Differential Sources for 2 Neural Signatures of Target Detection: An Electrocorticography Study.

Electrophysiology and neuroimaging provide conflicting evidence for the neural contributions to target detection. Scalp electroencephalography (EEG) studies localize the P3b event-related potential component mainly to parietal cortex, whereas neuroimaging studies report activations in both frontal and parietal cortices. We addressed this discrepancy by examining the sources that generate the target-detection process using electrocorticography (ECoG). We recorded ECoG activity from cortex in 14 patients undergoing epilepsy monitoring, as they performed an auditory or visual target-detection task. We examined target-related responses in 2 domains: high frequency band (HFB) activity and the P3b. Across tasks, we observed a greater proportion of electrodes that showed target-specific HFB power relative to P3b over frontal cortex, but their proportions over parietal cortex were comparable. Notably, there was minimal overlap in the electrodes that showed target-specific HFB and P3b activity. These results revealed that the target-detection process is characterized by at least 2 different neural markers with distinct cortical distributions. Our findings suggest that separate neural mechanisms are driving the differential patterns of activity observed in scalp EEG and neuroimaging studies, with the P3b reflecting EEG findings and HFB activity reflecting neuroimaging findings, highlighting the notion that target detection is not a unitary phenomenon.

Network dynamics predict improvement in working memory performance following donepezil administration in healthy young adults.

Attentional selection in the context of goal-directed behavior involves top-down modulation to enhance the contrast between relevant and irrelevant stimuli via enhancement and suppression of sensory cortical activity. Acetylcholine (ACh) is believed to be involved mechanistically in such attention processes. The objective of the current study was to examine the effects of donepezil, a cholinesterase inhibitor that increases synaptic levels of ACh, on the relationship between performance and network dynamics during a visual working memory (WM) task involving relevant and irrelevant stimuli. Electroencephalogram (EEG) activity was recorded in 14 healthy young adults while they performed a selective face/scene working memory task. Each participant received either placebo or donepezil (5mg, orally) on two different visits in a double-blinded study. To investigate the effects of donepezil on brain network dynamics we utilized a novel EEG-based Brain Network Activation (BNA) analysis method that isolates location-time-frequency interrelations among event-related potential (ERP) peaks and extracts condition-specific networks. The activation level of the network modulated by donepezil, reflected in terms of the degree of its dynamical organization, was positively correlated with WM performance. Further analyses revealed that the frontal-posterior theta-alpha sub-network comprised the critical regions whose activation level correlated with beneficial effects on cognitive performance. These results indicate that condition-specific EEG network analysis could potentially serve to predict beneficial effects of therapeutic treatment in working memory.

Single trial discrimination of individual finger movements on one hand: a combined MEG and EEG study.

It is crucial to understand what brain signals can be decoded from single trials with different recording techniques for the development of Brain-Machine Interfaces. A specific challenge for non-invasive recording methods are activations confined to small spatial areas on the cortex such as the finger representation of one hand. Here we study the information content of single trial brain activity in non-invasive MEG and EEG recordings elicited by finger movements of one hand. We investigate the feasibility of decoding which of four fingers of one hand performed a slight button press. With MEG we demonstrate reliable discrimination of single button presses performed with the thumb, the index, the middle or the little finger (average over all subjects and fingers 57%, best subject 70%, empirical guessing level: 25.1%). EEG decoding performance was less robust (average over all subjects and fingers 43%, best subject 54%, empirical guessing level 25.1%). Spatiotemporal patterns of amplitude variations in the time series provided best information for discriminating finger movements. Non-phase-locked changes of mu and beta oscillations were less predictive. Movement related high gamma oscillations were observed in average induced oscillation amplitudes in the MEG but did not provide sufficient information about the finger's identity in single trials. Importantly, pre-movement neuronal activity provided information about the preparation of the movement of a specific finger. Our study demonstrates the potential of non-invasive MEG to provide informative features for individual finger control in a Brain-Machine Interface neuroprosthesis.

Anterior cingulate cortex and cognitive control: neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex.

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring.

Executive functions after orbital or lateral prefrontal lesions: neuropsychological profiles and self-reported executive functions in everyday living.

OBJECTIVE: This study examined the effects of chronic focal lesions to the lateral prefrontal cortex (LPFC) or orbitofrontal cortex (OFC) on neuropsychological test performance and self-reported executive functioning in everyday living. METHODS: Fourteen adults with OFC lesions were compared to 10 patients with LPFC injuries and 21 healthy controls. Neuropsychological tests with emphasis on measures of cognitive executive function were administered along with the Behavior Rating Inventory of Executive Functions (BRIEF-A) and a psychiatric screening instrument. RESULTS: The LPFC group differed from healthy controls on neuropsychological tests of sustained mental effort, response inhibition, working memory and mental switching, while the BRIEF-A provided more clinically important information on deficits in everyday life in the OFC group compared to the LPFC group. Correlations between neuropsychological test results and BRIEF-A were weak, while the BRIEF-A correlated strongly with emotional distress. CONCLUSIONS: It was demonstrated that LPFC damage is particularly prone to cause cognitive executive deficit, while OFC injury is more strongly associated with self-reported dysexecutive symptoms in everyday living. The study illustrates the challenge of identifying executive deficit in individual patients and the lack of strong anatomical specificity of the currently employed methods. There is a need for an integrative methodological approach where standard testing batteries are supplemented with neuropsychiatric and frontal-specific rating scales.

Personalized transcranial alternating current stimulation improves sleep quality: Initial findings.

Insufficient sleep is a major health issue. Inadequate sleep is associated with an array of poor health outcomes, including cardiovascular disease, diabetes, obesity, certain forms of cancer, Alzheimer's disease, depression, anxiety, and suicidality. Given concerns with typical sedative hypnotic drugs for treating sleep difficulties, there is a compelling need for alternative interventions. Here, we report results of a non-invasive electrical brain stimulation approach to optimizing sleep involving transcranial alternating current stimulation (tACS). A total of 25 participants (mean age: 46.3, S.D. ± 12.4, 15 females) were recruited for a null-stimulation controlled (Control condition), within subjects, randomized crossed design, that included two variants of an active condition involving 15 min pre-sleep tACS stimulation. To evaluate the impact on sleep quality, the two active tACS stimulation conditions were designed to modulate sleep-dependent neural activity in the theta/alpha frequency bands, with both stimulation types applied to all subjects in separate sessions. The first tACS condition used a fixed stimulation pattern across all participants, a pattern composed of stimulation at 5 and 10 Hz. The second tACS condition used a personalized stimulation approach with the stimulation frequencies determined by each individual's peak EEG frequencies in the 4-6 Hz and 9-11 Hz bands. Personalized tACS stimulation increased sleep quantity (duration) by 22 min compared to a Control condition (p = 0.04), and 19 min compared to Fixed tACS stimulation (p = 0.03). Fixed stimulation did not significantly increase sleep duration compared to Control (mean: 3 min; p = 0.75). For sleep onset, the Personalized tACS stimulation resulted in reducing the onset by 28% compared to the Fixed tACS stimulation (6 min faster, p = 0.02). For a Poor Sleep sub-group (n = 13) categorized with Clinical Insomnia and a high insomnia severity, Personalized tACS stimulation improved sleep duration by 33 min compared to Fixed stimulation (p = 0.02), and 30 min compared to Control condition (p < 0.1). Together, these results suggest that Personalized stimulation improves sleep quantity and time taken to fall asleep relative to Control and Fixed stimulation providing motivation for larger-scale trials for Personalized tACS as a sleep therapeutic, including for those with insomnia.

Modeling a complex micro-multileaf collimator using the standard BEAMnrc distribution.

PURPOSE: The component modules in the standard BEAMnrc istribution may appear to be insufficient to model micro-multileaf collimators that have trifaceted leaf ends and complex leaf profiles. This note indicates, however, that accurate Monte Carlo simulations of radiotherapy beams defined by a complex collimation device can be completed using BEAMnrc's standard VARMLC component module. METHODS: That this simple collimator model can produce spatially and dosimetrically accurate microcollimated fields is illustrated using comparisons with ion chamber and film measurements of the dose deposited by square and irregular fields incident on planar, homogeneous water phantoms. RESULTS: Monte Carlo dose calculations for on-axis and off-axis fields are shown to produce good agreement with experimental values, even on close examination of the penumbrae. CONCLUSIONS: The use of a VARMLC model of the micro-multileaf collimator, along with a commissioned model of the associated linear accelerator, is therefore recommended as an alternative to the development or use of in-house or third-party component modules for simulating stereotactic radiotherapy and radiosurgery treatments. Simulation parameters for the VARMLC model are provided which should allow other researchers to adapt and use this model to study clinical stereotactic radiotherapy treatments.

Roles of ventral versus dorsal pathways in language production: An awake language mapping study.

Human language is organized along two main processing streams connecting posterior temporal cortex and inferior frontal cortex in the left hemisphere, travelling dorsal and ventral to the Sylvian fissure. Some views propose a dorsal motor versus ventral semantic division. Others propose division by combinatorial mechanism, with the dorsal stream responsible for combining elements into a sequence and the ventral stream for forming semantic dependencies independent of sequential order. We acquired data from direct cortical stimulation in the left hemisphere in 17 neurosurgical patients and subcortical resection in a subset of 10 patients as part of awake language mapping. Two language tasks were employed: a sentence generation (SG) task tested the ability to form sequential and semantic dependencies, and a picture-word interference (PWI) task manipulated semantic interference. Results show increased error rates in the SG versus PWI task during subcortical testing in the dorsal stream territory, and high error rates in both tasks in the ventral stream territory. Connectivity maps derived from diffusion imaging and seeded in the tumor sites show that patients with more errors in the SG than in the PWI task had tumor locations associated with a dorsal stream connectivity pattern. Patients with the opposite pattern of results had tumor locations associated with a more ventral stream connectivity pattern. These findings provide initial evidence using fiber tract disruption with electrical stimulation that the dorsal pathways are critical for organizing words in a sequence necessary for sentence generation, and the ventral pathways are critical for processing semantic dependencies.

Prefrontal-cingulate interactions in action monitoring.

We found that medial frontal cortex activity associated with action monitoring (detecting errors and behavioral conflict) depended on activity in the lateral prefrontal cortex. We recorded the error-related negativity (ERN), an event-related brain potential proposed to reflect anterior cingulate action monitoring, from individuals with lateral prefrontal damage or age-matched or young control participants. In controls, error trials generated greater ERN activity than correct trials. In individuals with lateral prefrontal damage, however, correct-trial ERN activity was equal to error-trial ERN activity. Lateral prefrontal damage also affected corrective behavior. Thus the lateral prefrontal cortex seemed to interact with the anterior cingulate cortex in monitoring behavior and in guiding compensatory systems.

Prefrontal modulation of visual processing in humans.

Single neuron, evoked potential and metabolic techniques show that attention influences visual processing in extrastriate cortex. We provide anatomical, electrophysiological and behavioral evidence that prefrontal cortex regulates neuronal activity in extrastriate cortex during visual discrimination. Event-related potentials (ERPs) were recorded during a visual detection task in patients with damage in dorsolateral prefrontal cortex. Prefrontal damage reduced neuronal activity in extrastriate cortex of the lesioned hemisphere. These electrophysiological abnormalities, beginning 125 ms after stimulation and lasting for another 500 ms, were accompanied by behavioral deficits in detection ability in the contralesional hemifield. The results provide evidence for intrahemispheric prefrontal modulation of visual processing.

The functional neuroanatomy of working memory: contributions of human brain lesion studies.

Studies of patients with focal brain lesions remain critical components of research programs attempting to understand human brain function. Whereas functional imaging typically reveals activity in distributed brain regions that are involved in a task, lesion studies can define which of these brain regions are necessary for a cognitive process. Further, lesion studies are less critical regarding the selection of baseline conditions needed in functional brain imaging research. Lesion studies suggest a functional subdivision of the visuospatial sketchpad of working memory with a ventral stream reaching from occipital to temporal cortex supporting object recognition and a dorsal stream connecting the occipital with parietal cortex enabling spatial operations. The phonological loop can be divided into a phonological short-term store in inferior parietal cortex and an articulatory subvocal rehearsal process relying on brain areas necessary for speech production, i.e. Broca's area, the supplementary motor association area and possibly the cerebellum. More uncertainty exists regarding the role of the prefrontal cortex in working memory. Whereas single cell studies in non-human primates and functional imaging studies in humans have suggested an extension of the ventral and dorsal path into different subregions of the prefrontal cortex, lesion studies together with recent single-cell and imaging studies point to a non-mnemonic role of the prefrontal cortex, including attentional control of sensory processing, integration of information from different domains, stimulus selection and monitoring of information held in memory. Our own data argue against a modulatory view of the prefrontal cortex and suggest that processes supporting working memory are distributed along ventral and dorsal lateral prefrontal cortex.

Specifying the role of the left prefrontal cortex in word selection.

Word selection allows us to choose words during language production. This is often viewed as a competitive process wherein a lexical representation is retrieved among semantically-related alternatives. The left prefrontal cortex (LPFC) is thought to help overcome competition for word selection through top-down control. However, whether the LPFC is always necessary for word selection remains unclear. We tested 6 LPFC-injured patients and controls in two picture naming paradigms varying in terms of item repetition. Both paradigms elicited the expected semantic interference effects (SIE), reflecting interference caused by semantically-related representations in word selection. However, LPFC patients as a group showed a larger SIE than controls only in the paradigm involving item repetition. We argue that item repetition increases interference caused by semantically-related alternatives, resulting in increased LPFC-dependent cognitive control demands. The remaining network of brain regions associated with word selection appears to be sufficient when items are not repeated.

Mechanisms of human attention: event-related potentials and oscillations.

Electrophysiological and hemodynamical responses of the brain allow investigation of the neural origins of human attention. We review attention-related brain responses from auditory and visual tasks employing oddball and novelty paradigms. Dipole localization and intracranial recordings as well as functional magnetic resonance imaging reveal multiple areas involved in generating and modulating attentional brain responses. In addition, the influence of brain lesions of circumscribed areas of the human cortex onto attentional mechanisms are reviewed. While it is obvious that damaged brain tissue no longer functions properly, it has also been shown that functions of non-lesioned brain areas are impaired due to loss of modulatory influence of the lesioned area. Both early (P1 and N1) and late (P3) event-related potentials are modulated by excitatatory and inhibitory mechanisms. Oscillatory EEG-correlates of attention in the alpha and gamma frequency range also show attentional modulation.

Aging decreases auditory event-related potentials to unexpected stimuli in humans.

A P300 event-related potential (P3a) was recorded to unexpected, deviant auditory stimuli requiring no behavioral response. This brain potential underwent systematic latency prolongation and amplitude decrease with advancing age. The age-related changes paralleled those of the P300 (P3b) recorded in target detection tasks. These results provide physiological evidence of a decremented CNS response to unexpected stimuli with aging.

Recovery from GABA-mediated hemiplegia in young and aged rats: effects of catecholaminergic manipulations.

We investigated the participation of catecholaminergic mechanisms in the functional recovery from motor cortex lesions in young (9 months) and aged (26 months) rats. The animals were studied during the recovery period from an hemiplegic syndrome secondary to small motor cortex lesions potentiated by the localized, chronic (7 days) infusion of GABA into the lesion site. Acute administration of haloperidol (0.1 mg/kg IP) to these recovered animals induced a re-emergence of the contralateral motor syndrome in both groups. In the young group, the haloperidol-induced hemiplegia lasted one day whereas in the aged animals the deficit was significantly prolonged lasting three days. Apomorphine administration (0.5 mg/kg IP) prior to or immediately after haloperidol injection failed to prevent or reverse the reappearance of the motor deficit. Adult animals recovered from motor cortex aspirations performed 7 to 12 months prior were refractory to haloperidol effects. Amphetamine administration to young rats treated chronically with saline or GABA infusion into the somatomotor region also failed to alter the clinical evolution of the motor deficit. The evidence suggests that dopaminergic mechanisms are involved in the functional recovery from brain lesions and that these mechanisms are most susceptible to neuroleptic blockade during the early post-lesional period. The deleterious effects of dopaminergic blockade are heightened in aged populations. The use of dopaminergic antagonists in brain-lesioned subjects, and particularly in geriatric populations, is considered potentially harmful, particularly in the early stages of the recovery process.

Age-related prefrontal alterations during auditory memory.

Event-related potentials were recorded from young and elderly subjects while they performed a modified auditory Sternberg memory task. Aging was associated with a decrease in frontal activation, suggesting that prefrontal alterations may be central to age-related impairments in auditory working memory. Young subjects showed significant serial position effects electrophysiologically, while elderly subjects showed no recency effects for P3 latency and no serial position effects for N4 and SFN amplitude. This finding, in combination with increased false alarm rates in the elderly, suggest that the two group of subjects employed different cortico-limbic circuits to perform the task.

Chewing oscillopsia. A case of voluntary visual illusions of movement.

A 60-year-old man had a history of frontal headaches and chewing-related oscillopsia. Examination disclosed a retro-orbital epidermoid cyst that had eroded through the lateral orbital wall and under the temporalis muscle. The illusion of movement was due to mechanical displacement of the tumor mass and eye by contraction of the temporalis muscle. Removal of the cyst produced complete remission of the oscillopsia.

Cortico-limbic circuits and novelty: a review of EEG and blood flow data.

Novelty detection is a fundamental capacity of all mammalian nervous systems /64/. The ability to orient to unexpected events is critical for both survival and normal memory function /82/. The mechanisms whereby the brain detects and responds to novelty have become of increasing interest to neuroscientists. A review is provided of human electrophysiological and blood flow data focused on delineating the neural systems engaged by novelty. Electrophysiological recording of event-related potentials (ERPs) has shown that novel stimuli activate a distributed network involving prefrontal and posterior association cortex as well as the hippocampus /4,23,24,32,33,36,86,88/. Activation of this network facilitates subsequent memory for novel events /27/. Neural modeling provides additional support for a prominent role of novelty in normal memory function /43/. Blood flow studies employing PET and fMRI have also begun to define the neural regions activated by novelty. The blood flow data provide converging evidence on the role of the hippocampus and cortical association regions in the processing of novelty /30,66,75,76/. The results of the behavioral, ERP and blood flow research confirm that a distributed neocortical-limbic circuit is activated by stimulus novelty. These distributed circuits maintain a template of the recent past /74/. Deviations from the template activate a neocortical-limbic network facilitating behavioral response to and memory storage of novel events.

Electrophysiologic evidence of increased distractibility after dorsolateral prefrontal lesions.

Patients with left prefrontal lesions and control subjects showed enhanced event-related potentials (ERPs) to attended tone sequences presented in a dichotic attention task. ERP enhancements were comparable at short and long interstimulus intervals (ISIs), and did not depend upon whether attended stimuli were preceded by other attended stimuli or by distracting stimuli in the opposite ear. In contrast, patients with right prefrontal lesions showed absent ERP attention effects to contralateral (left ear) tones at all ISIs, and reduced attention effects to ipsilateral tones at long ISIs and when these were preceded by distracting sounds. The results are consistent with an asymmetric organization of dorsolateral prefrontal cortex, and indicate that increased distractibility may contribute to the attention disorders that follow prefrontal lesions.

Right-sided neglect in a left-hander: evidence for reversed hemispheric specialization of attention capacity.

Severe hemi-spatial neglect, anosognosia, contralateral hypokinesia, aprosodia, and visual-spatial constructive difficulties--typically seen in right-handers with right hemisphere lesions--were observed in a left-handed patient with an acute left frontal cortical and subcortical infarct. There was no evidence of accompanying aphasia and the neglect syndrome gradually resolved over a 2-week period. The assumption by the left hemisphere of a classic right hemisphere attention, visuo-spatial and prosodic superiority may represent a case of reversed hemispheric specialization.