Lateralized effect of pallidal stimulation on self-mutilation in Lesch-Nyhan disease.

Lesch-Nyhan disease (LND) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. This syndrome is characterized by hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia. The authors describe the case of a 15-year-old boy who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. This case is the first reported instance of LND treated with DBS in which the stimulation was interrupted and the self-mutilation returned in a lateralized fashion. The findings indicate that the neurobehavioral aspect of LND is lateralized and that contralateral GPi stimulation is responsible for lateralized improvement in self-injurious behavior.

Traumatic intracranial hemorrhage in patients taking dabigatran: report of 3 cases and review of the literature.

BACKGROUND AND IMPORTANCE: Dabigatran is a direct thrombin inhibitor gaining popularity as a stroke prevention agent in patients with atrial fibrillation. In comparison with warfarin, dabigatran showed superiority in stroke prevention, but lower rates of major hemorrhage and intracerebral hemorrhage. Although warfarin has a well-established reversal strategy, there is far less experience reversing dabigatran. CLINICAL PRESENTATION: We present our experience with 3 patients who experienced an intracranial hemorrhage either spontaneously or after low-energy cranial trauma and review the available literature describing dabigatran use in patients with traumatic brain injury. CONCLUSION: Intracranial hemorrhage in patients taking anticoagulants and/or antiplatelets can have either a benign or malignant clinical course. At this time, there is little experience with dabigatran reversal; however, several strategies for rapid reversal have been proposed. All patients with intracranial hemorrhage taking dabigatran should be admitted for close neurological monitoring and serial imaging.

Sensory-motor interactions for vocal pitch monitoring in non-primary human auditory cortex.

The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (-100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70-150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control.

Human auditory cortical activation during self-vocalization.

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex.

Descending brain neurons in larval lamprey: spinal projection patterns and initiation of locomotion.

In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord.

Movements and muscle activity initiated by brain locomotor areas in semi-intact preparations from larval lamprey.

In in vitro brain/spinal cord preparations from larval lamprey, locomotor-like ventral root burst activity can be initiated by pharmacological (i.e., "chemical") microstimulation in several brain areas: rostrolateral rhombencephalon (RLR); dorsolateral mesencephalon (DLM); ventromedial diencephalon (VMD); and reticular nuclei. However, the quality and symmetry of rhythmic movements that would result from this in vitro burst activity have not been investigated in detail. In the present study, pharmacological microstimulation was applied to the above brain locomotor areas in semi-intact preparations from larval lamprey. First, bilateral pharmacological microstimulation in the VMD, DLM, or RLR initiated symmetrical swimming movements and coordinated muscle burst activity that were virtually identical to those during free swimming in whole animals. Unilateral microstimulation in these brain areas usually elicited asymmetrical undulatory movements. Second, with synaptic transmission blocked in the brain, bilateral pharmacological microstimulation in parts of the anterior (ARRN), middle (MRRN), or posterior (PRRN) rhombencephalic reticular nucleus also initiated symmetrical swimming movements and muscle burst activity. Stimulation in effective sites in the ARRN or PRRN initiated higher-frequency locomotor movements than stimulation in effective sites in the MRRN. Unilateral stimulation in reticular nuclei elicited asymmetrical rhythmic undulations or uncoordinated movements. The present study is the first to demonstrate in the lamprey that stimulation in higher-order locomotor areas (RLR, VMD, DLM) or reticular nuclei initiates and sustains symmetrical, well-coordinated locomotor movements and muscle activity. Finally, bilateral stimulation was a more physiologically realistic test of the function of these brain areas than unilateral stimulation.

Disruption of left-right reciprocal coupling in the spinal cord of larval lamprey abolishes brain-initiated locomotor activity.

In this study, contributions of left-right reciprocal coupling mediated by commissural interneurons in spinal locomotor networks to rhythmogenesis were examined in larval lamprey that had longitudinal midline lesions in the rostral spinal cord [8 --> 30% body length (BL), relative distance from the head] or caudal spinal cord (30 --> 50% BL). Motor activity was initiated from brain locomotor command systems in whole animals or in vitro brain/spinal cord preparations. After midline lesions in the caudal spinal cord in whole animals and in vitro preparations, left-right alternating burst activity could be initiated in rostral and usually caudal regions of spinal motor networks. In in vitro preparations, blocking synaptic transmission in the rostral cord abolished burst activity in caudal hemi-spinal cords. After midline lesions in the rostral spinal cord in whole animals, left-right alternating muscle burst activity was present in the caudal and sometimes the rostral body. After spinal cord transections at 30% BL, rhythmic burst activity usually was no longer generated by rostral hemi-spinal cords. For in vitro preparations, very slow burst activity was sometimes present in isolated right and left rostral hemi-spinal cords, but the rhythmicity for this activity appeared to originate from the brain, and the parameters of the activity were significantly different from those for normal locomotor activity. In summary, in larval lamprey under these experimental conditions, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling contributes to both phase control and rhythmogenesis.