Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n = 47) and posterior (n = 20) lesions. Patients and controls (n = 35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left—phonemic and right—design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions.

In this study we report a patient (A.N.G.) who, following a malignant left frontal meningioma impinging upon Brodmann area 45, presented a 'pure' dynamic aphasia. Her spontaneous speech was markedly reduced in the absence of any syntactical impairment. Her naming, repetition and reading skills were completely normal. Two experimental investigations were carried out. The first investigation found that A.N.G. had a profound impairment in phrase and sentence generation tasks given a verbal context. However, her verbal generative skills were normal when she was asked to describe pictorial scenes and complex actions. Moreover, it was found that A.N.G. had no difficulty ordering the constituent words of a sentence. Thus, it was concluded that her verbal planning skills were intact. The second investigation tested a hypothesis that dynamic aphasia is due to an inability to select a verbal response option whenever the stimulus activates many competing verbal responses. Predictions based upon this hypothesis were confirmed on three different verbal generation tasks. It was found that our patient's grave verbal generative impairment was present for tasks involving stimuli which activate many potential responses. However, it was absent for tasks involving stimuli which activate few or only a single 'prepotent' response. The findings are discussed with reference to traditional interpretations of dynamic aphasia and more general interpretations of prefrontal cortex functioning. On the basis of a computational model of prefrontal cortex functioning, we propose that pure dynamic aphasia may be caused by damage to a 'context' module containing units responsible for selection of verbal response options. Moreover, it is suggested that our findings support the view that Brodmann area 45 is involved in verbal response generation to stimuli which activate many potential response options.

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated neurological disorder that (among other severe neuropsychiatric symptoms) affects cognition. This study aimed to summarize current knowledge regarding the rates, nature, and predictors of neuropsychological dysfunction in patients recovering from anti-NMDAR encephalitis. Method: A systematic review of studies describing neuropsychological outcomes following anti-NMDAR encephalitis was conducted. Electronic databases Medline, PsycINFO, EMBASE, and CINAHL were searched from inception to September 2016. Results were summarized using descriptive statistics and a series of chi-square analyses. Results: Of 4030 identified studies, 44 were included. These reported neuropsychological outcomes for 109 treated patients (83.5% female, M_age = 22.5 years, range = 2–67) recovering from anti-NMDAR encephalitis. High rates of neuropsychological dysfunction were identified, with diverse impairments of variable severity documented in >75% of patients at assessments conducted during acute, subacute, and longer term recovery periods. Despite this, cognitive outcomes were ultimately considered favorable in most cases (74.3%). This estimate does not account for the potential impact of relapses. The frequency of impairments in overall intellectual functioning, language, attention, working memory, and visuospatial functions were significantly higher within the acute recovery period than in later phases of convalescence. However, rates of impaired processing speed, episodic memory, and aspects of executive functioning were consistent across time points. Adverse neuropsychological outcomes occurred at significantly higher frequency in patients where immunotherapy was delayed, χ²(1, N = 66) = 10.84, p < .003. Conclusions: Neuropsychological deficits are prevalent at all points of recovery from anti-NMDAR encephalitis, although improvement in cognitive outcomes can be expected as patients recover. Some cognitive deficits may be less likely than others to resolve. Close neuropsychological monitoring is warranted in this population. Longitudinal studies of neuropsychological functioning of patients with anti-NMDAR encephalitis are needed to accurately inform prognosis.

Different theoretical interpretations have been offered in order to account for a specific language impairment termed dynamic aphasia. We report a patient (CH) who presented with a dynamic aphasia in the context of nonfluent progressive aphasia. CH had the hallmark of reduced spontaneous speech in the context of preserved naming, reading, and single word repetition and comprehension. Articulatory and grammatical difficulties were also present. CH had a very severe verbal generation impairment despite being able to describe pictorial scenes and action sequences well. In the experimental investigations CH was severely impaired in word, phrase, and sentence generation tasks when many competing responses were activated by a stimulus. By contrast, he could generate verbal responses satisfactorily when a dominant response was activated by a stimulus. For the first time, we demonstrated that the verbal generation impairment was specific to the production of language. Strikingly, our patient was unimpaired on a number of nonverbal generation tasks (e.g., design fluency, gesture fluency, and motor movement generation). MRI revealed focal left frontal atrophy that predominantly affected Brodmann's Areas 44 and 45. Our findings are discussed with reference to alternative accounts of dynamic aphasia and models of speech production. We interpret our patient's impairment as being underpinned by an inability to select between competing verbal response options. This interpretation converges with evidence from the neuroimaging literature, which implicates the left inferior frontal gyrus in the selection of a response among competing information. We conclude that the left posterior inferior frontal gyrus is involved in the generation of verbal output, and specifically in the selection between competing verbal responses.

Verbal initiation, suppression and strategy generation/use are cognitive processes widely held to be supported by the frontal cortex. The Hayling Test was designed to tap these cognitive processes within the same sentence completion task. There are few studies specifically investigating the neural correlates of the Hayling Test but it has been primarily used to detect frontal lobe damage. This study investigates the components of the Hayling Test in a large sample of patients with unselected focal frontal (n = 60) and posterior (n = 30) lesions. Patients and controls (n = 40) matched for education, age and sex were administered the Hayling Test as well as background cognitive tests. The standard Hayling Test clinical measures (initiation response time, suppression response time, suppression errors and overall score), composite errors scores and strategy-based responses were calculated. Lesions were analysed by classical frontal/posterior subdivisions as well as a finer-grained frontal localization method and a specific contrast method that is somewhat analogous to voxel-based lesion mapping methods. Thus, patients with right lateral, left lateral and superior medial lesions were compared to controls and patients with right lateral lesions were compared to all other patients. The results show that all four standard Hayling Test clinical measures are sensitive to frontal lobe damage although only the suppression error and overall scores were specific to the frontal region. Although all frontal patients produced blatant suppression errors, a specific right lateral frontal effect was revealed for producing errors that were subtly wrong. In addition, frontal patients overall produced fewer correct responses indicative of developing an appropriate strategy but only the right lateral group showed a significant deficit. This problem in strategy attainment and implementation could explain, at least in part, the suppression error impairment. Contrary to previous studies there was no specific frontal effect for verbal initiation. Overall, our results support a role for the right lateral frontal region in verbal suppression and, for the first time, in strategy generation/use.