Mark D. Allen

Functional neuroimaging evidence for high cognitive effort on the Word Memory Test in the absence of external incentives.

Primary objective: This study presents data from a functional neuroimaging experiment which brings into question whether poor performance on the Word Memory Test (WMT) can be construed as straightforward evidence for ‘poor effort’ in the context of cognitive assessment, as asserted in a recent report in this journal. Methods and procedures: Functional magnetic resonance image (fMRI) data were acquired from four participants without brain injury who engaged in the delayed recognition (DR) portion of Greens WMT protocol. Outcomes and results: Compared to a simple perceptual identification control task, this study found a highly reliable activation pattern across all participants which was restricted almost exclusively to cortical areas most commonly associated with task difficulty, memory load, concentration and other forms of cognitive effort These areas include dorsolateral prefrontal cortex, anterior insula, superior parietal cortex and the dorsal anterior cingulate. Conclusions: These findings demonstrate that the WMT activates numerous cortical regions that are critical for cognitive effort. Given the extensive neural network necessary to perform the WMT, this study raises important questions about what WMT ‘failure’ truly means in patients with traumatic brain injury, who have increased likelihood of disruption within this neural network of vision, language, attention, effort and working memory.

An fMRI study of sex differences in brain activation during object naming.

We present a neuroimaging experiment that examines whether males and females use distinct brain systems while performing a confrontational naming task, with specific attention to the possibility of laterality differences, as suggested by some theories of sex differences in language processing. We further address whether sex-based differences in functional brain organization might interact with object category distinctions, given that previous behavioral studies have shown some consistent processing differences between the sexes with respect to tools versus plants. Functional magnetic resonance imaging (fMRI) data were collected from 26 participants (13 males and 13 females). Main effect and interaction analyses reveal no discernable laterality differences between the sexes. All other results, however, were consistent with previous object-naming studies. Global effects revealed dominant foci in fusiform gyrus, left posterior middle temporal gyrus, left basal ganglia/thalamus, left middle/inferior frontal gyri, left frontal operculum, left supplementary motor area/dorsal anterior cingulate, and left pre-central gyrus. Main contrasts for tools versus plants were likewise consistent with previous fMRI studies. Although men and women showed no discernable activation differences, hemispheric or otherwise, when collapsed across object categories, sex-by-category analyses showed selective activation for females in dorsal anterior cingulate gyrus and left posterior middle temporal gyrus for tools, and selective activation for males in left posterior middle temporal gyrus for plants. We discuss the relevance of these sex-by-category effects to previous behavioral findings and theories that relate to vocabulary differences between the sexes.

A functional neuroimaging analysis of the Trail Making Test-B: Implications for clinical application

Recent progress has been made using fMRI as a clinical assessment tool, often employing analogues of traditional “paper and pencil” tests. The Trail Making Test (TMT), popular for years as a neuropsychological exam, has been largely ignored in the realm of neuroimaging, most likely because its physical format and administration does not lend itself to straightforward adaptation as an fMRI paradigm. Likewise, there is relatively more ambiguity about the neural systems associated with this test than many other tests of comparable clinical use. In this study, we describe an fMRI version of Trail Making Test-B (TMTB) that maintains the core functionality of the TMT while optimizing its use for both research and clinical settings. Subjects (N = 32) were administered the Functional Trail Making Test-B (f-TMTB). Brain region activations elicited by the f-TMTB were consistent with expectations given by prior TMT neurophysiological studies, including significant activations in the ventral and dorsal visual pathways and the medial pre-supplementary motor area. The f-TMTB was further evaluated for concurrent validity with the traditional TMTB using an additional sample of control subjects (N = 100). Together, these results support the f-TMTB as a viable neuroimaging adaptation of the TMT that is optimized to evoke maximally robust fMRI activation with minimal time and equipment requirements.

An fMRI investigation of emotional processing of body shape in bulimia nervosa

OBJECTIVE Cognitive-behavioral theories of eating disorder etiology emphasize the role of body-oriented self-schemas. Examination of brain regions associated with self-referencing, such as medial prefrontal cortex (mPFC), during processing of body-related stimuli can thus be utilized to evaluate such theories. METHOD Twelve women with bulima nervosa (BN) and 12 comparison women underwent functional brain imaging while viewing images of women with either thin or overweight bodies in a self-referencing context. RESULTS For thin bodies, there was no significant mPFC activation for either group. For overweight bodies, mPFC activation was significantly greater for BN patients, with a focus in subregions associated with emotional processing. DISCUSSION These findings are consistent with cognitive models of eating disorders which posit that negative body-related stimuli are more central to self-schemas and more emotionally provocative in persons with eating disorders, lending support to treatment and prevention interventions that emphasize body overvaluation as a primary target of change.

Clinical Application of Standardized Cognitive Assessment Using fMRI. II. Verbal Fluency

In this study, we describe an fMRI version of the verbal fluency test. This is the second in a series of fMRI adaptations of classical neuropsychological tests, for which normative samples of functional activation have been collected from unimpaired control subjects and structured in a manner that makes individual patient evaluation possible in terms of familiar z-score distributions. This fMRI protocol is shown to have strong convergent validity with the FAS phonemic fluency test and to elicit activation patterns highly consistent with a large body of previous neuroimaging studies of verbal fluency. We also present a case study, in which we report concurrent data from a patient with selective deficits in verbal processing, using both conventional neuropsychological and fMRI approaches. These analyses reveal striking correspondences between the deficits present in this patient on cognitive performance tests and the equally selective patterns of deviation present in his fMRI data.

Different patterns of cerebral activation in genuine and malingered cognitive effort during performance on the Word Memory Test

Primary objective: The Word Memory Test (WMT) is a popular symptom validity test in which individuals are required to remember and recall semantically-related word pairs. Research shows successful WMT completion employs a wide neural network which is involved in tasks requiring high cognitive effort. The primary purpose of this study was to replicate earlier fMRI findings using a larger sample and extend previous findings by including male and female subjects. The second purpose was to investigate the neural networks involved during intentional malingering on the WMT. Research design: For all trials, a time-series ANCOVA design was implemented using SPM5 software. Methods and procedures: Ten subjects (five male and five female) underwent fMRI imaging while completing the WMT in full-effort and simulated poor effort conditions. Main outcome and results: Full-effort trials found activation peaks in dorsolateral prefrontal cortex, superior parietal lobe, anterior cingulate, bilateral lingual cortices and anterior insula/frontal operculum, supporting earlier findings. Simulated poor effort trials had similar foci of activation, with additional peak strength in surrounding cortical regions identified previously as relevant to simulated malingering. No sex differences were observed in either condition. Conclusions: These findings demonstrate the neural underpinnings of WMT performance in normal and simulated performance.

Clinical Application of Standardized Cognitive Assessment Using fMRI. I. Matrix Reasoning

Functional MRI is increasingly recognized for its potential as a powerful new tool in clinical neuropsychology. This is likely due to the fact that, with some degree of innovation, it is possible to convert practically any familiar cognitive test into one that can be performed in the MRI scanning environment. However, like any assessment approach, meaningful interpretation of fMRI data for the purpose of patient evaluation crucially requires normative data derived from a sample of unimpaired persons, against which individual patients may be compared. Currently, no such normative data are available for any fMRI-based cognitive testing protocol. In this paper, we report the first of a series of fMRI-compatible cognitive assessment protocols, a matrix reasoning test (f-MRT), for which normative samples of functional activation have been collected from unimpaired control subjects and structured in a manner that makes individual patient evaluation possible in terms of familiar z-score distributions. Practical application of the f-MRT is demonstrated via a contrastive case-study of two individuals with cognitive impairment in which fMRI data identifies subtleties in patient deficits otherwise missed by conventional measures of performance.

The functional magnetic resonance imaging-based verbal fluency test in obsessive-compulsive disorder.

Clinical use of functional magnetic resonance imaging (fMRI) in obsessive–compulsive disorder (OCD) is limited by a relative absence of fMRI task development, standardization, and normative performance databases. We investigated the fMRI-based verbal fluency test (f-VFT) by quantitatively evaluating brain activation patterns in OCD participants (8 females and 4 males) compared with a normative database (16 females and 16 males). At the group level, OCD participants and references had highly similar activation in left-hemisphere language regions, including the precentral/premotor cortex, thalamus, basal ganglia, and inferior frontal gyrus/frontal operculum. At the interindividual level, however, the OCD group had highly variable activation patterns in the dorsal and ventral regions of the pre-supplementary motor area (pre-SMA) that may correspond with differences in demographic and clinical variables. Further, there were significant correlations in the OCD participants between pre-SMA dorsal and ventral activation and between dorsal pre-SMA activation and perfectionism. Our findings suggest considerable functional anatomical overlap in left-hemisphere language regions between OCD participants and references but significantly higher pre-SMA interindividual variability in OCD compared to the reference group that may be relevant in clinical fMRI application and the theoretical understanding of OCD.

Assessment of brain activity during memory encoding in a narcolepsy patient on and off modafinil using normative fMRI data

We present behavioral and functional magnetic resonance imaging (fMRI) findings of a 20-year-old female with narcolepsy who completed a standardized fMRI-adapted face memory task both ‘off’ and ‘on’ modafinil compared to a normative sample (N = 38). The patient showed poor recognition performance off modafinil (z = −2.03) but intact performance on modafinil (z = 0.78). fMRI results showed atypical activation during memory encoding off modafinil, with frontal lobe hypoactivity, but hippocampal hyperactivity, whereas all brain regions showed more normalized activation on modafinil. Results from this limited study suggest hippocampal and frontal alterations in individuals with narcolepsy. Further, the results suggest the hypothesis that modafinil may affect brain activation in some people with narcolepsy.

The preservation of verb subcategory knowledge in a spoken language comprehension deficit.

Patient WBN has a lexical-semantic deficit resulting in impaired performance on language comprehension tasks that require access to verb meanings in both single-word and sentence contexts. However, WBN shows no such comprehension impairment with respect to lexical syntax. Specifically, he performs without error on comprehension tasks that rely on knowledge of lexical-specific verb subcategory requirements. This performance pattern supports theories of lexical representation and processing in which lexical syntactic information may be encoded and retrieved independently from lexical semantic information.