We investigate the extent to which functional circuits coupling cortical and subthalamic activity are multiple and segregated by frequency in untreated Parkinson's disease (PD). To this end, we recorded EEG and local field potentials (LFPs) from macroelectrodes inserted into the subthalamic nucleus area (SA) in nine awake patients following functional neurosurgery for PD. Patients were studied after overnight withdrawal of medication. Coherence between EEG and SA LFPs was apparent in the theta (3-7 Hz), alpha (8-13 Hz), lower beta (14-20 Hz) and upper beta (21-32 Hz) bands, although activity in the alpha and upper beta bands dominated. Theta coherence predominantly involved mesial and lateral areas, alpha and lower beta coherence the mesial and ipsilateral motor areas, and upper beta coherence the midline cortex. SA LFPs led EEG in the theta band. In contrast, EEG led the depth LFP in the lower and upper beta bands. SA LFP activity in the alpha band could either lead or lag EEG. Thus there are several functional sub-loops between the subthalamic area and cerebral cortical motor regions, distinguished by their frequency, cortical topography and temporal relationships. Tuning to distinct frequencies may provide a means of marking and segregating related processing, over and above any anatomical segregation of processing streams.

No abstract

We used the P300 component to investigate how changes in local context influenced the ability to detect target stimuli. Local context was defined as the occurrence of a short predictive series of stimuli before delivery of a target event. EEG was recorded in 12 subjects during auditory and visual sessions. Stimuli were presented in the center of the auditory and visual field and consisted of 15% targets (1000 Hz tone or downward facing triangle) and 85% of equal amounts of three types of standards (1500 Hz, 2000 Hz and 2500 Hz tones or triangles facing left, upwards and right). Recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a three-standard predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. Peak target P300 (P3b) amplitude and latency were evaluated for targets after predictive and non-predictive sequences using conventional averaging and a novel single-trial analysis procedure. Reaction times were shorter for predictable targets than for nonpredicted targets. P3b latency was shorter for predicted targets than for non-predictive targets, and there were no significant P3b amplitude differences between predicted and random targets, as determined by both conventional averaging and single-trial analysis. Comparable effects on amplitude and latency were observed in both the auditory and visual modalities. The results indicate that local context has differential effects on P3b amplitude and latency, and exerts modality independent effects on cognitive processing.

Selective processing of task-relevant stimuli is critical for goal-directed behavior. We used electrocorticography to assess the spatio-temporal dynamics of cortical activation during a simple phonological target detection task, in which subjects press a button when a prespecified target syllable sound is heard. Simultaneous surface potential recordings during this task revealed a highly ordered temporal progression of high gamma (HG, 70– 200 Hz) activity across the lateral hemisphere in less than 1 sec. The sequence demonstrated concurrent regional sensory processing of speech syllables in the posterior superior temporal gyrus (STG) and speech motor cortex, and then transitioned to sequential task-dependent processing from prefrontal cortex (PFC), to the final motor response in the hand sensorimotor cortex. STG activation was modestly enhanced for target over nontarget sounds, supporting a selective gain mechanism in early sensory processing, whereas PFC was entirely selective to targets, supporting its role in guiding response behavior. These results reveal that target detection is not a single cognitive event, but rather a process of progressive target selectivity that involves large-scale rapid parallel and serial processing in sensory, cognitive, and motor structures to support goal-directed human behavior.

This paper tests the hypothesis that patients with schizophrenia have a deficit in selectively attending to predictable events. We used dynamic causal modeling (DCM) of electrophysiological responses – to predictable and unpredictable visual targets – to quantify the effective connectivity within and between cortical sources in the visual hierarchy in 25 schizophrenia patients and 25 age-matched controls. We found evidence for marked differences between normal subjects and schizophrenia patients in the strength of extrinsic backward connections from higher hierarchical levels to lower levels within the visual system. In addition, we show that not only do schizophrenia subjects have abnormal connectivity but also that they fail to adjust or optimize this connectivity when events can be predicted. Thus, the differential intrinsic recurrent connectivity observed during processing of predictable versus unpredictable targets was markedly attenuated in schizophrenia patients compared with controls, suggesting a failure to modulate the sensitivity of neurons responsible for passing sensory information of prediction errors up the visual cortical hierarchy. The findings support the proposed role of abnormal connectivity in the neuropathology and pathophysiology of schizophrenia.