Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex

Abstract:

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local–global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

Authors:

• Olgerta Asko

• Alejandro Omar Blenkmann

• Sabine Liliana Leske

• Maja Dyhre Foldal

• Anais Llorens

• Ingrid Funderud

• Torstein R Meling

• Robert T Knight

• Tor Endestad

• Anne-Kristin Solbakk

Date: 2024

DOI: https://doi.org/10.7554/eLife.86386

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Ramping dynamics and theta oscillations reflect dissociable signatures during rule-guided human behavior

abstract:

Contextual cues and prior evidence guide human goal-directed behavior. The neurophysiological mechanisms that implement contextual priors to guide subsequent actions in the human brain remain unclear. Using intracranial electroencephalography (iEEG), we demonstrate that increasing uncertainty introduces a shift from a purely oscillatory to a mixed processing regime with an additional ramping component. Oscillatory and ramping dynamics reflect dissociable signatures, which likely differentially contribute to the encoding and transfer of different cognitive variables in a cue-guided motor task. The results support the idea that prefrontal activity encodes rules and ensuing actions in distinct coding subspaces, while theta oscillations synchronize the prefrontal-motor network, possibly to guide action execution. Collectively, our results reveal how two key features of large-scale neural population activity, namely continuous ramping dynamics and oscillatory synchrony, jointly support rule-guided human behavior.

Authors:

• Jan Weber

• Anne-Kristin Solbakk

• Alejandro O. Blenkmann

• Anais Llorens

• Ingrid Funderud

• Sabine Leske

• Pål Gunnar Larsson

• Lugoslav Ivanovic

• Robert T. Knight

• Tor Endestad

• Randolph F. Helfrich

Date: 2024

DOI: https://doi.org/10.1038/s41467-023-44571-7

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Preservation of Interference Effects in Working Memory After Orbitofrontal Damage

Abstract:

Orbitofrontal cortex (OFC) is implicated in multiple cognitive processes, including inhibitory control, context memory, recency judgment, and choice behavior. Despite an emerging understanding of the role of OFC in memory and executive control, its necessity for core working memory (WM) operations remains undefined. Here, we assessed the impact of OFC damage on interference effects in WM using a Recent Probes task based on the Sternberg item-recognition task (1966). Subjects were asked to memorize a set of letters and then indicate whether a probe letter was presented in a particular set. Four conditions were created according to the forthcoming response (“yes”/“no”) and the recency of the probe (presented in the previous trial set or not). We compared behavioral and electroencephalography (EEG) responses between healthy subjects (n = 14) and patients with bilateral OFC damage (n = 14). Both groups had the same recency pattern of slower reaction time (RT) when the probe was presented in the previous trial but not in the current one, reflecting the proactive interference (PI). The within-group electrophysiological results showed no condition difference during letter encoding and maintenance. In contrast, event-related potentials (ERPs) to probes showed distinct within-group condition effects, and condition by group effects. The response and recency effects for controls occurred within the same time window (300–500 ms after probe onset) and were observed in two distinct spatial groups including right centro-posterior and left frontal electrodes. Both clusters showed ERP differences elicited by the response effect, and one cluster was also sensitive to the recency manipulation. Condition differences for the OFC group involved two different clusters, encompassing only left hemisphere electrodes and occurring during two consecutive time windows (345–463 ms and 565–710 ms). Both clusters were sensitive to the response effect, but no recency effect was found despite the behavioral recency effect. Although the groups had different electrophysiological responses, the maintenance of letters in WM, the evaluation of the context of the probe, and the decision to accept or reject a probed letter were preserved in OFC patients. The results suggest that neural reorganization may contribute to intact recency judgment and response after OFC damage.

Authors:

• Anaïs Llorens

• Ingrid Funderud

• Alejandro O Blenkmann

• James Lubell

• Maja Foldal

• Sabine Leske

• Rene Huster

• Torstein R Meling

• Robert T Knight

• Anne-Kristin Solbakk

• Tor Endestad

Date: 2020

DOI: https://doi.org/10.3389/fnhum.2019.00445

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Auditory deviance detection in the human insula: An intracranial EEG study

Abstract:

The human insula is known to be involved in auditory processing, but knowledge about its precise functional role and the underlying electrophysiology is limited. To assess its role in automatic auditory deviance detection we analyzed the EEG high frequency activity (HFA; 75–145 Hz) and ERPs from 90 intracranial insular channels across 16 patients undergoing pre-surgical intracranial monitoring for epilepsy treatment. Subjects passively listened to a stream of standard and deviant tones differing in four physical dimensions: intensity, frequency, location or time. HFA responses to auditory stimuli were found in the short and long gyri, and the anterior, superior, and inferior segments of the circular sulcus of the insular cortex. Only a subset of channels in the inferior segment of the circular sulcus of the insula showed HFA deviance detection responses, i.e., a greater and longer latency response to specific deviants relative to standards. Auditory deviancy processing was also later in the insula when compared with the superior temporal cortex. ERP results were more widespread and supported the HFA insular findings. These results provide evidence that the human insula is engaged during auditory deviance detection.

Authors:

• Alejandro O Blenkmann

• Santiago Collavini

• James Lubell

• Anaïs Llorens

• Ingrid Funderud

• Jugoslav Ivanovic

• Pål G Larsson

• Torstein R Meling

• Tristan Bekinschtein

• Silvia Kochen

• Tor Endestad

• Robert T Knight

• Anne-Kristin Solbakk

Date: 2019

DOI: https://doi.org/10.1016/j.cortex.2019.09.002

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Lesions to the fronto-parietal network impact alpha-band phase synchrony and cognitive control

Abstract:

Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10–12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility.

Authors:

• Sepideh Sadaghiani

• Pascasie L Dombert

• Marianne Løvstad

• Ingrid Funderud

• Torstein R Meling

• Tor Endestad

• Robert T Knight

• Anne-Kristin Solbakk

• Mark D’Esposito

Date: 2018

DOI: 10.1093/cercor/bhy296

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Orbitofrontal damage reduces auditory sensory response in humans

AUTHORS

• Julia W.Y. Kam

• Anne-Kristin Solbakk

• Ingrid Funderud

• Tor Endestad

• Torstein R. Meling

• Robert T. Knight

Date: 2017

DOI: 10.1016/j.cortex.2017.12.023.

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Impact of orbitofrontal lesions on electrophysiological signals in a stop signal task

Authors:

• Anne-Kristin Solbakk

• Ingrid Funderud

• Tor Endestad

• Torstein Meling

• Magnus Lindgren

• Robert T. Knight

• Ulrike M. Krämer

Date: 2014

DOI: 10.1162/jocn_a_00561

PubMed: 24392904

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Abstract:

Behavioral inhibition and performance monitoring are critical cognitive functions supported by distributed neural networks including the pFC. We examined neurophysiological correlates of motor response inhibition and action monitoring in patients with focal orbitofrontal (OFC) lesions (n = 12) after resection of a primary intracranial tumor or contusion because of traumatic brain injury. Healthy participants served as controls (n = 14). Participants performed a visual stop signal task. We analyzed behavioral performance as well as event-related brain potentials and oscillations. Inhibition difficulty was adjusted individually to yield an equal amount of successful inhibitions across participants. RTs of patients and controls did not differ significantly in go trials or in failed stop trials, and no differences were observed in estimated stop signal RT. However, electrophysiological response patterns during task performance distinguished the groups. Patients with OFC lesions had enhanced P3 amplitudes to congruent condition go signals and to stop signals. In stop trials, patients had attenuated N2 and error-related negativity, but enhanced error positivity. Patients also showed enhanced and prolonged post-error beta band increases for stop errors. This effect was particularly evident in patients whose lesion extended to the subgenual cingulate cortex. In summary, although response inhibition was not impaired, the diminished stop N2 and ERN support a critical role of the OFC in action monitoring. Moreover, the increased stop P3, error positivity, and post-error beta response indicate that OFC injury affected action outcome evaluation and support the notion that the OFC is relevant for the processing of abstract reinforcers such as performing correctly in the task.

Preparatory attention after lesions to the lateral or orbital prefrontal cortex: an event-related potential study

Authors:

• Ingrid Funderud

• Marianne Lovstad

• Magnus Lindgren

• Tor Endestad

• Paulina Due-Tønnesse

• Torstein Meling

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2013

PubMed: 23831520

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Abstract:

The prefrontal cortex (PFC) plays a central role in preparatory and anticipatory attentional processes. To investigate whether subregions of the PFC play differential roles in these processes we investigated the effect of focal lesions to either lateral prefrontal (lateral PFC; n=11) or orbitofrontal cortex (OFC; n=13) on the contingent negative variation (CNV), an electrophysiological index of preparatory brain processes. The CNV was studied using a Go/NoGo delayed response task where an auditory S1 signaled whether or not an upcoming visual S2 was a Go or a NoGo stimulus. Neither early (500–1000 ms) nor late (3200–3700 ms) phase Go trial CNV amplitude was reduced for any of the patient groups in comparison to controls. However, the lateral PFC group showed enhanced Go trial early CNV and reduced late CNV Go/NoGo differentiation. These data suggests that normal orienting and evaluation as reflected by the CNV is intact after OFC lesions. The enhanced early CNV after lateral PFC damage may be due to failure in inhibition and the reduced late CNV difference wave confirms a deficit in preparatory attention after damage to this frontal subregion.

Differential Go/NoGo activity in both contingent negative variation and spectral power

Authors:

• Ingrid Funderud

• Magnus Lindgren

• Marianne Lovstad

• Tor Endestad

• Bradley Voytek

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.1371/journal.pone.0048504

PubMed: 23119040

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Abstract:

We investigated whether both the contingent negative variation (CNV), an event-related potential index of preparatory brain activity, and event-related oscillatory EEG activity differentiated Go and NoGo trials in a delayed response task. CNV and spectral power (4-100 Hz) were calculated from EEG activity in the preparatory interval in 16 healthy adult participants. As previously reported, CNV amplitudes were higher in Go compared to NoGo trials. In addition, event-related spectral power of the Go condition was reduced in the theta to low gamma range compared to the NoGo condition, confirming that preparing to respond is associated with modulation of event-related spectral activity as well as the CNV. Altogether, the impact of the experimental manipulation on both slow event-related potentials and oscillatory EEG activity may reflect coordinated dynamic changes in the excitability of distributed neural networks involved in preparation.

Anterior Cingulate Cortex and Cognitive Control: Neuropsychological and Electrophysiological Findings in Two Patients with Lesions to Dorsomedial Prefrontal Cortex

Authors:

• Marianne Lovstad

• Ingrid Funderud

• Torstein Meling

• Ulrike M. Krämer

• Bradley Voytek

• Paulina Due-Tønnesse

• Tor Endestad

• Magnus Lindgren

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.1016/j.bandc.2012.07.008

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Abstract:

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.

Contribution of Subregions of Human Frontal Cortex to Novelty Processing

Authors:

• Marianne Lovstad

• Ingrid Funderud

• Magnus Lindgren

• Tor Endestad

• Paulina Due-Tønnesse

• Torstein Meling

• Bradley Voytek

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.1162/jocn_a_00099

PubMed: 21812562

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Abstract:

Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.

The role of the lateral prefrontal cortex in inhibitory motor control

Authors:

• Ulrike M. Krämer

• Anne-Kristin Solbakk

• Ingrid Funderud

• Marianne Lovstad

• Tor Endestad

• Robert T. Knight

Date: 2012

DOI: 10.1016/j.cortex.2012.05.003

PubMed: 22699024

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Abstract:

Research on inhibitory motor control has implicated several prefrontal as well as subcortical and parietal regions in response inhibition. Whether prefrontal regions are critical for inhibition, attention or task-set representation is still under debate. We investigated the influence of the lateral prefrontal cortex (PFC) in a response inhibition task by using cognitive electrophysiology in prefrontal lesion patients. Patients and age- and education-matched controls performed in a visual Stop-signal task featuring lateralized stimuli, designed to challenge either the intact or lesioned hemisphere. Participants also underwent a purely behavioral Go/Nogo task, which included a manipulation of inhibition difficulty (blocks with 50 vs. 80% go-trials) and a Change-signal task that required switching to an alternative response. Patients and controls did not differ in their inhibitory speed (stop-signal and change-signal reaction time, SSRT and CSRT), but patients made more errors in the Go/Nogo task and showed more variable performance. The behavioral data stress the role of the PFC in maintaining inhibitory control but not in actual inhibition. These results support a dissociation between action cancellation and PFC-dependent action restraint. Laplacian transformed event-related potentials (ERPs) revealed reduced parietal activity in PFC patients in response to the stop-signals, and increased frontal activity over the intact hemisphere. This electrophysiological finding supports altered PFC-dependent visual processing of the stop-signal in parietal areas and compensatory activity in the intact frontal cortex. No group differences were found in the mu and beta decrease as measures of response preparation and inhibition at electrodes over sensorimotor cortex. Taken together, the data provide evidence for a central role of the lateral PFC in attentional control in the context of response inhibition.

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

Authors:

• Marianne Lovstad

• Ingrid Funderud

• Tor Endestad

• Paulina Due-Tønnesse

• Torstein Meling

• Magnus Lindgren

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.3109/02699052.2012.698787

PubMed: 22731818

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Abstract:

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.