A role of beta oscillatory synchrony in biasing response competition?

Beta-range oscillatory activity measured over the motor cortex and beta synchrony between cortex and spinal cord can be up- or downregulated in anticipation of a postural challenge or the initiation of movement. Based on these properties of beta activity in the preparation for future events, the present investigation addressed whether simultaneous up- and downregulation of beta activity might act as an online mechanism to suppress and select competing responses. Measures of local and long-range beta synchrony were obtained from electroencephalographic and electromyographic signals recorded during a cued choice reaction task. Analyses focused on task-related changes in beta synchrony during a 2-s delay period between cue and response signal. Analyzed separately, none of the beta measures (spectral power, corticospinal coherence, corticospinal phase synchronization) showed simultaneous up- and downregulation over opposite hemispheres controlling the competing responses. However, the combined pattern of beta measures showed beta power desynchronization associated with selection of a response and increased corticospinal coherence and phase synchronization associated with suppression of a response. These results indicate that concurrent up- and downregulation of different components of beta oscillatory activity is likely to have a functional role in response selection, resembling attentional modulation of alpha activity in visual selection.

Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations.

A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.

Brain activity correlates differentially with increasing temporal complexity of rhythms during initialisation, synchronisation, and continuation phases of paced finger tapping.

Activity in parts of the human motor system has been shown to correlate with the complexity of performed motor sequences in terms of the number of limbs moved, number of movements, and number of trajectories. Here, we searched for activity correlating with temporal complexity, in terms of the number of different intervals produced in the sequence, using an overlearned tapping task. Our task was divided into three phases: movement selection and initiation (initiate), synchronisation of finger tapping with an external auditory cue (synchronise), and continued tapping in absence of the auditory pacer (continue). Comparisons between synchronisation and continuation showed a pattern in keeping with prior neuroimaging studies of paced finger tapping. Thus, activation of bilateral SMA and basal ganglia was greater in continuation tapping than in synchronisation tapping. Parametric analysis revealed activity correlating with temporal complexity during initiate in bilateral supplementary and pre-supplementary motor cortex (SMA and preSMA), rostral dorsal premotor cortex (PMC), basal ganglia, and dorsolateral prefrontal cortex (DLPFC), among other areas. During synchronise, correlated activity was observed in bilateral SMA, more caudal dorsal and ventral PMC, right DLPFC and right primary motor cortex. No correlated activity was observed during continue at P<0.01 (corrected, cluster level), though left angular gyrus was active at P<0.05. We suggest that the preSMA and rostral dorsal PMC activities during initiate may be associated with selection of timing parameters, while activation in centromedial prefrontal cortex during both initiate and synchronise may be associated with temporal error monitoring or correction. The absence of activity significantly correlated with temporal complexity during continue suggests that, once an overlearned timed movement sequence has been selected and initiated, there is no further adjustment of the timing control processes related to its continued production in absence of external cues.

Attention and movement-related motor cortex activation: a high-density EEG study of spatial stimulus-response compatibility.

Visual spatial attentional activation of motor areas has been documented in single cell neurophysiology and functional imaging studies of the brain. Here, we investigate a candidate event-related brain potential representing visuospatial attentional activity in motor areas of the cortex. The investigation aimed to elucidate the neural origin and the functional characteristics of this brain potential, which has been labelled N2cc and is typically observed in spatial stimulus-response compatibility tasks. High-density EEG was recorded in 10 subjects while they performed a Simon-type spatial stimulus-response compatibility task and a control task where the same stimuli were assigned to Go-Nogo response alternatives. The N2cc showed a time course parallel to the posteriorly distributed N2pc, associated with visuospatial selection. Scalp distribution and current source density reconstructions allowed a spatial separation of N2pc and centrally distributed N2cc and were compatible with a source for the N2cc in the lateral premotor cortex. Comparisons across tasks demonstrated that the N2cc depends on bilateral response readiness, ruling out an exclusively attentional interpretation. Instead, the activity appears associated with visuospatial attentional processes that serve the selection and suppression of competing responses, in accord with a function of the dorsal premotor cortex in response selection. Together, the results consolidate the N2cc as a new ERP component relevant to the investigation of visuospatial motor processes.

Phonological effects on the auditory N400 event-related brain potential.

We report 3 experiments exploring the responsiveness of the auditory N400 event-related potential to the phonological relations between word or non-word targets and preceding prime words. When subjects had to decide whether primes and targets rhymed, non-rhyming words produced greater negativity in the N400 time range than rhyming words. The same effect was obtained when these targets were spoken by another voice than the prime words, suggesting that the effect is determined by phonological factors, and not merely by a physical-acoustic mismatch (Experiment 1). In the rhyming task, the differential N400 for non-rhyming vs. rhyming words was equally pronounced for non-rhyming vs. rhyming non-words (Experiment 2). In a lexical decision task on the same stimuli, a difference between non-rhyming and rhyming targets was obtained for words, but not for non-words (Experiment 3). The results show that the auditory N400 is sensitive to phonological variables. It is further proposed that phonological effects on the auditory N400 are not manifestations unique to phonological processes that demand conscious attention, but may also reflect operations that are performed automatically during auditory word recognition.

Magneto-encephalographic correlates of the lateralized readiness potential.

To determine the onset of movement-related EEG activity accompanying stimulus-induced movements, it is commonly isolated from overlapping stimulus-related activity by a subtraction procedure, yielding the lateralized readiness potential (LRP). In order to elucidate the generation of the LRP and to explore whether magnetoencephalographic (MEG) measures have advantages over the LRP as a measure of response selection, MEG activity was recorded in four healthy adults during self-paced and stimulus-induced hand movements. Self-paced movements were preceded by readiness fields in all subjects, explained by sources in contralateral and (for 2/8 response sides) also ipsilateral hemispheres. Movement-related activity preceding stimulus-induced movements could only be modeled adequately when stimulus-related activity was removed by subtracting MEG signals for left and right hand movements. Thus identified source locations showed no systematic deviation from the sources for readiness fields, supporting a generation of the movement-related activity in primary motor cortex. The corresponding source waveforms allowed latency determinations of motor cortex activity as markers for response-choice timing. MEG thus provides information on the time course of hand-specific motor cortex activation for each hemisphere separately, where the electro-encephalographic LRP provides a composite measure for both hemispheres.

Magnetic stimulation of the dorsal premotor cortex modulates the Simon effect.

In choice reaction tasks, subjects typically respond faster when the relative spatial positions of stimulus and response match than when they do not match. A prominent explanation attributes this 'Simon effect' to automatic response activation elicited by spatial correspondence, which facilitates or competes with the controlled selection of the response demanded by the stimulus. To test this account, we applied repetitive transcranial magnetic stimulation (rTMS) on the dorsal premotor cortex (PMd), as this area may subserve the inhibitory control of automatic response activation. Temporary interference with PMd was predicted to release the automatic activation from inhibition and thereby enhance the Simon effect. The results confirmed a modulation for trials following an incompatible trial, providing new evidence for competition between automatic and controlled response activation as a mechanism underlying the Simon effect.

The five percent electrode system for high-resolution EEG and ERP measurements.

OBJECTIVE: A system for electrode placement is described. It is designed for studies on topography and source analysis of spontaneous and evoked EEG activity. METHOD: The proposed system is based on the extended International 10-20 system which contains 74 electrodes, and extends this system up to 345 electrode locations. RESULTS: The positioning and nomenclature of the electrode system is described, and a subset of locations is proposed as especially useful for modern EEG/ERP systems, often having 128 channels available. CONCLUSION: Similar to the extension of the 10-20 system to the 10-10 system ("10% system"), proposed in 1985, the goal of this new extension to a 10-5 system is to further promote standardization in high-resolution EEG studies.

Absence of gaze direction effects on EEG measures of sensorimotor function.

OBJECTIVE: Gaze direction is known to modulate the activation patterns of sensorimotor areas as seen at the single cell level and in functional magnetic resonance imaging (fMRI). To determine whether such gaze direction effects can be observed in scalp-recorded electroencephalogram (EEG) measures of sensorimotor function we investigated somatosensory evoked potentials (SEPs) and steady state movement related cortical potentials (MRPs). METHODS: In two separate experiments, SEPs were elicited by electrical stimulation of the median nerve (experiment 1) and steady state MRPs were induced by 2 Hz tapping paced by an auditory cue (experiment 2), while subjects directed their gaze 15 degrees to the left or to the right. RESULTS: Gaze direction failed to produce any appreciable differences in the waveforms of the SEPs or MRPs. In particular, there was no effect on peak amplitude, peak latency and peak scalp topography measures of SEP and MRP components, or on spatial or temporal parameters of dipole models of the underlying cortical generators. Additional frequency domain analyses did not reveal reliable gaze-related changes in induced power at electrode sites overlying somatosensory and motor areas, or in coherence between pairs of parietal, central and frontal electrodes, across a broad range of frequencies. CONCLUSIONS: EEG measures of sensorimotor function, obtained in a non-visual motor task, are insensitive to modulatory effects of gaze direction in sensorimotor areas that are observable with fMRI.

Overlap of attention and movement-related activity in lateralized event-related brain potentials.

OBJECTIVE: In tasks that involve lateralized visuospatial attention and a lateralized motor response, the associated brain electrical potentials, i.e. the attention-related N2pc and the lateralized readiness potential, typically overlap at central scalp sites. The manifestation of the N2pc at central electrode sites is commonly attributed to electric volume conduction effects, assuming the N2pc to be generated in occipito-temporal brain areas. We evaluated this explanation in a simulation study. METHODS: Using a forward modeling approach with a realistically shaped volume conduction model, we calculated the range of amplitude ratios between occipital and central electrode sites when a single source is assumed in area V4 or in area TO, at the temporo-occipital convexity. RESULTS: A comparison of the simulated amplitude ratios with reported data indicates that volume conduction effects from the investigated source origins in the occipito-temporal region are insufficient to explain the experimental data. CONCLUSIONS: We conclude that the anterior spread of the N2pc from its occipito-temporal maximum to central electrode sites is probably due to simultaneous attention-related activity in posterior and central brain areas.

Evoked potential measures of auditory cortical function and auditory comprehension in aphasia.

This study investigated the relation between severity of auditory comprehension impairment in aphasia and the functional integrity of the posterior superior temporal region as evaluated by middle- and long-latency auditory evoked potentials and dipole source analysis. AEPs were studied in 20 stroke patients and in age-matched controls. AEPs and language data were collected 1 year or more post onset, and were compared to performance early after onset. Patients were differentiated in a group with severe and a group with moderate to recovered auditory comprehension impairment. Significant asymmetries of auditory evoked dipole source potentials were more frequent in the severely impaired group. However, a severe auditory comprehension deficit was not incompatible with normal AEPs. The results confirm the importance of the posterior superior temporal region for auditory language comprehension, but the correlation between AEP asymmetry and auditory comprehension seems due to the close spatial relation of AEP generating substrate and posterior language area rather than to partial overlap. Dipole source analysis of AEPs proved to be a valuable method for the assessment of interhemispheric asymmetries, enhancing the sensitivity of AEPs to unilateral damage of auditory cortex.

Movement-related potential measures of different modes of movement selection in Parkinson's disease.

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.

Vascular insufficiency of the cervical cord due to hyperextension of the spine.

A patient with acute transverse myelopathy after minor trauma due to hyperextension of the neck is reported. The pattern of neurologic deficit favors the diagnosis of acute central cervical spinal cord syndrome. The proposed causative mechanism is temporary vascular insufficiency of the spinal cord. The architecture of vascular supply of the spinal cord and specific cerebrospinal fluid abnormalities in this patient are compatible with the diagnosis. The differential diagnosis of traumatic vascular spinal cord lesions is discussed.

Genetic and environmental risk factors in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial disorder, caused by a combination of age, genetics and environmental factors. Nigral cells are susceptible to multiple causes of derangement of normal cell function, all of which may contribute to the same Parkinson phenotype. Autosomal dominant alpha-synuclein-gene PD represents one of the pure genetic forms, whereas cases of sporadic PD probably depend more on age and environmental factors, MPTP-Parkinsonism being the purest example of an environmentally caused Parkinson phenotype. This review suggests that pesticides-herbicides, smoking and head trauma probably represent the most eligible candidates for environmental factors involved in provoking PD or influencing its natural course.

GM2-gangliosidosis. Clinical and biochemical aspects of four cases.

We discuss four cases of GM2-gangliosidosis. In one of them the biochemical diagnostic confirmation was difficult. This case revealed striking discrepancies between the results of different methods of enzyme assay. The hexosaminidase A determination based on pH inactivation is not always reliable; assay with natural substrate may be necessary. However, the results with the newly developed substrate 4-MU-GlcNac-6-SO4 are promising and it seems to be a good alternative to the traditional (pH or heat) inactivation procedures. The deficiency can be shown in leukocytes, plasma and fibroblasts with the 6-sulfated substrate. The carrier state seems better reflected in plasma hexosaminidase A than in leukocyte hexaminidase A levels.

Maintaining grip: anticipatory and reactive EEG responses to load perturbations.

Previous behavioral work has shown the existence of both anticipatory and reactive grip force responses to predictable load perturbations, but how the brain implements anticipatory control remains unclear. Here we recorded electroencephalographs while participants were subjected to predictable and unpredictable external load perturbations. Participants used precision grip to maintain the position of an object perturbed by load force pulses. The load perturbations were either distributed randomly over an interval 700- to 4,300-ms (unpredictable condition) or they were periodic with interval 2,000 ms (predictable condition). Preparation for the predictable load perturbation was manifested in slow preparatory brain potentials and in electromyographic and force signals recorded concurrently. Preparation modulated the long-latency reflex elicited by load perturbations with a higher amplitude reflex response for unpredictable compared with predictable perturbations. Importantly, this modulation was also reflected in the amplitude of sensorimotor cortex potentials just preceding the long-latency reflex. Together, these results support a transcortical pathway for the long-latency reflex and a central modulation of the reflex grip force response.

On the possibility of independent activation of bilateral mismatch negativity (MMN) generators.

Event-related potential (ERP) studies on auditory selective attention have suggested that the neuronal traces underlying the mismatch negativity (MMN) develop separately for left and right ear inputs. We investigated whether this feature of the MMN could be exploited to activate the MMN generators in each hemisphere independently. Given the location of the MMN sources, this would allow separate assessment of left and right hemisphere auditory cortical structures. The MMN was elicited in a dichotic oddball paradigm using stimuli and conditions of stimulation that should optimize transmission of left and right ear stimuli to the contralateral auditory cortices. The MMN demonstrated no interhemispheric asymmetries, indicating that the bilateral MMN generators were symmetrically involved. The results of a supplementary experiment provide evidence for the simultaneous existence of multiple traces for MMN generation.

Failed suppression of direct visuomotor activation in Parkinson's disease.

The response times in choice-reaction tasks are faster when the relative spatial positions of stimulus and response match than when they do not match, even when the spatial relation is irrelevant to response choice. This spatial stimulus-response (S--R) compatibility effect (i.e., the Simon effect) is attributed in part to the automatic activation of spatially corresponding responses, which need to be suppressed when the spatial location of stimulus and correct response do not correspond. The present study tested patients with Parkinson's disease and healthy control subjects in a spatial S--R compatibility task in order to investigate whether basal ganglia dysfunction in Parkinson's disease leads to disinhibition of direct visuomotor activation. High-density event-related brain potential recordings were used to chart the cortical activity accompanying attentional orientation and response selection. Response time measures demonstrated a failure to inhibit automatic response activation in Parkinson patients, which was revealed by taking into account a sequence-dependent modulation of the Simon effect. Event-related potential (ERP) recordings demonstrated that visuospatial orientation to target stimuli was accompanied by signal-locked activity above motor areas of the cortex, with similar latencies but an enhanced amplitude in patients compared to control subjects. The results suggest that inhibitory modulation of automatic, stimulus-driven, visuomotor activation occurs after the initial sensory activation of motor cortical areas. The failed inhibition in Parkinson's disease appears therefore related to a disturbance in processes that prevent early attention-related visuomotor activation, within motor areas, from actually evoking a response.