Wolfgang Kruse

Coherent oscillations: A mechanism of feature linking in the visual cortex?

Primary visual coding can be characterized by the receptive field (RF) properties of single neurons. Subject of this paper is our search for a global,second coding step beyond the RF-concept that links related features in a visual scene. In recent models of visual coding, oscillatory activities have been proposed to constitute such linking signals. We tested the neurophysiological relevance of this hypothesis for the visual system. Single and multiple spikes as well as local field potentials were recorded simultaneously from several locations in the primary visual cortex (A17 and A18) using 7 or 19 individually advanceable fibermicroelectrodes (250 or 330 μm apart).Stimulusevoked (SE)-resonances of 35–85 Hz were found in these three types of signals throughout the visual cortex when the primary coding channels were activated by their specific stimuli. Stimulus position, orientation, movement direction and velocity, ocularity and stationary flicker caused specific SE-resonances.Coherent SE-resonances were found at distant cortical positions when at least one of the primary coding properties was similar. Coherence was found1) within a vertical cortex column,2) between neighbouring hypercolumns, and3) between two different cortical areas. We assume that the coherence of SE-resonances is mediated by recurrent excitatory intra- and inter-areal connections via phase locking between assemblies that represent the linking features of the actual visual scene. Visually related activities are, thus, transiently labelled by a temporal code that signalizes their momentary association.

Direct Current Stimulation over V5 Enhances Visuomotor Coordination by Improving Motion Perception in Humans

The primary aim of this study was to determine the extent to which human MT+/V5, an extrastriate visual area known to mediate motion processing, is involved in visuomotor coordination. To pursue this we increased or decreased the excitability of MT+/V5, primary motor, and primary visual cortex by the application of 7 min of anodal and cathodal transcranial direct current stimulation (tDCS) in healthy human subjects while they were performing a visuomotor tracking task involving hand movements. The percentage of correct tracking movements increased specifically during and immediately after cathodal stimulation, which decreases cortical excitability, only when V5 was stimulated. None of the other stimulation conditions affected visuomotor performance. We propose that the improvement in performance caused by cathodal tDCS of V5 is due to a focusing effect on to the complex motion perception conditions involved in this task. This hypothesis was proven by additional experiments: Testing simple and complex motion perception in dot kinetograms, we found that a diminution in excitability induced by cathodal stimulation improved the subjects perception of the direction of the coherent motion only if this was presented among random dots (complex motion perception), and worsened it if only one motion direction was presented (simple movement perception). Our data suggest that area V5 is critically involved in complex motion perception and identification processes important for visuomotor coordination. The results also raise the possibility of the usefulness of tDCS in rehabilitation strategies for neurological patients with visuomotor disorders.

Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans

Performance of visuo‐motor tasks requires the transfer of visual data to motor performance and depends highly on visual perception and cognitive processing, mainly during the learning phase. The primary aim of this study was to determine if the human middle temporal (MT)+/V5, an extrastriate visual area that is known to mediate motion processing, and the primary motor cortex are involved in learning of visuo‐motor coordination tasks. To pursue this, we increased or decreased MT+/V5, primary contralateral motor (M1) and primary visual cortex excitability by 10 min of anodal or cathodal transcranial direct current stimulation in healthy human subjects during the learning phase of a visually guided tracking task. The percentage of correct tracking movements increased significantly in the early learning phase during anodal stimulation, but only when the left V5 or M1 was stimulated. Cathodal stimulation had no significant effect. Also, stimulation of the primary visual cortex was not effective for this kind of task. Our data suggest that the areas V5 and M1 are involved in the early phase of learning of visuo‐motor coordination.

Differences of monkey and human overt attention under natural conditions

Rhesus monkeys are widely used as animal models of human attention. Such research rests upon the assumption that similar mechanisms underlie attention in both species. Here, we directly compare the influence of low-level stimulus features on overt attention in monkeys and humans under natural conditions. We recorded eye-movements in humans and rhesus monkeys during free-viewing of natural images. We find that intrinsic low-level features, such luminance-contrast, texture-contrast and saliency-as predicted by a standard model, are elevated at fixation points in the majority of images. These correlative effects are not significantly different between species. However, local image modifications affect both species differently: moderate modifications, which are in the range of natural fluctuations, attract overt attention in monkeys significantly stronger than they do in humans. In addition, humans show a higher inter-individual consistency regarding which locations they fixate than monkeys, in spite of the similarity for intrinsic low-level features. Taken together, these data demonstrate that-under natural conditions-low-level stimulus features affect attention in monkeys and humans differently.

Delayed postnatal loss of P/Q type calcium channels recapitulates the absence epilepsy, dyskinesia, and ataxia phenotypes of genomic Cacna1A mutations

Inherited loss of P/Q-type calcium channel function causes human absence epilepsy, episodic dyskinesia, and ataxia, but the molecular “birthdate” of the neurological syndrome and its dependence on prenatal pathophysiology is unknown. Since these channels mediate transmitter release at synapses throughout the brain and are expressed early in embryonic development, delineating the critical circuitry and onset underlying each of the emergent phenotypes requires targeted control of gene expression. To visualize P/Q-type Ca2+ channels and dissect their role in neuronal networks at distinct developmental stages, we created a novel conditional Cacna1a knock-in mouse by inserting the floxed green fluorescent protein derivative Citrine into the first exon of Cacna1a and then crossed it with a postnatally expressing PCP2-Cre line for delayed Purkinje cell (PC) gene deletion within the cerebellum and sparsely in forebrain (purky). PCs in purky mice lacked P/Q-type calcium channel protein and currents within the first month after birth, displayed altered spontaneous firing, and showed impaired neurotransmission. Unexpectedly, adult purky mice exhibited the full spectrum of neurological deficits seen in mice with genomic Cacna1a ablation. Our results show that the ataxia, dyskinesia, and absence epilepsy caused by inherited disorders of the P/Q-type channel arise from signaling defects beginning in late infancy, revealing an early window of opportunity for therapeutic intervention.

Motor Cortical Activity during Interception of Moving Targets

The single-unit activity of 831 cells was recorded in the arm area of the motor cortex of tow monkeys while the monkeys intercepted a moving visual stimulus (interception task) or remained immobile during presentation of the same moving stimulus (no-go task). The moving target traveled on an oblique path from either lower corner of a screen toward the vertical meridian, and its movement time (0.5,1.0, or 1.5 sec) and velocity profile (accelerating, decelerating, or constant velocity) were pseudorandomly varied. The moving target had to be intercepted within 130 msec of target arrival at an interception point. By comparing motor cortical activity at the single-neuron tasks, we tested whether information about parameters of moving target is represented in the primary motor cortex to generate appropriate motor responses. A substantial number of neurons displayed modulation of their activity during the no-go task, and this activity was often affected by the stimulus parameters. These results suggest a role of motor cortex in specifying the timing of movement initiation based on information about target motion. In addition, there was a lack of systematic relation between the onset times of neural activity in the interception and no-go task, suggesting that processing of information concerning target motion and generation of hand movement occurs in parallel. Finally, the activity in the most motor cortical neurons was modulated according to an estimate of the time-to-target interception, raising the possibility that time-to-interception may be coded in the motor cortical activity.

Optogenetic control of motor coordination by Gi/o protein-coupled vertebrate rhodopsin in cerebellar Purkinje cells.

G protein-coupled receptors are involved in the modulation of complex neuronal networks in the brain. To investigate the impact of a cell-specific Gi/o protein-mediated signaling pathway on brain function, we created a new optogenetic mouse model in which the Gi/o protein-coupled receptor vertebrate rhodopsin can be cell-specifically expressed with the aid of Cre recombinase. Here we use this mouse model to study the functional impact of Gi/o modulation in cerebellar Purkinje cells (PCs). We show that in vivo light activation of vertebrate rhodopsin specifically expressed in PCs reduces simple spike firing that is comparable with the reduction in firing observed for the activation of cerebellar Gi/o-coupled GABAB receptors. Notably, the light exposure of the cerebellar vermis in freely moving mice changes the motor behavior. Thus, our studies directly demonstrate that spike modulation via Gi/o-mediated signaling in cerebellar PCs affects motor coordination and show a new promising approach for studying the physiological function of G protein-coupled receptor-mediated signaling in a cell type-specific manner.

Spinocerebellar Ataxia Type 6 Protein Aggregates Cause Deficits in Motor Learning and Cerebellar Plasticity

Spinocerebellar ataxia type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming subunits of P/Q-type Ca2+ channels (Cav2.1) and is characterized by CT protein aggregates found in cerebellar Purkinje cells (PCs). One hypothesis regarding SCA6 disease is that a CT fragment of the Cav2.1 channel, which is detected specifically in cytosolic and nuclear fractions in SCA6 patients, is associated with the SCA6 pathogenesis. To test this hypothesis, we expressed P/Q-type channel protein fragments from two different human CT splice variants, as predicted from SCA6 patients, in PCs of mice using viral and transgenic approaches. These splice variants represent a short (CT-short without polyQs) and a long (CT-long with 27 polyQs) CT fragment. Our results show that the different splice variants of the CTs differentially distribute within PCs, i.e., the short CTs reveal predominantly nuclear inclusions, whereas the long CTs prominently reveal both nuclear and cytoplasmic aggregates. Postnatal expression of CTs in PCs in mice reveals that only CT-long causes SCA6-like symptoms, i.e., deficits in eyeblink conditioning (EBC), ataxia, and PC degeneration. The physiological phenotypes associated specifically with the long CT fragment can be explained by an impairment of LTD and LTP at the parallel fiber-to-PC synapse and alteration in spontaneous PC activity. Thus, our results suggest that the polyQ carrying the CT fragment of the P/Q-type channel is sufficient to cause SCA6 pathogenesis in mice and identifies EBC as a new diagnostic strategy to evaluate Ca2+ channel-mediated human diseases.

The role of V5 (hMT+) in visually guided hand movements: an fMRI study

Electrophysiological studies in animals suggest that visuomotor control of forelimb and eye movements involves reciprocal connections between several areas (striate, extrastriate, parietal, motor and premotor) related to movement performance and visuospatial coding of movement direction. The extrastriate area MT [V5 (hMT+) in humans] located in the ‘dorsal pathway’ of the primate brain is specialized in the processing of visual motion information. The aim of our study was to investigate the functional role of V5 (hMT+) in the control of visually guided hand movements and to identify the corresponding cortex activation implicated in the visuomotor tasks using functional magnetic resonance imaging. Eight human subjects performed visually guided hand movements, either continuously tracking a horizontally moving target or performing ballistic tracking movements of a cursor to an eccentric stationary target while fixating a central fixation cross. The tracking movements were back‐projected onto the screen using a cursor which was moved by an MRI‐compatible joystick. Both conditions activated area V5 (hMT+), right more than left, particularly during continuous tracking. In addition, a large‐scale sensorimotor circuit which included sensorimotor cortex, premotor cortex, striatum, thalamus and cerebellum as well as a number of cortical areas along the intraparietal sulcus in both hemispheres were activated. Because activity was increased in V5 (hMT+) during continuous tracking but not during ballistic tracking as compared to motion perception, it has a pivotal role during the visual control of forelimb movements as well.

Somatosensory-Motor Neuronal Activity in the Superior Colliculus of the Primate

The superior colliculus (SC) in primates plays an important role in orienting gaze and arms toward novel stimuli. Here we ask whether neurons in the intermediate and deep layers of the SC are also involved in the interaction with objects. In two trained monkeys we found a large number of SC units that were specifically activated when the monkeys contacted and pushed a target that had been reached with either hand. These neurons, however, were silent when the monkeys simply looked at or reached for the target but did not touch it. The activity related to interacting with objects was spatially tuned and increased with push strength. Neurons in the SC with this type of activity may be involved in a somatosensory-motor feedback loop that monitors the force of the active muscles together with the spatial position of the limb required for proper interaction with an object.