Physiological Targets for Orthostatic Hypotension: Improving Nonpharmacological Interventions in Patients with Orthostatic Cerebral Hypoperfusion.

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.

Cardiovascular Autonomic Regulation, ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance.

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of ≥ 30 bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO2 and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N = 108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO2 during 10 min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO2 show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

Cardiovascular disease risks in adult Native and Mexican Americans with a history of alcohol use disorders: association with cardiovascular autonomic control.

Hypertension and obesity are serious health problems that have been associated with an increased risk of cardiovascular disease (CVD). We recently showed a relationship between hypertension, obesity and cardiovagal control in a sample of Native and Mexican Americans at high risk of alcohol use disorders (AUD). While studies have shown that Native and Mexican Americans exhibit high rates of AUD, the consequences of AUD on CVD risk factors and their relationship with cardiovascular autonomic control is not well understood in these ethnic groups. This study investigated whether an association could be demonstrated between cardiovascular autonomic control and several CVD risk factors in Native and Mexican American men and women (n = 228) who are literate in English and are residing legally in San Diego County. Participants with lifetime history of AUD showed higher rates of systolic and diastolic hypertension and obesity than participants without lifetime AUD. Lifetime AUD was significantly associated with reduced HR response to deep breathing (HRDB) measure of cardiovagal control, higher current drinking quantity, and obesity. Reduced HRDB was also associated with increased systolic pre-hypertension or hypertension (pre-/hypertension) and with higher diastolic blood pressure in a linear regression model that included several diagnostic and demographic variables. HRDB and time- and frequency-domain measures of cardiovagal control were significantly reduced in participants with diastolic pre-/hypertension. These data suggest that lower cardiovagal control may play a role in the prevalence of systolic and diastolic pre-/hypertension in a community sample with a history of alcohol and substance use disorders.

Sensory Gating Deficits in First-Episode Psychosis: Evidence From Neurophysiology, Psychophysiology, and Neuropsychology.

Sensory gating deficits are commonly found in patients with schizophrenia. However, there is still scarce research on this issue. Thirty-eight patients with first-episode psychosis (FEP) were compared to thirty-eight controls. A condition-test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used (i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention and vigilance). The ERP components measured were P50, N1, and P2. The PPI intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing speed and attention/vigilance cognitive domains were selected. FEP patients showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and in all the MCCB subtests selected. We obtained significant relationships in N1 with PPI-60, and with one MCCB subtest for processing speed. In addition, this same subtest showed significant association with P2. Therefore, sensory gating functioning is widely impaired since the very early stages of schizophrenia.

CHRNA5 and CHRNA3 variants and level of neuroticism in young adult Mexican American men and women.

A lifetime history of alcohol dependence has been associated with elevations in neuroticism in Mexican American young adults. The identification of genetic markers associated with neuroticism and their influence on the development of alcohol use disorders (AUD) may contribute to our understanding of the relationship between personality traits and the increased risk of AUD in Mexican Americans. The purpose of this study was to investigate associations between neuroticism and 13 single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine (nAChR) α5-subunit (CHRNA5) and α3-subunit (CHRNA3) genes in young adult Mexican American men and women. Participants were 465 young adult Mexican American men and women who are literate in English and are residing legally in San Diego County. Each participant gave a blood sample and completed a structured diagnostic interview. Neuroticism was assessed using the Maudsley Personality Inventory. The minor alleles of four CHRNA5 polymorphisms (rs588765, rs601079, rs680244 and rs555018) and three CHRNA3 polymorphisms (rs578776, rs6495307 and rs3743078) showed associations with neuroticism. Several of these SNPs also displayed nominal associations with DSM-IV alcohol and nicotine dependence, but tests of mediation suggested that these relations could be partially explained by the presence of co-occurring neuroticism. These findings suggest that genetic variations in nicotinic receptor genes may influence the development of neuroticism, which in turn is involved in the development of AUDs and nicotine dependence in Mexican American young adults.

Hypermorphic mutation of the voltage-gated sodium channel encoding gene Scn10a causes a dramatic stimulus-dependent neurobehavioral phenotype.

The voltage-gated sodium channel Na(v)1.8 is known to function in the transmission of pain signals induced by cold, heat, and mechanical stimuli. Sequence variants of human Na(v)1.8 have been linked to altered cardiac conduction. We identified an allele of Scn10a encoding the α-subunit of Na(v)1.8 among mice homozygous for N-ethyl-N-nitrosourea-induced mutations. The allele creates a dominant neurobehavioral phenotype termed Possum, characterized by transient whole-body tonic immobility induced by pinching the skin at the back of the neck ("scruffing"). The Possum mutation enhanced Na(v)1.8 sodium currents and neuronal excitability and heightened sensitivity of mutants to cold stimuli. Striking electroencephalographic changes were observed concomitant with the scruffing-induced behavioral change. In addition, electrocardiography demonstrated that Possum mice exhibited marked sinus bradycardia and R-R variability upon scruffing, abrogated by infusion of atropine. However, atropine failed to prevent or mitigate the tonic immobility response. Hyperactive sodium conduction via Na(v)1.8 thus leads to a complex neurobehavioral phenotype, which resembles catatonia in schizophrenic humans and tonic immobility in other mammals upon application of a discrete stimulus; no other form of mechanosensory stimulus could induce the immobility phenotype. Our data confirm the involvement of Na(v)1.8 in transducing pain initiated by cold and additionally implicate Na(v)1.8 in previously unknown functions in the central nervous system and heart.

Impairment of memory consolidation by galanin correlates with in vivo inhibition of both LTP and CREB phosphorylation.

Changes in the state of CREB phosphorylation and in LTP in the hippocampus have been associated with learning and memory. Here we show that galanin, the neuropeptide released in the hippocampal formation from cholinergic and noradrenergic fibers, that has been shown to produce impairments in memory consolidation in the Morris water maze task inhibits both LTP and CREB phosphorylation in the rat hippocampus in vivo. While there are many transmitters regulating CREB phosphorylation none has been shown to suppress behaviorally-induced hippocampal CREB phosphorylation as potently as galanin. The in vivo inhibition of dentate gyrus-LTP and of CREB phosphorylation by the agonist occupancy of GalR1 and GalR2-type galanin receptors provides strong in vivo cellular and molecular correlates to galanin-induced learning deficits and designates galanin as a major regulator of the memory consolidation process.

Contingent and non-contingent effects of low-dose ethanol on GABA neuron activity in the ventral tegmental area.

Ventral tegmental area (VTA) GABA neurons appear to be critical regulators of mesocorticolimbic dopamine (DA) neurotransmission, which has been implicated in alcohol reward. The aim of this study was to evaluate the effects of low-dose "non-contingent" intravenous (IV) ethanol (0.01-0.1 g/kg) on VTA GABA neuron firing rate and synaptic responses, as well as VTA GABA neuron firing rate during low-dose "contingent" IV ethanol self-administration. Intravenous administration of 0.01-0.03 g/kg ethanol significantly increased VTA GABA neuron firing rate and afferent-evoked synaptic responses. In the runway self-administration paradigm, presentation of an olfactory cue (S+; almond extract) or no-cue (S-; no odor) in the Start box was paired with IV administration of low-dose ethanol (0.01 g/kg) or saline in the Target box. Runway excursion times decreased significantly in association during S+, and increased significantly during S- conditions. The firing rate of VTA GABA neurons markedly increased when rats received 0.01 g/kg IV ethanol in the Target box. VTA GABA neuron firing increased in the Start box of the runway in association with S+, but not S-. These findings demonstrate that VTA GABA neurons are activated by low-dose IV ethanol and that their firing rate increases in anticipation of ethanol reward.

Differential effects of acute alcohol on EEG and sedative responses in adolescent and adult Wistar rats.

Age-related developmental differences in sensitivity to the acute effects of alcohol may play an important role in the development of alcoholism. The present study was designed to evaluate the acute effects of alcohol on cortical electroencephalogram (EEG) in adolescent (P36) and adult (P78) Wistar rats. Five minutes of EEG was recorded after administration of 0, 0.75 or 1.5 g/kg alcohol. The righting reflex was performed to measure the sedative effects of alcohol (3.5 g/kg) and total sleeping time for each rat. Our results showed that alcohol (1.5 g/kg) increased power in the 1-2 Hz band and decreased the power in the 32-50 Hz band in the parietal cortical region of adolescent rats. Alcohol (1.5 g/kg) also increased stability of the EEG power in the slow-wave frequency bands (2-4 Hz, 4-6 Hz, and 6-8 Hz) of adolescent rats. In the frontal cortex of adult rats, but not in adolescent rats, alcohol (1.5 or 0.75 g/kg) decreased the power in the 16-32 Hz frequency band. Alcohol (1.5 g/kg) differentially increased power in a multiple of slow-wave frequency bands (2-4 Hz and 4-6 Hz) in the parietal cortex of adult rats as compared to adolescent rats. Adolescent rats were shown significantly shorter sleeping time and higher blood alcohol levels after regaining reflex than adult rats. Our results provide additional evidence of age-related differences in the effects of acute alcohol on cortical EEG, sedation and tolerance.

Differential effects of acute alcohol on prepulse inhibition and event-related potentials in adolescent and adult Wistar rats.

BACKGROUND: Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram. However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). METHODS: Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. RESULTS: Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse + pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. CONCLUSIONS: These data suggest that alcohol's effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol-influenced response to PPI.

Electrophysiological effects of dizocilpine (MK-801) in adult rats exposed to ethanol during adolescence.

BACKGROUND: Despite evidence showing persistent changes in N-methyl-D-aspartate (NMDA)-receptor function following ethanol (EtOH) exposure, the contribution of NMDA systems to the long-term neurophysiological consequences of adolescent EtOH exposure is unclear. The aims of this study were the following: (1) to determine whether adolescent EtOH exposure produces neurophysiological changes after a prolonged withdrawal period in adult rats and (2) to assess protracted alterations in neurophysiological responses to the NMDA antagonist MK-801 in adult rats exposed to EtOH during adolescence. METHODS: Adolescent male Wistar rats were exposed to EtOH vapor for 12 h/d for 5 weeks. The effects of MK-801 (0.0 to 0.1 mg/kg, intraperitoneally) on the electroencephalogram (EEG) and auditory event-related potentials (ERPs) were assessed after 8 weeks of abstinence from EtOH. RESULTS: Experiments in aim 1 revealed that adolescent EtOH exposure reduced EEG variability in the frontal cortex in the 4 to 6 Hz band but had no effect on cortical and hippocampal EEG power and ERPs. Experiments in aim 2 showed that MK-801 significantly reduced EEG power in the parietal cortex (4 to 6 Hz, 6 to 8 Hz, 8 to 16 Hz, 16 to 32 Hz) and hippocampus (16 to 32 Hz) and EEG variability in the parietal cortex (6 to 8 Hz, 16 to 32 Hz) following adolescent EtOH exposure. MK-801 produced a significant decrease in hippocampal EEG variability (4 to 6 Hz, 8 to 16 Hz, 16 to 32 Hz) in control, but not in EtOH-exposed rats. MK-801 reduced frontal P1 ERP amplitude and latency in response to the rare tone in EtOH-exposed rats compared to controls. In contrast, MK-801 significantly reduced P3 ERP amplitude and latency in control, but not in EtOH-exposed rats. CONCLUSIONS: The effects of MK-801 on hippocampal EEG variability and P3 ERP amplitude and latency are significantly attenuated after a prolonged withdrawal period following adolescent EtOH exposure. However, the inhibitory effects of MK-801 on cortical and hippocampal EEG power were enhanced in rats exposed to EtOH during adolescence. Taken together, these data suggest protracted changes in NMDA systems following adolescent EtOH exposure.

Investigation of vagal afferent functioning using the Heartbeat Event Related Potential.

Although there has been much support for HRV Biofeedback as an effective intervention for various disorders, there is a lack of comprehension of the underlying mechanisms. The predominant theories of increased vagal efferents and baroreflex gain are insufficient in explaining the frequent observations that HRV Biofeedback impacts changes in constructs beyond ANS mediation, such as emotion regulation, attentional control, and self-regulatory reserve. It has been suspected that vagal afferent functioning may be the underlying mechanism, but little research has explored this. Previously, researchers measured cortical evoked potentials contingent to the heart, or an indication of vagal afferent functioning (Schandry et al., 1986). Twenty-five participants were randomly stratified to HRV Biofeedback or EMG Biofeedback for four sessions. Repeated measures ANOVAs revealed that the HRV group exhibited statistically significantly increased baseline Heartbeat Event-Related Potentials (updated term for 'evoked potential') while the relaxation control group did not. The results of this study provide initial support to the premise that HRV Biofeedback stimulates changes in the vagal afferent pathway that are longer lasting than simply the short term effects of breathing.

Contributions of neuronal prion protein on sleep recovery and stress response following sleep deprivation.

In order to gain insights on the function of the cellular prion protein (PrP(C)) sleep and the levels of the stress hormones corticosterone (CORT) and the adrenocorticotropic hormone (ACTH) before and after sleep deprivation (SD) were compared in two wild type (WT) mice strains and the following three PrP(C) transgenic lines: mice null for PrP(C) (mPrP(0/0)) and mice with specific and central expression of PrP in neurons (NSE-HPrP/mPrP(0/0)) or in glia cells (GFAP-HPrP/mPrP(0/0)). After SD mPrP(0/0) mice showed a larger degree of sleep fragmentation and of latency to enter rapid eye movement (REM) and non-REM sleep (NREM) than WT. During sleep recovery, the amount of NREM sleep and the slow-wave activity (SWA) were reduced in mPrP(0/0) mice. After SD, CORT and ACTH levels have distinct patterns in WT and mPrP(0/0). The NREM and SWA deficit was restored in NSE-HPrP/mPrP(0/0) mice but not in GFAP-HPrP/mPrP(0/0). Hormonal profile was only partially restored in NSE-HPrP/mPrP(0/0) mice and was similar to that of mPrP(0/0) and GFAP-HPrP/mPrP(0/0) mice. These findings demonstrate that neuronal, but not non-neuronal, PrP(C) is involved in sleep homeostasis and sleep continuity. They also suggest that neuronal PrP(c)-dependent hormonal regulation of HPA axis may contribute to the sleep homeostasis.

Electrophysiological and cerebrovascular effects of the alpha-secretase-derived form of amyloid precursor protein in young and middle-aged rats.

Cleavage of the beta-amyloid precursor protein (APP) by alpha-secretase releases a secreted form of APP (sAPP) from cells. sAPP is released from neurons in an activity-dependent manner and is believed to play roles in synaptic plasticity and neuroprotection. We determined whether sAPP modulates electrophysiological and cerebrovascular processes in vivo. The effects of recombinant sAPP, applied by intracerebroventricular infusion, on hippocampal and cortical electroencephalographic (EEG) activity and hippocampal blood flow in young adult and middle-aged Long-Evans rats were measured. sAPP increased the power spectrum density of low frequency EEG bands in the hippocampus and cortex of middle-aged rats without affecting hippocampal blood flow. The neurophysiological effects of sAPP were observed in middle-aged, but not in young rats. The results of this study indicate that hippocampal and cortical electrophysiological processes are sensitive to sAPP, whereas the cerebral vasculature may not be regulated by sAPP. The age-dependent change in the sensitivity of neuronal activity to sAPP suggests the possibility of an important role for this APP product in brain functioning in mid life.

Electrophysiological responses to affective stimuli in Mexican Americans: Relationship to alcohol dependence and personality traits.

The relationship between the P450 component elicited by affective stimuli and: a personal history of alcohol dependence, antisocial personality disorder/conduct disorder (ASPD/CD) or affective anxiety disorders (ANYAXAF) was examined in Mexican Americans, a group with high rates of heavy drinking. Data from two hundred and twenty two young adults between the ages of 18 and 30 were used in the analyses. ERPs were collected using a task that required discrimination between faces with neutral, sad and happy facial expressions. DSM-IIIR diagnoses were obtained using a structured interview and personality traits were indexed using the Maudsley personality inventory. Men had significantly diminished P450 responses, when compared to women which were further reduced in men with ASPD/CD; whereas, a significant increase in P450 amplitudes was seen in those participants with ANYAXAF. P450 amplitudes were also significantly increased in men with high extraversion scores and in women with high neuroticism scores. No significant associations were seen between the P450 amplitude and the diagnosis of alcohol dependence. These data suggest that interpretations of P450 responses in Mexican Americans need to take into account the interactions between gender, the affective valence of the eliciting stimuli, as well as psychiatric status.

Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons.

Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in particular in cholinergic neurons located in the mesopontine tegmental area, including the pedunculopontine tegmental (PPT) and lateral dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local administration of UII into the PPT nucleus increases REM sleep without inducing changes in the cortical blood flow. Intracerebroventricular injection of UII enhances both REM sleep and wakefulness and reduces slow-wave sleep 2. Intracerebroventricular, but not local, administration of UII increases cortical blood flow. Moreover, whole-cell recordings from rat-brain slices show that UII selectively excites cholinergic PPT neurons via an inward current and membrane depolarization that were accompanied by membrane conductance decreases. This effect does not depend on action potential generation or fast synaptic transmission because it persisted in the presence of TTX and antagonists of ionotropic glutamate, GABA, and glycine receptors. Collectively, these results suggest that UII plays a role in the regulation of REM sleep independently of its cerebrovascular actions by directly activating cholinergic brainstem neurons.

Neuropsychology and neuropharmacology of P3a and P3b.

Perspectives on the P300 event-related brain potential (ERP) are reviewed by outlining the distinction between the P3a and P3b subcomponents. The critical factor for eliciting P3a is how target/standard discrimination difficulty rather than novelty modulates task processing. The neural loci of P3a and P3b generation are sketched and a theoretical model is developed. P3a originates from stimulus-driven disruption of frontal attention engagement during task processing. P3b originates when temporal-parietal mechanisms process the stimulus information for memory storage. The neuropharmacological implications of this view are then outlined by evaluating how acute and chronic use of ethanol, marijuana, and nicotine affect P3a and P3b. The findings suggest that the circuit underlying ERP generation is influenced in a different ways for acute intake and varies between chronic use levels across drugs. Theoretical implications are assessed.

Using magnetoencephalography to study patterns of brain magnetic activity in Alzheimer's disease.

The use of magnetoencephalography to study neurophysiologic abnormalities associated with Alzheimer's disease is reviewed. The most consistent observation is that Alzheimer's disease patients exhibit an increase in focal slow-wave activity that covaried with cognitive performance. It is still unclear whether generation of focal slow-wave activity precedes or is a consequence of Alzheimer's disease-related neuropathology. Also reviewed is the use of magnetoencephalography to identify early functional changes preceding the diagnosis of dementia. Magnetoencephalography detected neurophysiologic abnormalities associated with cognitive deficits before the diagnosis of mild cognitive impairment. This is supported by evidence presented suggesting that some patients with subjective cognitive complaints, without evidence of dementia, show an increase in focal slow-wave generators. Further research is needed to determine whether the outstanding spatial and temporal resolution of the magnetoencephalography technique could complement other neuroimaging techniques in identifying neurophysiologic abnormalities preceding the diagnosis of Alzheimer's disease and mild cognitive impairment.

Magnetoencephalogram recording from secondary motor areas during imagined movements.

This study determined whether the activity of the secondary motor cortex (M2) could be recorded during imagined movements (IM) of the right and left hand using magnetoencephalography (MEG). Results during IM were compared with a somatosensory trial during a passive tactile stimulation in one subject. During the somatosensory trial, dipoles were detected in somatosensory (SS) and motor primary (M1) areas, scoring 94.4-98.4% for SS, 1.6-5.6% for M1 and 0% for M2. During the IM trial, dipoles were detected in SS, M1 and M2 areas, scoring 61.1-68.8% for SS, 2.6-9.3% for M1 and 28.6-29.6% for M2. These data support the hypothesis that M2 areas are activated during imagined hand movements. This study aims for the development of a diagnosis test for patients with motor deficits by evaluating the whole somatomotor network with specific interest in M2 areas.