Altered prefrontal function with aging: insights into age-associated cognitive decline

Authors:

• Anne-Kristin Solbakk

• Galit Fuhrmann Alpert

• Ansgar J. Furst

• Laura A. Hale

• Tatsuhide Oga

• Sundari Chetty

• Natasha Pickard

• Robert T. Knight

Date: 2008

DOI: 10.1016/j.brainres.2008.07.060

PubMed: 18691562

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Abstract:

We examined the effects of aging on visuo-spatial attention. Participants performed a bi-field visual selective attention task consisting of infrequent target and task-irrelevant novel stimuli randomly embedded among repeated standards in either attended or unattended visual fields. Blood oxygenation level dependent (BOLD) responses to the different classes of stimuli were measured using functional magnetic resonance imaging. The older group had slower reaction times to targets, and committed more false alarms but had comparable detection accuracy to young controls. Attended target and novel stimuli activated comparable widely distributed attention networks, including anterior and posterior association cortex, in both groups. The older group had reduced spatial extent of activation in several regions, including prefrontal, basal ganglia, and visual processing areas. In particular, the anterior cingulate and superior frontal gyrus showed more restricted activation in older compared with young adults across all attentional conditions and stimulus categories. The spatial extent of activations correlated with task performance in both age groups, but the regional pattern of association between hemodynamic responses and behavior differed between the groups. Whereas the young subjects relied on posterior regions, the older subjects engaged frontal areas. The results indicate that aging alters the functioning of neural networks subserving visual attention, and that these changes are related to cognitive performance.

Mentalizing about emotion and its relationship to empathy

Authors:

• Christine I. Hooker

• Sara C. Verosky

• Laura T. Germine

• Robert T. Knight

• Mark D'Esposito

Date: 2008

DOI: 10.1093/scan/nsn019

PubMed: 19015112

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Abstract:

Mentalizing involves the ability to predict someone else’s behavior based on their belief state. More advanced mentalizing skills involve integrating knowledge about beliefs with knowledge about the emotional impact of those beliefs. Recent research indicates that advanced mentalizing skills may be related to the capacity to empathize with others. However, it is not clear what aspect of mentalizing is most related to empathy. In this study, we used a novel, advanced mentalizing task to identify neural mechanisms involved in predicting a future emotional response based on a belief state. Subjects viewed social scenes in which one character had a False Belief and one character had a True Belief. In the primary condition, subjects were asked to predict what emotion the False Belief Character would feel if they had a full understanding about the situation. We found that neural regions related to both mentalizing and emotion were involved when predicting a future emotional response, including the superior temporal sulcus, medial prefrontal cortex, temporal poles, somatosensory related cortices (SRC), inferior frontal gyrus and thalamus. In addition, greater neural activity in primarily emotion-related regions, including right SRC and bilateral thalamus, when predicting emotional response was significantly correlated with more self-reported empathy. The findings suggest that predicting emotional response involves generating and using internal affective representations and that greater use of these affective representations when trying to understand the emotional experience of others is related to more empathy.

Age-related top down suppression deficit in the early stages of cortical visual memory processing

Authors:

• Adam Gazzaley

• Wesley Clapp

• Jon Kelley

• Kevin McEvoy

• Robert T. Knight

• Mark D'Esposito

Date: 2008

DOI: 10.1073/pnas.0806074105

PubMed: 18765818

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Abstract:

In this study, electroencephalography (EEG) was used to examine the relationship between two leading hypotheses of cognitive aging, the inhibitory deficit and the processing speed hypothesis. We show that older adults exhibit a selective deficit in suppressing task-irrelevant information during visual working memory encoding, but only in the early stages of visual processing. Thus, the employment of suppressive mechanisms are not abolished with aging but rather delayed in time, revealing a decline in processing speed that is selective for the inhibition of irrelevant information. EEG spectral analysis of signals from frontal regions suggests that this results from excessive attention to distracting information early in the time course of viewing irrelevant stimuli. Subdividing the older population based on working memory performance revealed that impaired suppression of distracting information early in the visual processing stream is associated with poorer memory of task-relevant information. Thus, these data reconcile two cognitive aging hypotheses by revealing that an interaction of deficits in inhibition and processing speed contributes to agerelated cognitive impairment.

Localization of neurosurgically implanted electrodes via photograph–MRI–radiograph coregistration

Authors:

• Sarang S. Dalal

• Erik Edwards

• Heidi E. Kirsch

• Nicholas M. Barbaro

• Robert T. Knight

• Srikantan S. Nagarajan

Date: 2008

DOI: 10.1016/j.jneumeth.2008.06.028

PubMed: 18657573

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Abstract:

Intracranial electroencephalography (iEEG) is clinically indicated for medically refractory epilepsy and is a promising approach for developing neural prosthetics. These recordings also provide valuable data for cognitive neuroscience research. Accurate localization of iEEG electrodes is essential for evaluating specific brain regions underlying the electrodes that indicate normal or pathological activity, as well as for relating research findings to neuroimaging and lesion studies. However, electrodes are frequently tucked underneath the edge of a craniotomy, inserted via a burr hole, or placed deep within the brain, where their locations cannot be verified visually or with neuronavigational systems. We show that one existing method, registration of postimplant computed tomography (CT) with preoperative magnetic resonance imaging (MRI), can result in errors exceeding 1 cm. We present a novel method for localizing iEEG electrodes using routinely acquired surgical photographs, X-ray radiographs, and magnetic resonance imaging scans. Known control points are used to compute projective transforms that link the different image sets, ultimately allowing hidden electrodes to be localized, in addition to refining the location of manually registered visible electrodes. As the technique does not require any calibration between the different image modalities, it can be applied to existing image databases. The final result is a set of electrode positions on the patient’s rendered MRI yielding locations relative to sulcal and gyral landmarks on individual anatomy, as well as MNI coordinates. We demonstrate the results of our method in eight epilepsy patients implanted with electrode grids spanning the left hemisphere.

The influence of personality on neural mechanisms of observational fear and reward learning

Authors:

• Christine I. Hooker

• Sara C. Verosky

• Asako Miyakawa

• Robert T. Knight

• Mark D'Esposito

Date: 2008

DOI: 10.1016/j.neuropsychologia.2008.05.005

PubMed: 18573512

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Abstract:

Fear and reward learning can occur through direct experience or observation. Both channels can enhance survival or create maladaptive behavior. We used fMRI to isolate neural mechanisms of observational fear and reward learning and investigate whether neural response varied according to individual differences in neuroticism and extraversion. Participants learned object-emotion associations by observing a woman respond with fearful (or neutral) and happy (or neutral) facial expressions to novel objects. The amygdala–hippocampal complex was active when learning the object-fear association, and the hippocampus was active when learning the object-happy association. After learning, objects were presented alone; amygdala activity was greater for the fear (vs. neutral) and happy (vs. neutral) associated object. Importantly, greater amygdala–hippocampal activity during fear (vs. neutral) learning predicted better recognition of learned objects on a subsequent memory test. Furthermore, personality modulated neural mechanisms of learning. Neuroticism positively correlated with neural activity in the amygdala and hippocampus during fear (vs. neutral) learning. Low extraversion/high introversion was related to faster behavioral predictions of the fearful and neutral expressions during fear learning. In addition, low extraversion/high introversion was related to greater amygdala activity during happy (vs. neutral) learning, happy (vs. neutral) object recognition, and faster reaction times for predicting happy and neutral expressions during reward learning. These findings suggest that neuroticism is associated with an increased sensitivity in the neural mechanism for fear learning which leads to enhanced encoding of fear associations, and that low extraversion/high introversion is related to enhanced conditionability for both fear and reward learning.

Detecting violations of sensory expectancies following cerebellar degeneration: a mismatch negativity study

Authors:

• Torgeir Moberget

• Christina M. Karns

• Leon Y. Deouell

• Magnus Lindgren

• Robert T. Knight

• Richard B. Ivry

Date: 2008

DOI: 10.1016/j.neuropsychologia.2008.03.016

PubMed: 18486157

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Abstract:

Two hypotheses concerning cerebellar function and predictive behavior are the sensory prediction hypothesis and the timing hypothesis. The former postulates that the cerebellum is critical in generating expectancies regarding forthcoming sensory information. The latter postulates that this structure is critical in generating expectancies that are precisely timed; for example, the expected duration of an event or the time between events. As such, the timing hypothesis constitutes a more specific form of prediction. The present experiment contrasted these two hypotheses by examining the mismatch negativity (MMN) response in patients with cerebellar cortical atrophy and matched controls. While watching a silent movie, a stream of task-irrelevant sounds was presented. A standard sound was presented 60% of the time, whereas the remaining sounds deviated from the standard on one of four dimensions: duration, intensity, pitch, or location. The timing between stimuli was either periodic or aperiodic. Based on the sensory prediction hypothesis, the MMN for the patients should be abnormal across all four dimensions. In contrast, the timing hypothesis would predict a selective impairment of the duration MMN. Moreover, the timing hypothesis would also predict that the enhancement of the MMN observed in controls when the stimuli are presented periodically should be attenuated in the patients. Compared to controls, the patients exhibited a delayed latency in the MMN to duration deviants and a similar trend for the intensity deviants, while pitch and location MMNs did not differ between groups. Periodicity had limited and somewhat inconsistent effects. The present results are at odds with a general role for the cerebellum in sensory prediction and provide partial support for the timing hypothesis.

No disillusions in auditory extinction: perceiving a melody comprised of unperceived notes

Authors:

• Leon Y. Deouell

• D. Deutsch

• Nachum Soroker

• Robert T. Knight

Date: 2008

DOI: 10.3389/neuro.09.015.2007

PubMed: 18958228

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Abstract:

The formation of coherent percepts requires grouping together spatio-temporally disparate sensory inputs. Two major questions arise: (1) is awareness necessary for this process; and (2) can non-conscious elements of the sensory input be grouped into a conscious percept? To address this question, we tested two patients suffering from severe left auditory extinction following right hemisphere damage. In extinction, patients are unaware of the presence of left side stimuli when they are presented simultaneously with right side stimuli. We used the ‘scale illusion’ to test whether extinguished tones on the left can be incorporated into the content of conscious awareness. In the scale illusion, healthy listeners obtain the illusion of distinct melodies, which are the result of grouping of information from both ears into illusory auditory streams. We show that the two patients were susceptible to the scale illusion while being consciously unaware of the stimuli presented on their left. This suggests that awareness is not necessary for auditory grouping and non-conscious elements can be incorporated into a conscious percept.

Five-dimensional neuroimaging: localization of the time-frequency dynamics of cortical activity

Authors:

• Sarang S. Dalal

• Adrian G. Guggisberg

• Erik Edwards

• Kensuke Sekihara

• Anne M. Findlay

• Ryan T. Canolty

• Mitchel S. Berger

• Robert T. Knight

• Nicholas M. Barbaro

• Heidi E. Kirsch

• Srikantan S. Nagarajan

Date: 2008

DOI: 10.1016/j.neuroimage.2008.01.023

PubMed: 18356081

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Abstract:

The spatiotemporal dynamics of cortical oscillations across human brain regions remain poorly understood because of a lack of adequately validated methods for reconstructing such activity from noninvasive electrophysiological data. In this paper, we present a novel adaptive spatial filtering algorithm optimized for robust source time– frequency reconstruction from magnetoencephalography (MEG) and electroencephalography (EEG) data. The efficacy of the method is demonstrated with simulated sources and is also applied to real MEG data from a self-paced finger movement task. The algorithm reliably reveals modulations both in the beta band (12–30 Hz) and high gamma band (65–90 Hz) in sensorimotor cortex. The performance is validated by both across-subjects statistical comparisons and by intracranial electrocorticography (ECoG) data from two epilepsy patients. Inter- estingly, we also reliably observed high frequency activity (30–300 Hz) in the cerebellum, although with variable locations and frequencies across subjects. The proposed algorithm is highly parallelizable and runs efficiently on modern high-performance computing clusters. This method enables the ultimate promise of MEG and EEG for five- dimensional imaging of space, time, and frequency activity in the brain and renders it applicable for widespread studies of human cortical dynamics during cognition.

Spatio-temporal dynamics of neural mechanisms underlying component operations in working memory

Authors:

• Brian T. Miller

• Leon Y. Deouell

• Cathrine Dam

• Robert T. Knight

• Mark D'Esposito

Date: 2008

DOI: 10.1016/j.brainres.2008.01.059

PubMed: 18358455

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Abstract:

Neuroimaging and neurophysiology evidence suggests that component operations in working memory (WM) emerge from the coordinated interaction of posterior perceptual cortices with heteromodal regions in the prefrontal and parietal cortices. Still, little is known about bottom– up and top–down signaling during the formation and retrieval of WM representations. In the current set of experiments, we combine complementary fMRI and EEG measures to obtain high-resolution spatial and temporal measures of neural activity during WM encoding and retrieval processes. Across both experiments, participants performed a face delayed recognition WM task in which the nature of sensory input across stages was held constant. In experiment 1, we utilized a latency-resolved fMRI approach to assess temporal parameters of the BOLD response during stage-specific encoding and retrieval waveforms. Relative to the latency at encoding, the PFC exhibited an earlier peak of fMRI activity at retrieval showing stage-specific differences in the temporal dynamics of PFC engagement across WM operations. In experiment 2, we analyzed the first 200 ms of the ERP response during this WM task providing a more sensitive temporal measure of these differences. Divergence of the ERP pattern during encoding and retrieval began as early as 60 ms post-stimulus. The parallel fMRI and ERP results during memory-guided decisions support a key role of the PFC in top–down biasing of perceptual processing and reveal rapid differences across WM component operations in the presence of identical bottom–up sensory input.

Neurovascular Coupling

Authors:

• Brian Pasley

• Ralph D. Freeman

Date: 2008

DOI: doi:10.4249/scholarpedia.5340

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Superior Temporal Sulcus—It’s My Area: Or Is It?

Authors:

• Grit Hein

• Robert T. Knight

Date: 2008

DOI: 10.1162/jocn.2008.20148

PubMed: 18457502

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Abstract:

The superior temporal sulcus (STS) is the chameleon of the human brain. Several research areas claim the STS as the host brain region for their particular behavior of interest. Some see it as one of the core structures for theory of mind. For others, it is the main region for audiovisual integration. It plays an important role in biological motion perception, but is also claimed to be essential for speech processing and processing of faces. We review the foci of activations in the STS from multiple functional magnetic resonance imaging studies, focusing on theory of mind, audiovisual integration, motion processing, speech processing, and face processing. The results indicate a differentiation of the STS region in an anterior portion, mainly involved in speech processing, and a posterior portion recruited by cognitive demands of all these different research areas. The latter finding argues against a strict functional subdivision of the STS. In line with anatomical evidence from tracer studies, we propose that the function of the STS varies depending on the nature of network coactivations with different regions in the frontal cortex and medialtemporal lobe. This view is more in keeping with the notion that the same brain region can support different cognitive operations depending on task-dependent network connections, emphasizing the role of network connectivity analysis in neuroimaging.

Spatiotemporal dynamics of word processing in the human brain

Authors:

• Ryan T. Canolty

• Maryam Soltani

• Sarang S. Dalal

• Erik Edwards

• Nina F. Dronkers

• Srikantan S. Nagarajan

• Heidi E. Kirsch

• Nicholas M. Barbaro

• Robert T. Knight

Date: 2007

PubMed: 18982128

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Abstract:

We examined the spatiotemporal dynamics of word processing by recording the electrocorticogram (ECoG) from the lateral frontotemporal cortex of neurosurgical patients chronically implanted with subdural electrode grids. Subjects engaged in a target detection task where proper names served as infrequent targets embedded in a stream of task-irrelevant verbs and nonwords. Verbs described actions related to the hand (e.g, throw) or mouth (e.g., blow), while unintelligible nonwords were sounds which matched the verbs in duration, intensity, temporal modulation, and power spectrum. Complex oscillatory dynamics were observed in the delta, theta, alpha, beta, low, and high gamma (HG) bands in response to presentation of all stimulus types. HG activity (80-200 Hz) in the ECoG tracked the spatiotemporal dynamics of word processing and identified a network of cortical structures involved in early word processing. HG was used to determine the relative onset, peak, and offset times of local cortical activation during word processing. Listening to verbs compared to nonwords sequentially activates first the posterior superior temporal gyrus (post-STG), then the middle superior temporal gyrus (mid-STG), followed by the superior temporal sulcus (STS). We also observed strong phase-locking between pairs of electrodes in the theta band, with weaker phase-locking occurring in the delta, alpha, and beta frequency ranges. These results provide details on the first few hundred milliseconds of the spatiotemporal evolution of cortical activity during word processing and provide evidence consistent with the hypothesis that an oscillatory hierarchy coordinates the flow of information between distinct cortical regions during goal-directed behavior.

Transcranial magnetic stimulation elicits coupled neural and hemodynamic consequences

Authors:

• Brian Pasley

• Elena A. Allen

• T. Duong

• Ralph D. Freeman

Date: 2007

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Abstract:

Transcranial magnetic stimulation (TMS) is an increasingly common technique used to selectively modify neural processing. However, application of TMS is limited by uncertainty concerning its physiological effects. We applied TMS to the cat visual cortex and evaluated the neural and hemodynamic consequences. Short TMS pulse trains elicited initial activation (~1 minute) and prolonged suppression (5 to 10 minutes) of neural responses. Furthermore, TMS disrupted the temporal structure of activity by altering phase relationships between neural signals. Despite the complexity of this response, neural changes were faithfully reflected in hemodynamic signals; quantitative coupling was present over a range of stimulation parameters. These results demonstrate long-lasting neural responses to TMS and support the use of hemodynamic-based neuroimaging to effectively monitor these changes over time.

Emotionally arousing stimuli compete with attention to the left hemispace

Authors:

• Kaisa M. Hartikainen

• Keith H. Ogawa

• Maryam Soltani

• Robert T. Knight

Date: 2007

PubMed: 18007189

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Abstract:

Rapid interaction of the emotional and attentional networks is critical for adaptive behavior. Here, we examined the effects of emotional stimulation on hemifield attention allocation using event-related potential and behavioral measures. Participants performed a visual-discrimination task on nonemotional targets presented randomly in the left or right hemifield. A brief task-irrelevant emotional (pleasant or unpleasant; 150-ms duration) or neutral picture was presented centrally 350 ms before the next target (150-ms duration). Unpleasant stimuli interfered with the left visual field attention capacity, slowing behavioral responses to attended left field stimuli. In keeping with the behavioral data, event-related potential responses to nonemotional attended left field stimuli were reduced over the right parietal regions when preceded by an unpleasant event. The results provide electrophysiological and behavioral evidence that unpleasant, emotionally arousing stimuli interfere with the right hemisphere-dependent attention capacity.

Response anticipation and response conflict: an ERP and fMRI study

Authors:

• Jin Fan

• Rachel Kolster

• Jamshid Ghajar

• Minah Suh

• Robert T. Knight

• Ranjeeta Sarkar

• Bruce D. McCandliss

Date: 2007

PubMed: 17329424

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Abstract:

Response anticipation and response conflict processes are supported by executive control. However, few neuroimaging studies have attempted to study the relationship between these two processes in the same experimental session. In this study, we isolated brain activity associated with response anticipation (after a cue to prepare vs relax) and with response conflict (responding to a target with incongruent vs congruent flankers) and examined the independence and interaction of brain networks supporting these processes using event-related potentials (ERPs) and functional magnetic resonance imaging. Response anticipation generated a contingent negative variation ERP that correlated with shorter reaction times, and was associated with activation of a thalamo-cortico-striatal network, as well as increased gamma band power in frontal and parietal regions, and decreased spectral power in theta, alpha, and beta bands in most regions. Response conflict was associated with increased activation in the anterior cingulate cortex (ACC) and prefrontal cortex of the executive control network, with an overlap in activation with response anticipation in regions including the middle frontal gyrus, ACC, and superior parietal lobule. Although the executive control network showed increased activation in response to unanticipated versus anticipated targets, the response conflict effect was not altered by response anticipation. These results suggest that common regions of a dorsal frontoparietal network and the ACC are engaged in the flexible control of a wide range of executive processes, and that response anticipation modulates overall activity in the executive control network but does not interact with response conflict processing.

Positive mood and sleep disturbance in acquired mania following temporal lobe damage

Authors:

• June Gruber

• Julie N. Lemoine

• Robert T. Knight

• Allison G. Harvey

Date: 2007

PubMed: 17952718

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Abstract:

PRIMARY OBJECTIVE: To determine the mood profile and sleep functioning of a patient with left anterior temporal region damage characterized by post-operative symptoms of mania. METHODS AND PROCEDURES: In a structured clinical assessment, the patient's mood status, psychiatric diagnosis and sleep functioning - sleep onset latency, total sleep time, wake after sleep onset - were assessed. The sleep-wake cycle and daily mood was measured for 11 consecutive days. RESULTS: The patient met diagnostic criteria for bipolar disorder (excluding the requirement that the disturbance must not be due to a medical disorder) and delayed sleep-phase syndrome. Across 11 days, the patient exhibited elevated positive, but not negative, mood. Correlational analyses indicated a possible association between mood and sleep disturbance. CONCLUSIONS: This pattern of findings implicates the temporal lobe in positive mood regulation and sleep-related impairments.

Mood and sleep dysregulation in acquired mania following temporal lobe damage

Authors:

• June Gruber

• Julie N. Lemoine

• Robert T. Knight

• Allison G. Harvey

Date: 2007

PubMed: 17952718

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Abstract:

PRIMARY OBJECTIVE: To determine the mood profile and sleep functioning of a patient with left anterior temporal region damage characterized by post-operative symptoms of mania. METHODS AND PROCEDURES: In a structured clinical assessment, the patient's mood status, psychiatric diagnosis and sleep functioning - sleep onset latency, total sleep time, wake after sleep onset - were assessed. The sleep-wake cycle and daily mood was measured for 11 consecutive days. RESULTS: The patient met diagnostic criteria for bipolar disorder (excluding the requirement that the disturbance must not be due to a medical disorder) and delayed sleep-phase syndrome. Across 11 days, the patient exhibited elevated positive, but not negative, mood. Correlational analyses indicated a possible association between mood and sleep disturbance. CONCLUSIONS: This pattern of findings implicates the temporal lobe in positive mood regulation and sleep-related impairments.

Cerebral responses to change in spatial location of unattended sounds

Authors:

• Leon Y. Deouell

• Aaron S. Heller

• Rafael Malach

• Mark D'Esposito

• Robert T. Knight

Date: 2007

DOI: 10.1016/j.neuron.2007.08.019

PubMed: 17880900

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Abstract:

The neural basis of spatial processing in the auditory cortex has been controversial. Human fMRI studies suggest that a part of the planum temporale (PT) is involved in auditory spatial processing, but it was recently argued that this region is active only when the task requires voluntary spatial localization. If this is the case, then this region cannot harbor an ongoing spa- tial representation of the acoustic environment. In contrast, we show in three fMRI experiments that a region in the human medial PT is sensitive to background auditory spatial changes, even when subjects are not engaged in a spatial lo- calization task, and in fact attend the visual mo- dality. During such times, this area responded to rare location shifts, and even more so when spatial variation increased, consistent with spatially selective adaptation. Thus, acoustic space is represented in the human PT even when sound processing is not required by the ongoing task.

Neural networks debunk phrenology

Authors:

• Robert T. Knight

Date: 2007

PubMed: 17569852

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Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex

Authors:

• Brian Pasley

• B. A. Inglis

• Ralph D. Freeman

Date: 2007

PubMed: 17113313

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Abstract:

The sustained negative blood oxygenation level-dependent (BOLD) response in functional MRI is observed universally, but its interpretation is controversial. The origin of the negative response is of fundamental importance because it could provide a measurement of neural deactivation. However, a substantial component of the negative response may be due to a non-neural hemodynamic artifact. To distinguish these possibilities, we have measured evoked BOLD, cerebral blood flow (CBF), and oxygen metabolism responses to a fixed visual stimulus from two different baseline conditions. One is a normal resting baseline, and the other is a lower baseline induced by a sustained negative response. For both baseline conditions, CBF and oxygen metabolism responses reach the same peak amplitude. Consequently, evoked responses from the negative baseline are larger than those from the resting baseline. The larger metabolic response from negative baseline presumably reflects a greater neural response that is required to reach the same peak amplitude as that from resting baseline. Furthermore, the ratio of CBF to oxygen metabolism remains approximately the same from both baseline states (approximately 2:1). This tight coupling between hemodynamic and metabolic components implies that the magnitude of any hemodynamic artifact is inconsequential. We conclude that the negative response is a functionally significant index of neural deactivation in early visual cortex.