Dynamic changes in the tuning of striate neurons to the shapes of cross-shaped figures

Time slice analysis was used to study the dynamics of tuning to the shapes of cross-shaped figures flashing in the receptive fields of 83 neurons in the primary visual cortex (field 17) of the cat brain. Tuning was assessed in terms of the numbers of spikes in the overall response and its sequential 20-msec fragments. Only 11.7% of neurons produced reproducibly developing spike responses to a given shape (defined as the angle between the lines), i.e., had a preferred cross-shaped figure. In the remaining cases (88.3%), tuning of neurons to the shape of the cross showed dynamic changes. In 7.2% of cases, changes in the preferred shape of the cross occurred monophasically; changes were biphasic in 27.0% of cases, while in the remaining 54.1% of cases, the dynamics in changes in the preferred cross shape were undulatory. The tuning of receptive field zones is assessed as the cause of these effects and their difference from the previously observed dynamics of preferred orientations of single bars and cross-shaped figures; the functional significance of these effects is also discussed.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 10, pp. 1216–1225, October, 2003.     

Characteristics of the responses of visual cortex neurons with sensitivity to bars or cross-shaped figures in cats

The magnitudes and latent periods of spike responses were recorded from 280 individual neurons tuned to the orientation of light bars or cross-shaped figures in the primary visual cortex (field 17) of the cat. In control experimental conditions, half of 195 cells preferred the bar (first group), the remainder preferring crosses (second group); the responses of neurons of the first group to bars and crosses were of similar magnitude, while in the second group, responses to crosses were significantly larger than responses to bars. The latent periods of responses to optimal bars in the first group of neurons were shorter than those in the second group, and became longer on exposure to crosses, while latent periods in the second group were shorter on exposure to crosses. In conditions of local bicuculline blockade of intracortical inhibition, about a quarter of 85 neurons were sensitive only to the bar, regardless of the presence or absence of inhibition. The remaining neurons were sensitive to crosses in at least one of the states and continued to have responses which were smaller in terms of absolute magnitude than the responses of group 1 neurons. The significance of these data for understanding the mechanisms of tuning of striate neurons to signal features and the temporal sequence of their operation is discussed. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 2, pp. 152–163, February, 2006.     

Reduced intracortical inhibition and facilitation of corticospinal neurons in musicians

Interhemispheric inhibition between motor cortices is reduced in musicians. In the present study we have assessed intracortical inhibition (ICI) and facilitation (ICF) within ipsilateral motor cortex in 15 musicians and 15 non-musician controls. Transcranial magnetic stimulation (TMS) was used to elicit muscle evoked potentials (MEPs) from left first dorsal interosseous (FDI) muscle at rest, and during voluntary index finger abduction (0.5 N). Paired TMS with subthreshold conditioning was used to test early ICI with interstimulus intervals (ISIs) 1-5 ms, and ICF with ISIs 8-15 ms. Suprathreshold conditioning was used to test late ICI with ISIs 100-200 ms. TMS thresholds were similar in musicians and controls both at rest and with weak voluntary activation of FDI, indicating that postsynaptic excitability of corticospinal neurons was similar in both groups. ICI was less effective in musicians with FDI at rest and active, but only with an ISI of 3 ms. ICF was less effective in musicians under both rest and active conditions, and this was independent of ISI. There were no differences in late ICI between musicians and controls. We conclude that ICI and ICF circuits which are activated by weak TMS have less influence on corticospinal neuron excitability in musicians. Because of the dependence on ISI, the most likely explanation for the reduced ICI in musicians is an alteration of the interaction between the ICI circuit and neural elements responsible for the later I-waves evoked in corticospinal neurons by TMS. Excitability of the neural elements producing early and late ICI is not altered in musicians. Reduced ICF in musicians could be due to reduced excitability of neurons responsible for ICF, or an altered balance of excitatory inputs to corticospinal neurons which favours neurons that are not acted upon by the ICF circuit. The reduced influence of ICI and ICF circuits on corticospinal neuron excitability in musicians is likely to reflect a training-induced adaptation. It is not clear at present whether these differences represent an adaptive change related to their extraordinary control of finger movements, or alternatively a maladaptive change induced by "overuse" of the hands from extensive training.     

Task-dependent changes of intracortical inhibition

 The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1–6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10–15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movementsinvolving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1–3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently. Received: 20 September 1996 / Accepted: 1 October 1997     

Blockade of intracortical inhibition in kitten striate cortex: Effects on receptive field properties and associated loss of ocular dominance plasticity

Summary We have investigated the importance of GABAergic inhibition for the receptive field properties and plasticity of cells in the visual cortex of kittens. Osmotic minipumps were used to continuously infuse the GABA-antagonist, bicuculline methiodide (BIC), into striate cortex. Extracellular recordings were made during BIC infusion to assess neuronal response properties during the blockade of inhibition. Recordings were also made from other kittens after concurrent monocular deprivation and BIC infusion to investigate the importance of response selectivity for ocular dominance plasticity. The minipump delivery technique was used to produce a large volume of cortex presumably free of GABA-ergic inhibition. Compared to recordings in saline-infused control hemispheres, about half of the cells in bicuculline-infused hemispheres had abnormally low orientation selectivity. The low selectivity was generally accompanied by marked anomalies in several other receptive field properties. Particularly striking was the large size of the receptive fields. At eccentricities less than 10 deg many receptive fields subtended from 10 to over 30 deg of arc. The less selective neurons also had abnormal responses to flashed stimuli, giving strong transient responses to the onset and offset of large stationary stimuli which filled their receptive fields. These results imply that intracortical inhibition normally suppresses responses to stimuli within a large excitatory zone beyond the classical receptive field. Inhibition is necessary for the normal orientation selectivity of many cells, although the selectivity may be partially established by the cell's excitatory input. Additionally, intracortical inhibition appears to be necessary for the antagonism and segregation of ON and OFF receptive field subregions. In our study of plasticity, we exploited the fact that BIC treatment greatly increases the range of stimuli that activate cortical neurons. Kittens were monocularly deprived for 7 days concurrently with cortical infusion of BIC. After cessation of the drug treatment, physiological recordings were made. Response properties had returned to normal but neurons in BIC-infused hemispheres had a significantly reduced ocular dominance shift compared to neurons in control hemispheres. This is probably related to the reduced selectivity of cells during BIC infusion. The suggestion here is that there is diminished ocular dominance plasticity in BIC-infused hemispheres because of an increased probability of correlated activity between spontaneous discharge from the closed eye and the cortical activity evoked by the open eye afferents.     

Two phases of short-interval intracortical inhibition

Short-interval intracortical inhibition (SICI) is a widely used method to study cortical inhibition, and abnormalities have been found in several neurological and psychiatric disorders. Previous studies suggested that SICI involves two phases and the first phase may be explained by axonal refractoriness. Our objectives are to further investigate the mechanisms of the two phases of SICI. SICI was studied in 11 normal volunteers by a paired transcranial magnetic stimulation (TMS) paradigm applied to the left motor cortex with a subthreshold conditioning stimulus (80% resting motor threshold for rest condition and 95% active motor threshold for active condition) followed by a suprathreshold test stimulus at interstimulus intervals (ISIs) of 1–4.5 ms in steps of 0.5 ms. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. Three different test stimulus intensities adjusted to produce 0.2, 1 and 4 mV MEPs at rest were studied with the target muscle relaxed and during 20% maximum contraction. Maximum inhibition was observed at ISIs of 1 ms and 2.5 ms for the rest condition and the difference among ISIs was reduced with voluntary contraction. SICI increased with larger test MEP amplitude and decreased with voluntary contraction. At test MEP of 0.2 mV, some subjects showed facilitation and this is likely related to short-interval intracortical facilitation. For rest SICI, the correlation between adjacent ISIs was much higher from 3 to 4.5 ms than from 1 to 2.5 ms or between 1 and 2.5 ms. There was no correlation between SICI at different test MEP amplitudes. We conclude that maximum SICI at ISIs of 1 and 2.5 ms are mediated by different mechanisms. SICI at 1 ms cannot be fully explained by axonal refractoriness and synaptic inhibition may be involved. SICI is a complex phenomenon and inhibition at different ISIs may be mediated by different inhibitory circuits.     

A long-lasting change in ocular dominance of kitten striate neurons induced by reversible unilateral blockade of tonic retinal discharges

Summary The effect of reversible blockade of tonic retinal discharges upon the excitability of binocular visual cortical neurons was studied in kittens during the critical period. Following the direct application of a small amount of blocking agent to the unilateral optic nerve, the responsiveness of single cortical neurons to ipsilateral eye (non-blocked side) stimulation was enhanced while that to contralateral stimulation was suppressed. Changes started soon after blocking and were long lasting, over 1 hour, compared with the duration of blocking (7 min) as measured at the level of the lateral geniculate nucleus. This effect was found to be age-dependent: in older kittens which were out of the critical period, results were ambiguous and in young adult cats the same treatment induced no obvious changes. The results favor the idea of binocular competition at postsynaptic sites of the geniculo-cortical projection during the critical period. Furthermore, tonic afferent activity in the visual system is proposed as one of the primary carriers of effects of the environmental manipulation of visual inputs in the developing visual cortex. This is consistent with the previous notion that tonic afferent activity is indispensable for maintenance of existing synaptic contacts in the matured brain.     

Contribution of intracortical inhibition in voluntary muscle relaxation

Terminating a voluntary muscle contraction is an important aspect of motor control, and yet, its neurophysiology is unclear. The objective of this study was to determine the role of short-interval intracortical inhibition (SICI) by comparing SICIs during relaxation from a power grip versus during a sustained power grip at the matching muscle activity level. Right-handed healthy young adults gripped and relaxed from power grip following auditory cues. The relaxation period was determined as the time for the flexor digitorum superficialis (FDS) muscle to reach its pre-contraction baseline level after the cue to relax. SICI during relaxation was obtained at different times into the relaxation period in two separate studies (70, 80, 90 % into relaxation in Study 1; 25, 50, 75 % into relaxation in Study 2). In addition, SICI during sustained contraction was assessed while subjects maintained a power grip at the matching FDS EMG levels (obtained during relaxation, for both Studies). Results showed that the mean SICI was greater during relaxation than during sustained contraction at the matching muscle activity level in both Studies (p < 0.05), indicating increased activation of intracortical inhibitory circuits for muscle relaxation. SICI gradually increased from 25 to 50 and 75 % into relaxation (Study 2, p < 0.05), but did not change from 70 to 80 and 90 % into relaxation (Study 1). MEP decreased with progression of relaxation (p < 0.05) in both Studies, reflecting gradual decreases in corticomotor excitability. This work supports the hypothesis that relaxation from a voluntary muscle contraction involves inhibitory activity in the primary motor cortex.     

Long-interval intracortical inhibition in a human hand muscle

When two motor cortical stimuli are delivered with an interstimulus interval of 50–200 ms, the response (motor evoked potential; MEP) to the second stimulus is typically suppressed. This phenomenon is termed long-interval intracortical inhibition (LICI), although data from one subject suggest that facilitation is possible. Moreover, we recently showed that suppression can be mediated at a spinal level. We characterized LICI more fully by exploring a broad range of contraction strengths and test stimulus intensities. MEPs were evoked in first dorsal interosseous by transcranial magnetic stimulation over the motor cortex. Single test and paired (conditioning-test interval of 100 ms) stimuli at intensities of 100–160% resting motor threshold were delivered at rest or during brief contractions of 10, 25, or 100% maximal voluntary force. Inhibition or facilitation was quantified with the standard ratio in which conditioned MEPs were expressed as a percentage of unconditioned MEPs. Inhibition was greatest at weak–moderate contraction strengths and least at rest and during maximal efforts. Both at rest and during maximal efforts, MEPs evoked by strong stimuli were facilitated. In a subset of subjects, cervicomedullary stimulation was used to activate the corticospinal tract to identify possible spinal influences on changes to MEPs. Contraction strength and test stimulus intensity each had different effects on unconditioned and conditioned MEP size, and hence, LICI is highly dependent on both factors. Further, because motoneurons are facilitated during contraction but disfacilitated after a strong conditioning stimulus, the standard ratio of LICI is of questionable validity during voluntary contractions.     

Role of intracortical inhibition in selective hand muscle activation

Previous studies have shown that intracortical inhibition (ICI) plays an important role in shaping the output from primary motor cortex (M1). This study explored the muscle specificity and temporal modulation of ICI during the performance of a phasic index finger flexion task. Fifteen subjects were asked to rest their dominant hand on a computer mouse and depress the mouse button using their index finger in time with a 1-Hz auditory metronome, while keeping the rest of their hand as relaxed as possible. Responses to single- and paired-pulse transcranial magnetic stimulation were recorded from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles while subjects were at rest and during "on" and "off" phases of the task. For FDI during the on phase, motor evoked potential (MEP) amplitude and pretrigger EMG increased and ICI decreased, as expected. This pattern of modulation was also observed for APB in seven subjects. The remaining eight subjects demonstrated a decrease in MEP amplitude and increase in ICI for APB during the on phase. This was associated with significantly less APB activation during the on phase. These findings suggest that an increase in ICI and decrease in corticospinal excitability can prevent unwanted muscle activation in a muscle-specific, temporally modulated manner.     

Interrelation of tuning characteristics to bar, cross and corner in striate neurons

Characteristics of responses and background activity, as well as of tuning to a single bar orientation and to cross or corner shape and orientation have been compared in one third (561174) of neurons in the cat striate cortex. Shortening of the response latency to cross vs bar, to corner vs bar and to corner vs cross was revealed in most of the units studied. Direct correlation between the response and tuning characteristics for bar, cross and corner was revealed: units with better tuning to one type of stimulus were typically better tuned to the other types of stimuli. At the middle cortical depth (700-1200 microm from the surface) we found a reliable improvement of response magnitude and latency, cross/bar response ratio and selectivity of tuning in comparison with more superficial and deeper layers. Although we could not find a direct correlation between characteristics of tuning to figures and the type of the receptive field (simple, complex or hypercomplex), our data pointed to a lower cross/bar ratio and selectivity of tuning in the units with small receptive fields. The functional implication of neuronal sensitivity to cross and corner and possible meaning of correlation between their functional characteristics are discussed.     

Short-interval intracortical inhibition and manual dexterity in healthy aging

Short-interval intracortical inhibition (SICI) acting on the first dorsal interosseus was measured using paired-pulse transcranial magnetic stimulation (interstimulus interval=2ms) in samples of young and healthy older subjects and correlated with manual dexterity measured with the Purdue Pegboard test and two isometric force-matching tasks. There was an age-related decrease in SICI and an age-related decline in all dexterity measures. The level of SICI was not correlated with any of the dexterity measures, but the appearance of atypical facilitation (rather than inhibition) in some subjects was associated with impaired pegboard performance but not force-matching performance. We conclude that SICI at rest is reduced with healthy aging but this loss of SICI does not directly contribute to the loss of dexterity; a shift in the balance of facilitatory and inhibitory processes in motor cortex to facilitation might interfere with sequenced hand movements.     

Heterogeneity in the responses of adjacent neurons to natural stimuli in cat striate cortex

When presented with simple stimuli like bars and gratings, adjacent neurons in striate cortex exhibit shared selectivity for multiple stimulus dimensions, such as orientation, direction, and spatial frequency. This has led to the idea that local averaging of neuronal responses provides a more reliable representation of stimulus properties. However, when stimulated with complex, time-varying natural scenes (i.e., movies), striate neurons exhibit highly sparse responses. This raises the question of how much response heterogeneity the local population exhibits when stimulated with movies, and how it varies with separation distance between cells. We investigated this question by simultaneously recording the responses of groups of neurons in cat striate cortex to the repeated presentation of movies using silicon probes in a multi-tetrode configuration. We found, first, that the responses of striate neurons to movies are brief (tens of milliseconds), decorrelated, and exhibit high population sparseness. Second, we found that adjacent neurons differed significantly in their peak firing rates even when they responded to the same frames of a movie. Third, pairs of adjacent neurons recorded on the same tetrodes exhibited as much heterogeneity in their responses as pairs recorded by different tetrodes. These findings demonstrate that complex natural scenes evoke highly heterogeneous responses within local populations, suggesting that response redundancy in a cortical column is substantially lower than previously thought.     

Characterisation of paired-pulse transcranial magnetic stimulation conditions yielding intracortical inhibition or I-wave facilitation using a threshold-hunting paradigm

Short-interval, paired-pulse transcranial magnetic stimulation (TMS) is usually used to demonstrate intracortical inhibition. It was shown recently that with short-interval, paired-pulse TMS a facilitation – called intracortical I-wave facilitation – can also be demonstrated. It was the aim of this study to investigate which stimulus conditions lead to intracortical inhibition and what conditions yield an intracortical I-wave facilitation in a hand muscle of normal subjects. Paired-pulse TMS responses with an interstimulus interval of 1.2 ms were obtained from the abductor digiti minimi muscle of four normal subjects. A threshold-hunting paradigm with hunting through first or second stimulus variation was used to obtain a curve of threshold-pair strengths. All subjects showed two branches of stimulus interaction on this diagram. If the first stimulus of a threshold pair was below approximately 65% of resting motor threshold it modified the response primarily due to the second stimulus through intracortical inhibition. However, if the first stimulus of a threshold pair exceeded approximately 65% of resting motor threshold it became responsible for the spinal action-potential initiation. The subsequent second stimulus served as a ”booster” for the ongoing intracortical I-wave activity, making it impossible to observe the intracortical inhibition evoked by the first stimulus. Received: 25 March 1999 / Accepted: 8 June 1999     

Changes of intracortical inhibition during motor imagery in human subjects

Paired-pulse transcranial magnetic stimulation with a conditioning-test paradigm was used to assess changes of corticocortical inhibition and facilitation during mental simulation of sequential finger movements in normal subjects. The cortico-cortical inhibition (at interstimulus interval, ISI, of 3 ms) was significantly reduced in the relaxed opponens pollicis (OP) muscle during motor imagery, regardless of the absolute size of the test motor evoked potential. The amount of cortico-cortical inhibition was similar to that observed during a mild voluntary contraction of the OP. No change of cortico-cortical facilitation was observed at the ISI of 12 ms. The data support the hypothesis that similar neural structures, including the primary motor cortex, are activated during both mental simulation and actual execution of motor activities.