Clinical Neurophysiology - Articles in Press

The segmental palmar test in diagnosing carpal tunnel syndrome reassessed - Corrected Proof

Kristel M. Kasius, Franka Claes, Wim I.M. Verhagen, Jan Meulstee — 2012-05-18

Highlights: ► Slowing of sensory nerve conduction velocity in the median nerve distal to the carpal tunnel is frequently found in carpal tunnel syndrome. ► In contrast, slowing of forearm median nerve conduction velocity is less frequent in these patients. ► Therefore, comparing the median nerve conduction velocities of the forearm with the wrist segment provides a greater sensitivity than comparing the palm with the wrist segment, in the segmental palmar test.Abstract: Objective: To test our hypothesis that comparing the sensory nerve conduction velocity of the median nerve across the wrist with that of the forearm is more sensitive than comparing it with that of the palm in the electrodiagnostic confirmation of carpal tunnel syndrome (CTS).Methods: One hundred and fifty seven consecutive patients with clinically defined CTS were prospectively included and electrophysiologically examined. Antidromic nerve conduction velocities were measured in 3 segments of the median nerve: forearm, wrist, and palm. Differences and ratios in nerve conduction velocities were computed between the forearm and wrist and between the palm and wrist segments.Results: Comparing the median nerve conduction velocities of the forearm with the wrist segment provides a greater sensitivity (79.6% and 82.8% for the second and third digit, respectively) than comparing the palm with the wrist segment (65.6% and 65.0%). Applying the ratio leads to slightly higher sensitivities for both comparisons.Conclusions: The modified segmental palmar test is a sensitive, robust and easily applicable method in diagnosing CTS.Significance: We recommend to use the median nerve sensory conduction velocity in the forearm as a reference in the segmental palmar test instead of that in the palm.

Visual distance cues modulate neuromagnetic auditory N1m responses - Corrected Proof

2012-05-18

Highlights: ► Auditory distance perception can rely on sound intensity as a cue and can be additionally modulated by vision. ► We found that the N1m MEG component generated in auditory cortex was enhanced when a sound was paired with a distant compared to a close visual cue. ► This result suggests an audio–visual interaction at an early stage in the auditory cortex, possibly related to cue integration for auditory distance processing.Abstract: Objective: Auditory distance judgment relies on several acoustic cues and can be modulated by visual information. Sound intensity serves as one such cue as it decreases with increasing distance. In this magnetoencephalography (MEG) experiment, we tested whether N1m MEG responses, previously described to scale with sound intensity, are modulated by visual distance cues.Methods: We recorded behavioral and MEG data from 15 healthy normal hearing participants. Noise bursts at different sound pressure levels were paired with synchronous visual cues at different distances. We hypothesized that noise paired with far visual cues will be represented louder and result in increased N1m amplitudes compared to a pairing with close visual cues. This might be based on a compensation of visually induced distance when processing loudness.Results: Psychophysically, we observed no significant modulation of loudness judgments by visual cues. However, N1m MEG responses at about 100ms after stimulus onset were significantly stronger with distal compared to proximal visual cues in the left auditory cortex.Conclusions: Our results suggest an audio–visual interaction at an early stage in the left auditory cortex, possibly related to cue integration for auditory distance processing.Significance: Sound distance processing could prove itself as a promising model system for the investigation of intra-modal and cross-modal integration principles.

Effect of concentration and mode of intrathecal baclofen administration on soleus H-reflex in patients with muscle hypertonia - Corrected Proof

Dobrivoje S. Stokic, Stuart A. Yablon — 2012-05-18

Abstract: Objectives: Assess spinal reflex excitability after increasing intrathecal baclofen (ITB) flow by manipulation of drug concentration and mode of administration.Methods: The effect of concentration was assessed by comparing changes in H-reflex (H/M ratio) 1–6h after a 50μg ITB bolus at 50μg/ml concentration administered manually via lumbar puncture (LP, duration 1–2min, n=27) to a 50μg bolus at 500μg/ml concentration programmed through the pump and delivered via intrathecal catheter (IC, duration 10min) above simple continuous dose (25–100μg/day, n=16). The effect of mode of administration was assessed by comparing peak changes in H/M ratio after 50μg IC bolus above simple continuous dose (complex continuous mode, n=27) to simple continuous mode only (n=22) at equivalent daily doses (75–150μg/day).Results: H/M decrease was faster and overall greater after LP than IC bolus (mean 1-h 77% vs. 63%, p=0.012; 1–6h 91% vs. 82%, p<0.001, respectively). H/M ratio also decreased significantly more with complex (91%) than simple continuous mode of administration (78%, p=0.025).Conclusions: Lower ITB concentration and complex continuous mode of administration lead to greater decrease in H/M ratio.Significance: Decreased spinal reflex excitability after adjustment of drug and pump parameters to increase ITB flow may result in better clinical response.

On relative frequency estimation of transcranial magnetic stimulation motor threshold - Corrected Proof

Friedemann Awiszus — 2012-05-16

In recent IFCN guidelines for diagnostic transcranial magnetic stimulation () relative frequency estimation of cortical motor threshold (CMT) is promoted (e.g. the lowest stimulus intensity which produces more than 5 MEPs with 10 stimuli). Although such an estimation procedure is widely used within TMS laboratories () the mathematical properties of the relative frequency estimator for CMT have never been rigorously evaluated so far.

EEG onset of a seizure during TMS from a focus independent of the stimulation site - Corrected Proof

2012-05-14

The risk of a seizure in temporal association with a TMS session in a patient with epilepsy is less than 2%, both for single and paired-pulse TMS () and for repetitive TMS (rTMS) (). With rare exceptions (), TMS-associated seizures in epilepsy patients have been clinically similar to the patients’ typical spontaneous seizures, leaving uncertainty as to whether they are causally related to stimulation. Here we describe a patient with an epileptic brain malformation who, while undergoing paired-pulse TMS over a cortical region distant from his seizure focus, had a spontaneous seizure of his usual semiology, with demonstrated ictal EEG onset from his expected epileptogenic focus.

The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage - Corrected Proof

L.M.P. Giuliano, K.F. Nunes, G.M. Manzano — 2012-05-11

Highlights: ► The P18 component of the median nerve SEP can be recorded from a posterior to anterior neck montage. ► Vibration of the palm of the hand reduces the amplitude of all components except P18 and N18. ► Double-pulse stimulation attenuates the amplitude of the P18 component, as has been described for the positive component of the spinal cord dorsum potential.Abstract: Objective: To investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation.Methods: Somatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects of simultaneous vibration of the hand were evaluated. In five subjects, responses after double-pulse stimulation (ISI 20ms) were evaluated.Results: The P18 component was identified in all subjects. Vibration reduced the amplitude of all components except the P18 and N18. Double-pulse stimulation reduced the amplitude of the P18 and the N18 components without significantly changing the amplitude of the other components.Conclusions: The posterior to anterior neck montage allows for recording the P18 component. The amplitude reduction of all components during vibration, except N18 and P18, is interpreted as reflecting inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively. The reduction in the P18 component after double-pulse stimulation is compatible with previous observations on the positive component of cord dorsum potentials.Significance: Studying this component may add to the knowledge of the function of the spinal cord in humans.

Validity of the finger tapping test in Parkinson’s disease, elderly and young healthy subjects: Is there a role for central fatigue? - Corrected Proof

2012-05-07

Abstract: Objective: The main goal of this work is to evaluate the validity of the finger tapping test (FT) to detect alterations in rhythm formation.Methods: We use FT to study the alterations in motor rhythm in three different groups: Parkinson’s patients, elderly healthy controls, and young healthy control subjects (HY). The test was performed in COMFORT and FAST tapping modes and repeated on two different days.Results: For the variables analyzed (frequency and variability) both modes were repeatable in all groups. Also, intra-class correlation coefficients showed excellent levels of consistency between days. The test clearly differentiated the groups in both FAST and COMFORT modes. However, when fatigue was analyzed, a decrease in the tapping frequency was observed in HY during the FAST mode only. The amplitude of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) was early-potentiated but not delayed-depressed, both for COMFORT and FAST modes. This suggests that fatigue was not of cortico-spinal origin. Other forms of central fatigue are discussed.Conclusions: FT at FAST mode is not a valid test to detect differences in rhythm formation across the groups studied; fatigue is a confounding variable in some groups if the test is performed as fast as possible.Significance: COMFORT mode is recommended in protocols including the FT for evaluating rhythm formation.

Patients in a vegetative state following traumatic brain injury display a reduced intracortical modulation - Corrected Proof

2012-05-04

Highlights: ► In this study we hypothesized that an abnormal intracortical modulation, for example caused by diffuse axonal damage with GABAergic dysfunction, may be a salient feature observed in patients in a vegetative state (VS) following a traumatic brain injury. ► Using transcranial magnetic stimulation, we found that both intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects. ► Our findings reveal interesting developments about interneuronal cortical dysfunction in patients in VS.Abstract: Objective: Patients in coma who fail to wake develop a condition known as a vegetative state (VS). While we know that some cortical activities exist in patients in VS, it remains unclear whether interneuronal modulation can be abnormal in the cerebral cortex of these patients. The aim of the study was to evaluate the inhibitory and excitatory interneuronal circuits in patients in VS following a traumatic brain injury.Methods: Cortical excitability was studied in 5 VS patients and in 10 healthy subjects using paired pulses transcranial magnetic stimulation (TMS). Resting motor threshold and intracortical inhibition and facilitation at short intervals (2 and 10ms, respectively) were evaluated. Two patients were studied again after their level of consciousness transitioned into a minimally conscious state (MCS).Results: Both intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects (p<0.05). In addition, these results did not significantly change in the 2 patients who evolved into a MCS.Conclusions: This is the first report showing an abnormal cortical excitability in patients in VS.Significance: Our findings suggest a pathophysiological base for future work aiming to restore the lack of interneuronal transmission in patients in VS.

Correlation between compound muscle action potential amplitude and duration in axonal and demyelinating polyneuropathy - Corrected Proof

2012-05-04

Highlights: ► More knowledge about the relation between compound muscle action potential amplitude and duration in axonal lesions and demyelination may help to reveal the pathophysiology in polyneuropathies. ► Severe decrease in amplitude in demyelinating polyneuropathies is probably due to the increase in duration secondary to temporal dispersion. ► The relationship between compound muscle action potential amplitude and duration show supplementary electrodiagnostic potential in demyelinating polyneuropathies.Abstract: Objective: To get a better understanding of pathophysiology in polyneuropathies (PNPs) by correlating compound muscle action potential (CMAP) amplitude with duration.Methods: A total of 145 motor nerve conduction studies (MNCS) in 53 axonal and 132 MNCS in 45 demyelinating PNPs were analyzed. Peroneal and tibial MNCS were done by surface stimulation while for median and ulnar nerves near nerve or surface stimulations were used. CMAP amplitude and duration were compared in axonal and demyelination PNPs. Relationships between amplitude and duration of distally and proximally evoked CMAP were examined using regression analysis.Results: CMAP amplitude was lower and duration was increased in all examined nerves in demyelinating PNPs than in axonal PNPs. In demyelinating PNPs, an inverse linear correlation between amplitude and duration was seen in distally and proximally evoked CMAP in all examined nerves. In axonal PNPs, there was no correlation in any of the nerves neither in distally nor in proximally evoked CMAP.Conclusions: Distal CMAP duration and the relationship between CMAP amplitude and duration show supplementary electrodiagnostic potential in demyelinating PNPs.Significance: More knowledge about the relation between amplitude and duration in axonal lesions and demyelination may help to reveal the pathophysiology in PNPs. Significant correlation between amplitude and duration in demyelination may suggest that the severe decrease in amplitude in demyelinating PNPs is probably due to the increase in duration secondary to temporal dispersion.

Cortical processing of musical sounds in children with Cochlear Implants - Corrected Proof

2012-05-03

Highlights: ► We found similar ERP waveforms in children with Cochlear Implants (CIs) as in normal hearing controls for changes of fundamental frequency, musical instrument, sound duration, presence of temporal gaps, and for decrements but not increments of sound intensity. ► CI children had smaller and earlier P1 responses possibly reflecting differences in primary auditory cortex processing. ► CI childrens’ MMN responses reflected less accurate neural detection of changes of musical instrument, sound duration, and temporal envelope (gaps), while their P3a responses indicated less accurate involuntary attention switching to changes in musical instrument.Abstract: Objective: We studied the neurocognitive mechanisms of musical instrument sound perception in children with Cochlear Implants (CIs) and in children with normal hearing (NH).Methods: ERPs were recorded in a new multi-feature change-detection paradigm. Three magnitudes of change in fundamental frequency, musical instrument, duration, intensity increments and decrements, and presence of a temporal gap were presented amongst repeating 295Hz piano tones. Independent Component Analysis was utilized to remove artifacts caused by the Cochlear Implants.Results: The ERPs were similar in the two groups across all perceptual dimensions except for intensity increment deviants. CI children had smaller and earlier P1 responses compared to controls, and their MMN responses showed less accurate neural detection of changes of musical instrument, sound duration, and temporal structure. P3a responses suggested that poor neural detection of musical instruments affected their involuntary attention shift.Conclusions: The similarities of neurocognitive processing are surprising in the light of the limited auditory input provided by the CI, suggesting that many types of changes are adequately processed by the CI children.Significance: Our results indicate that CI children’s auditory cortical functioning may be enhanced, and difficulties in auditory perception and in attention switching towards sound events alleviated, by multisensory musical activities.

Somatosensory High Frequency Oscillations reflect clinical fluctuations in migraine - Corrected Proof

2012-05-03

Highlights: ► High Frequency Oscillations (HFOs) changes were recorded in 28 migraine patients and correlated to spontaneous clinical fluctuations. ► Presynaptic HFOs were enhanced in spontaneously improved patients, whereas they were abnormally reduced in worsening ones. ► HFO recording could represent a useful marker to evaluate migraine progression and neurophysiological underpinnings of prophylactic drugs.Abstract: Objective: It has been demonstrated that the early part of 600Hz High Frequency Oscillations (HFOs), probably generated in the terminal part of thalamo-cortical somatosensory radiations, are abnormally reduced between attacks in migraineurs. We aimed at verifying whether spontaneous clinical fluctuations in migraine are correlated to HFO changes.Methods: We recorded somatosensory evoked potentials in 28 migraine patients. Clinical fluctuations (number of attacks in the 6months preceding and following the test) were correlated to the HFOs’ amplitudes. Moreover, eight out of 28 patients underwent a longer follow-up, including HFO control and clinical observation during the 12months following the baseline recording.Results: The amplitude of early presynaptic HFOs was significantly correlated to the clinical evolution, since spontaneous worsening was associated with reduced presynaptic HFOs, whereas spontaneous improvement was associated with enhanced presynaptic HFOs (correlation test, p<0.05). No correlation was found between the amplitude of postsynaptic HFOs and clinical fluctuations. Patients undergoing longer follow-up showed substantially unchanged HFOs, accordingly with their stable clinical condition.Conclusions: HFOs’ enhancement in spontaneously improved patients can reflect the increased activity of brainstem arousal related structures, which in turn increases the thalamo-cortical drive and the cortical lateral inhibition mediated by GABAergic interneurons.Significance: HFOs’ recording could represent a useful tool in the functional assessment of migraine.

Baseline EEG theta/beta ratio and punishment sensitivity as biomarkers for feedback-related negativity (FRN) and risk-taking - Corrected Proof

S.A.A. Massar, V. Rossi, D.J.L.G. Schutter, J.L. Kenemans — 2012-04-30

Abstract: Objective: Feedback-related negativity (FRN) is associated with reinforcement learning and punishment sensitivity. Furthermore, reinforcement learning proficiency can be predicted from pre-task baseline EEG theta/beta ratio. In this study it was examined whether there was a relation between baseline theta/beta ratio in rest and FRN amplitude during a gambling task, and if such a correlation would be related to theta activity or to beta activity.Methods: Baseline EEG and a self-report measure of punishment sensitivity (BIS) were obtained from 52 healthy volunteers. FRN was recorded during a gambling task.Results: FRN amplitude was negatively correlated with theta/beta ratio in high BIS individuals. Furthermore, source localization indicated that baseline theta activity generated in the anterior cingulate cortex (ACC) accounted for this correlation. For low BIS individuals no correlation was found.Conclusions: An association between high baseline theta/beta ratio with low amplitude FRN and high risk-taking can be found in individuals who score sufficiently high on the BIS scale. This relationship is carried mostly by baseline theta activity, but not by beta activity.Significance: This link between baseline brain activity, self-report measures and feedback processing may contribute to further understanding the biological basis of conditions that are accompanied by abnormal theta/beta ratio and reward processing, such as attention deficit hyper activity disorder (ADHD).

Differential control of H-reflex amplitude in different weight-bearing conditions in young and elderly subjects - Corrected Proof

Masaaki Tsuruike, Koichi Kitano, David M. Koceja, Zachary A. Riley — 2012-04-30

Highlights: ► The soleus (SOL) maximum evoked H-reflex (H-max) was associated with the corresponding background EMG (bEMG) activity for the elderly subjects who increased the bEMG activity as they increased their body-weight-bearing conditions. ► The young subjects had an ability to modulate their descending tonic ongoing presynaptic inhibition imposed on the Ia afferents of the femoral nerve (FN) from non-weight-bearing condition to weight-bearing condition, whereas the elderly subjects did not. ► In the elderly group, it is considered that input from the vestibulospinal tract is insufficient to induce presynaptic inhibition upon Ia fibre connection to the motoneuron.Abstract: Objective: This study measured the modulation of conditioned (femoral nerve, paired-stimuli) and unconditioned soleus H-reflexes in young and elderly subjects when changing weight-bearing (WB) requirements and body position.Methods: Conditioned and unconditioned H-reflexes were examined in 14 elderly subjects and 11 young subjects during six different WB conditions: (1) lying supine with no WB, (2) supine position inclined by 30° with 50% WB, (3) standing with 50%, (4) 75%, (5) 100% and (6) 125% WB.Results: The elderly subjects had consistently higher background soleus EMG activity across the WB conditions compared to the young. Femoral nerve conditioning caused facilitation of the H-reflex that changed across WB conditions in the young subjects, but not in the elderly subjects. Finally, elderly subjects had less depression with paired-stimulation (PRD) across WB conditions, which was not observed in the young subjects.Conclusions: The elderly may have more direct activation of motoneurons from descending pathways, coupled with less segmental spinal control of inhibitory interneurons, as evidenced by the increased background soleus activity, H/M-max ratios and the lack of modulatory control observed when conditioning the H-reflex.Significance: There was an age-specific response from descending and segmental pathways during conditions that involved either different WB requirements or changes in body position.

Heartbeat evoked potentials mirror altered body perception in depressed patients - Corrected Proof

Janneke Terhaar, Filipa Campos Viola, Karl-Jürgen Bär, Stefan Debener — 2012-04-27

Highlights: ► Heartbeat evoked potentials are objective markers of altered bodily awareness. ► Reduced interoception in major depression has been shown in comparison to controls. ► Interoception in depression may be linked to decreased capacity for decision-making.Abstract: Objective: Awareness of stimuli originating inside of the body (interoceptive awareness) is thought to have an impact on psychopathology. The aim of the present study was to analyze whether heartbeat perception accuracy is reduced in depressed patients. Furthermore, we investigated whether putative differences are reflected in heartbeat-evoked potentials.Method: We assessed the heartbeat perception score in 16 depressed patients and in matched healthy controls. A 63-channel EEG was recorded while participants counted pseudo-randomly presented target tones or heartbeats during a fixed number of cardiac cycles. ECG R-waves served as the trigger for EEG averaging. The cardiac-field artifact was minimized using independent component analysis and current–source density.Results: Behaviorally, the depressed sample showed less accurate heartbeat perception in comparison to the control group (p=.011). The two groups also demonstrated psychophysiological differences, showing that heartbeat-evoked potentials were significantly reduced in depressed patients.Conclusions: Our results suggest that heartbeat evoked potentials are objective markers of altered bodily awareness. Reduced interoception during depression may be linked to alexithymia, as well as to both decreased capacity for decision-making and for cognitive processing.Significance: It may be helpful to practice interoceptive awareness to improve depressive symptoms, for example by practicing meditation.

Mismatch negativity and low frequency oscillations in schizophrenia families - Corrected Proof

L. Elliot Hong, Lauren V. Moran, Xiaoming Du, Patricio O’Donnell, Ann Summerfelt — 2012-04-27

Highlights: ► Schizophrenia patients showed significantly augmented lower range frequency activities in beta, alpha, theta, and delta ranges during the MMN paradigm. ► MMN and theta-alpha oscillations were significantly heritable traits. ► Low frequency activities were robustly associated with MMN, although the exact relationships were altered by schizophrenia.Abstract: Objective: Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members.Methods: We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits.Results: We found that (1) MMN was reduced in patients (p<0.001) and SSP subjects (p=0.047) but not in relatives (p=0.42); (2) there were augmented 1–20Hz oscillations in patients (p=0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5–12Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR2=21.4–23.9%, all p<0.001), while delta (<5Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h2=0.56, p=0.002) and theta-alpha (h2=0.55, p=0.004) were heritable traits.Conclusions: Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm.Significance: The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.

Age-related changes in the control of perturbation-evoked and voluntary arm movements - Corrected Proof

Tyler B. Weaver, Lauren E. Hamilton, Craig D. Tokuno — 2012-04-27

Highlights: ► Ageing leads to changes in the ability to produce perturbation-evoked arm responses following an unexpected loss of balance. ► Altering the predictability of the handrail location affects electromyographic and kinematic arm responses in both young and older adults. ► Age-related differences in arm responses are independent of handrail predictability and movement task (i.e., perturbation-evoked versus voluntary reaching), suggesting that ageing leads to a deterioration in neural mechanisms that are common to both reactive and voluntary arm movements.Abstract: Objective: This study examined how handrail location predictability affects perturbation-evoked arm responses in young and older adults and whether age-related changes in perturbation-evoked arm responses are specific to mechanisms associated with reactive postural control.Methods: Young and older adults reached for a handrail in response to a support surface translation (perturbation-evoked) or to a visual cue (voluntary). For both movement tasks, the handrail location was made predictable or unpredictable to the participant. Electromyographic (EMG) activity and kinematics of the reaching arm were recorded to quantify the arm response.Results: Posterior deltoid EMG activity during perturbation-evoked and voluntary movements were delayed by 15–74ms (p<0.001) and 16% smaller (p=0.024) when the handrail was in an unpredictable compared to a predictable location. While ageing resulted in a 12–16ms delayed initiation of EMG activity during perturbation-evoked reaching (p=0.003), the effects of handrail predictability and movement task did not interact with age.Conclusions: Age-related differences in perturbation-evoked arm responses are independent of both handrail location predictability and movement task.Significance: Age-related differences in perturbation-evoked arm responses cannot be solely attributed to declines in reactive postural control. Rather, ageing leads to a deterioration of neural mechanisms common to both perturbation-evoked and voluntary arm movements.

Frequency-domain EEG source analysis for acute tonic cold pain perception - Corrected Proof

Shiyun Shao, Kaiquan Shen, Ke Yu, Einar P.V. Wilder-Smith, Xiaoping Li — 2012-04-26

Highlights: ► Tonic cold pain induces significantly decreased source activity in low-frequency (<12Hz) bands but mainly increased activity in high-frequency (>12Hz) bands in multiple brain regions. ► Neuronal electrical activities that significantly correlated with subjective pain ratings are localized in the prefrontal and cingulate cortices. ► The findings have important implications for developing objective pain assessment methods and cortical neuromodulation based pain interventions.Abstract: Objective: To investigate electrocortical responses to tonic cold pain by frequency-domain electroencephalogram (EEG) source analysis, and to identify potential electrocortical indices of acute tonic pain.Methods: Scalp EEG data were recorded from 26 healthy subjects under tonic cold pain (CP) and no-pain control (NP) conditions. EEG power spectra and the standardized low-resolution brain electromagnetic tomography (sLORETA) localized EEG cortical sources were compared between the two conditions in five frequency bands: 1–4Hz, 4–8Hz, 8–12Hz, 12–18Hz and 18–30Hz.Results: In line with the EEG power spectral results, the source power significantly differed between the CP and NP conditions in 8–12Hz (CP NP) in extensive brain regions. Besides, there were also significantly different 4–8Hz and 12–18Hz source activities between the two conditions. Among the significant source activities, the left medial frontal and left superior frontal 4–8Hz activities, the anterior cingulate 8–12Hz activity and the posterior cingulate 12–18Hz activity showed significant negative correlations with subjective pain ratings.Conclusions: The brain’s perception of tonic cold pain was characterized by cortical source power changes across different frequency bands in multiple brain regions. Oscillatory activities that significantly correlated with subjective pain ratings were found in the prefrontal and cingulate regions.Significance: These findings may offer useful measures for objective pain assessment and provide a basis for pain treatment by modulation of neural oscillations at specific frequencies in specific brain regions.

The relationship between Bayesian motor unit number estimation and histological measurements of motor neurons in wild-type and SOD1G93A mice - Corrected Proof

2012-04-23

Abstract: Objective: To assess the relationship between Bayesian MUNE and histological motor neuron counts in wild-type mice and in an animal model of ALS.Methods: We performed Bayesian MUNE paired with histological counts of motor neurons in the lumbar spinal cord of wild-type mice and transgenic SOD1G93A mice that show progressive weakness over time. We evaluated the number of acetylcholine endplates that were innervated by a presynaptic nerve.Results: In wild-type mice, the motor unit number in the gastrocnemius muscle estimated by Bayesian MUNE was approximately half the number of motor neurons in the region of the spinal cord that contains the cell bodies of the motor neurons supplying the hindlimb crural flexor muscles. In SOD1G93A mice, motor neuron numbers declined over time. This was associated with motor endplate denervation at the end-stage of disease.Conclusion: The number of motor neurons in the spinal cord of wild-type mice is proportional to the number of motor units estimated by Bayesian MUNE. In SOD1G93A mice, there is a lower number of estimated motor units compared to the number of spinal cord motor neurons at the end-stage of disease, and this is associated with disruption of the neuromuscular junction.Significance: Our finding that the Bayesian MUNE method gives estimates of motor unit numbers that are proportional to the numbers of motor neurons in the spinal cord supports the clinical use of Bayesian MUNE in monitoring motor unit loss in ALS patients.

Quantitative studies of lower motor neuron degeneration in amyotrophic lateral sclerosis: Evidence for exponential decay of motor unit numbers and greatest rate of loss at the site of onset - Corrected Proof

F. Baumann, R.D. Henderson, P. Gareth Ridall, A.N. Pettitt, Pamela A. McCombe — 2012-04-23

Abstract: Objective: To use our Bayesian method of motor unit number estimation (MUNE) to evaluate lower motor neuron degeneration in ALS.Methods: In subjects with ALS we performed serial MUNE studies. We examined the repeatability of the test and then determined whether the loss of MUs was fitted by an exponential or Weibull distribution.Results: The decline in motor unit (MU) numbers was well-fitted by an exponential decay curve. We calculated the half life of MUs in the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and/or extensor digitorum brevis (EDB) muscles. The mean half life of the MUs of ADM muscle was greater than those of the APB or EDB muscles. The half-life of MUs was less in the ADM muscle of subjects with upper limb than in those with lower limb onset.Conclusions: The rate of loss of lower motor neurons in ALS is exponential, the motor units of the APB decay more quickly than those of the ADM muscle and the rate of loss of motor units is greater at the site of onset of disease.Significance: This shows that the Bayesian MUNE method is useful in following the course and exploring the clinical features of ALS.

Estimating the value of estimation - Corrected Proof

Mamede de Carvalho — 2012-04-20

The concept of motor unit was first recognized by Sir Charles Sherrington () by defining it as the spinal motor neuron and its axon together with the muscle fibers it activates. The possibility to investigate the number of motor units in a muscle is of major interest for a number of reasons: it gives information about the number and function of lower motor neurons; it permits to understand the physiology and plasticity (reinnervation potential) of the peripheral axon and neuromuscular junction (); it is a tool for following the number of lower motor neurons in degenerative disorders, like in amyotrophic lateral sclerosis (ALS), as well as to test the potential benefit of therapeutic interventions ().

Somatomotor mu rhythm amplitude correlates with rigidity during deep brain stimulation in Parkinsonian patients - Corrected Proof

2012-04-18

Highlights: ► The spatiotemporal signal space separation (tSSS) method makes magnetoencephalography (MEG) measurements feasible in deep brain stimulation (DBS) patients. ► During DBS, rigidity correlated with somatomotor mu rhythm strength when eyes were open. ► The peak frequency of occipital alpha rhythm correlated negatively with Unified Parkinson’s Disease Rating Scale (UPDRS) total motor and rigidity subscores.Abstract: Objective: Parkinsonian patients have abnormal oscillatory activity within the basal ganglia-thalamocortical circuitry. Particularly, excessive beta band oscillations are thought to be associated with akinesia. We studied whether cortical spontaneous activity is modified by deep brain stimulation (DBS) in advanced Parkinson’s disease and if the modifications are related to the clinical symptoms.Methods: We studied the effects of bilateral electrical stimulation of subthalamic nucleus (STN) on cortical spontaneous activity by magnetoencephalography (MEG) in 11 Parkinsonian patients. The artifacts produced by DBS were suppressed by tSSS algorithm.Results: During DBS, UPDRS (Unified Parkinson’s Disease Rating Scale) rigidity scores correlated with 6–10Hz and 12–20Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6–10Hz and 21–30Hz and occipital alpha source strengths when eyes open.Occipital alpha strength decreased during DBS when eyes closed. The peak frequency of occipital alpha rhythm correlated negatively with total UPDRS motor scores and with rigidity subscores, when eyes closed.Conclusion: STN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS.Significance: MEG combined with an appropriate artifact rejection method enables studies of DBS effects in Parkinson’s disease and presumably also in the other emerging DBS indications.

Multimodality language mapping in patients with left-hemispheric language dominance on Wada test - Corrected Proof

2012-04-16

Highlights: ► Measurement of event-related gamma-oscillations at 50–120Hz detected language sites more frequently than electrical stimulation in epileptic patients with left-hemispheric language dominance on Wada test. ► Stimulation of sites showing event-related augmentation of gamma-oscillations more frequently resulted in temporary language-related symptoms, compared to that of the other sites. ► Cortical resection of sites showing event-related augmentation of gamma-oscillations resulted in dysphasic symptoms in an epileptic patient, while electrical stimulation failed to identify the language sites.Abstract: Objective: We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test.Methods: We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions.Results: Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p<0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p<0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation.Conclusions: Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance.Significance: Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.

Gamma-oscillations from bench to bed - Corrected Proof

Thomas Grunwald, Johannes Sarnthein — 2012-04-16

In the presurgical evaluation of patients with pharmacoresistant epilepsies, the borders between disciplines tend to oscillate. In particular, the necessity to evaluate the functional capacity of a cortical area that has been shown to be epileptogenic and is thus being considered for resection often makes it impossible not to trespass between neurophysiology and neuropsychology. In epilepsy surgery, the principle of “first, do no harm”, often blurs the distinction between “bed and bench”: findings from basic sciences that implicate a certain brain region in specific neurological or neuropsychological functions must be taken into account when an elective resection of a structure is considered – even if resection might relieve the patient from frequent intolerable seizures. That may seem to go without saying and, in fact, several examinations that are used routinely in modern presurgical evaluation are really shortcuts in the path from bench to bed. It may be an excuse that there are still are no generally accepted protocols for examinations such as the intracarotid amobarbital (“Wada”) test or language mapping by electro-stimulation, be the latter intrasurgical or by chronically implanted subdural electrodes. On the other hand, the opposite way “from bed to bench and back” has a famous history in epilepsy surgery: a new area of memory research followed Brenda Milner’s analysis of the famous anterograde amnesia caused by the resection of both hippocampi in Henry Molaison (H.M.) and, eventually, this has led to important clinical applications in both neuropsychology and neurophysiology.

Oscillatory modulations in human fusiform cortex during motion-induced blindness: Intracranial recording - Corrected Proof

Naoyuki Matsuzaki, Csaba Juhász, Eishi Asano — 2012-04-16

Highlights: ► High-gamma activity at 80–150Hz was attenuated in a fusiform site around illusory disappearance of a visual target. ► The distribution of delta phases in the fusiform site became skewed immediately prior to the illusory disappearance of the visual target. ► High-gamma activity was augmented in the fusiform site around reappearance of the visual target.Abstract: Objective: Motion-induced blindness (MIB) is an illusory phenomenon, in which a static target surrounded by moving distracters is perceived to disappear. We determined the electrocorticographic (ECoG) correlates of MIB.Methods: While undergoing intracranial ECoG recording, a patient with focal epilepsy was instructed to report the transitions of a visual target, which was designed to illusorily or physically disappear and reappear. We then determined the neural modulations associated with illusory and physical transitions of the target. We also tested whether the phase of local delta activity could predict exclusively illusory transitions.Results: High-gamma activity at 80–150Hz was attenuated in the fusiform region prior to the reports of illusory and real visual target disappearance. Conversely, such high-gamma activity was augmented prior to the report of real target reappearance. Exclusively around illusory disappearance but not around real one, the delta phases in the fusiform region showed a highly skewed distribution with preference of the negative peak.Conclusions: Neuronal modulations in the fusiform region may be involved in visual awareness, while spontaneous fluctuations of neural states entrained on delta rhythm may be involved in generation of MIB.Significance: Our study increases our understanding of the mechanisms of visual awareness.

Heartbeat evoked potentials: A new possible clinical biomarker for depression based on the somatic marker hypothesis - Corrected Proof

Ryouhei Ishii, Leonides Canuet — 2012-04-13

Since the annual costs of major depressive disorder (MDD) are continuously increasing worldwide (), the development of objective biomarkers for diagnosis and treatment of MDD should be an urgent issue. Although no objective measurements have been proven to be ready for clinical application as biomarkers for MDD, several brain functional measures, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), might be promising for future application (). Especially, electrophysiological measures seem to be particularly practical biomarkers to help diagnosis and treatment of MDD because of their easiness, inexpensiveness and non-invasiveness ().

Electrodiagnostic criteria for Guillain–Barrè syndrome: A critical revision and the need for an update - Corrected Proof

Antonino Uncini, Satoshi Kuwabara — 2012-04-05

Highlights: ► In addition to axonal degeneration, the pathophysiology of acute motor axonal neuropathy (AMAN) is characterised by reversible conduction failure (RCF) which can be recognised only by serial recordings. ► The current electrodiagnostic criteria for Guillain–Barré syndrome (GBS) do not consider RCF, and may erroneously classify patients with AMAN with RCF as acute inflammatory demyelinating polyradiculoneuropathy or AMAN with axonal degeneration. ► More reliable electrodiagnostic criteria should be devised, taking RCF into account, focussing on temporal dispersion and including the requirement of serial recordings, for both diagnosis and prognosis.Abstract: Electrophysiology plays a determinant role in Guillain–Barré syndrome (GBS) diagnosis, classification of the subtypes and in establishing prognosis. In the last three decades, different electrodiagnostic criteria sets have been proposed for acute inflammatory demyelinating neuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). Criteria sets for AIDP varied for the parameters indicative of demyelination considered, for the cut-off limits and the number of required abnormalities (all a priori established) showing different sensitivities. Criteria sets for AMAN and AMSAN were proposed on the initial assumption that these subtypes were pathologically characterised by simple axonal degeneration. However, some AMAN patients show transient conduction block/slowing in intermediate and distal nerve segments, mimicking demyelination but without the development of abnormal temporal dispersion, named reversible conduction failure (RCF). The lack of distinction between RCF and demyelinating conduction block leads to fallaciously classify AMAN patients with RCF as AIDP or AMAN with axonal degeneration. Serial electrophysiological studies are mandatory for proper diagnosis of GBS subtypes, identification of pathophysiological mechanisms and prognosis. More reliable electrodiagnostic criteria should be devised to distinguish axonal and demyelinating subtypes of GBS, taking into consideration the RCF pattern and focussing on temporal dispersion.

Everything you always wanted to know about nerve, but were afraid to ask - Corrected Proof

Luca Padua — 2012-04-05

In this issue there is an article by Datema and colleagues () on the diagnostic yield of Neuropads® and water immersion skin wrinkling (WISW) for the diagnosis of small fiber neuropathy (SFN). Neuropads® and WISW have been tested on patients affected with different forms of clinically diagnosed (on the basis of symptoms) small fiber neuropathy, and healthy controls.

Discriminating preictal and interictal states in patients with temporal lobe epilepsy using wavelet analysis of intracerebral EEG - Corrected Proof

Kais Gadhoumi, Jean-Marc Lina, Jean Gotman — 2012-04-05

Highlights: ► Preictal and interictal epochs are distinguishable in some patients using EEG measures of similarity with a reference state defined from the immediate preictal period. ► Wavelet energy and entropy characterize the state underlying EEG epochs. ► Discriminability between preictal and interictal states varies with frequency bands.Abstract: Objective: Identification of consistent distinguishing features between preictal and interictal periods in the EEG is an essential step towards performing seizure prediction. We propose a novel method to separate preictal and interictal states based on the analysis of the high frequency activity of intracerebral EEGs in patients with mesial temporal lobe epilepsy.Methods: Wavelet energy and entropy were computed in sliding window fashion from preictal and interictal epochs. A comparison of their organization in a 2 dimensional space was carried out using three features quantifying the similarities between their underlying states and a reference state. A discriminant analysis was then used in the features space to classify epochs. Performance was assessed based on sensitivity and false positive rates and validation was performed using a bootstrapping approach.Results: Preictal and interictal epochs were discriminable in most patients on a subset of channels that were found to be close or within the seizure onset zone.Conclusions: Preictal and interictal states were separable using measures of similarity with the reference state. Discriminability varies with frequency bands.Significance: This method is useful to discriminate preictal from interictal states in intracerebral EEGs and could be useful for seizure prediction.

Are glial cells responsible for transcranial direct current stimulation? - Corrected Proof

Bradley J. Roth — 2012-04-05

“A mind that is stretched by a new idea can never go back to its original dimensions”.— Oliver Wendell Holmes We all know the scientific method: you form a hypothesis about how something works, then you design experiments that can test the hypothesis, accepting or rejecting it. The most creative step in this process is conceiving the hypothesis. In this issue of Clinical Neurophysiology, Ruohonen and Karhu present a new hypothesis of how transcranial direct current stimulation (tDCS) affects the brain (). The essence of their idea is this: tDCS affects the glial cells, not the neurons directly.

tDCS possibly stimulates glial cells - Corrected Proof

Jarmo Ruohonen, Jari Karhu — 2012-04-05

Highlights: ► It is theoretically possible that tDCS stimulates glial cells instead of neurons. ► Calculations indicate that transmembrane potential change is of similar magnitude as observed physiologically in astrocytes during neuronal activation. ► Possibility to stimulate non-invasely glial cells would be a great therapeutic breakthrough.Abstract: Objective: Explore the possibility that transcranial direct current stimulation (tDCS) of the brain affects glial cells.Methods: Cable theory is used to estimate roughly transmembrane potential in neurons and glial cells. tDCS is additionally compared to neuronal stimulation techniques for which the mechanisms are well known.Results: Theoretical calculations indicated that tDCS can affect the glial transmembrane potential. The change is similar to what is physiologically observed in astrocytes during neuronal activation. In neurons, transmembrane potential changes are much weaker than the threshold for eliciting action potentials.Conclusions: Based on simplified cable theory, tDCS may affect glial cells’ transmembrane potential and thereby the balance of neurotransmitters. No physiological evidence or proof is available, however.Significance: It is an exciting possibility that tDCS could manipulate glial cells because they are active participants in brain function, and have multiple essential roles in the human brain. This approach may change greatly the therapeutic potential of tDCS, and also affects the safety considerations.

The diagnostic value of water immersion skin wrinkling and Neuropads® in small fiber neuropathy - Corrected Proof

Mirjam Datema, J. Gert van Dijk, Elske Hoitsma — 2012-04-04

Highlights: ► The Neuropad® and water immersion skin wrinkling (WISW) are simple tests that can be useful in order to support the diagnosis of small fiber neuropathy. ► The sensitivity of the Neuropad® was 29% and specificity 93%. The sensitivity of WISW was 66% and specificity 70%. ► When both test results are abnormal the diagnosis small fiber neuropathy is highly likely (Specificity 97%).Abstract: Objective: To investigate the diagnostic yield of two simple tests for small fiber neuropathy (SFN): Neuropads® and water immersion skin wrinkling (WISW).Methods: We studied 35 patients clinically diagnosed with SFN and 61 age- and sex-matched healthy controls. Wrinkling was judged as absent (abnormal), or present (normal) after immersion of the hands for 30min. Neuropads® are plasters impregnated with cobalt blue that are applied with to the soles of the feet. These remain blue when feet are dry (abnormal) or turn pink when there is some moisture (normal).Results: The sensitivity of the Neuropad® was 29% and its specificity 93%. The sensitivity of WISW was 66% and its specificity 70%. Regarding abnormality of at least one test to define the combination as abnormal yielded a sensitivity of 71% and specificity 67%. When both tests had to be abnormal to judge the combination abnormal, sensitivity was 23% and specificity 97%.Conclusions: The Neuropad® has a high specificity, so an abnormal result can be used to confirm SFN. WISW has a moderate sensitivity and specificity. Combining these two tests can be helpful: when both tests are abnormal the diagnosis SFN is highly likely.Significance: The Neuropad® and WISW can be helpful in daily practice by supporting the diagnosis SFN.

Wavelet packet-based independent component analysis for feature extraction from motor imagery EEG of complex movements - Corrected Proof

Zhongxing Zhou, Baikun Wan — 2012-03-30

Highlights: ► This study developed a wavelet packet-based independent component analysis (WPICA) method to extract the event-related de-synchronisation and synchronisation (ERD/ERS) patterns in different frequency bands during complex motor imagery of lower limb action. ► The criterion for principal independent component selection and the procedures of the WPICA method were demonstrated. ► The performance of the WPICA method was assessed by comparison with the traditional ICA method.Abstract: Objective: The main goal of this study was to develop a novel spatial filtering method for better extracting the feature information underlying the event-related de-synchronisation and synchronisation (ERD/ERS) during complex motor imagery of lower limb action.Methods: The algorithm used a wavelet packet-based independent component analysis (WPICA) method to extract the ERD/ERS patterns in different frequency bands. Time–frequency decomposition in the wavelet packet domain was designed to avoid the statistical correlation between different electroencephalographic (EEG) rhythms. The subband-specific principal components were extracted after independent component analysis and projected back to the time–frequency domain of corresponding electrodes for better fitting the varying EEG spatial distributions.Results: The present method was tested with the EEG data from 10 human subjects performing three complex mental tasks (i.e., imagery standing up, imagery left/right foot movement combined with homolateral hand movement). A classification rate of about 80% was achieved using the WPICA-based technique, which is better than the traditional ICA method with the rate of 72.30% and the non-spatial filtering condition of 68.34%.Conclusions: We developed a novel spatial filtering method based on WPICA to extract the ERD/ERS patterns in different frequency bands. The overall performance of this algorithm was better than that of the conventional methods.Significance: The current method promised to provide an effective way for ERD/ERS patterns recognition and thus could improve the pattern classification performance of complex mental tasks from scalp EEGs.

Focal brain cooling terminates the faster frequency components of epileptic discharges induced by penicillin G in anesthetized rats - Corrected Proof

2012-03-29

Highlights: ► Epileptic discharges (EDs) in superficial layers were induced with penicillin G. ► Focal brain cooling preferentially terminated the faster frequency components of EDs. ► Frequency analysis demonstrated that cooling below 25°C may be an effective treatment for epilepsy.Abstract: Objective: The goal of the study was to investigate the effects of focal brain cooling on epileptic discharges (EDs) and background rhythms in the sensorimotor cortex of anesthetized rats using spectral analysis of electroencephalography (EEG).Methods: Penicillin G was administered intracortically into superficial layers of the left sensorimotor cortex and EDs were induced. Focal brain cooling was achieved using a cooling device attached to the cortical surface. The cortical surface was cooled to 25°C, 20°C and 15°C, and EEG was continuously recorded just beneath the cooling device. EEG spectral powers were determined using fast Fourier transform before and during cooling.Results: Penicillin G induced EDs and increased the Alpha and Beta power spectra. Cooling suppressed EDs with an effect that depended on the brain temperature. Cooling to 25°C attenuated Beta powers, cooling to 20°C attenuated Alpha and Beta powers, and cooling to 15°C suppressed spectral powers ranging from Delta to Beta bands.Conclusions: These results suggest that focal brain cooling can terminate EDs in the cortex and suppress spectral powers with a temperature-dependent effect.Significance: These findings may contribute to development of a new clinical treatment for patients with epilepsy.

Altered face inversion effect and association between face N170 reduction and social dysfunction in patients with schizophrenia - Corrected Proof

2012-03-28

Highlights: ► Normal controls showed a significant increase in N170 amplitude to inverted faces compared to upright faces while schizophrenic patients showed no such findings, whereas both groups showed no significant differences in N170 amplitude evoked by inverted and upright motor cars. ► There was a significant association between social dysfunction and face-N170 reduction in schizophrenia. ► This study revealed the association between deficits of face-specific configuration processing and social dysfunction in schizophrenia.Abstract: Objective: There is accumulating evidence that schizophrenics may have deficits in facial recognition, which has been related to disease-specific disturbances in normal social interaction. Neurophysiologically, face inversion results in an amplitude increase of the event-related potential (ERP) component N170. This face inversion effect (FIE) presumably reflects a disruption of face-specific configuration processing. The present study investigated FIE and the associations between social functioning and N170 in patients with schizophrenia.Methods: The subjects consisted of 15 schizophrenics and 15 controls. Event-related potentials (ERPs) to upright and inverted neutral faces and cars were recorded. The relationships between the Social Functioning Scale (SFS) scores and N170 amplitude to upright faces or cars were also evaluated.Results: Normal controls exhibited a significant FIE of the N170 amplitude, while schizophrenics showed no FIE. In both normal controls and schizophrenics, no inversion effect was observed for car stimuli. For face stimuli, schizophrenics showed significant bilateral N170 reduction; additionally, in schizophrenics, but not in controls, the SFS was significantly correlated with N170 amplitudes to upright faces.Conclusions: These results indicate face-specific configuration processing deficits and significant associations between face-N170 reduction and social dysfunction in schizophrenia.Significance: Abnormal face-specific configuration processing may underlie some of the social dysfunctions in schizophrenia.

Contrast-response functions of the multifocal steady-state VEP (MSV) - Corrected Proof

S.N. Abdullah, Vaegan, M.Y. Boon, T. Maddess — 2012-03-23

Highlights: ► Contrast response functions for spatial frequency doubling stimuli were recordable using a few repeats of a 20s stimulus. ► The results indicated interesting physiology at contrasts below 10% and near the fovea. ► Separately measured long-range nonlinear interactions between visual field regions appeared to arise from extrastriate cortical areas.Abstract: Objectives: To measure contrast-response functions (CRFs) for 9 visual field (VF) regions and nonlinear interactions between regions using a multifocal steady-state VEP (MSV).Methods: Ten normal adults were tested (51.7±16.9yr, 5 females). Stimuli resembling those of the Frequency Doubling Technology (FDT) perimeter were presented in 9 VF regions simultaneously, which were modulated at incommensurate temporal frequencies (mean 19.7Hz). Responses were recorded to 11 contrasts from 3% to 89%, using 8 scalp electrodes. Two repeats of a 20s duration stimulus were averaged for each contrast.Results: The CRFs were log-linear except for a depression near 7% contrast (p=0.0008), which was prominent in the central VF. The effects of VF region, stimulus frequency and recording electrode were significant (all p<0.016). Significant responses at frequencies corresponding to interactions between VF regions also appeared. Electrodes that were best for the interactions and second harmonic responses differed, suggesting different cortical sources.Conclusions: Despite short recording durations the saturating CRFs meant that significant responses could be measured to low contrasts, and be distinguished from nonlinear interactions.Significance: Recording MSVs to low contrast FDT-like stimuli might be useful for quantifying damage by glaucoma and other visual disorders.

Nerve conduction studies of the sural nerve: Normative data from a single-center experience - Corrected Proof

Marco Luigetti, Davide Quaranta, Anna Modoni, Maria Lucia Mereu, Mauro Lo Monaco — 2012-03-23

The sural nerve is the most frequently studied sensory nerve in the lower limbs of patients with peripheral neuropathy because it is accessible for nerve biopsy, thus allowing a correlation between pathological and neurophysiological findings (). Nerve conduction studies of the sural nerve are a crucial diagnostic tool in both axonal and demyelinating form of neuropathies (). The amplitude of sensory nerve action potential (SNAP) of the sural nerve may also be used to monitor the progression of neuropathy or response to therapies (). However, the significant variations exist in the normal range of sural nerve conduction studies among normal subjects, as they are influenced by different parameters (). A recent paper showed a negative correlation of SNAP amplitude with age and height ().

Pathophysiology of unilateral asterixis due to thalamic lesion - Corrected Proof

2012-03-19

Highlights: ► Two cases with unilateral asterixis caused by an infarction in the lateral thalamus were studied by using electrophysiological and neuroimaging methods. ► Averaging of electroencephalogram (EEG) time locked to the asterixis revealed rhythmic oscillations of a beta band at the central area contralateral to the affected hand. ► The present study for the first time demonstrated that the asterixis due to a thalamic lesion is mediated by the sensorimotor cortex, which is subjected to excessive inhibition.Abstract: Objective: Unilateral asterixis has been reported in patients with thalamic lesion. This study aims at elucidating the pathophysiology of the thalamic asterixis.Methods: Two cases with unilateral asterixis caused by an infarction in the lateral thalamus were studied by analysing the asterixis-related cortical activities, transcranial magnetic stimulation (TMS) for motor cortex excitability and probabilistic diffusion tractography for the thalamo-cortical connectivity.Results: Averaging of electroencephalogram (EEG) time-locked to the asterixis revealed rhythmic oscillations of a beta band at the central area contralateral to the affected hand. TMS revealed a decrease in the motor evoked potential (MEP) amplitude and a prolongation of the silent period (SP). The anatomical mapping of connections between the thalamus and cortical areas using a diffusion-weighted image (DWI) showed that the lateral thalamus involved by the infarction was connected to the premotor cortex, the primary motor cortex (M1) and the primary somatosensory cortex (S1) of the corresponding hemisphere.Conclusions: The thalamic asterixis is mediated by the sensorimotor cortex, which is subjected to excessive inhibition as a result of the thalamic lesion involving the ventral lateral nucleus.Significance: This is the first demonstration of participation of the sensorimotor cortex in the generation of asterixis due to the lateral thalamic lesion.

Functional dissociation of brain rhythms in social coordination - Corrected Proof

Muhammad Naeem, Girijesh Prasad, David R. Watson, J.A. Scott Kelso — 2012-03-19

Highlights: ► Spectral separation of sub-bands in the mu domain was used to identify neural processes in tasks requiring real-time social interaction: changes in the lower mu band were diffuse and non-specific; changes in the upper mu band were highly related to coupling measures of intentional social coordination. ► In the upper mu-band event-related synchronization was associated with uncoupled behavior whereas event-related de-synchronization denoted coupled behaviors. ► Coupled coordinated behavior displayed clear hemisphere predispositions: L>R in the in-phase and R>L in the anti-phase tasks.Abstract: Objectives: The goal of this research was to investigate sub-band modulations in the mu domain in dyads performing different social coordination tasks.Methods: Dyads of subjects performed rhythmic finger movement under three different task conditions: intrinsic – maintain self-produced movement while ignoring their partner’s movement; in-phase – synchronize with partner; and anti-phase – maintain syncopation with partner. Movement profiles of the dyads were used to estimate a synchronization index (SI) to verify differences in coordination according to each task. EEG was recorded during task performance and at baseline (partner’s actions hidden from view). Log power ratios of mu band activity (active against baseline) were used to assess the relative levels of synchronization/de-synchronization in both the upper and lower mu bands.Results: Results confirm a functional dissociation of lower (8–10Hz) and upper (10–12Hz) mu bands in social coordination tasks. Lower mu band activity was independent of specific modulations across tasks and hemispheric preferences. Upper mu band activity was sensitive to coordination tasks and exhibited marked differences between the hemispheres. Accentuated de-synchronization of right relative to left hemisphere in the anti-phase task appeared related to the greater demand of perceptual-motor discrimination. Left hemisphere de-synchronization in both in-phase and anti-phase coordination was interpreted in terms of successful production of imitation. Right hemisphere synchronization in the intrinsic task was interpreted as inhibition of an imitative response tendency.Conclusions: Functional dissociation of lower and upper mu band and hemispheric preferences exists in real-time social coordination.Significance: This research attests to the merit of analyzing sub-band activity in the alpha-mu domain in order to identify neural correlates of social coordination. Such ‘neuromarkers’ may be relevant for brain disorders such as apraxia and autism.

Scalp- and sLORETA-derived loudness dependence of auditory evoked potentials (LDAEPs) in unmedicated depressed males and females and healthy controls - Corrected Proof

Natalia Jaworska, Pierre Blier, Wendy Fusee, Verner Knott — 2012-03-19

Highlights: ► The loudness dependence of auditory evoked potentials (LDAEP) was unaltered in depression, though the LDAEP derived from primary auditory cortex activity correlated negatively with depression ratings. ► Smaller auditory evoked potentials (AEPs) existed in depressed versus control males. ► Females had enhanced cortical responses to auditory stimuli.Abstract: Objective: As major depressive disorder (MDD) is associated with altered 5-HT activity, we probed intensity-dependent auditory evoked potentials (AEPs) and loudness dependence of the AEP (LDAEP) slopes, shown pre-clinically to be inversely related to 5-HT activity, in MDD.Methods: AEPs and LDAEP slopes were measured in MDD (N=50; 27 females) and controls (N=43; 23 females). Correlations between scalp AEPs/LDAEPs and low-resolution electromagnetic tomography (sLORETA)-derived indices were assessed.Results: Smaller scalp intensity-dependent N1 and N1/P2 amplitudes in MDD versus control males and longer P2 latencies in MDD versus control females were found; no LDAEP group differences existed. Females had greater scalp AEPs, steeper N1 and N1/P2 scalp LDAEPs as well as greater intensity-dependent primary auditory cortex activation during the N1 than males. Scalp LDAEPs correlated weak-moderately with sLORETA counterparts. P2 LDAEP-sLORETA correlated negatively with MADRS scores. Female P2 and N1/P2 LDAEP-sLORETA correlated negatively with HAMD-17 and MADRS scores.Conclusions: MDD was not associated with altered LDAEPs. Impaired processing or potentiated inhibition of auditory stimuli was found in MDD males; longer processing existed in MDD females. Inverse relationships between LDAEPs and clinical scores may be related to treatment history, personality and/or MDD features.Significance: MDD was not associated with an altered LDAEP, though subtle AEPs alterations were noted in MDD.

Do impairments in facial analysis underlie impaired social functioning in schizophrenia? - Corrected Proof

Dean F. Salisbury — 2012-03-19

Schizophrenia remains a costly public health issue, both emotionally for those afflicted and their family members, and financially, with less than half of those ill able to work even part time for the rest of their lives. The lifelong need for care impacts the productivity of their families as well. Wu and colleagues (; see ) estimated that 2002 US costs for the direct care of schizophrenia were $32billion, with another $32.4billion in lost productivity and other “indirect” costs, including $21.6billion due to patient unemployment. The costs have not gone down in the decade since. Clearly, research that advances our understanding of the underlying causes of social and occupational disability in schizophrenia and that aids in development of new interventions has a huge upside. Although cognitive problems play a large part in the difficulty people suffering from schizophrenia have in regaining meaningful employment, as do symptoms easily exacerbated by mild stressors, impaired social functioning during interpersonal interactions may be the greatest impediment. Persons with schizophrenia often avoid the company of others due to a pervasive sense of social awkwardness, a disconnect from others, misinterpreting subtle social cues during interactions, or, couched in terms of current ideas of theory of mind, an inability to accurately assess the wants, thoughts, and intentions of others.

Regional EEG alpha power, coherence, and behavioral symptomatology in autism spectrum disorder - Corrected Proof

2012-03-14

Highlights: ► EEG Alpha power and coherence were analyzed in conjunction with two behaviors associated with autism spectrum disorder (ASD) attention to details and social interaction difficulties. ► ASD participants generated relatively greater alpha power in the eyes-open condition than control participants, and control participants demonstrated greater occipital alpha suppression for the eyes-open condition than did participants with ASD. ► Among adults with ASD, eyes-open alpha power and coherence in posterior brain regions were inversely correlated with preferential attention to details, consistent with anatomical models of narrow minicolumnar structure in ASD.Abstract: Objective: Although distinct patterns of resting brain electrical activity (EEG) and functional connectivity are believed to distinguish individuals with autism spectrum disorders (ASD) from their unimpaired peers, researchers have only recently begun to link patterns of brain activity and connectivity to behavior in ASD.Method: We examined regional eyes-closed and eyes-open EEG alpha power and coherence at rest in relation to self-reported perceptual and social behavior in 15 adults diagnosed with ASD and a matched comparison group of 16 unimpaired adults.Results: The groups did not differ on eyes-closed EEG alpha power or coherence, but adults with ASD showed less alpha suppression for the eyes-open condition than did controls. In the ASD group, preferential attention to detail (perceptual domain) was associated with lower levels of alpha activity and reduced coherence in posterior regions. No relations between social interaction difficulties (social domain) and alpha measures were found for either group alone.Conclusions: These relations suggest that the processing of perceptual details may be carried out by relatively less synchronized neuronal units in adults with ASD, and may be relatively automatic.Significance: Findings are discussed in relation to recent models of narrow minicolumnar brain structure and reduced functional neural connectivity in ASD.

In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation - Corrected Proof

2012-03-14

Highlights: ► The neuronal firing patterns during interictal epileptiform discharges (IEDs) and after single pulse electrical stimulation (SPES) can be described as burst-only, suppression-only, burst–suppression or no-change. ► Similar neuronal firing patterns can be observed during IEDs and after SPES. ► IEDs and responses to SPES appear to activate similar and generic cortical mechanisms, which may explain transient cognitive impairment.Abstract: Objective: To describe neuronal firing patterns observed during human spontaneous interictal epileptiform discharges (IEDs) and responses to single pulse electrical stimulation (SPES).Methods: Activity of single neurons was recorded during IEDs and after SPES in 11 consecutive patients assessed with depth EEG electrodes and attached microelectrodes.Results: A total of 66 neurons were recorded during IEDs and 151 during SPES. We have found essentially similar patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of high frequency firing lasting less than 100ms (in 39% and 25% of local neurons, respectively for IED and SPES); (b) a period of suppression in firing lasting around 100–1300ms (in 19% and 14%, respectively); (c) a burst followed by suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%, respectively).Conclusions: The similarities in neuronal firing patterns associated with IEDs and SPES suggest that, although both phenomena are initiated differently, they result in the activation of a common cortical mechanism, probably initiated by brief synchronised burst firing in some cells followed by long inhibition.Significance: The findings provide direct in vivo human evidence to further comprehend the pathophysiology of human focal epilepsy.

Ocular and cervical vestibular evoked myogenic potentials in multiple sclerosis patients - Corrected Proof

Sibel Gazioglu, Cavit Boz — 2012-03-14

Highlights: ► Multiple sclerosis patients showed high frequency of abnormality in vestibular evoked myogenic potentials (VEMPs) tests, especially in ocular VEMP tests. ► VEMP abnormalities were not correlated with brainstem clinical or magnetic resonance imaging lesions. ► VEMP abnormalities were significantly correlated with expanded disability status scale (EDSS).Abstract: Objective: Vestibular evoked myogenic potentials (VEMPs) are thought to provide useful information about brainstem functions, as the neural pathways of both ocular and cervical VEMPs pass through the brainstem. The aim of this study was to investigate the clinical value of ocular and cervical VEMP tests in the evaluation of brainstem involvement in multiple sclerosis (MS) patients and to assess their relation with clinical and cranial MRI findings.Methods: Ocular and cervical VEMPs were recorded in 62 MS patients and 35 age and sex matched healthy volunteers. The latencies, amplitude asymmetry ratios of both VEMP responses and abnormality ratios (prolonged latencies and absent responses) were compared between the MS patients and the control group and among the groups of MS patients.Results: oVEMP mean n1 and p1 latencies and cVEMP mean p13 latency were significantly prolonged in MS patients. Although the abnormality ratios of both VEMPs were higher in patients with brainstem clinical or MRI lesions, the correlation was not statistically significant. Both ocular and cervical VEMP latencies were significantly correlated with expanded disability status scale.Conclusions: Although there is no significant correlation with clinical or MRI findings, MS patients show high frequency of abnormality in VEMP tests, especially in oVEMP tests.Significance: VEMP tests may be useful as an adjunct test in the evaluation of brainstem dysfunction in MS patients.

Repeated sessions of sub-threshold 20-Hz rTMS. Potential cumulative effects in a brain-injured patient - Corrected Proof

M. Cavinato, V. Iaia, F. Piccione — 2012-03-14

Based on its ability to change cortical excitability, repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for several disorders with putatively altered level of activity in cortical circuits (). In the last decades, rTMS has represented a novel diagnostic and therapeutic technique with application in neurology, psychiatry, and rehabilitation medicine. Treatment protocols for rTMS are widely applied in stroke, major depression, and epilepsy and generally consist of multiple sessions of stimulation administered with different modalities and duration.

Limb segment load inhibits post activation depression of soleus H-reflex in humans - Corrected Proof

Shih-Chiao Tseng, Richard K. Shields — 2012-03-14

Highlights: ► Limb segment load resulted in a predominant inhibition of post activation depression in humans, but minimally modulated the response in a subject with SCI. ► The inhibition of post activation depression was directly related to the magnitude of the limb segment load. ► These findings highlight whether limb load can influence spinal neuronal reorganization from the acute to the chronic state after SCI.Abstract: Objective: We investigated the effect of various doses of limb segment load on soleus H-reflex amplitude and post activation depression in healthy individuals. We also explored the influence of limb segment load on spinal circuitry in one individual with chronic SCI.Methods: Twenty-eight healthy adults and one SCI subject received compressive loads applied to the top of their knee at varied doses of load (10%, 25%, and 50% of the body weight). Soleus H-reflexes were measured before (baseline) and during the loading phase.Results: There were no significant differences in H-reflex amplitudes during the 50% BW load-on phase as compared to either baseline session or the load-off phase. However, the post activation depression was decreased over 9% (p<0.05) during the load-on phase compared to the load-off phase and scaled according to load (50%>25%>10%). The post activation depression ratio also appears less responsive to varying loads after chronic SCI.Conclusions: Limb segment load decreases post-activation depression in humans. These findings suggest that the mechanism associated with post activation depression is modulated by limb segment load, and may be influenced by spinal reorganization after SCI.Significance: Future studies will determine if various levels of spasticity modulate the response of limb segment load on post activation depression in those with acute and chronic SCI.

Improving the diagnostic yield of EEG tests - Corrected Proof

Marc R. Nuwer — 2012-03-14

In this issue of Clinical Neurophysiology, Faulkner and colleagues report on the diagnostic yield of ambulatory EEG monitoring (). They measured the latency of recording time to the identification of diagnostic epileptic discharges. Most discharges were identified within 48h. Generalized discharges appeared more quickly than focal discharges.

Diagnostic value of cauda equina motor conduction time in lumbar spinal stenosis - Corrected Proof

2012-03-14

Highlights: ► The prolongation of cauda equina motor conduction time was statistically significant in the lumbar spinal stenosis (LSS) group. ► Lumbar laminar electrical stimulation is an easy and reliable method to demonstrate motor conduction delay in cauda equina. ► In LSS, chronic compression may occur earlier in the cauda equina root fibers within the spinal canal.Abstract: Objective: Lumbar spinal stenosis (LSS) is a chronic degenerative disease with pain in the back, buttocks and legs aggrevated by walking and relieved after rest without associated vascular disease of lower extremities observed in patients between 50 and 60years. Several studies, using different methods indicated an association between slowing or blocking of root-nerve conduction and LSS. None of the previous research had applied the more conceivable methods such as recording the cauda equina potentials from the lumbar level or stimulating the spinal roots within the canal using either leg nerves or muscles. In this study, electrical lumbar laminar stimulation was used to demonstrate prolongation of cauda equina motor conduction time in lumbar spinal stenosis.Methods: Twenty-one LSS patients and age matched 15 normal control subjects were included in the study. Lumbar laminar electrical stimulation from L1 and L5 vertebra levels were applied by needle electrodes. Compound muscle action potential (CMAP) from gastrocnemius muscles were recorded bilaterally. Latency difference of CMAPs obtained from L1 and L5 spine levels were accepted as the cauda equina motor conduction time (CEMCT).Results: CEMCT was significantly longer in patient group when compared to normal controls. Mean latency difference was 3.59±1.07msec on the right side, 3.49±1.07msec on the left side in LSS group, it was 1.45±0.65msec on the right side, 1.35±0.68msec on the left side on normal control group (p<0.0001).Conclusions: The prolongation of CEMCT was statistically and individually significant in patient group. This may indicate that lower lumbosacral motor roots were locally and chronically compressed due to lumbar spinal stenosis. Lumbar spinal stenosis may have induced local demyelination at the cauda equina level.Significance: Since the prolongation of CEMCT was found only in patients with LSS, the method of laminar stimulation can be chosen for patients with uncertain diagnosis of LSS.

Detection of temporal lobe seizures and identification of lateralisation from audified EEG - Corrected Proof

H. Khamis, A. Mohamed, S. Simpson, A. McEwan — 2012-03-14

Highlights: ► Outlines a simple method for audification of EEG signals for the purpose of seizure detection and seizure focus lateralisation. ► With only 2h of training, non expert subjects can detect seizures from audified EEG signals of 2 difference electrodes with a comparable degree of accuracy as can be done visually from review of EEG traces using the 10–20 electrode placement by an expert electroencephalographer. ► Using this method, predictions of seizure lateralisation are more accurate for the seizures which are easiest to detect.Abstract: Objective: To investigate the accuracy of human listeners in identifying epileptic seizures and seizure lateralisation from audified EEG signals.Methods: EEG data from 17 temporal lobe epilepsy patients (9 male, 8 female; aged 23–55) was converted to audio format by 60× time compression. Using a subset of 19% of the data, five auditory participants (2 female, 3 male; aged 23–58) were trained to identify seizures and their lateralisation by listening to audified EEG signals from difference electrodes P3-T5 and P4-T6. Following training, seizure detection performance of the auditory participants was tested using the remaining data.Results: Allowing a 5s auditory time margin for successful detection, the mean sensitivity of the five auditory participants was 89.6% (SD 8.3%) with a false detection rate of only 0.0068/h (SD 0.0077/h). The mean accuracy of seizure lateralisation identification was 77.6% (SD 7.1%).Conclusions: With a limited amount of training, humans can detect seizures and seizure lateralisation from audified EEG signals of electrodes P3-T5 and P4-T6 with accuracy comparable to visual assessment of full EEG traces (21 electrodes) by an expert encephalographer.Significance: A more efficient and accurate clinical tool for assessing EEG data based on audification may be developed, which will improve diagnosis and treatment of epilepsy.

Externally cued inphase bimanual training enhances preparatory premotor activity - Corrected Proof

Alison L. Smith, W. Richard Staines — 2012-03-09

Highlights: ► The measure of single-session training-related cortical activity modulation requires specific measurement tools depending upon training type (externally cued versus self-paced). ► Comparison of the cued MRP and self-paced BP reveal similar latencies, yet differing amplitudes and cortical localization. ► The preparatory periods of the visually-cued MRP and self-paced BP are generated by the lateral premotor cortex and SMA, respectively.Abstract: Objective: Previous studies have demonstrated that cortical potentials representing motor preparation for visually-cued movements are enhanced following a single session of visually-cued bimanual movement training (BMT). The neuroanatomical sources that contribute to these rapid training-induced adaptations were unclear. To address this, we compared cortical potentials associated with motor preparation for visually-cued (movement-related potential, MRP) and self-paced (Bereitschaftspotential, BP) movements and investigated adaptations of these following BMT.Methods: EEG recorded the cued MRP and self-paced BP during two experiments. In experiment one, pre and post self-paced unimanual trials were interspersed with cued inphase BMT. In experiment two, self-paced and visually-cued movement trials were performed to assess the differences between and the contributing neural sources to the cued MRP and self-paced BP.Results: Inphase BMT does not affect the early BP. Source localization analysis revealed that the preparatory portion of the cued MRP and self-paced BP are generated by the lateral premotor cortex and the supplementary motor area, respectively.Conclusions: The early cued MRP and self-paced BP have unique cortical generators and are independently modulated by specific training types.Significance: These novel findings have implications for interpreting rapid, single-session, training adaptations previously observed. These cortical potentials may also be useful measurement tools to gauge within-session cortical modulations in response to specific modes of rehabilitative training in the stroke population.

Neurophysiological analyses of asterixis utilizing innovative approaches - Corrected Proof

Hideyuki Matsumoto, Yoshikazu Ugawa — 2012-03-09

An interesting study on asterixis by Inoue et al. has been published in the present issue of Clinical Neurophysiology (). In this report, the researchers demonstrate several novel findings in patients with unilateral asterixis using neurophysiological techniques and a neuroimaging method. To date, there are numerous neurophysiological studies of “positive” myoclonus (), but not many of “negative” myoclonus, i.e. asterixis. In fact, only a few neurophysiological studies of patients with bilateral asterixis have been reported, in which neurophysiological methods such as simultaneous electroencephalography (EEG) and electromyography (EMG) recording, silent period-locked back averaging (SPLA), long loop reflex (C-reflex), sensory evoked potential (SEP), and transcranial magnetic stimulation (TMS) were used (). Thus, the pathophysiological mechanisms underlying asterixis have not been well researched. The transient nature of this negative phenomenon conceivably prevents researchers from investigating asterixis in detail.