BOLD Signal in Both Ipsilateral and Contralateral Retinotopic Cortex Modulates with Perceptual Fading

Under conditions of visual fixation, perceptual fading occurs when a stationary object, though present in the world and continually casting light upon the retina, vanishes from visual consciousness. The neural correlates of the consciousness of such an object will presumably modulate in activity with the onset and cessation of perceptual fading.

Method

In order to localize the neural correlates of perceptual fading, a green disk that had been individually set to be equiluminant with the orange background, was presented in one of the four visual quadrants; Subjects indicated with a button press whether or not the disk was subjectively visible as it perceptually faded in and out.

Results

Blood oxygen-level dependent (BOLD) signal in V1 and ventral retinotopic areas V2v and V3v decreases when the disk subjectively disappears, and increases when it subjectively reappears. This effect occurs in early visual areas both ipsilaterally and contralaterally to the fading figure. That is, it occurs regardless of whether the fading stimulus is presented inside or outside of the corresponding portion of visual field. In addition, we find that the microsaccade rate rises before and after perceptual transitions from not seeing to seeing the disk, and decreases before perceptual transitions from seeing to not seeing the disk. These BOLD signal changes could be driven by a global process that operates across contralateral and ipsilateral visual cortex or by a confounding factor, such as microsaccade rate.     

rTMS of the Left Dorsolateral Prefrontal Cortex Modulates Dopamine Release in the Ipsilateral Anterior Cingulate Cortex and Orbitofrontal Cortex

Background

Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson''s disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA).

Methodology/Principal Findings

Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [¹¹C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [¹¹C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [¹¹C]FLB 457 BP following right DLPFC rTMS.

Conclusions/Significance

To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [¹¹C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases.     

Effect of β-Bungarotoxin on the Release of Endogenous Amino Acids from the Sensorimotor Cortex

Abstract: β-Bungarotoxin, a snake neurotoxin purified from the venom of Bungarus multicinctus , caused a significant increase in the in vivo release of glutamate from the superfused sensorimotor cortex of awake animals. A smaller effect on GABA release was observed, but no change was detected in the release of six other amino acids measured. The effects on glutamate and GABA release were entirely blocked by tetrodotoxin (1 μM) and were reversible when the cortical tissue was washed with saline.     

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

Background

Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores.

Methods and Findings

In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05).

Conclusion

Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.     

A Comparison of the Ipsilateral Cortical Projections to the Dorsal and Ventral Subdivisions of the Macaque Premotor Cortex

The cortical connections of the dorsal (PMd) and ventral (PMv) subdivisions of the premotor area (PM, lateral area 6) were studied in four monkeys (Macaca fascicularis) through the use of retrograde tracers. In two animals, tracer was injected ventral to the arcuate sulcus (PMv), in a region from which forelimb movements could be elicited by intracortical microstimulation (ICMS). Tracer injections dorsal to the arcuate sulcus (PMd) were made in two locations. In one animal, tracer was injected caudal to the genu of the arcuate sulcus (in caudal PMd [cPMd], where ICMS was effective in eliciting forelimb movements); in another animal, it was injected rostral to the genu of the arcuate sulcus (in rostral PMd [rPMd], where ICMS was ineffective in eliciting movements). Retrogradely labeled neurons were counted in the ipsilateral hemisphere and located in cytoarchitectonically identified areas of the frontal and parietal lobes. Although both PMv and PMd were found to receive inputs from other motor areas, the prefrontal cortex, and the parietal cortex, there were differences in the topography and the relative strength of projections from these areas.

There were few common inputs to PMv and PMd; only the supplementary eye fields projected to all three areas studied. Interconnections within PMd or PMv appeared to link hindlimb and forelimb representations, and forelimb and face representations; however, connections between PMd and PMv were sparse. Areas cPMd and PMv were found to receive inputs from other motor areas—the primary motor area, the supplementary motor area, and the cingulate motor area—but the topography and strength of projections from these areas varied. Area rPMd was found to receive sparse inputs, if any, from these motor areas. The frontal eye field (area 8a) was found to project to PMv and rPMd, and area 46 was labeled substantially only from rPMd. Parietal projections to PMv were found to originate from a variety of somatosensory and visual areas, including the second somatosensory cortex and related areas in the parietal operculum of the lateral sulcus, as well as areas 5, 7a, and 7b, and the anterior intraparietal area. By contrast, projections to cPMd arose only from area 5. Visual areas 7m and the medial intraparietal area were labeled from rPMd. Relatively more parietal neurons were labeled after tracer injections in PMv than in PMd. Thus, PMv and PMd appear to be parts of separate, parallel networks for movement control.     

Contribution of the Resting-State Functional Connectivity of the Contralesional Primary Sensorimotor Cortex to Motor Recovery after Subcortical Stroke

It remains uncertain if the contralesional primary sensorimotor cortex (CL_PSMC) contributes to motor recovery after stroke. Here we investigated longitudinal changes in the resting-state functional connectivity (rsFC) of the CL_PSMC and their association with motor recovery. Thirteen patients who had experienced subcortical stroke underwent a series of resting-state fMRI and clinical assessments over a period of 1 year at 5 time points, i.e., within the first week, at 2 weeks, 1 month, 3 months, and 1 year after stroke onset. Thirteen age- and gender-matched healthy subjects were recruited as controls. The CL_PSMC was defined as a region centered at the voxel that had greatest activation during hand motion task. The dynamic changes in the rsFCs of the CL_PSMC within the whole brain were evaluated and correlated with the Motricity Index (MI) scores. Compared with healthy controls, the rsFCs of the CL_PSMC with the bilateral PSMC were initially decreased, then gradually increased, and finally restored to the normal level 1 year later. Moreover, the dynamic change in the inter-hemispheric rsFC between the bilateral PSMC in these patients was positively correlated with the MI scores. However, the intra-hemispheric rsFC of the CL_PSMC was not correlated with the MI scores. This study shows dynamic changes in the rsFCs of the CL_PSMC after stroke and suggests that the increased inter-hemispheric rsFC between the bilateral PSMC may facilitate motor recovery in stroke patients. However, generalization of our findings is limited by the small sample size of our study and needs to be confirmed.     

Homologous Muscle Contraction during Unilateral Movement Does Not Show a Dominant Effect on Leg Representation of the Ipsilateral Primary Motor Cortex

Co-activation of homo- and heterotopic representations in the primary motor cortex (M1) ipsilateral to a unilateral motor task has been observed in neuroimaging studies. Further analysis showed that the ipsilateral M1 is involved in motor execution along with the contralateral M1 in humans. Additionally, transcranial magnetic stimulation (TMS) studies have revealed that the size of the co-activation in the ipsilateral M1 has a muscle-dominant effect in the upper limbs, with a prominent decline of inhibition within the ipsilateral M1 occurring when a homologous muscle contracts. However, the homologous muscle-dominant effect in the ipsilateral M1 is less clear in the lower limbs. The present study investigates the response of corticospinal output and intracortical inhibition in the leg representation of the ipsilateral M1 during a unilateral motor task, with homo- or heterogeneous muscles. We assessed functional changes within the ipsilateral M1 and in corticospinal outputs associated with different contracting muscles in 15 right-handed healthy subjects. Motor tasks were performed with the right-side limb, including movements of the upper and lower limbs. TMS paradigms were measured, consisting of short-interval intracortical inhibition (SICI) and recruitment curves (RCs) of motor evoked potentials (MEPs) in the right M1, and responses were recorded from the left rectus femoris (RF) and left tibialis anterior (TA) muscles. TMS results showed that significant declines in SICI and prominent increases in MEPs of the left TA and left RF during unilateral movements. Cortical activations were associated with the muscles contracting during the movements. The present data demonstrate that activation of the ipsilateral M1 on leg representation could be increased during unilateral movement. However, no homologous muscle-dominant effect was evident in the leg muscles. The results may reflect that functional coupling of bilateral leg muscles is a reciprocal movement.     

The Refinement of Ipsilateral Eye Retinotopic Maps Is Increased by Removing the Dominant Contralateral Eye in Adult Mice

Background

Shortly after eye opening, initially disorganized visual cortex circuitry is rapidly refined to form smooth retinotopic maps. This process asymptotes long before adulthood, but it is unknown whether further refinement is possible. Prior work from our lab has shown that the retinotopic map of the non-dominant ipsilateral eye develops faster when the dominant contralateral eye is removed. We examined whether input from the contralateral eye might also limit the ultimate refinement of the ipsilateral eye retinotopic map in adults. In addition, we examined whether the increased refinement involved the recruitment of adjacent cortical area.

Methodology/Principal Findings

By surgically implanting a chronic optical window over visual cortex in mice, we repeatedly measured the degree of retinotopic map refinement using quantitative intrinsic signal optical imaging over four weeks. We removed the contralateral eye and observed that the retinotopic map for the ipsilateral eye was further refined and the maximum magnitude of response increased. However, these changes were not accompanied by an increase in the area of responsive cortex.

Conclusions/Significance

Since the retinotopic map was functionally refined to a greater degree without taking over adjacent cortical area, we conclude that input from the contralateral eye limits the normal refinement of visual cortical circuitry in mice. These findings suggest that the refinement capacity of cortical circuitry is normally saturated.     

Increased Low-Frequency Oscillation Amplitude of Sensorimotor Cortex Associated with the Severity of Structural Impairment in Cervical Myelopathy

Decreases in metabolites and increased motor-related, but decreased sensory-related activation of the sensorimotor cortex (SMC) have been observed in patients with cervical myelopathy (CM) using advanced MRI techniques. However, the nature of intrinsic neuronal activity in the SMC, and the relationship between cerebral function and structural damage of the spinal cord in patients with CM are not fully understood. The purpose of this study was to assess intrinsic neuronal activity by calculating the regional amplitude of low frequency fluctuations (ALFF) using resting-state functional MRI (rs-fMRI), and correlations with clinical and imaging indices. Nineteen patients and 19 age- and sex-matched healthy subjects underwent rs-fMRI scans. ALFF measurements were performed in the SMC, a key brain network likely to impaired or reorganized patients with CM. Compared with healthy subjects, increased amplitude of cortical low-frequency oscillations (LFO) was observed in the right precentral gyrus, right postcentral gyrus, and left supplementary motor area. Furthermore, increased z-ALFF values in the right precentral gyrus and right postcentral gyrus correlated with decreased fractional anisotropy values at the C2 level, which indicated increased intrinsic neuronal activity in the SMC corresponding to the structural impairment in the spinal cord of patients with CM. These findings suggest a complex and diverging relationship of cortical functional reorganization and distal spinal anatomical compression in patients with CM and, thus, add important information in understanding how spinal cord integrity may be a factor in the intrinsic covariance of spontaneous low-frequency fluctuations of BOLD signals involved in cortical plasticity.     

Expression of Cytoskeletal Proteins in Neurons of the Rat Sensorimotor Cortex upon Hypoperfusion of the Brain and Sensitization by Cerebral Antigen

Neurophysiology - Relatively mild disturbances in the blood supply of the rat brain provided by ligation of one common carotid artery leading to relatively mild disturbances of the cerebral blood...     

Action of Dopaminergic Agents on the Impulse Activity of Sensorimotor Cortex Neurons of Cats Performing a Conditioned Motor Task

We demonstrate that dopamine itself, a selective dopamine D1 receptor agonist, SKF 38393, and a selective dopamine D2 receptor agonist, quinpirole, exert both facilitatory and suppressive effects on neuronal activity in the sensorimotor cortex of the cat, which is related to a conditioned movement. These effects are mediated by activation of dopamine receptors. Our data can be used for understanding the mechanisms underlying modulation of the excitability of central neurons during various behavioral events under the influence of dopamine.     

Spontaneous and Amphetamine-Evoked Release of Cerebellar Noradrenaline After Sensorimotor Cortex Contusion: An In Vivo Microdialysis Study in the Awake Rat

Abstract: Microdialysis sampling combined with HPLC was used to assess spontaneous and d -amphetamine (AMPH)-evoked release of noradrenaline (NA) in the cerebellum 1 day after probe implantation and 1 day after contusion of the right sensorimotor cortex (SMCX) in rats. In normal controls the mean β SEM basal NA release was 10.08 β 0.97 pg in the left cerebellar hemisphere and 8.21 β 1.17 pg in the right hemisphere 22–24 h after probe implantation. The average β SEM NA release in a 3-h period after administration of AMPH (2 mg/kg, i.p.) increased to 453 β 47.35 pg in the left and to 402 β 49.95 pg in the right cerebellar hemisphere. NA release (range of 413–951% increase over baseline) was maximal 20–40 min postdrug, returned to basal levels within 5 h, and remained unchanged for the 22–24-h postdrug measurement period. Animals with a focal SMCX contusion had a marked depression of both spontaneous and AMPH-evoked NA release. Mean β SEM basal NA release was 4.84 β 1.09 pg in the left and 4.95 β 0.43 pg in the right cerebellar hemisphere from 22 to 24 h postinjury, with NA levels increasing to 259 β 75.44 and 219 β 23.45 pg in the respective hemispheres over a 3-h period after AMPH. The maximal AMPH-induced increase in NA release ranged from 522 to 1,088% of basal levels in contused rats, with NA release returning to predrug levels within 5 h and remaining depressed for at least 48 h postinjury. These data indicate that although neocortical injury results in a bilateral reduction of extracellular levels of NA in cerebellum, AMPH-releasable NA stores are present in the cerebellum. These effects may be related to locomotor impairments and AMPH-facilitated behavioral" recovery after cortical injury.     

Intrathecal Delivery of IL-6 Reactivates the Intrinsic Growth Capacity of Pyramidal Cells in the Sensorimotor Cortex after Spinal Cord Injury

We have previously demonstrated the growth-promoting effect of intrathecal delivery of recombinant rat IL-6 immediately after corticospinal tract (CST) injury. Our present study aims to further clarify whether intrathecal delivery of IL-6 after CST injury could reactivate the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex which project long axons to the spinal cord. We examined, by ELISA, levels of cyclic adenosine monophosphate (cAMP), adenylyl cyclase (AC, which synthesizes cAMP), phosphodiesterases (PDE, which degrades cAMP), and, by RT-PCR, the expression of regeneration-associated genes in the rat sensorimotor cortex after intrathecal delivery of IL-6 for 7 days, started immediately after CST injury. Furthermore, we injected retrograde neuronal tracer Fluorogold (FG) to the spinal cord to label pyramidal cells in the sensorimotor cortex, layers V and VI, combined with βIII-tubulin immunostaining, then we analyzed by immunohistochemisty and western blot the expression of the co-receptor gp-130 of IL-6 family, and pSTAT3 and mTOR, downstream IL-6/JAK/STAT3 and PI3K/AKT/mTOR signaling pathways respectively. We showed that intrathecal delivery of IL-6 elevated cAMP level and upregulated the expression of regeneration-associated genes including GAP-43, SPRR1A, CAP-23 and JUN-B, and the expression of pSTAT3 and mTOR in pyramidal cells of the sensorimotor cortex. In contrast, AG490, an inhibitor of JAK, partially blocked these effects of IL-6. All these results indicate that intrathecal delivery of IL-6 immediately after spinal cord injury can reactivate the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex and these effects of IL-6 were partially JAK/STAT3-dependent.