http://www.40hz.net/engel_2010_curr_opin.pdf

Beta-band oscillations--signalling the status quo?

In this review, we consider the potential functional role of beta-band oscillations, which at present is not yet well understood. We discuss evidence from recent studies on top-down mechanisms involved in cognitive processing, on the motor system and on the pathophysiology of movement disorders that suggest a unifying hypothesis: beta-band activity seems related to the maintenance of the current sensorimotor or cognitive state. We hypothesize that beta oscillations and/or coupling in the beta-band are expressed more strongly if the maintenance of the status quo is intended or predicted, than if a change is expected. Moreover, we suggest that pathological enhancement of beta-band activity is likely to result in an abnormal persistence of the status quo and a deterioration of flexible behavioural and cognitive control.

Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.

/pdf/neurophysiological-and-computational-principles-of-cortical-48xnk4ixsg.pdf

Neurophysiological and Computational Principles of Cortical Rhythms in Cognition

The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treat- ments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full

/pdf/the-movement-disorder-society-evidence-based-medicine-review-2fyuhos0nl.pdf

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease

Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches.

The scientific and clinical basis for the treatment of Parkinson disease (2009)

The Human Thalamus Processes Syntactic and Semantic Language Violations

Movement-related processing results in the modulation of neuronal synchronization over several electroencephalography (EEG) frequency ranges, including alpha- (8-12 Hz) and beta-band (14-30 Hz). Whether modulation patterns differ across sites within the motor system remains unclear, but could denote how information is conveyed across the cortico-basal network. We therefore compared the event-related synchronization/desynchronization (ERS/ERD) in recordings from the scalp, basal ganglia and thalamic structures during a motor task. Simultaneous depth and scalp EEG were recorded in 13 patients, undergoing deep brain stimulation of the thalamic ventral intermediate nucleus (VIM) or the subthalamic nucleus (STN). They performed a choice-reaction task with pre-cued Go-signals, instructive for either left- or right-sided button presses. In the beta-band, pre-cues and Go-signals were followed by ERD starting well before and peaking at task execution, uniformly in all cortical and subcortical recordings. In contrast, a comparable alpha-band ERD was only seen at the scalp, whereas mirror-like ERS were observed in the motor-inhibitory STN. In VIM, which receives strong somatosensory afferences, a major alpha-ERD upon the Go-signal did not start until the motor response. These dissociations of task-related Alpha- and Beta-band dynamics tag a functional diversity in cortico-basal networks, which are simultaneously active in motor processing. Whereas the uniform downregulation of Beta-activity points to an anti-kinetic operation mode throughout the motor system, site-dependent courses of Alpha-synchronization rather reflect the coordination of activity levels in functionally divergent motor structures during the preparation and execution of movements.

Task-related differential dynamics of EEG alpha- and beta-band synchronization in cortico-basal motor structures.

Background: Motor deficits in Parkinson’s disease (PD) are reduced by deep brain stimulation (DBS) of the subthalamic nucleus (STN), but the impact of this therapy on dysarthrophonic problems in PD remains controversial. We therefore aimed to disentangle the effects of STN DBS on the speech skills of long-term treated patients. Methods: Under continued medication, speech and motor functions of 19 patients with PD with bilateral STN DBS were studied when their therapeutic stimulation was active (STIM-ON) versus switched off (STIM-OFF). Per condition, perceptual speech ratings were given by: (i) the patients themselves, (ii) the treating physician, and (iii) professional speech therapists. Furthermore, single speech parameters were measured with a battery of technical exams in both STIM-ON and STIM-OFF. Results: STN DBS significantly worsened speech performance according to all perceptual rating methods applied. In contrast, technical measures showed DBS-induced improvements of single speech dimensions affected by the PD-specific motor disorder. These changes occurred independently of the reduction of motor impairment, which was consistently effectuated by STN DBS. Conclusion: In parallel to the beneficial effects on the motor symptoms of PD, STN DBS reduces designated disease-inherent dysarthrophonic symptoms, such as glottic tremor. However, these actions on speech are predominantly outweighed by the general dysarthrogenic effects of STN DBS, probably based on a decline of complex (eg, prosodic) functions. Thus, stimulation-induced speech impairment should be considered a likely problem in the course of this treatment.

https://jnnp.bmj.com/content/jnnp/79/5/522.full.pdf

Effects of subthalamic deep brain stimulation on dysarthrophonia in Parkinson’s disease

Levodopa/Carbidopa intestinal gel infusion (LCIG) for Parkinson's disease is under debate to provoke polyneuropathy (PNP). In our cohort of 20 thus treated patients, two developed debilitating axonal PNP with deficient pyridoxin and folate levels, and marginal cobalamin. Homocysteine was highly elevated. The neuropathies responded to vitamin replacement. We assume that LCIG can provoke PNP most likely of malnutritional origin. To avoid this side effect, the assessment of predisposing factors before treatment as well as neurophysiological and laboratory screenings appear necessary.

Malnutritional neuropathy under intestinal levodopa infusion

The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinson's disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the "overdose hypothesis" which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patients' actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks.

/pdf/differential-influence-of-levodopa-on-reward-based-learning-1zyo460yth.pdf

Frank Marzinzik

Papers

The Human Thalamus Processes Syntactic and Semantic Language Violations

Task-related differential dynamics of EEG alpha- and beta-band synchronization in cortico-basal motor structures.

Effects of subthalamic deep brain stimulation on dysarthrophonia in Parkinson’s disease

Malnutritional neuropathy under intestinal levodopa infusion

Differential Influence of Levodopa on Reward-Based Learning in Parkinson's Disease