Pär Halje

Body ownership and embodiment: Vestibular and multisensory mechanisms

Body ownership and embodiment are two fundamental mechanisms of self-consciousness. The present article reviews neurological data about paroxysmal illusions during which body ownership and embodiment are affected differentially: autoscopic phenomena (out-of-body experience, heautoscopy, autoscopic hallucination, feeling-of-a-presence) and the room tilt illusion. We suggest that autoscopic phenomena and room tilt illusion are related to different types of failures to integrate body-related information (vestibular, proprioceptive and tactile cues) in addition to a mismatch between vestibular and visual references. In these patients, altered body ownership and embodiment has been shown to occur due to pathological activity at the temporoparietal junction and other vestibular-related areas arguing for a key importance of vestibular processing. We also review the possibilities of manipulating body ownership and embodiment in healthy subjects through exposition to weightlessness as well as caloric and galvanic stimulation of the peripheral vestibular apparatus. In healthy subjects, disturbed self-processing might be related to interference of vestibular stimulation with vestibular cortex leading to disintegration of bodily information and altered body ownership and embodiment. We finally propose a differential contribution of the vestibular cortical areas to the different forms of altered body ownership and embodiment.

Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations.

The standard pharmacological treatment for Parkinsons disease using the dopamine precursor levodopa is unfortunately limited by gradual development of disabling involuntary movements for which the underlying causes are poorly understood. Here we show that levodopa-induced dyskinesia in hemiparkinsonian rats is strongly associated with pronounced 80 Hz local field potential oscillations in the primary motor cortex following levodopa treatment. When this oscillation is interrupted by application of a dopamine antagonist onto the cortical surface the dyskinetic symptoms disappear. The finding that abnormal cortical oscillations are a key pathophysiological mechanism calls for a revision of the prevailing hypothesis that links levodopa-induced dyskinesia to an altered sensitivity to dopamine only in the striatum. Apart from having important implications for the treatment of Parkinsons disease, the discovered pathophysiological mechanism may also play a role in several other psychiatric and neurological conditions involving cortical dysfunction.

Alpha band oscillations correlate with illusory self-location induced by virtual reality

Neuroscience of the self has focused on high‐level mechanisms related to language, memory or imagery of the self. However, recent evidence suggests that low‐level mechanisms such as multisensory and sensorimotor integration may play a fundamental role in self‐related processing. Here we used virtual reality technology and visuo‐tactile conflict to study such low‐level mechanisms and manipulate where participants experienced their self to be localized (self‐location). Frequency analysis and electrical neuroimaging of co‐recorded high‐resolution electroencephalography revealed body‐specific alpha band power modulations in bilateral sensorimotor cortices. Furthermore, alpha power in the medial prefrontal cortex (mPFC) was correlated with the degree of experimentally manipulated self‐location. We argue that these alpha oscillations in sensorimotor cortex and mPFC reflect self‐location as manipulated through multisensory conflict.

Spatiotemporal dynamics of visual vertical judgments: early and late brain mechanisms as revealed by high-density electrical neuroimaging

Constructing and updating an internal model of verticality is fundamental for maintaining an erect posture and facilitating visuo-spatial processing. The judgment of the visual vertical (VV) has been intensively studied in psychophysical investigations and relies mainly on the integration of visual and vestibular signals, although a contribution of postural and somatosensory signals has been reported. Here we used high-density 192-channel evoked potential (EP) mapping and distributed source localization techniques to reveal the neural mechanisms of VV judgments. VV judgments (judging the orientation of visual lines with respect to the subjective vertical) were performed with and without a tilted visual frame. EP mapping revealed a sequence of neural processing steps (EP maps) of which two were specific for VV judgments. An early EP map, observed at ∼75-105 ms post-stimulus, was localized in right lateral temporo-occipital cortex. A later EP map (∼260-290 ms) was localized in bilateral temporo-occipital and parieto-occipital cortex. These data suggest that early VV-related neural processing involves the lateral and ventral visual stream and is related to visual processing concerning orientation, attention and comparison. The later, more dorsal, activation involves multimodal cortex subtending a constantly available and updated internal model of the vertical that we can refer to for the control of ones posture, actions, and visuo-spatial processing.

Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.

Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method--epidural spinal cord stimulation (SCS)--has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD.

Feeling in control of your footsteps: conscious gait monitoring and the auditory consequences of footsteps

A fundamental aspect of the “I” of conscious experience is that the self is experienced as a single coherent representation of the entire, spatially situated body. The purpose of the present study was to investigate agency for the entire body. We provided participants with performance-related auditory cues and induced online sensorimotor conflicts in free walking conditions investigating the limits of human consciousness in moving agents. We show that the control of full-body locomotion and the building of a conscious experience of it are at least partially distinct brain processes. The comparable effects on agency using audio-motor and visuo-motor cues as found in the present and previous agency work may reflect common supramodal mechanisms in conscious action monitoring. Our data may help to refine the scientific criteria of selfhood and are of relevance for the investigation of neurological and psychiatric patients with disturbance of selfhood.

Mechanisms underlying cortical resonant states: implications for levodopa-induced dyskinesia

Abstract A common observation in recordings of neuronal activity from the cerebral cortex is that populations of neurons show patterns of synchronized oscillatory activity. However, it has been suggested that neuronal synchronization can, in certain pathological conditions, become excessive and possibly have a pathogenic role. In particular, aberrant oscillatory activation patterns have been implicated in conditions involving cortical dysfunction. We here review the mechanisms thought to be involved in the generation of cortical oscillations and discuss their relevance in relation to a recent finding indicating that high-frequency oscillations in the cerebral cortex have an important role in the generation of levodopa-induced dyskinesia. On the basis of these insights, it is suggested that the identification of physiological changes associated with symptoms of disease is a particularly important first step toward a more rapid development of novel treatment strategies.

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

To date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia.

A system for automated tracking of motor components in neurophysiological research.

In the study of motor systems it is often necessary to track the movements of an experimental animal in great detail to allow for interpretation of recorded brain signals corresponding to different control signals. This task becomes increasingly difficult when analyzing complex compound movements in freely moving animals. One example of a complex motor behavior that can be studied in rodents is the skilled reaching test where animals are trained to use their forepaws to grasp small food objects, in many ways similar to human hand use. To fully exploit this model in neurophysiological research it is desirable to describe the kinematics at the level of movements around individual joints in 3D space since this permits analyses of how neuronal control signals relate to complex movement patterns. To this end, we have developed an automated system that estimates the paw pose using an anatomical paw model and recorded video images from six different image planes in rats chronically implanted with recording electrodes in neuronal circuits involved in selection and execution of forelimb movements. The kinematic description provided by the system allowed for a decomposition of reaching movements into a subset of motor components. Interestingly, firing rates of individual neurons were found to be modulated in relation to the actuation of these motor components suggesting that sets of motor primitives may constitute building blocks for the encoding of movement commands in motor circuits. The designed system will, thus, enable a more detailed analytical approach in neurophysiological studies of motor systems.

Untangling Cortico-Striatal Connectivity and Cross-Frequency Coupling in L-DOPA-Induced Dyskinesia

We simultaneously recorded local field potentials (LFPs) in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analyzed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80-Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the control state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.