Attentional inhibition in patients with focal frontal lobe lesions

Patients with unilateral, frontal lobe damage and matched controls performed an identity negative priming task as a measure of inhibition in selective attention. Control participants demonstrated a normal negative priming effect, as evidenced by slower reaction times when a previously to-be-ignored item became the target on a subsequent trial (distractor suppression). On the other hand, patients with left medial frontal lobe damage showed positive priming in the distractor suppression condition suggesting facilitation of distractor information. Patients with right frontal lobe damage showed an unreliable pattern of negative priming, some demonstrating an absence of negative priming and others demonstrating enhanced negative priming in the distractor suppression condition. Neither patient group nor controls demonstrated slower responses on a target-to-distractor condition included to evaluate a noninhibitory (i.e., episodic retrieval) account of negative priming. Taken together, our results suggest that (a) the negative priming effect represents active inhibition of a distractor representation, rather than a noninhibitory mismatch between retrieval episodes, and (b) that the frontal lobes, especially the left frontal lobes, contribute to this active inhibition.     

Spatial selective attention and inhibition in schizophrenia patients during acute psychosis and at 4-month follow-up.

BACKGROUND: Attentional abnormalities may lie at the core of cognitive symptoms in schizophrenia, but it is unclear how they relate to symptoms. The major aim of our study was to understand the relation between spatial attention and clinical symptoms from acute to chronic state. METHODS: Thirty-six acutely psychotic schizophrenia patients and 42 matched control subjects were assessed on three spatial attention measures: target location detection, interference (concurrent inhibition of distractor), and negative priming (subsequent inhibition of distractor). Symptoms were assessed by the Positive and Negative Syndrome Assessment Scale. Four months later, the same subjects were re-tested, and symptoms were re-assessed. RESULTS: Symptoms were significantly reduced at the follow-up. Schizophrenia patients were slower at detecting target location than control subjects, but they improved significantly over time. Schizophrenia patients and control subjects did not differ on the interference task. Negative priming was abolished during acute psychosis, but 4 months later it was restored. Positive symptoms were correlated with reduced negative priming but not with interference, nor with target detection. Negative priming during acute psychosis was significantly correlated with the clinical symptoms at the follow-up. CONCLUSIONS: These results suggest that reduced negative priming may be associated with increased clinical, symptoms especially the positive symptoms.     

Spatial negative priming in early Alzheimer's disease: evidence for reduced cognitive inhibition.

Some studies of negative priming and other tasks assumed to reflect inhibitory functions suggest a decline in inhibitory processes in Alzheimer's disease. However, none of the measures used in previous studies can be interpreted as an unambiguous reflection of distractor inhibition. The present study investigates whether reductions in negative priming associated with Alzheimer's disease reflect reduced distractor inhibition, rather than perceptual review processes. Individuals with early Alzheimer's disease were predicted to show reduced negative priming on a spatial localization task designed to provide an unambiguous measure of distractor inhibition. Sixteen clinical participants showed significantly less negative priming than old and young healthy control groups, which is interpreted as evidence for reduced distractor inhibition in early dementia. A second analysis indicated that, within the clinical sample only, negative priming effect size was significantly correlated with prime trial response speed. Clinical participants showing the least negative priming were slower to respond to an initial stimulus. The results may mean that people with early Alzheimer's disease have a reduced capacity to use excitatory as well as inhibitory processes in selection.     

Dissociation of attentional processes in patients with focal frontal and posterior lesions.

A location-based ('select-what, respond-where') priming task was used to examine three measures of selective attention (interference (INT), negative priming (NP), and inhibition of return (IOR)) as a function of focal brain pathology and the complexity of target selection. Control subjects showed different patterns of performance for the three attentional measures as a function of complexity, suggesting some independence among INT, NP, and IOR. Brain-damaged subjects showed significant response slowing, as well as a number of lesion-specific attentional abnormalities. Right frontal (including bifrontal) damage resulted in proportionally increased interference related to task complexity. Left posterior damage increased IOR in the most complex task, while left frontal damage reversed the control pattern of IOR as a function of complexity. Right hemisphere (right posterior and right frontal damage) pathology resulted in a virtual loss of negative priming at all levels of task complexity; left and bifrontal damage resulted in diminished NP only related to increases in the complexity of selection. INT, NP, and IOR are mediated by different brain regions and their expression can be modulated by the complexity of the selection task.     

Neuroimaging correlates of negative priming.

Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.     

Selective visual attention in patients with frontal lobe lesions or Parkinson's disease.

Visual selective attention and response competition were tested in patients with frontal lobe lesions or with Parkinson's disease, and matched normal controls. The target stimuli were presented with flanking distractors that were either compatible, incompatible, or neutral to the target stimulus. The distance between the target and distractors was systematically varied. A control condition without distractors was also included. Subjects' response times to target stimuli and accuracy were measured. Both patient groups responded significantly slower and less accurately than their respective matched normal controls across all interference conditions and spatial distances. However, they did not show significantly greater interference or facilitation effects. Thus, the data suggest that the cognitive processes underlying selective attention are, in general, spared in patients with frontal lobe lesions or basal ganglia dysfunction.     

Lack of inhibition in Parkinson's disease: evidence from a lexical decision task

Persons affected by Parkinson's disease (PD) often show an increased semantic priming effect from target words in lexical decision tasks (hyper-priming) as compared to age-matched controls. In this study, a lexical decision task was used to investigate both semantic priming (Experiment 1) and repetition priming (Experiment 2) from distractor words in PD patients and age-matched controls. With this negative priming procedure, target words in successive trials are never related, and therefore participants always have to switch between unrelated target words. Instead, it is the distractor prime word that is either related or unrelated to the subsequent target, giving the measure of priming. Results showed that PD patients demonstrated a robust effect of positive semantic priming from distractor words. Participants from the control group did not show any semantic priming effect (positive or negative) from distractors. Similarly, PD patients showed positive repetition priming from distractor words, but the control group showed significant repetition negative priming. These results support the view that the hyper-priming effect typically shown by persons with Parkinson's disease is the result of impaired inhibitory processes required to control word activation during reading.     

Cognitive inhibition and psychopathology: toward a less simplistic conceptualization

"Cognitive inhibition" is a concept that has found a firm place in the interpretation of performance by normal subjects on tasks involving adherence to a plan and suppression of incorrect responses to distractors. The presence of "negative priming" is the classical indicator of cognitive inhibition. Negative priming occurs when, in a sequence of stimuli each of which is composed of a target and a distractor, the distractor of the first stimulus becomes the target of the second stimulus: reaction time to the second stimulus is slowed because of the inhibition applied to the distractor of the first stimulus. The concept has been extended to the interpretation of pathological behavior and symptoms. Pathological subjects have been found to show deficient negative priming. Thus, negative ideation in depression as well as intrusive paranoid associations in schizophrenia have been related to a deficit in the capacity to inhibit inappropriate representations. In this paper, we briefly review some of the experimental evidence from normal subjects that has contributed to the acceptance of cognitive inhibition as a key process in the control of normal cognition, as well as more recent evidence that has led to a revision of the concept. Negative priming in normal subjects has been found to be dependent upon characteristics of the experimental situation as perceived by the subject. In particular, priming is observed when the subject anticipates difficulty in determining the response and proceeds with caution. Thus, inhibition is not an automatic "brake" applied to irrelevant material, but rather the product of strategic considerations within the experimental situation. This revision of the cognitive inhibition hypothesis leads to a re-interpretation of the apparently deficient cognitive inhibition seen in depressed or schizophrenic subjects. According to this more recent interpretation, deficient cognitive inhibition in pathological subjects can be seen as a less adaptive strategic adjustment to the task. The pathology seems to touch higher-level executive functions rather than a deficient inhibitory "brake". In depressed subjects, abnormal performance in selective attention tasks could be related to the underlying pathology in two ways: some depressed subjects show a marked lack of energy and a psychomotor slowing: these subjects do not exhibit normal negative priming, probably because of a reduction of cognitive resources. Other depressed subjects show abnormal performance as reflected by negative priming greater than normal: this result could be related to an exaggerated tendency to verify a correct response. Schizophrenic subjects show a lack of negative priming that seems most plausibly to be related to an ineffectual integration of the experimental instructions concerning both speed and accuracy in the response. This re-interpretation of the cognitive deficiency in pathological patients provides a better fit with recent experimental results from normal subjects, and with cognitive deficits measured in pathological subjects.     

Intact implicit memory in patients with frontal lobe lesions.

Patients with frontal lobe lesions and control subjects were administered tests of word-stem completion priming. In this implicit memory test, subjects are first presented words (e.g. MOTEL, PARADE) in an incidental learning paradigm. Following word presentation, subjects are shown word stems (e.g. MOT, PAR) and asked to produce the first word that comes to mind. Patients with frontal lobe lesions exhibited normal levels of word-stem completion. These findings indicate that implicit memory can operate normally despite damage to the prefrontal cortex. The present results substantiate previous neuropsychological and positron emission tomography findings which indicate that word priming depends critically on posterior cortical areas.     

Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location

There were three primary objectives: to examine the usefulness of the Stroop interference effect as a measure of frontal lobe function; to investigate the possibility of distinct lesion effects for word reading or color naming; and to specifically determine the brain regions necessary for the performance of the incongruent condition. Fifty-one patients with single focal brain lesions in frontal and non-frontal regions and 26 normal control subjects (CTL) were administered the word reading, color naming and incongruent conditions of the Stroop task. Only frontal lesions produced significant impairment. Patients with posterior lesions were not significantly deficient in any condition. Damage to the left dorsolateral frontal lobe resulted in increased errors and slowness in response speed for color naming. Contrary to Perret (Neuropsychology, 1974; 12: 323-330), lesions of the left frontal lobe did not result in a selective interference deficit on the Stroop incongruent condition. Rather, bilateral superior medial frontal damage was associated with increased errors and slowness in response time for the incongruent condition. This result is interpreted as failure of maintenance of consistent activation of the intended response in the incongruent Stroop condition. The results and conclusion are compatible with the prevalent theories of both the Stroop effect and the role of the superior medial frontal regions. The role of the anterior cingulate cortex on performance of the Stroop task is likely related to task and patient context.     

Interference and inhibition in tasks of selective attention by persons with and without mental retardation

Persons with mental retardation often exhibit greater interference in visual selective attention tasks than do persons matched with them on CA. My goal here was to evaluate whether differences in distractor interference between persons with and without mental retardation may be related to differences in negative priming. Fifteen participants with mental retardation, 15 without mental retardation matched on CA, and 15 without mental retardation matched on MA participated in three selective attention tasks, which were chosen to elicit small, medium, and large group differences in interference, respectively. The failure to engage in inhibitory processes by the participants with mental retardation in these tasks of selective attention was related to increased distractor interference.     

Semantic priming in patients with right frontal lobe lesions.

Patients with unilateral, right frontal lobe damage (N=13) and matched controls (N=20) performed a task of lexical ambiguity resolution in order to explore the contribution of right frontal regions to lexical-semantic priming. Word triplets consisting of balanced homographs were presented to participants in four conditions: concordant, discordant, neutral, and unrelated. Controls demonstrated facilitation for concordant meanings of homographs, as evidenced by their faster reaction times in the concordant relative to the unrelated (baseline) condition, as well as a lack of facilitation for the discordant meaning relative to the neutral and concordant conditions. Results in patients with right frontal lobe damage differed depending on the site of the lesion. Patients with lesions restricted to the right medial frontal lobe only showed facilitation in the neutral condition, while those with lesions encroaching upon the right dorsolateral region demonstrated facilitation of both discordant and concordant meanings relative to the baseline condition. These results support a role for the right frontal lobe in semantic priming and suggest possible specialization within the right prefrontal cortex for the processing of lexical-semantic information.     

Assessing markers of working memory function in dissociative identity disorder using neutral stimuli: a comparison with clinical and general population samples

OBJECTIVES: Memory functioning is a central conceptual and phenomenological aspect of dissociative identity disorder (DID). Most empirical work on memory functions in DID has focused on retrieval deficits either within or between dissociated identities. The current study attempted to remedy the scant attention given to working memory functioning. METHOD: In samples representing the DID, non-clinical, depressed, posttraumatic stress disorder (PTSD) and psychosis populations (n = 10 per group), neutral stimuli were used to examine three markers of working memory functioning: one measuring inhibition; one assessing facilitation; and one measuring interference. RESULTS: With the exception of the psychosis sample all groups displayed significant negative priming in the distractor inhibition condition. Facilitation effects were demonstrated by the DID and PTSD groups only. Interference effects were evident in all samples, though the DID and non-clinical groups demonstrated significantly more interference than the psychosis cohort. Distractor inhibition was related to overall schizotypy scores, and dissociation was related to scores in the facilitation condition. CONCLUSIONS: The DID sample displayed a completely distinct functional working memory profile to the psychosis sample when assessed with emotionally neutral stimuli. However, the working memory profile in the DID sample was not entirely dissimilar to the other comparison groups.     

Similarities in negative priming between persons with and those without mental retardation of equal chronological age

Adolescents with and those without mental retardation participated in a negative priming procedure in two experiments. They identified letters to stimulus displays presented in pairs. Negative priming was observed as the slowing of response times when the distractor in the first display (prime) became the target in the second display (probe). In the standard procedure, all displays include one target and one distractor. In our modification, prime displays occasionally included a distractor without a target. Although adolescents with mental retardation typically do not exhibit negative priming when responding on the basis of stimulus identity, they did so with single letter primes in these experiments.     

Distractibility after unilateral resections from the frontal and anterior cingulate cortex in humans

The prefrontal and anterior cingulate cortex figure prominently in current models of directed attention. The efficacy of selective attention was studied in a distractibility study carried out with patients who had unilateral surgical excisions from the frontal cortex with or without involvement of the cingulate gyrus, patients with unilateral anterior temporal resections, and normal control subjects. In Task A, participants responded to target stimuli presented at the foveal location in the presence or absence of distracting peripheral stimuli that appeared 200 ms before the target's onset. The presence of a distractor caused a comparable increase in reaction times to targets across all groups. In Task B, a distractor appeared during every trial but it appeared at a new location on 12% of the trials. A comparable transient increase in reaction times was observed in patients with frontal cortical resections that spared the anterior cingulate gyrus, patients with anterior temporal lobe resections, and the normal control group. Thus, lesions restricted to the prefrontal cortex need not impair the ability to attend and respond to a target event in the presence of distraction. Interestingly, no distracting effect was observed during Task B in patients with lesions that invaded the anterior cingulate gyrus, suggesting that this cortical region is involved in responding to or habituating to environmental stimuli.     

Role of the left amygdala and right orbital frontal cortex in emotional interference resolution facilitation in working memory

Previous research has shown that emotional information aids conflict resolution in working memory (Levens & Phelps, 2008). Using a Recency-probes working memory (WM) paradigm, Levens and Phelps found that positive and negative emotional stimuli reduced the amount of interference created when information that was once relevant conflicted with currently relevant information, suggesting that emotional information facilitates interference resolution in WM. To determine what regions of the prefrontal cortex (PFC) and temporal lobes are critical to the influence of emotional stimuli on interference resolution, we conducted a Recency-probes emotion paradigm with right and left unilateral frontal and temporal lobe lesion patients. The frontal lobe lesion patient group comprised individuals with unilateral ventral and dorsal PFC lesions. The temporal lobe lesion patient group comprised individuals with lesions of the amygdala and surrounding structures. Results indicate that when the left amygdala is damaged, emotional facilitation of interference resolution is absent (equal emotional and neutral interference levels), when the right orbital frontal cortex (OFC) is damaged, in contrast, emotional interference resolution is impaired (emotional interference levels are higher than neutral levels are). Based on these unique patterns we propose specific contributions for these regions in the emotional facilitation of interference resolution in WM.     

Cognitive disturbances in Parkinson's disease

To test the hypothesis that the cognitive impairments that accompany Parkinson's disease (PD) arise from frontal lobe dysfunction, patients with idiopathic PD and controls were tested on a neuropsychological battery that included measures of anterograde memory, visuospatial perception, and naming, as well as several tests that are known to be sensitive to lesions of the frontal lobes. PD patients of normal mental status as measured by the Mini-Mental State Examination performed normally on the naming, line orientation, and verbal recognition memory tests but exhibited deficits on verbal recall. On tests of frontal lobe function, these patients showed mild deficits on a category fluency task and on the Wisconsin Card Sorting Test. However, their errors on the latter were not typical of patients with frontal lesions, and they performed normally on a letter fluency task and exhibited normal release from proactive interference. Patients of lower than normal mental status performed poorly on nearly all of the cognitive tasks including confrontational naming, line orientation, and recognition memory, suggesting that their cerebral dysfunction extended beyond subcortical-frontal circuits. The present study supports the usefulness of the Mini-Mental State Examination for cognitive screening of PD patients, but does not support the hypothesis that the cognitive impairments in PD arise principally from disruption of frontal lobe functioning.     

Overestimation and Unreliability in “Feeling-of-Doing” Judgments about Temporal Ordering Performance: Impaired Self-Awareness Following Frontal Lobe Damage

“Feeling-of-doing” accuracy in a temporal ordering task in 33 patients with frontal lobe lesions and a matched control group was investigated. The temporal ordering task used word lists that had high, medium, or no semantic interrelatedness. Patients with frontal lobe lesions showed an impairment in temporal ordering across all three word lists. Both groups performed better on the lists with higher semantic interrelatedness. Patients with frontal lobe lesions overestimated their ability to order words accurately. On the less semantically interrelated lists, metamemory judgment in patients with frontal lesions did not correlate with their performance. These results indicate that both temporal order judgment and metacognitive decisions about temporal order judgment are subserved by the prefrontal cortex and further clarifies the role of the frontal lobes in behavioral monitoring.     

Supervisory attentional system in nonamnesic alcoholic men.

BACKGROUND: Many studies have shown that recently detoxified alcoholic persons perform poorly on tasks thought to be sensitive to frontal lobe damage, supporting the hypothesis that the frontal lobes are highly vulnerable to chronic alcohol consumption. However, it appeared that most of the executive tasks used in these studies also involved nonexecutive components, and these tasks had been shown to be impaired as a result of nonfrontal lobe lesions. In this study, we examined further the "frontal lobe vulnerability" hypothesis using executive tasks, proved to be associated with frontal lobe functioning, that allowed us to distinguish the relative importance of executive and nonexecutive processes. METHOD: Thirty recently detoxified asymptomatic male alcoholic inpatients and 30 control subjects were tested for planning, inhibition, rule detection, and coordination of dual task, as well as the speed of processing and nonexecutive functions (such as short-term memory storage). RESULTS: Alcoholics performed worse than controls in almost all tasks assessing executive functions. However, they were not slower than the controls and showed normal results for nonexecutive functions. CONCLUSIONS: Chronic alcohol consumption seems to be associated with severe executive function deficits, which are still present after a protracted period of alcohol abstinence. These data support the idea that the cognitive deficits in recently detoxified sober alcoholic subjects are due, at least partly, to frontal lobe dysfunctioning.     

Frontal lobes and inhibitory function

Neuropsychological studies using traditional tasks of inhibitory functions, such as the Wisconsin card sorting test (WCST) and the Go/No-Go Task have revealed that the frontal lobe is responsible for several types of inhibitory functions. However, the detailed psychological nature of the inhibitory functions and the precise location of their critical foci within the frontal lobe remain to be investigated. Functional magnetic resonance imaging provides spatial and temporal resolution that allowed us to illuminate at least 4 frontal regions involved in inhibitory functions: the dorsolateral, ventrolateral, and rostral parts of the frontal lobe and the presupplementary motor area (preSMA). The ventrolateral part of the frontal lobe in the right hemisphere was activated during response inhibition. The preSMA in the left hemisphere was activated during inhibition of proactive interference immediately after the dimension changes of the WCST. The rostral part of the frontal lobe in the left hemisphere was activated during inhibition long after the dimension changes. The dorsolateral part of the frontal lobe in the left hemisphere was activated at the dimension changes in the first time, but not in the second time. These findings provide clues to our understanding of functional differentiation of inhibitory functions and their localization in the frontal lobe.