Activity In Right Prefrontal Cortex Research Articles

A two-site, open-label, non-randomized trial comparing Focal Electrically-Administered Seizure Therapy (FEAST) and right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UBP ECT)

BackgroundFocal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT. MethodsUsing a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD24). ResultsIn the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD24 score over time (F1,35 = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance. ConclusionsFEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.

The role of 5-HT in response inhibition and re-engagement

In animal and human research, the neurotransmitter serotonin (5-HT) has been implicated in inhibitory control. Using functional magnetic resonance imaging (fMRI), the present study investigated the acute effects of pharmacological modulation of the serotonergic system on brain activation during response inhibition and re-engagement in healthy human volunteers. In a randomized double-blind placebo-controlled cross-over design 14 men received either a single oral dose of the selective serotonin reuptake inhibitor (SSRI) escitalopram (10mg) or a placebo. At the time of the expected plasma peak concentration, participants performed a stop–change task during fMRI. Escitalopram did not affect behavioural performance, since the main effect did not reveal significant differences between reaction times of go-, stop- or change-trials. During successful response inhibition, escitalopram, however, was associated with enhanced brain activation in right prefrontal cortex, right supplementary/pre-motor and bilateral cingulate cortex, and subcortical regions. During inhibition failures, escitalopram also modulated a broad network of brain regions, including anterior cingulate, right parietal cortex, right orbitofrontal cortex, and areas in right temporal cortex and subcortical regions. During response re-engagement escitalopram increased brain activation in right inferior frontal gyrus and precuneus as well as in left middle temporal gyrus. The results implicate the involvement of 5-HT in neural regulation of response inhibition and re-engagement. This study also provides evidence that 5-HT affects both action restraint and action cancellation through modulation of activation of brain areas. The results support the view for a fronto-striatal circuitry for response inhibition in conjunction with serotonin.

Trait BIS predicts alpha asymmetry and P300 in a Go/No‐Go task

Inspired by the revised Behavioural Inhibition System (BIS) theory the present study probed the association between individual differences in Trait BIS and electroencephalogram indicators of conflict processing/inhibition. Sixty‐nine male participants either high or low in Trait BIS completed a Go/No‐Go task while the electroencephalogram was recorded. As expected, Trait BIS was associated with the No‐Go‐anteriorisation of the P300 event‐related potential (i.e. an index of response inhibition presumably generated in the dorsal anterior cingulate—an area implicated in conflict processing) and with No‐ Go‐related changes towards left frontal alpha activity (i.e. presumably more activity in right prefrontal cortex—an area implicated in response inhibition). These findings support the role of conflict processing attributed to BIS functioning in the revised theory. Copyright © 2009 John Wiley & Sons, Ltd.

The Detection of Communicative Signals Directed at the Self in Infant Prefrontal Cortex

A precondition for successful communication between people is the detection of signals indicating the intention to communicate, such as eye contact or calling a person's name. In adults, establishing communication by eye contact or calling a person's name results in overlapping activity in right prefrontal cortex, suggesting that, regardless of modality, the intention to communicate is detected by the same brain region. We measured prefrontal cortex responses in 5-month-olds using near-infrared spectroscopy (NIRS) to examine the neural basis of detecting communicative signals across modalities in early development. Infants watched human faces that either signaled eye contact or directed their gaze away from the infant, and they also listened to voices that addressed them with their own name or another name. The results revealed that infants recruit adjacent but non-overlapping regions in the left dorsal prefrontal cortex when they process eye contact and own name. Moreover, infants that responded sensitively to eye contact in the one prefrontal region were also more likely to respond sensitively to their own name in the adjacent prefrontal region as revealed in a correlation analysis, suggesting that responding to communicative signals in these two regions might be functionally related. These NIRS results suggest that infants selectively process and attend to communicative signals directed at them. However, unlike adults, infants do not seem to recruit a common prefrontal region when processing communicative signals of different modalities. The implications of these findings for our understanding of infants’ developing communicative abilities are discussed.

Structure–Function Correlates of Cognitive Decline in Aging

To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

Redefining implicit and explicit memory: the functional neuroanatomy of priming, remembering, and control of retrieval.

We used event-related functional MRI to study awareness of prior episodes during memory retrieval and its relationship to the intention to retrieve memories. Participants completed cues with words from a prior list (intentional test) or with the first words that came to mind (incidental test). During both tests, explicit memory was separated from priming in the absence of explicit memory. Priming was associated with hemodynamic decreases in left fusiform gyrus and bilateral frontal and occipital brain regions; explicit memory was associated with bilateral parietal and temporal and left frontal increases. Retrieval intention did not change these patterns but was associated with activity in right prefrontal cortex. Our results provide firm evidence that implicit and explicit memory have distinct functional neuroanatomies, and that strategic control of retrieval engages brain structures distinct from those involved in both implicit and explicit memory. They have critical implications for theories of memory and consciousness, which often equate consciousness with control.

A face to remember: emotional expression modulates prefrontal activity during memory formation

Emotion can exert a modulatory role on episodic memory. Several studies have shown that negative stimuli (e.g., words, pictures) are better remembered than neutral ones. Although facial expressions are powerful emotional stimuli and have been shown to influence perception and attention processes, little is known about their effect on memory. We used functional magnetic resonance imaging (fMRI) in humans to investigate the effects of expression (happy, neutral, and fearful) on prefrontal cortex (PFC) activity during the encoding of faces, using a subsequent memory effect paradigm. Our results show that activity in right PFC predicted memory for faces, regardless of expression, while a homotopic region in the left hemisphere was associated with successful encoding only for faces with an emotional expression. These findings are consistent with the proposed role of right dorsolateral PFC in successful encoding of nonverbal material, but also suggest that left DLPFC may be a site where integration of memory and emotional processes occurs. This study sheds new light on the current controversy regarding the hemispheric lateralization of PFC in memory encoding.

Functional neuroimaging of speech perception in infants.

Human infants begin to acquire their native language in the first months of life. To determine which brain regions support language processing at this young age, we measured with functional magnetic resonance imaging the brain activity evoked by normal and reversed speech in awake and sleeping 3-month-old infants. Left-lateralized brain regions similar to those of adults, including the superior temporal and angular gyri, were already active in infants. Additional activation in right prefrontal cortex was seen only in awake infants processing normal speech. Thus, precursors of adult cortical language areas are already active in infants, well before the onset of speech production.

Parietal dysfunction is associated with increased outcome-related decision-making in schizophrenia patients

Background: Decision-making is a complex process and depends on a network of fronto-parietal and cingulate areas. Decision-making dysfunctions in schizophrenia patients are characterized by an alternation between stereotypic and unpredictable responses. This study tested the hypothesis that schizophrenia patients show less decision-making-related activation in the prefrontal and parietal cortex. Methods: Fifteen schizophrenia patients were matched with fifteen normal comparison subjects. During functional magnetic resonance imaging (fMRI) scanning, subjects were tested on the two-choice prediction task (predicting the location of a randomly presented stimulus) and the two-choice response task (responding according to the location of the stimulus). Results: Schizophrenia patients relative to comparison subjects generated more outcome-dependent responses. Schizophrenia patients and normal comparison subjects showed decision-making-related activation in right prefrontal cortex, insula, anterior cingulate, and bilateral precuneus. Schizophrenia patients showed less activation in inferior, medial prefrontal, and right superior temporal cortex and more activation in the postcentral and inferior parietal cortex. Decision-making-related activation in both right prefrontal and bilateral parietal cortex was higher in medicated compared to unmedicated schizophrenia patients. Conclusions: These results support the hypothesis that the interaction between prefrontal and parietal cortex during decision-making by schizophrenia patients is dysregulated, which results in an increased outcome-dependent response selection.

Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation.

Patients with irritable bowel syndrome (IBS) show evidence of altered perceptual responses to visceral stimuli, consistent with altered processing of visceral afferent information by the brain. In the current study, brain responses to anticipated and delivered rectal balloon distension were assessed. Changes in regional cerebral blood flow were measured using H2(15)O-water positron emission tomography in 12 nonconstipated IBS patients and 12 healthy control subjects. Regional cerebral blood flow responses to moderate rectal distension (45 mm Hg) and anticipated but undelivered distension were assessed before and after a series of repetitive noxious (60-mm Hg) sigmoid distensions. Brain regions activated by actual and simulated distensions were similar in both groups. Compared with control subjects, patients with IBS showed lateralized activation of right prefrontal cortex; reduced activation of perigenual cortex, temporal lobe, and brain stem; but enhanced activation of rostral anterior cingulate and posterior cingulate cortices. IBS patients show altered brain responses to rectal stimuli, regardless of whether these stimuli are actually delivered or simply anticipated. These alterations are consistent with reported alterations in autonomic and perceptual responses and may be related to altered central noradrenergic modulation.

Conscious and Unconscious Processing of Nonverbal Predictability in Wernicke's Area

The association of nonverbal predictability and brain activation was examined using functional magnetic resonance imaging in humans. Participants regarded four squares displayed horizontally across a screen and counted the incidence of a particular color. A repeating spatial sequence with varying levels of predictability was embedded within a random color presentation. Both Wernicke's area and its right homolog displayed a negative correlation with temporal predictability, and this effect was independent of individuals' conscious awareness of the sequence. When individuals were made aware of the underlying sequential predictability, a widespread network of cortical regions displayed activity that correlated with the predictability. Conscious processing of predictability resulted in a positive correlation to activity in right prefrontal cortex but a negative correlation in posterior parietal cortex. These results suggest that conscious processing of predictability invokes a large-scale cortical network, but independently of awareness, Wernicke's area processes predictive events in time and may not be exclusively associated with language.

Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia.

Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology.

Understanding neural interactions in learning and memory using functional neuroimaging.

Neuroimaging methods such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) provide a unique opportunity to explore activity across the entire human brain in many different behaviors. An important additional feature is the ability to examine interacting neural systems using methods that focus on the covariances of activity. Two of these methods, partial least squares and structural equation modeling, are presented with specific examples. Shifting prefrontal and limbic interactions were observed in a working memory task for faces. In an episodic memory retrieval study, the activity of right prefrontal cortex was related to either memory search or successful retrieval depending on its interactions with other brain regions. This latter observation implies that regional activity must be evaluated within the neural context in which it occurs. The general hypothesis that learning and memory are emergent properties of network interactions is discussed, emphasizing that a region can play a different role across many functions and that role is governed by its interactions with anatomically related regions.

Making memories: brain activity that predicts how well visual experience will be remembered.

Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.

Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory.

Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.

Brain regions associated with acquisition and retrieval of verbal episodic memory.

It is widely held that conscious recall of past experiences involves a specific system--episodic memory. Patients with amnesia have gross impairments of episodic memory while other kinds of memory remain intact, suggesting that a separable brain system underlies episodic memory. We have used positron emission tomography (PET) to identify components of this system in normal volunteers. A dual-task interference paradigm was used to isolate brain areas associated with acquisition, and a cueing paradigm to isolate the areas concerned with retrieval from verbal episodic memory. Acquisition was associated with activity in the left prefrontal cortex and the retrosplenial area, whereas retrieval was associated with activity in right prefrontal cortex and the precuneus. Our results provide clear evidence that episodic memory involves a network of specific prefrontal and posterior structures which can be fractionated into different component processes.