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E Vaadia

Publications and source records attributed to E Vaadia.

At least 19 recordsLinked to original sources

Timing of bimanual movements in human and non-human primates in relation to neuronal activity in primary motor cortex and supplementary motor area.

This study investigates the timing of bimanual movements in a combined behavioral and physiological approach. Human subjects and rhesus monkeys performed the same bimanual task. In monkeys, we simultaneously recorded neuronal activity in the two hemispheres of primary motor cortex (MI) or supplementary motor area (SMA), and related it to bimanual coordination in the temporal domain. Both for monkeys and humans, the reaction times of bimanual movements never significantly exceeded the reaction times of the slower arm in unimanual movements. Consistent with this, the longest delay between neural activity onset in SMA and MI and movement initiation was observed in unimanual movements of the slower arm and not in bimanual movements. Both results suggest that the programming of bimanual movements does not require more processing time than unimanual movements. They are also consistent with the view that bimanual movements are programmed in a single process, rather than by combining two separate unimanual movement plans. In both humans and monkeys, movement initiation was highly correlated between the arms. However, once movements began, the temporal correlation between the arms progressively declined. Movement decorrelation was accompanied by a net decorrelation of neuronal population activity in MI and SMA, suggesting a functional connection between neuronal interactions and the level of bimanual coupling and decoupling. The similarity of neuronal activities in MI and SMA in relationship to behavioral timing lends support to the idea that both areas are involved in the temporal coordination of the arms.

Adult↗

Neuronal populations in primary motor cortex encode bimanual arm movements.

Previous studies have shown that activity of neuronal populations in the primary motor cortex (MI), processed by the population vector method, faithfully predicts upcoming movements. In our previous studies we found that single neurons responded differently during movements of one arm vs. combined movements of the two arms. It was, therefore, not clear whether the population vector approach could produce reliable movement predictions also for bimanual movements. This study tests this question by comparing the predictive quality of population vectors for unimanual and bimanual arm movements. We designed a bimanual motor task that requires coordinated movements of the two arms, in which each arm may move in eight directions, and recorded single unit activity in the MI of two rhesus (Macaca mulatta) monkeys during the performance of unimanual and bimanual arm movements. We analysed the activity of 212 MI cells from both hemispheres and found that, despite bimanual related activity, the directional tuning and preferred directions of most cells were preserved in unimanual and bimanual movements. We demonstrate that population vectors, constructed from the activity of MI cells, predict accurately the direction of movement both for unimanual and for bimanual movements even when the two arms move simultaneously in different directions.

Action Potentials↗

Single-unit activity related to bimanual arm movements in the primary and supplementary motor cortices.

Single units were recorded from the primary motor (MI) and supplementary motor (SMA) areas of Rhesus monkeys performing one-arm (unimanual) and two-arm (bimanual) proximal reaching tasks. During execution of the bimanual movements, the task related activity of about one-half the neurons in each area (MI: 129/232, SMA: 107/206) differed from the activity during similar displacements of one arm while the other was stationary. The bulk of this "bimanual-related" activity could not be explained by any linear combination of activities during unimanual reaching or by differences in kinematics or recorded EMG activity. The bimanual-related activity was relatively insensitive to trial-to-trial variations in muscular activity or arm kinematics. For example, trials where bimanual arm movements differed the most from their unimanual controls did not correspond to the ones where the largest bimanual neural effects were observed. Cortical localization established by using a mixture of surface landmarks, electromyographic recordings, microstimulation, and sensory testing suggests that the recorded neurons were not limited to areas specifically involved with postural muscles. By rejecting this range of alternative explanations, we conclude that neural activity in MI as well as SMA can reflect specialized cortical processing associated with bimanual movements.

Animals↗

Failure in identification of overlapping spikes from multiple neuron activity causes artificial correlations.

Recording of multiple neurons from a single electrode is common practice during extra-cellular recordings. Separation and sorting of spikes originating from the different neurons can be performed either on-line or off-line using multiple methods for pattern matching. However, all spike sorting techniques fail either fully or partially in identifying spikes from multiple neurons when they overlap due to occurrence within a short time interval. This failure, that we termed the 'shadowing effect', causes the well-known phenomenon of decreased cross-correlation at zero offset. However, the shadowing effect also causes other artifacts in the auto and cross-correlation of the recorded neurons. These artifacts are significant mainly in brain areas with high firing rate or increased firing synchrony leading to a high probability of spike overlap. Cross correlation of cells recorded from the same electrodes tends to reflect the autocorrelation functions of the two cells, even when there are no functional interactions between the cells. Therefore, the cross-correlation function tends to have a short-term (about the length of the refractory period) peak. A long-term (hundreds of milliseconds to a few seconds) trough in the cross-correlation can be seen in cells with bursting and pausing activities recorded from the same electrode. Even the autocorrelation functions of the recorded neurons feature firing properties of other neurons recorded from the same electrode. Examples of these effects are given from our recordings in the globus pallidus of behaving primates and from the literature. Results of simulations of independent simple model neurons exhibit the same properties as the recorded neurons. The effect is analyzed and can be estimated to enable better evaluation of the underlying firing patterns and the actual synchronization of neighboring neurons recorded by a single electrode.

Action Potentials↗

Activity of pallidal and striatal tonically active neurons is correlated in mptp-treated monkeys but not in normal monkeys.

The goal of this study is to assess the function of tonically active neurons (TANs) of the striatum and their malfunction in the parkinsonian state. We recorded multiple spike trains of striatal TANs and pallidal neurons, which are the main target of striatal projections. Recordings were performed in two vervet monkeys before and after the induction of tremulous parkinsonism by systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). We then calculated cross-correlograms between TANs and pallidal neurons to evaluate the interactions between them. In the normal monkeys, only 1.3% (2/152) of the cross-correlograms displayed significant peaks, and 8.6% (13/152) displayed significant oscillations. After MPTP treatment, 42.8% (83/194) of the cross-correlograms displayed significant peaks or troughs, or both, and 58.8% (114/194) displayed significant 3-19 Hz periodic oscillations. The frequency content of the coherent oscillations matched the frequency content of the activity of individual TANs, but was only weakly related to that of individual pallidal cells. These results confirm the notion that in the normal state neurons in the basal ganglia tend to fire independently, whereas in the parkinsonian state they exhibit synchronized oscillatory activity. The low level of correlated activity in the normal state demonstrates that TANs have only a slight effect on pallidal activity during execution of familiar behavior. The high level of oscillatory correlated activity in the parkinsonian state further suggests that coherent oscillations of the whole basal ganglia circuitry underlie the clinical features of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Local field potentials related to bimanual movements in the primary and supplementary motor cortices.

We recorded local field potentials (LFP) in primary (MI) and supplementary (SMA) motor areas of rhesus monkey cortex in order to compare movement-evoked potentials (mEP) in bimanual and unimanual movements with single-unit activity recorded concurrently. The mEP was often different during bimanual and unimanual movements (a "bimanual-related" effect), but, unlike the single units, the size of the mEP in both MI and SMA was always greater during bimanual movements than during unimanual movements. This increase primarily reflected an increase in the late positive peak of the mEP, a result that may reflect greater overall cortical activation during bimanual movements. In addition, analysis of the mEP revealed differences between MI and SMA not seen in the single-unit activity. mEP in MI had greater contralateral preference than in SMA. Also, SMA mEP was more correlated to the single-unit activity than in MI. This greater correlation was also more apparent in the late peaks of the mEP than in the early peaks and may reflect a greater influence of recurrent activation in SMA than in MI. Our results further reinforce the idea that unimanual and bimanual movements are represented differently both in MI and in SMA and also show that a complex relationship between spikes of individual neurons and LFP may reflect the different input-output relations of different cortical areas.

Action Potentials↗

Neural interactions between motor cortical hemispheres during bimanual and unimanual arm movements.

Cortico-cortical connections through the corpus callosum are a major candidate for mediating bimanual coordination. However, aside from the deficits observed after lesioning this connection, little positive evidence indicates its function in bimanual tasks. In order to address this issue, we simultaneously recorded neuronal activity at multiple sites within the arm area of motor cortex in both hemispheres of awake primates performing different bimanual and unimanual movements. By employing an adapted form of the joint peri-stimulus time histogram technique, we discovered rapid movement-related correlation changes between the local field potentials (LFPs) of the two hemispheres that escaped detection by time-averaged cross-correlation methods. The frequency and amplitude of dynamic modifications in correlations between the hemispheres were similar to those within the same hemisphere. As in previous EEG studies, we found that, on average, correlation decreased during movements. However, a subset of recording site pairs did show transiently increased correlations around movement onset (57% of all pairs and conditions in monkey G, 39% in monkey P). In interhemispheric pairs, these increases were consistently related to the mode of coupling between the two arms. Both the correlations between the movements themselves and the interhemispheric LFP correlation increases were strongest during bimanual symmetric movements, and weaker during bimanual asymmetric and unimanual movements. Increased correlations occurred mainly around movement onset, whilst decreases in correlation dominated during movement execution. The task-specific way in which interhemispheric correlations are modulated is compatible with the notion that interactions between the hemispheres contribute to behavioural coupling between the arms.

Animals↗

Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine vervet model of parkinsonism.

To investigate the role of the basal ganglia in parkinsonian tremor, we recorded hand tremor and simultaneous activity of several neurons in the external and internal segments of the globus pallidus (GPe and GPi) in two vervet monkeys, before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and development of parkinsonism with tremor of 5 and 11 Hz. In healthy monkeys, only 11% (20/174) of the GPe cells and 3% (1/29) of the GPi cells displayed significant 3-19 Hz oscillations. After MPTP treatment, 39% (107/271) of the GPe cells and 43% (26/61) of the GPi cells developed significant oscillations. Oscillation frequencies of single cells after MPTP treatment were bimodally distributed around 7 and 13 Hz. For 10% of the oscillatory cells that were recorded during tremor periods, there was a significant tendency for the tremor and neuronal oscillations to appear simultaneously. Cross-correlation analysis revealed a very low level of correlated activity between pallidal neurons in the normal state; 95.6% (477/499) of the pairs were not correlated, and oscillatory cross-correlograms were found in only 1% (5/499) of the pairs. After MPTP treatment, the correlations increased dramatically, and 40% (432/1080) of the cross-correlograms had significant oscillations, centered around 13-14 Hz. Phase shifts of the cross-correlograms of GPe pairs, but not of GPi, were clustered around 0 degrees. The results illustrate that MPTP treatment changes the pattern of activity and synchronization in the GPe and GPi. These changes are related to the symptoms of Parkinson's disease and especially to the parkinsonian tremor.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Neural coding: higher-order temporal patterns in the neurostatistics of cell assemblies.

Recent advances in the technology of multiunit recordings make it possible to test Hebb's hypothesis that neurons do not function in isolation but are organized in assemblies. This has created the need for statistical approaches to detecting the presence of spatiotemporal patterns of more than two neurons in neuron spike train data. We mention three possible measures for the presence of higher-order patterns of neural activation--coefficients of log-linear models, connected cumulants, and redundancies--and present arguments in favor of the coefficients of log-linear models. We present test statistics for detecting the presence of higher-order interactions in spike train data by parameterizing these interactions in terms of coefficients of log-linear models. We also present a Bayesian approach for inferring the existence or absence of interactions and estimating their strength. The two methods, the frequentist and the Bayesian one, are shown to be consistent in the sense that interactions that are detected by either method also tend to be detected by the other. A heuristic for the analysis of temporal patterns is also proposed. Finally, a Bayesian test is presented that establishes stochastic differences between recorded segments of data. The methods are applied to experimental data and synthetic data drawn from our statistical models. Our experimental data are drawn from multiunit recordings in the prefrontal cortex of behaving monkeys, the somatosensory cortex of anesthetized rats, and multiunit recordings in the visual cortex of behaving monkeys.

Action Potentials↗

Frontal cognitive impairments and saccadic deficits in low-dose MPTP-treated monkeys.

There is considerable overlap between the cognitive deficits observed in humans with frontal lobe damage and those described in patients with Parkinson's disease. Similar frontal impairments have been found in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) primate model of Parkinsonism. Here we provide quantitative documentation of the cognitive, oculomotor, and skeletomotor dysfunctions of monkeys trained on a frontal task and treated with low-doses (LD) of MPTP. Two rhesus monkeys were trained to perform a spatial delayed-response task with frequent alternations between two behavioral modes (GO and NO-GO). After control recordings, the monkeys were treated with one placebo and successive LD MPTP courses. Monkey C developed motor Parkinsonian signs after a fourth course of medium-dose (MD) MPTP and later was treated with combined dopaminergic therapy (CDoT). There were no gross motor changes after the LD MPTP courses, and the average movement time (MT) did not increase. However, reaction time (RT) increased significantly. Both RT and MT were further increased in the symptomatic state, under CDoT. Self-initiated saccades became hypometric after LD MPTP treatments and their frequency decreased. Visually triggered saccades were affected to a lesser extent by the LD MPTP treatments. All saccadic parameters declined further in the symptomatic state and improved partially during CDoT. The number of GO mode (no-response, location, and early release) errors increased after MPTP treatment. The monkeys made more perseverative errors while switching from the GO to the NO-GO mode. Saccadic eye movement patterns suggest that frontal deficits were involved in most observed errors. CDoT had a differential effect on the behavioral errors. It decreased omission errors but did not improve location errors or perseverative errors. Tyrosine hydroxylase immunohistochemistry showed moderate ( approximately 70-80%) reduction in the number of dopaminergic neurons in the substantia nigra pars compacta after MPTP treatment. These results show that cognitive and motor disorders can be dissociated in the LD MPTP model and that cognitive and oculomotor impairments develop before the onset of skeletal motor symptoms. The behavioral and saccadic deficits probably result from the marked reduction of dopaminergic neurons in the midbrain. We suggest that these behavioral changes result from modified neuronal activity in the frontal cortex.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Primary motor cortex is involved in bimanual coordination.

Many voluntary movements involve coordination between the limbs. However, there have been very few attempts to study the neuronal mechanisms that mediate this coordination. Here we have studied the activity of cortical neurons while monkeys performed tasks that required coordination between the two arms. We found that most neurons in the primary motor cortex (MI) show activity specific to bimanual movements (bimanual-related activity), which is strikingly different from the activity of the same neurons during unimanual movements. Moreover, units in the supplementary motor area (SMA; the area of cortex most often associated with bimanual coordination) showed no more bimanual-related activity than units in MI. Our results challenge the classic view that MI controls the contralateral (opposite) side of the body and that SMA is responsible for the coordination of the arms. Rather, our data suggest that both cortical areas share the control of bilateral coordination.

Animals↗

Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.

There are two views as to the character of basal-ganglia processing - processing by segregated parallel circuits or by information sharing. To distinguish between these views, we studied the simultaneous activity of neurons in the output stage of the basal ganglia with cross-correlation techniques. The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated. However, after dopamine depletion and induction of parkinsonism by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), oscillatory activity appeared and the firing of many neurons became correlated. We conclude that the normal dopaminergic system supports segregation of the functional subcircuits of the basal ganglia, and that a breakdown of this independent processing is a hallmark of Parkinson's disease.

Animals↗

Spatiotemporal structure of cortical activity: properties and behavioral relevance.

The study was designed to reveal occurrences of precise firing sequences (PFSs) in cortical activity and to test their behavioral relevance. Two monkeys were trained to perform a delayed-response paradigm and to open puzzle boxes. Extracellular activity was recorded from neurons in premotor and prefrontal areas with an array of six microelectrodes. An algorithm was developed to detect PFSs, defined as a set of three spikes and two intervals with a precision of +/-1 ms repeating significantly more than expected by chance. The expected level of repetition was computed based on the firing rate and the pairwise correlation of the participating units, assuming a Poisson distribution of event counts. Accordingly, the search for PFSs was corrected for rate modulations. PFSs were found in 24/25 recording sessions. Most PFSs (76%) were composed of spikes of more than one unit but usually not more than two units (67%). The PFSs spanned hundreds of milliseconds, and the average interval between two events within the PFSs was 200 ms. No traces of periodic oscillations were found in the PFS intervals. The bins of the matrix that were defined as PFSs were isolated temporally: the spikes that generated PFSs were not associated with high-frequency bursts or rapid coherent rate fluctuations. A given PFS tended to be correlated with the animal's behavior. Furthermore, for 19% of the PFS pairs that shared the same unit composition, each member of the pair was associated with a different type of behavior. The PFSs often appeared in clusters that were associated with particular phases of the behavior. The firing rate of single units did not provide a full explanation for the timing and structure of these clusters. A reduced spike train (RST) was defined for each unit by taking all spikes of that unit that were part of any PFS. In 88% of the cases the degree of modulation of the RST was higher than that of the complete spike train. The results suggest that relevant information is carried by the fine temporal structure of cortical activity. A coding scheme that involves such temporal structures is rich and sufficiently flexible to facilitate a rapid organization of cortical neurons into functional groups. The results can be accounted for by the synfire chain model, which suggests that cortical activity is mediated by synchronous activation of neural groups in a reverberatory mode.

Algorithms↗

Simultaneously recorded single units in the frontal cortex go through sequences of discrete and stable states in monkeys performing a delayed localization task.

To test whether spiking activity of six to eight simultaneously recorded neurons in the frontal cortex of a monkey can be characterized by a sequence of discrete and stable states, neuronal activity is analyzed by a hidden Markov model (HMM). Using the HMM method, we are able to detect distinct states of neuronal activity within which firing rates are approximately stationary. Transitions between states, as expressed by concomitant changes in the firing rates of several units, occur quite abruptly. The significance and consistency of the states are confirmed by comparison with simulated data. The detected states are specific to a monkey's response in a delayed localization task, allowing correct prediction of the response in approximately 90% of the trials. Similar predictive power is achieved by a model based simply on the response histograms (PSTH) of the units. The two models reach this predictive ability with different time courses: the PSTH model gains predictive power with a higher rate in the first second of the delay, and the HMM gains predictive power with higher rate in the next 3 sec. In this later period, conventional methods such as the PSTH cannot detect any firing rate modulations, but the HMM successfully captures transitions between distinct states that are specific to the monkey's behavioral response and occur at highly variable times from trial to trial. Our results suggest that neuronal activity in this later period is described best as transitions among distinct states that may reflect discrete steps in the monkey's mental processes.

Animals↗

Neuronal synchronization of tonically active neurons in the striatum of normal and parkinsonian primates.

1. Previous studies indicate that tonically active neurons (TANs) are the cholinergic interneurons of the striatum and predict that their activity is synchronized. To test whether TANs do fire synchronously, and whether dopamine depletion affects their synchronization, we recorded the simultaneous activity of several TANs in the putamens of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. Cross-correlation analysis revealed that most pairs of TANS (33 of 54; 61.1%) fire synchronously at +/- 60-ms delay. Correlated activity was more common between neurons with characteristic response to reward (17 of 19 pairs; 89.5%). 3. Cross-correlation study of 24 triplets of TANS showed synchronization of spiking activity of all 3 TANS in only 29.2% of cases (7 of 24 triplets). Correlated activity of two of three possible pairs was found in 25% of the cases. 4. After MPTP treatment and the development of parkinsonian symptoms, most TANS' auto- and cross-correlograms (22 of 28 units; 78.6%; and 23 of 28 pairs; 82.1%) became oscillatory. The number of correlated pairs was slightly increased (24 of 28; 85.7%). The strength of the synchronization was not significantly different from the normal values. 5. These findings support the notion that TANs function as distributed, partially overlapping synchronized networks. However, a normal dopaminergic system is not essential for synchronization of TANs; on the contrary, dopaminergic activity may even have a desynchronizing effect on the basal ganglia's system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

'Dynamics of neuronal interactions' cannot be explained by 'neuronal transients'.

In a recent paper, Vaadia et al. demonstrated that patterns of firing correlation between single neurons in the cortex of behaving monkeys can be modified within a fraction of a second. These changes occur in relation to sensory stimuli and behavioral events, and even without modulations of the neurons' firing rates. These findings call for a revision of prevailing models of neural coding that solely rely on single neuron firing rates. In a defense of these models, Friston put forward an alternative explanation, proposing that the observed correlation dynamics emerge solely from co-modulations of the firing rates of each of the neurons, while the strength of their interaction remains constant. To test this possibility we re-examined the data, adopting Friston's 'neuronal transients' model, and the associated equations and procedures. We found that, to explain the dynamic correlation between a pair of neurons, the alternative interpretation requires that each neuron's response to a single stimulus is composed of a relatively large number of independent components, which co-vary with their counterparts in the companion neuron. This large number of components and their shapes lead us to conclude that, although in principle possible, the neuronal transients model: (i) does not provide a simpler explanation of the experimental results; and (ii) cannot explain these results without itself deviating significantly from most rate code models.

Animals↗