Lateral Prefrontal Cortex Damage Research Articles

Prefrontal lesions disrupt oscillatory signatures of spatiotemporal integration in working memory

How does the human brain integrate spatial and temporal information into unified mnemonic representations? Building on classic theories of feature binding, we first define the oscillatory signatures of integrating ‘where’ and ‘when’ information in working memory (WM) and then investigate the role of prefrontal cortex (PFC) in spatiotemporal integration. Fourteen individuals with lateral PFC damage and 20 healthy controls completed a visuospatial WM task while electroencephalography (EEG) was recorded. On each trial, two shapes were presented sequentially in a top/bottom spatial orientation. We defined EEG signatures of spatiotemporal integration by comparing the maintenance of two possible where-when configurations: the first shape presented on top and the reverse. Frontal delta-theta (δθ; 2–7 Hz) activity, frontal-posterior δθ functional connectivity, lateral posterior event-related potentials, and mesial posterior alpha phase-to-gamma amplitude coupling dissociated the two configurations in controls. WM performance and frontal and mesial posterior signatures of spatiotemporal integration were diminished in PFC lesion patients, whereas lateral posterior signatures were intact. These findings reveal both PFC-dependent and independent substrates of spatiotemporal integration and link optimal performance to PFC.

Retrospective time estimation following damage to the prefrontal cortex.

Time estimation in patients with prefrontal cortex (PFC) damage is often inaccurate. The relationship between PFC and estimation of short time intervals has been examined. However, it remains unclear whether PFC damage affects estimation of longer time intervals. Here, we investigated the ability of patients and healthy subjects to verbally estimate a period of 30min, using a method easily applied in clinical settings. In 99 patients with brain damage, we compared under and normal ranges of time in patients with PFC damage or damage to other brain areas with the chi-squared test. Subsequently, we conducted a discriminant analysis and a multiple linear regression analysis to identify specific brain areas affecting time estimation. We observed a significantly larger number of patients who overestimated 30min in the group with bilateral PFC damage compared to patients with damage to other regions. Discriminant analysis revealed that damage of right lateral PFC and left medial PFC contributed to discrimination between the normal range and overestimation groups. Multiple linear regression analysis indicated that right lateral PFC damage strongly affected overestimation of a 30-min interval. Neuropsychological test results revealed lower general cognitive function scores and orientation scores in overestimation group. The length of estimated time and the score of delayed word recall were negatively correlated. We propose that these may require encoding, maintenance, and updating of memory and are indirectly related to contextual memory. We discuss hypotheses on contextual memory segmentation and reconstruction to clarify the mechanism of impaired time overestimation in PFC-damaged patients.

Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.

There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.

Preparatory attention after lesions to the lateral or orbital prefrontal cortex – An event-related potentials study

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 (500–1000ms) nor late (3200–3700ms) 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.

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.

Monkeys Quickly Learn and Generalize Visual Categories without Lateral Prefrontal Cortex

Categorization is a basic mental process that helps individuals distinguish among groups of negative and positive objects, e.g., poisons and nutrients, or predators and prey. Monkey experiments have suggested that lateral prefrontal cortex (LPFC) participates in learning and processing visual categories. However, in humans category specific visual agnosia follows inferior temporal cortex but not LPFC damage. Here, we use a new behavioral approach to show that both normal monkeys and those with bilateral removal of LPFC learn and generalize perceptual categories of related visual stimuli rapidly without explicit instruction. These results strongly indicate that visual categorization occurs at some earlier stage of feed-forward processing, presumably in temporal cortex, without top-down information from LPFC.

Novelty Enhancements in Memory Are Dependent on Lateral Prefrontal Cortex

Physiological evidence indicates that several brain regions, including the medial temporal lobes and prefrontal cortex (PFC), are involved in processing events that are novel or distinctive in their immediate context. However, behavioral studies that investigate whether these regions are critical for producing stimulus novelty advantages in memory are limited. For example, evidence from an animal lesion study indicated that the PFC is involved in stimulus novelty effects, but this has not been examined in humans. In the current study, we used a von Restorff novelty paradigm to test a large cohort of lateral PFC patients (n = 16). We found that patients with lateral PFC damage were impaired in recollection- and familiarity-based recognition, and they did not exhibit a normal memory advantage for novel compared with non-novel items. These results provide neuropsychological evidence supporting a key role for the lateral PFC in producing stimulus novelty advantages in memory.

An Information-Theoretical Approach to Contextual Processing in the Human Brain: Evidence from Prefrontal Lesions

Context shapes perception, thought, and action, but little is known about the neural mechanisms supporting these modulations. Here, we addressed the role of lateral prefrontal cortex (PFC) in context updating and maintenance from an information-theoretic perspective. Ten patients with PFC lesions and 10 age-matched controls responded to bilaterally displayed visual targets intermixed with repetitive and novel distracters in 2 different task contexts. In a predictable context, targets were always preceded by a novel event, whereas this temporal contingency was removed in an unpredictable context condition. We applied information theory to the analysis and interpretation of behavioral and electrophysiological data. The results revealed deficits in both the selection and the suppression of familiar versus novel information mainly observed at the visual hemifield contralateral to PFC damage due to disrupted frontocortical and frontosubcortical connectivity. The findings support a deficit in the representation of the temporal contingency between contextually related novel and familiar stimulation subsequent to lateral PFC damage.

Distractibility during selection-for-action: differential deficits in Huntington’s disease and following frontal lobe damage

Selective attention can be measured through analysis of errors and reaction time (RT) for trials in which targets are presented alone compared with trials in which targets and distractors are presented. This study investigated selective attention using a reaching task, in which subjects made rapid reaches to targets. Thirty-seven patients with lesions of the prefrontal cortex (PFC) were compared with 19 healthy age- and IQ-matched volunteers and 18 patients with early-stage Huntington’s disease (HD), a neurodegenerative disease primarily affecting the basal ganglia. It was hypothesised that, if fronto-striatal circuits as a whole support selection-for-action, then the pattern of behavioural performance of both patient groups would be similar. Alternatively, if the functional roles of PFC and basal ganglia in selection-for-action are dissociable, then two different patterns would emerge. It was found that that both HD and frontal groups were significantly more distractible than controls for RT, but they had a different pattern of errors. Frontal patients made significantly more touches of the distractor location itself than did controls, while this was not the case for HD. It is argued that a reactive- inhibition mechanism, required in the circumstance of strong distractor activation, is affected by frontal damage, while a lateral- inhibition mechanism, invoked during the recruitment of selective attention, is affected in HD. Additionally, there were significant correlations between the degree of distractibility for RT and the extent of lateral PFC damage, and between cue-generated preparation and lateral PFC damage, thus highlighting the critical importance of lateral, rather than orbital or medial, PFC for attention to action.