Corticostriatal beta oscillation changes associated with cognitive function in Parkinson's disease.

Cognitive impairment is the most frequent non-motor symptom in Parkinson's disease and is associated with deficits in a number of cognitive functions including working memory. However, the pathophysiology of Parkinson's disease cognitive impairment is poorly understood. Beta oscillations have previously been shown to play an important role in cognitive functions including working memory encoding. Decreased dopamine in motor cortico-striato-thalamo-cortical (CSTC) circuits increases the spectral power of beta oscillations and results in Parkinson's disease motor symptoms. Analogous changes in parallel cognitive CSTC circuits involving the caudate and dorsolateral prefrontal cortex (DLPFC) may contribute to Parkinson's disease cognitive impairment. The objective of our study is to evaluate whether changes in beta oscillations in the caudate and DLPFC contribute to cognitive impairment in Parkinson's disease patients. To investigate this, we used local field potential recordings during deep brain stimulation surgery in 15 patients with Parkinson's disease. Local field potentials were recorded from DLPFC and caudate at rest and during a working memory task. We examined changes in beta oscillatory power during the working memory task as well as the relationship of beta oscillatory activity to preoperative cognitive status, as determined from neuropsychological testing results. We additionally conducted exploratory analyses on the relationship between cognitive impairment and task-based changes in spectral power in additional frequency bands. Spectral power of beta oscillations decreased in both DLPFC and caudate during working memory encoding and increased in these structures during feedback. Subjects with cognitive impairment had smaller decreases in caudate and DLPFC beta oscillatory power during encoding. In our exploratory analysis, we found that similar differences occurred in alpha frequencies in caudate and theta and alpha in DLPFC. Our findings suggest that oscillatory power changes in cognitive CSTC circuits may contribute to cognitive symptoms in patients with Parkinson's disease. These findings may inform the future development of novel neuromodulatory treatments for cognitive impairment in Parkinson's disease.

Comprehensive mapping of whisker-evoked responses reveals broad, sharply tuned thalamocortical input to layer 4 of barrel cortex.

Cortical neurons are organized in columns, distinguishable by their physiological properties and input-output organization. Columns are thought to be the fundamental information-processing modules of the cortex. The barrel cortex of rats and mice is an attractive model system for the study of cortical columns, because each column is defined by a layer 4 (L4) structure called a barrel, which can be clearly visualized. A great deal of information has been collected regarding the connectivity of neurons in barrel cortex, but the nature of the input to a given L4 barrel remains unclear. We measured this input by making comprehensive maps of whisker-evoked activity in L4 of rat barrel cortex using recordings of multiunit activity and current source density analysis of local field potential recordings of animals under light isoflurane anesthesia. We found that a large number of whiskers evoked a detectable response in each barrel (mean of 13 suprathreshold, 18 subthreshold) even after cortical activity was abolished by application of muscimol, a GABA(A) agonist. We confirmed these findings with intracellular recordings and single-unit extracellular recordings in vivo. This constitutes the first direct confirmation of the hypothesis that subcortical mechanisms mediate a substantial multiwhisker input to a given cortical barrel.

Evidence for frequency-dependent extracellular impedance from the transfer function between extracellular and intracellular potentials: intracellular-LFP transfer function.

We examine the properties of the transfer function F(T)=V(m)/V(LFP) between the intracellular membrane potential (V(m)) and the local field potential (V(LFP)) in cerebral cortex. We first show theoretically that, in the subthreshold regime, the frequency dependence of the extracellular medium and that of the membrane potential have a clear incidence on F(T). The calculation of F(T) from experiments and the matching with theoretical expressions is possible for desynchronized states where individual current sources can be considered as independent. Using a mean-field approximation, we obtain a method to estimate the impedance of the extracellular medium without injecting currents. We examine the transfer function for bipolar (differential) LFPs and compare to simultaneous recordings of V(m) and V(LFP) during desynchronized states in rat barrel cortex in vivo. The experimentally derived F(T) matches the one derived theoretically, only if one assumes that the impedance of the extracellular medium is frequency-dependent, and varies as 1/√ω (Warburg impedance) for frequencies between 3 and 500 Hz. This constitutes indirect evidence that the extracellular medium is non-resistive, which has many possible consequences for modeling LFPs.

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling.

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. Here we show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase-dependent adenosine production or A1-adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement of tone-discrimination abilities. We conclude that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.

Airway responses to the inhalation of cotton dust and cotton bract extracts.

BACKGROUND: Exposure to dust in the cotton industry is associated with respiratory dysfunction. Healthy subjects challenged with cotton bract extract (CBE) develop transient airway hyperresponsiveness. CBE, a major component of cotton dust, is potentially an important agent for studying byssinosis. OBJECTIVES: To compare airway responses to cotton dust extract (CDE) and CBE in healthy subjects. METHODS: In 21 healthy, non-smoking subjects we compared the effects of CBE and CDE in a double-blind random order, following a 10-min aerosol inhalation. The response to methacholine (MCh) 2 h following CBE or CDE was measured. Lung function was recorded using maximal (MEFV) and partial expiratory flow volume (PEFV) curves, measuring MEF at 60% of baseline vital capacity below total lung capacity [MEF40%(P)] on the PEFV curve. Responders were subjects who developed a 20% or greater fall in MEF40%(P) following extract challenge. Endotoxin levels were low for CBE (5.71 EU/mg) and CDE (31.88 EU/mg). RESULTS: There were 18 responders to CBE and 17 responders to CDE. The average maximal falls in MEF40%(P) were 70 +/- 4.9 and 70 +/- 4.4% of baseline (nonsignificant) following CBE and CDE, respectively. All subjects enhanced their MCh response following CBE or CDE. The MCh dose which reduced MEF40%(P) by 40% was identical for CBE and CDE (1.3 microg/ml). CONCLUSIONS: We conclude that CBE and CDE exert similar physiologic effects.