Inhibitory control in obsessive compulsive disorder: A systematic review and activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

BACKGROUND: Patients with obsessive compulsive disorder (OCD) often show deficits in inhibitory control, which may underlie poor control over obsessions and compulsions. Several functional magnetic resonance imaging (fMRI) experiments utilizing a variety of tasks have investigated the neural correlates of inhibitory control in OCD. Evidence from existing meta-analyses suggests aberrant activation of regions in fronto-striatal circuits during inhibitory control. However, new fMRI articles have since been published, and a more rigorous methodology for neuroimaging meta-analyses is now available. OBJECTIVES: First, to reevaluate the evidence for abnormal brain activation during performance of inhibitory control tasks in OCD while adhering to current best practices for meta-analyses, and second, to extend previous findings by separately assessing different subprocesses of inhibitory control. METHOD: We systematically searched Web of Knowledge, ScienceDirect, Scopus, PubMed and the functional BrainMap database for fMRI articles that compared activation during performance of inhibitory control tasks in patients with OCD and healthy control (HC) subjects. Thirty-five experiments from 21 articles met our criteria for inclusion. We first performed activation-likelihood-estimation meta-analyses to elucidate brain areas in which case-control activation differences converged across articles and tasks. We then aimed to extend previous work by separately evaluating experiments requiring inhibition of a prepotent response without execution of an alternative response (i.e., response inhibition) and experiments requiring inhibition of a prepotent response and execution of an alternative response (i.e., cognitive inhibition). RESULTS: The 35 experiments included a total of 394 patients and 410 controls. We did not find evidence of abnormal brain activation in OCD during inhibitory control when pooling data from all experiments. Analysis restricted to cognitive inhibition experiments showed abnormal activation of the dorsal anterior cingulate cortex (dACC; P = .04, cluster-level familywise error-corrected, cluster volume of 824 mm3). We did not have sufficient data to evaluate response inhibition experiments separately. CONCLUSION: Findings of abnormal brain activation in OCD from different inhibitory control tasks do not appear to converge on the same brain regions, but the dACC may be implicated in abnormal cognitive inhibition. Our findings highlight a need for experiments that specifically target subprocesses of inhibitory control to achieve a more differentiated understanding of the neural correlates for impaired inhibitory control in OCD.

Mapping grip-force related brain activity after a fatiguing motor task in multiple sclerosis.

BACKGROUND: Motor fatigue is common in multiple sclerosis (MS), but its pathophysiology is still poorly understood. Here we used functional magnetic resonance imaging (fMRI) to delineate how the acute induction of motor fatigue alters functional activity of the motor system and how these activity changes are related to motor fatigue. METHOD: Forty-four right-handed mildly disabled patients with relapsing-remitting MS and 25 healthy controls performed a maximal tonic precision grip with their right hand until they developed motor fatigue. Before and after the fatiguing task, participants performed a non-fatiguing tonic grip force task, producing 15-20% of their maximum grip force based on visual feedback. Task related brain activity was mapped with blood-oxygen level dependent fMRI at 3 T. Statistical parametric mapping was used to identify relative changes in task-related activation from the pre-fatigue to the recovery MRI session. RESULTS: Following fatigue induction, task performance was perturbed in both groups, and task-related activation increased in the right (ipsilateral) primary motor hand area. In patients with MS, task-related activity increased bilaterally during the recovery phase in the ventrolateral portion of the middle putamen and lateral prefrontal cortex relative to controls. The more patients increased task-related activity in left dorsal premotor cortex after the fatiguing task, the less they experienced motor fatigue during daily life. CONCLUSION: Patients with MS show enhanced functional engagement of the associative cortico-basal ganglia loop following acute induction of motor fatigue in the contralateral hand. This may reflect increased mental effort to generate movements in the recovery phase after fatigue induction. The ability to recruit the contralateral dorsal premotor cortex after fatigue induction may constitute a protective mechanism against experiencing motor fatigue in everyday life.

Sense of agency as synecdoche: Multiple neurobiological mechanisms may underlie the phenomenon summarized as sense of agency.

Functional magnetic resonance imaging (fMRI) studies on the sense of agency (SoA) have yielded heterogeneous findings identifying regional brain activity during tasks that probed SoA. In this review, we argue that the reason behind this between-study heterogeneity is a "synecdochic" way the field conceptualizes and studies SoA. Typically, a single feature is experimentally manipulated and then this is interpreted as covering all aspects of SoA. The purpose of this paper is to give an overview of the fMRI studies of SoA and attempt to provide meaningful categories whereby the heterogeneous findings may be classified. This classification is based on a separation of the experimental paradigms (Feedback Manipulations of ongoing movements, Action-Effect, and Sensory Attenuation) and type of report employed (implicit, explicit reports of graded or dichotic nature, and whether these concern self-other distinctions or sense of control). We only find that Feedback Manipulation and Action-Effect share common activation in supplementary motor area, insula and cerebellum in positive SoA and inferior frontal gyrus in the negative SoA, but observe large networks related to SoA only in Feedback Manipulation studies. To illustrate the advantages of this approach, we discuss the findings from an fMRI study which we conducted, within this framework.

White matter diffusivity and its correlations to state measures of psychopathology in male refugees with posttraumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a heterogenous condition and the underlying neurobiology is still poorly understood. In this study, we tested the hypothesis that PTSD is associated with microstructural changes in white matter (WM) fibre tracts that connect regions involved in emotional processing, memory, attention, and language. Furthermore, we examined how different response patterns to individualized trauma-provoking stimuli related to underlying WM microstructure. Sixty-nine trauma-affected male refugees with PTSD (N = 38) or without PTSD (N = 31) underwent clinical assessments and diffusion-weighted magnetic resonance imaging (DWI) of the whole brain at 3 Tesla. Diffusion tensor metrics were computed from DWI data and used to characterize regional white-matter microstructure. An automated tract segmentation method was used to extract diffusion tensor metrics from subject-based reconstructions of tract segments (ROI), including uncinate fasciculus (UF), cingulum bundle (CB), superior longitudinal fasciculus (SLF) in three subdivisions (SLF I - III), and fibre bundles connecting orbito-frontal cortex to striatum (OF-ST). Outside the scanner we obtained measures of immediate (state) arousal, avoidance and dissociation symptoms assessed in response to auditory exposure to a personal traumatic memory. Using mean FA of the middle part of each ROI, mixed ANOVA revealed a significant interaction between group, ROI and hemisphere. Post-hoc comparisons showed that, relative to refugees without PTSD, refugees with PTSD had lower FA in right CB, left SLF-I, bilateral OF-ST and bilateral SLF-II. Mean FA scaled negatively with avoidance in right CB while mean FA in bilateral UF scaled positively with individual scores reflecting dissociation symptoms. The results support a pathophysiological model of PTSD that implicates limbic structures, prefrontal cortex and striatum. The results also emphasize the need to consider PTSD's multifaceted manifestations when searching for functional-structural relationships.

Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis.

BACKGROUND: Smoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS. OBJECTIVE: To determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS). METHOD: In this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS. RESULTS: Smoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8-2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9--4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02-0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66--0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2--3.4, p = 0.0018). CONCLUSION: If validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS.

Assessing paedophilia based on the haemodynamic brain response to face images.

OBJECTIVES: Objective assessment of sexual preferences may be of relevance in the treatment and prognosis of child sexual offenders. Previous research has indicated that this can be achieved by pattern classification of brain responses to sexual child and adult images. Our recent research showed that human face processing is tuned to sexual age preferences. This observation prompted us to test whether paedophilia can be inferred based on the haemodynamic brain responses to adult and child faces. METHODS: Twenty-four men sexually attracted to prepubescent boys or girls (paedophiles) and 32 men sexually attracted to men or women (teleiophiles) were exposed to images of child and adult, male and female faces during a functional magnetic resonance imaging (fMRI) session. RESULTS: A cross-validated, automatic pattern classification algorithm of brain responses to facial stimuli yielded four misclassified participants (three false positives), corresponding to a specificity of 91% and a sensitivity of 95%. CONCLUSIONS: These results indicate that the functional response to facial stimuli can be reliably used for fMRI-based classification of paedophilia, bypassing the problem of showing child sexual stimuli to paedophiles.

Right-hemispheric processing of non-linguistic word features: implications for mapping language recovery after stroke.

Verbal stimuli often induce right-hemispheric activation in patients with aphasia after left-hemispheric stroke. This right-hemispheric activation is commonly attributed to functional reorganization within the language system. Yet previous evidence suggests that functional activation in right-hemispheric homologues of classic left-hemispheric language areas may partly be due to processing nonlinguistic perceptual features of verbal stimuli. We used functional MRI (fMRI) to clarify the role of the right hemisphere in the perception of nonlinguistic word features in healthy individuals. Participants made perceptual, semantic, or phonological decisions on the same set of auditorily and visually presented word stimuli. Perceptual decisions required judgements about stimulus-inherent changes in font size (visual modality) or fundamental frequency contour (auditory modality). The semantic judgement required subjects to decide whether a stimulus is natural or man-made; the phonologic decision required a decision on whether a stimulus contains two or three syllables. Compared to phonologic or semantic decision, nonlinguistic perceptual decisions resulted in a stronger right-hemispheric activation. Specifically, the right inferior frontal gyrus (IFG), an area previously suggested to support language recovery after left-hemispheric stroke, displayed modality-independent activation during perceptual processing of word stimuli. Our findings indicate that activation of the right hemisphere during language tasks may, in some instances, be driven by a "nonlinguistic perceptual processing" mode that focuses on nonlinguistic word features. This raises the possibility that stronger activation of right inferior frontal areas during language tasks in aphasic patients with left-hemispheric stroke may at least partially reflect increased attentional focus on nonlinguistic perceptual aspects of language.

A local signature of LTP- and LTD-like plasticity in human NREM sleep.

Paired associative stimulation (PAS) repeatedly pairs electrical nerve stimulation with transcranial magnetic stimulation of the contralateral motor hand area (M1(HAND)). Depending on the interstimulus interval, PAS can induce a long-term potentiation (LTP)-like facilitation or long-term depression (LTD)-like suppression of cortical excitability. In three experimental sessions, 12 awake men received PAS of the right median nerve and left M1(HAND) in the evening before sleep. To optimize the timing of paired stimulation in M1(HAND), the interstimulus interval of PAS was adjusted to the individual N20-latency of the somatosensory evoked potential to induce LTP-like effects (PAS(N20+2ms)), LTD-like effects (PAS(N20-5ms)), or no timing-dependent after-effects (PAS(control)). Motor-evoked potentials (MEPs) showed high interindividual variations in the conditioning effects of PAS(N20+2ms) and PAS(N20-5ms) on cortical excitability. However, PAS(control) allowed us to adjust for any unspecific stimulation effects and the MEP increase after PAS(N20+2ms) differed significantly from the MEP decrease after PAS(N20-5ms). PAS(N20+2ms) and PAS(N20-5ms) also had a differential effect on regional expression of slow waves and slow spindle activity during the first hour of subsequent non-rapid eye movement (NREM) sleep. At the electrode sites overlying the conditioned M1(HAND) and the adjacent premotor cortex, local expression of slow spindle activity was significantly correlated with interindividual differences in the efficacy of PAS(N20+2ms) and PAS(N20-5ms) to potentiate or suppress cortical excitability. This correlation indicates that PAS shapes the local regulation of slow sleep spindles during subsequent NREM sleep.