjects whether sensorimotor interaction and LTP-like plasticity can be observed in facial muscles as well as in limb muscles. Methods : Motor evoked potentials (MEPs) were evoked in the depressor angulis oris (DAO) muscle of 7 subjects. MEPs were recorded from the contralateral DAO at rest and during 10% maximal voluntary contraction (active condition). SAI was tested in 5 subjects, by pairing electrical stimulation (ES, intensity 3 times the perceptual threshold) of the facial nerve, with magnetic stimulation (TMS, 120% of motor threshold intensity) of the facial motor cortex. Intervals between ES and TMS were 5, 10, 15, 20, 25 and 30 ms. The LTP-like plasticity protocol (200 pairs of ES and TMS, 20 ms ISI, at 0.25 Hz) was tested in X subjects by evoking twenty MEPs in both resting and active conditions, before and at 0, 20 and 30 min after paired stimulation. Results : Facial nerve stimulation in the SAI paradigm had no significant affect on MEP amplitude, either in the active or in the relaxed DAO muscle. By contrast MEP amplitude at rest showed a trend of facilitation (p < 0,072) after the PAS protocol administration. When tested at rest this effect was observed at baseline and after 10 min. On the contrary MEP amplitude recorded during activity was significantly enhanced at 10 (p < 0,026) and 30 (p < 0,014) minutes after PAS. There was a significant difference between the time course in resting and active conditions (p < 0,019). Conclusions : These data show that there is no short latency afferent inhibition in the facial motor cortex, yet despite this, there is evidence for maintained LTP-like plasticity. Further studies are needed to understand how and why PAS works in facial muscles despite the absence of SAI. A larger sample is also required to confirm the PAS effect on resting DAO MEPs. A second point to be clarified is why the PAS time course at rest is different from that operating during active condition.

Spinal inhibition of descending command to soleus motoneurons is removed prior to dorsiflexion

It has recently been demonstrated that soleus motor-evoked potentials (MEPs) are facilitated prior to the onset of dorsiflexion. The purpose of this study was to examine if this could be explained by removal of spinal inhibition of the descending command to soleus motoneurons. To test this, we investigated how afferent inputs from the tibialis anterior muscle modulate the corticospinal activation of soleus spinal motoneurons at rest, during static contraction and prior to movement. MEPs activated by transcranial magnetic stimulation (TMS) and Hoffmann reflexes (H-reflexes), activated by electrical stimulation of the posterior tibial nerve (PTN), were conditioned by prior stimulation of the common peroneal nerve (CPN) at a variety of conditioning-test (CT) intervals. MEPs in the precontracted soleus muscle were inhibited when the TMS pulse was preceded by CPN stimulation with a CT interval of 35 ms, and they were facilitated for CT intervals of 50-55 ms. A similar inhibition of the soleus H-reflex was not observed. To investigate which descending pathways might be responsible for the afferent-evoked inhibition and facilitation, we examined the effect of CPN stimulation on short-latency facilitation (SLF) and long-latency facilitation (LLF) of the soleus H-reflex induced by a subthreshold TMS pulse at different CT intervals. SLF is known to reflect the excitability of the fastest conducting, corticomotoneuronal cells whereas LLF is believed to be caused by more indirect descending pathways. At CT intervals of 40-45 ms, the LLF was significantly more inhibited compared to the SLF when taking the effect on the H-reflex into account. Finally, we investigated how the CPN-induced inhibition and facilitation of the soleus MEP were modulated prior to dorsiflexion. Whereas the late facilitation (CT interval: 55 ms) was similar prior to dorsiflexion and at rest, no inhibition could be evoked at the earlier latency (CT interval: 35 ms) prior to onset of dorsiflexion. The observation that the CPN-induced inhibition of soleus MEPs disappears prior to onset of dorsiflexion may explain why soleus MEPs are facilitated prior to onset of dorsiflexion contraction. A possible mechanism involves the removal of inhibition of the descending command to the motoneurons at a spinal interneuronal level because the inhibition was seen in LLF and not in SLF, and the MEP inhibition was not observed in the H-reflex. The data illustrate that spinal interneuronal pathways modify descending commands to human spinal motoneurons and influence the size of MEPs elicited by TMS.

Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study

ObjectiveTo describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). MethodsFive members of a Chilean family with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions. ResultsCSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC. ConclusionA compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical inhibition. In addition, some aspects of interhemispheric inhibition are increased in the presence of a single ATP13A2 mutation.

The Level of Cortical Afferent Inhibition in Acute Stroke Correlates With Long-Term Functional Recovery in Humans

Using transcranial magnetic stimulation, we investigated short-interval intracortical inhibition and short-latency afferent inhibition in acute ischemic stroke. We evaluated short-interval intracortical inhibition and short-latency afferent inhibition in the affected hemisphere and unaffected hemisphere in 16 patients and correlated electrophysiological parameters with outcome at 6 months. Affected hemisphere short-latency afferent inhibition was significantly reduced in patients, and short-latency afferent inhibition level correlated with functional outcome. Reduced afferent inhibition in acute stroke correlates with long-term recovery.

Short latency afferent inhibition differs among the subtypes of mild cognitive impairment

Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and a diagnosis of clinically probable Alzheimer disease (AD). The role of the cholinergic system in MCI is not clearly defined and needs to be further investigated. A transcranial magnetic stimulation (TMS) protocol, the short latency afferent inhibition (SAI), may give direct information about the function of some cholinergic pathways in the human motor cortex. We aimed to evaluate in the present study the relationship of SAI to the specific clinical subtypes of MCI. SAI was examined in 20 patients with amnestic MCI (10 SD, 10 MD), twenty patients with nonamnestic MCI (10 SD, 10 MD) and ten control subjects. Motor threshold, central motor conduction time, intracortical inhibition and facilitation to paired-TMS were also evaluated. Mean SAI was significantly reduced in amnestic MCI-MD patients when compared with the controls, while it was not significantly different in amnestic MCI-SD patients and in nonamnestic patients. SAI was increased after administration of a single dose of donepezil in a subgroup of four amnestic MCI-MD patients. The other TMS parameters did not differ significantly between the four MCI groups and the control group. We demonstrated that this putative marker of central cholinergic activity differs among MCI subtypes. The amnestic-MD type of MCI might be a phenotype of incipient AD. However, this hypothesis would be better addressed in a longitudinal study of individual patients. TMS studies may be useful in identifying MCI individuals in whom cholinergic degeneration is occurred and therefore at increased risk of conversion to AD.

Homeostatic Modulation of Stimulation-Dependent Plasticity in Human Motor Cortex

Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, Motor evoked potential (MEP) amplitude inhibition is observed, the paradigm known as short-latency afferent inhibition (SLAI). Aiming to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of evoked response of somatosensory cortex (N(20)) (PAS(LTP)), and at ISI of N(20) shortened for 5 msec (PAS(LTD)) - protocols that mimic LTP-like changes in the human motor cortex. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Post-intervention MEP amplitudes following the TMS protocols of PAS(LTP) and PAS(LTD) were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PAS(LTP) MEP amplitudes were significantly decreased in case of PAS(LTP), while in the case of PAS(LTD) an upward trend was observed. In conclusions, a possible explanation for the seemingly paradoxical effect of PAS can be found in the mechanism of homeostatic modulation of plasticity. Those findings indicate the existence of complex relationships in the development of plasticity induced by stimulation, depending on the level of the previous motor cortex excitability.

Paired-pulse afferent modulation of TMS responses reveals a selective decrease in short latency afferent inhibition with age

Changes in motor cortical excitability were examined in 2 groups of participants, young (18–30 years of age, n = 25) and senior (65–82 years of age, n = 31), using paired-pulse afferent stimulation with transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) elicited by TMS at suprathreshold intensity (120% motor threshold) were first recorded in unconditioned trials (TMS alone) and then in conditioned trials, in which TMS pulses were preceded by median nerve stimulation at 3 different interstimulus intervals (ISI; 20, 50, and 200 ms). Conditioning of MEP responses revealed a similar pattern of modulation in the 2 age groups, with 2 periods of inhibition at 20- and 200-ms ISIs, separated by a period in which MEPs tended to return to baseline at a 50-ms ISI. Afferent-induced inhibition at the short interval (i.e., SAI 20-ms ISI), was selectively reduced in seniors, with half of them showing either low or no MEP suppression. Age-associated changes in SAI level were also good predictors of performance on tests of processing speed and dexterity. The selective decrease in SAI exhibited by many seniors is consistent with reported alterations in intracortical inhibition with age. Our observations also highlight the potential value of SAI, as a putative marker of central cholinergic activity, in predicting declines in motor and cognitive function with age.

Effects of theta burst stimulation on motor cortex excitability in Parkinson’s disease

ObjectiveLong-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson’s disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD. MethodsiTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS. ResultsAfter iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60min. Changes in intracortical circuits induced by iTBS were also similar for the different groups. ConclusionsiTBS produced similar effects on cortical excitability for PD patients and controls. SignificanceSpike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS.

Central cholinergic dysfunction measured “in vivo” correlates with different behavioral disorders in Alzheimer’s disease and dementia with Lewy body

Cholinergic deficits have been largely correlated to behavioral disorders in dementia. However, cholinergic deficits are not homogeneous and they are distributed differently in the basal forebrain and brainstem among Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The different cholinergic networks involved suggest different patterns of behavior symptomatology in the two groups. To correlate the deficit of cholinergic activity, measured invivo by the short latency afferent inhibition (SAI) technique, with the behavioral symptoms in patients affected by DLB and AD. Behavioral and neuropsychologic tests including Neuropsychiatric Inventory (NPI), mini-mental status examination (MMSE), and an extensive neuropsychologic investigation were administered to 18 DLB patients and 18 one-to-one matched AD patients. SAI data were compared with those from a control group of age-matched healthy individuals and the level of SAI in patients was correlated with behavioral measures. AD tended to be more impaired than DLB on long-term memory, whereas DLB were more impaired than AD on constructional praxis tasks. NPI total score was similar but with a different behavioural pattern in DLB and AD. In particular, delusions and hallucinations prevailed in DLB patients, whereas affective disturbances prevailed in AD patients. SAI was significantly reduced both in AD and DLB patients when compared with controls; SAI correlated with hallucinations in DLB patients and with euphoric manic state and disinhibition in AD patients. Reduction of cholinergic activity as evaluated by SAI measurement correlates with different behavior disorders in AD and DLB patients.

P26.5 Human brain cortical effective connectivity and excitability during short-latency afferent inhibition: a combined EEG TMS study

P26.5 Human brain cortical effective connectivity and excitability during short-latency afferent inhibition: a combined EEG TMS study

P14.18 Increased short latency afferent inhibition after anodal transcranial direct current stimulation

P14.18 Increased short latency afferent inhibition after anodal transcranial direct current stimulation

Increased short latency afferent inhibition after anodal transcranial direct current stimulation

Transcranial direct current stimulation (tDCS), a technique for central neuromodulation, has been recently proposed as possible treatment in several neurological and psychiatric diseases. Although shifts on focal brain excitability have been proposed to explain the clinical effects of tDCS, how tDCS-induced functional changes influence cortical interneurones is still largely unknown. The assessment of short latency afferent inhibition (SLAI) of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), provides the opportunity to test non-invasively interneuronal cholinergic circuits in the human motor cortex. The aim of the present study was to assess whether anodal tDCS can modulate interneuronal circuits involved in SLAI. Resting motor threshold (RMT), amplitude of unconditioned MEPs and SLAI were assessed in the dominant hemisphere of 12 healthy subjects (aged 21–37) before and after anodal tDCS (primary motor cortex, 13 min, 1 mA). SLAI was assessed delivering electrical conditioning stimuli to the median nerve at the wrist prior to test TMS given at the interstimulus interval (ISI) of 2 ms. Whereas RMT and the amplitude of unconditioned MEPs did not change after anodal tDCS, SLAI significantly increased. In conclusion, anodal tDCS-induced effects depend also on the modulation of cortical interneuronal circuits. The enhancement of cortical cholinergic activity assessed by SLAI could be an important mechanism explaining anodal tDCS action in several pathological conditions.

Cognitive function and cholinergic transmission in patients with subcortical vascular dementia and microbleeds: a TMS study

There has been little investigation on the association between cognitive impairment and the microbleeds (MBs) frequently seen in subcortical vascular dementia (SVaD). One possible mechanism of cognitive decline in individuals with SVaD could be disruption of cholinergic fibers by vascular lesions. Central cholinergic circuits in human brain can be tested non-invasively by means of a transcranial magnetic stimulation (TMS) protocol named short latency afferent inhibition (SAI) of motor cortex. In the present study, we used this test in SvaD patients with and without MBs. SAI was evaluated in 13 SVaD patients with MBs (MB-positive group) and the data were compared with those from a group of 15 SVaD patients without MBs (MB-negative group) and with those from 20 healthy subjects. Moreover, we studied covariation of individual SAI values with the Mini-Mental State Examination (MMSE) total score and subscores. SAI was significantly reduced in the MB-positive group when compared with the MB-negative group and the control subjects. Total MMSE score, "attention and calculation" and "orientation" subscores were significantly lower in the MB-positive group than in the MB-negative group; SAI showed a positive correlation with total MMSE score. Adjustment for age, gender, education, presence of lacunae, severe white matter hyperintensities or severe periventricular hyperintensities did not affect these findings. This study provides novel physiological evidence that MBs have an impact on central cholinergic function that is independent of the extent of associated white matter changes and ischaemic stroke. This finding shows that TMS have potential diagnostic and therapeutic implications. TMS studies may help in evaluating the causes of cognitive impairment in cerebrovascular diseases.

Momentary reward induce changes in excitability of primary motor cortex

Objective To investigate the human primary motor cortex (M1) excitability changes induced by momentary reward. Methods To test the changes in excitatory and inhibitory functions of M1, motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and short-latency afferent inhibition (SAI) were tested in the abductor pollicis brevis (APB) muscle of non-dominant hand in 14 healthy volunteers by transcranial magnetic stimulation (TMS) during a behavioral task in which subjects were pseudorandomly received either reward target or non-target stimuli in response to a cue. To control sensorimotor and attention effects, a sensorimotor control task was done replacing the reward target with non-reward target. Results The SICI was increased, and the SAI was decreased significantly during the presentation of the reward target stimuli. Those changes were not evident during non-reward target stimuli in the sensorimotor control task, indicating that this change is specific to momentary reward. Conclusions Momentary rewarding is associated with change in intracortical inhibitory circuits of M1. Significance: TMS may be a useful probe to study the reward system in health and in many diseases in which its dysfunction is suspected.

Evidence for the Specificity of Intracortical Inhibitory Dysfunction in Asymptomatic Concussed Athletes

Sports concussions affect thousands of individuals every year and are a major public health concern. Still, little is known about the long-term and cumulative effects of concussions on brain neurophysiology. The principal objective of this study was to investigate the long-lasting effects of multiple sports concussions on sensorimotor integration and somatosensory processing in a sample of 12 concussed athletes and 14 non-concussed athletes of similar age (mean, 23 years) and education (mean, 16 years). Right median nerve stimulation was paired with transcranial magnetic stimulation (TMS) of the left primary motor cortex to investigate sensorimotor integration with short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) at five interstimulus intervals (18, 20, 22, 100, 200 msec). Somatosensory evoked potentials (SEP) were recorded from the left centro-parietal region. We also investigated primary motor cortex inhibitory mechanisms with three TMS protocols: cortical silent period, long interval intracortical inhibition, and short interval intracortical inhibition. Motor evoked potentials were recorded from the right abductor pollicis brevis muscle. No differences were observed between groups for SAI, LAI, and SEP. However, cortical silent period duration was prolonged and long interval intracortical inhibition was enhanced in the concussed group. These findings suggest that multiple sports concussions lead to specific, long-term neurophysiological dysfunctions of intracortical inhibitory mechanisms in primary motor cortex while somatosensory processing and sensorimotor integration are spared. This study provides additional evidence for the presence of specific and stable alterations of GABA(B) receptor activity in primary motor cortex that may be of clinical value for prognosis and diagnosis.

Transcranial magnetic stimulation in Alzheimer’s disease: a neurophysiological marker of cortical hyperexcitability

Recently, neuropathological studies have shown an important motor cortex involvement in Alzheimer's disease (AD), even in its early stages, despite the lack of clinically evident motor deficit. Transcranial magnetic stimulation (TMS) studies have demonstrated that cortical excitability is enhanced in AD patients. This cortical hyperexcitability is believed to be a compensatory mechanism to execute voluntary movements, despite the progressive impairment of associative cortical areas. At present, it is not clear if these motor cortex excitability changes might be the expression of an involvement of intracortical excitatory glutamatergic circuits or an impairment of inhibitory cholinergic and, to a lesser extent, gabaergic activity. Although the main hypothesis for the pathogenesis of AD remains the degeneration of the basal forebrain cholinergic neurons, the development of specific TMS protocols, such as the paired-pulse TMS and the study of the short-latency afferent inhibition, points out the role of other neurotransmitters, such as gamma-amino-butyric acid, glutamate and dopamine. The potential therapeutic effect of repetitive TMS in restoring or compensating damaged cognitive functions, might become a possible rehabilitation tool in AD patients. Based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological brain aging, mild cognitive impairment, AD and other dementing disorders. The present review provides a perspective of these TMS techniques by further understanding the role of different neurotransmission pathways and plastic remodelling of neuronal networks in the pathogenesis of AD.

Transcranial Magnetic Stimulation in Different Current Directions Activates Separate Cortical Circuits

Transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) produces a series of corticospinal descending waves, with a direct (D) wave followed by several indirect (I) waves. TMS inducing posterior-anterior (PA) current in the brain predominantly recruits the early I1-wave, whereas anterior-posterior (AP) directed current preferentially recruits the late I3-wave. However, it is not known whether I-waves elicited by different current directions are mediated by the same neuronal populations. We studied the neuronal mechanisms mediating I-waves by examining the influence of short-latency afferent inhibition (SAI) on various I-waves. SAI was tested with electrical median nerve stimulation at the wrist followed by TMS to the contralateral M1 at different current directions. Surface electromyograms and single motor units were recorded from the first dorsal interosseous muscle. SAI was weaker for the AP compared with that for the PA current direction. With increasing median nerve stimulation intensities, SAI increased for the PA direction but showed a U-shaped relationship for the AP direction. SAI produced more inhibition of late I-waves generated by PA than those generated by AP current direction. We conclude that late I-waves generated by PA and AP current directions are mediated by different neuronal mechanisms.