Medial Frontal Regions Research Articles

Non-invasive Brain Stimulation for the Treatment of Gilles de la Tourette Syndrome.

Gilles de la Tourette Syndrome is a multifaceted neuropsychiatric disorder typically commencing in childhood and characterized by motor and phonic tics. Its pathophysiology is still incompletely understood. However, there is convincing evidence that structural and functional abnormalities in the basal ganglia, in cortico-striato-thalamo-cortical circuits, and some cortical areas including medial frontal regions and the prefrontal cortex as well as hyperactivity of the dopaminergic system are key findings. Conventional therapeutic approaches in addition to counseling comprise behavioral treatment, particularly habit reversal therapy, oral pharmacotherapy (antipsychotic medication, alpha-2-agonists) and botulinum toxin injections. In treatment-refractory Tourette syndrome, deep brain stimulation, particularly of the internal segment of the globus pallidus, is an option for a small minority of patients. Based on pathophysiological considerations, non-invasive brain stimulation might be a suitable alternative. Repetitive transcranial magnetic stimulation appears particularly attractive. It can lead to longer-lasting alterations of excitability and connectivity in cortical networks and inter-connected regions including the basal ganglia through the induction of neural plasticity. Stimulation of the primary motor and premotor cortex has so far not been shown to be clinically effective. Some studies, though, suggest that the supplementary motor area or the temporo-parietal junction might be more appropriate targets. In this manuscript, we will review the evidence for the usefulness of repetitive transcranial magnetic stimulation and transcranial electric stimulation as treatment options in Tourette syndrome. Based on pathophysiological considerations we will discuss the rational for other approaches of non-invasive brain stimulation including state informed repetitive transcranial magnetic stimulation.

Cortical hypometabolism associated with cognitive impairment of multiple system atrophy

IntroductionCognitive impairment is not uncommon in patients with multiple system atrophy (MSA). This study investigated the cortical metabolic changes of MSA and the cortical structure associated with cognitive impairment. MethodsThe study included probable/definite MSA patients who underwent fluorodeoxyglucose positron emission tomography and cognitive evaluation based on mini-mental status examination (MMSE). Cerebral metabolism of the entire MSA patients (n = 88) was compared with healthy controls (n = 19) by voxel-wise statistical parametric mapping. Eight brain regions of interest (ROIs) were selected accordingly: the dorsolateral prefrontal, medial superior frontal, insular, posterior parietal, precuneus, lateral temporal, medial temporal, and posterior cingulate regions. Using validated population-based norms, MSA patients were divided by MMSE z-scores into MSA with cognitive dysfunction (MSA-D, n = 30) and without cognitive dysfunction (MSA-ND, n = 58). Regional metabolism of the selected ROIs was compared between the MSA-D and MSA-ND groups by logistic regression models. Correlations between the regional metabolism of the selected ROIs and MMSE z-scores were analyzed with a linear regression model. ResultsVoxel-wise analysis showed hypometabolism in the frontal, temporal, parietal, and limbic areas in MSA patients than in controls. ROI-based comparisons showed that metabolism in the posterior cingulate (P = 0.006) and medial temporal (P = 0.039) regions was significantly lower in the MSA-D than in the MSA-ND group. The degree of posterior cingulate metabolism correlated significantly with MMSE z-score (P = 0.023). ConclusionsMSA shows fronto-temporo-parietal cortical involvement. Hypometabolism of the limbic regions is associated with cognitive impairment in MSA.

Volumetric brain magnetic resonance imaging analysis in children with obstructive sleep apnea

ObjectivesPediatric Obstructive Sleep Apnea (OSA) is associated with neurocognitive deficits. Cerebral structural alterations in the frontal cortex, cerebellum, and hippocampus have been reported in adult OSA patients. These brain areas are important for executive functioning, motor regulation of breathing, and memory function, respectively. Corresponding evidence comparing cerebral structures in pediatric OSA patients is limited. The objective of this study is to investigate MRI differences in cortical thickness and cortical volume in children with and without OSA. Study designProspective, single institutional case-control study. MethodsForty-five children were recruited at a pediatric tertiary care center (27 with OSA; mean age 9.9 ± 1.9 years, and 18 controls; mean age 10.5 ± 1.0 years). The OSA group underwent magnetic resonance imaging (MRI), polysomnography (PSG) and completed the Pediatric Daytime Sleepiness Scale (PDSS) and the Child's Sleep Habits Questionnaire (CSHQ). High-resolution T1-weighted MRI was utilized to examine cortical thickness and gray and white matter volume in children with OSA compared to a healthy group of demographically-comparable children without OSA selected from a pre-existing MRI dataset. ResultsChildren with OSA showed multiple regions of cortical thinning primarily in the left hemisphere. Reduced gray matter (GM) volume was noted in the OSA group in multiple frontal regions of the left hemisphere (superior frontal, rostral medial frontal, and caudal medial frontal regions). Reduced white matter (WM) volume in both the left and right hemisphere was observed in regions of the frontal, parietal, and occipital lobes in children with OSA. ConclusionThis study noted differences in cortical thickness and GM and WM regional brain volumes in children with OSA. These findings are consistent with other pediatric studies, which also report differences between healthy children and those with OSA. We found that the severity of OSA does not correlate with the extent of MRI alterations.

Neural Mechanisms of Memory Enhancement and Impairment Induced by Visual Statistical Learning.

Prior research has reported that the medial temporal, parietal, and frontal brain regions are associated with visual statistical learning (VSL). However, the neural mechanisms involved in both memory enhancement and impairment induced by VSL remain unknown. In this study, we examined this issue using event-related fMRI. fMRI data from the familiarization scan showed a difference in the activation level of the superior frontal gyrus (SFG) between structured triplets, where three objects appeared in the same order, and pseudorandom triplets. More importantly, the precentral gyrus and paracentral lobule responded more strongly to Old Turkic letters inserted into the structured triplets than to those inserted into the random triplets, at the end of the familiarization scan. Furthermore, fMRI data from the recognition memory test scan, where participants were asked to decide whether the objects or letters shown were old (presented during familiarization scan) or new, indicated that the middle frontal gyrus and SFG responded more strongly to objects from the structured triplets than to those from the random triplets, which overlapped with the brain regions associated with VSL. In contrast, the response of the lingual gyrus, superior temporal gyrus, and cuneus was weaker to letters inserted into the structured triplets than to those inserted into the random triplets, which did not overlap with the brain regions associated with observing the letters during the familiarization scan. These findings suggest that different brain regions are involved in memory enhancement and impairment induced by VSL.

Cerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer's Disease.

Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer's disease (AD). We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort. Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study Cognition Study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors. After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate & precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBF in the bilateral posterior and middle cingulate and parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions. Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as a staging biomarker of cognitive status.

Outcome prediction with resting-state functional connectivity after cardiac arrest

Predicting outcome in comatose patients after successful cardiopulmonary resuscitation is challenging. Our primary aim was to assess the potential contribution of resting-state-functional magnetic resonance imaging (RS-fMRI) in predicting neurological outcome. RS-fMRI was used to evaluate functional and effective connectivity within the default mode network in a cohort of 90 comatose patients and their impact on functional neurological outcome after 3 months. The RS-fMRI processing protocol comprises the evaluation of functional and effective connectivity within the default mode network. Seed-to-voxel and ROI-to-ROI feature analysis was performed as starting point for a supervised machine-learning approach. Classification of the Cerebral Performance Category (CPC) 1–3 (good to acceptable outcome) versus CPC 4–5 (adverse outcome) achieved a positive predictive value of 91.7%, sensitivity of 90.2%, and accuracy of 87.8%. A direct link to the level of consciousness and outcome after 3 months was identified for measures of segregation in the precuneus, in medial and right frontal regions. Thalamic connectivity appeared significantly reduced in patients without conscious response. Decreased within-network connectivity in the default mode network and within cortico-thalamic circuits correlated with clinical outcome after 3 months. Our results indicate a potential role of these markers for decision-making in comatose patients early after cardiac arrest.

Heart Rate and Respiration Affect the Functional Connectivity of Default Mode Network in Resting-State Functional Magnetic Resonance Imaging.

A growing number of brain imaging studies show functional connectivity (FC) between regions during emotional and cognitive tasks in humans. However, emotions are accompanied by changes in physiological parameters such as heart rate and respiration. These changes may affect blood oxygen level-dependent signals, as well as connectivity between brain areas. This study aimed to clarify the effects of physiological noise on the connectivity between areas related to the default mode network using resting-state functional magnetic resonance imaging (rs-fMRI). Healthy adult volunteers (age range: 19–51 years, mean age: 26.9 ± 9.1 years, 8 males and 8 females) underwent rs-fMRI for 10 min using a clinical 3T scanner (MAGNETOM Trio A Tim System, Siemens) with simultaneously recorded respiration and cardiac output. Physiological noise signals were subsequently removed from the acquired fMRI data using the DRIFTER toolbox. Image processing and analysis of the FC between areas related to the default mode network were performed using DPARSF. Network-Based Statistic (NBS) analysis of the functional connectome of the DMN and DMN-related area was used to perform three groups of comparison: without physiological noise correction, with cardiac noise correction, and with cardiac and respiratory noise correction. NBS analysis identified 36 networks with significant differences in three conditions in FC matrices. Post hoc comparison showed no differences between the three conditions, indicating that all three had the same networks. Among the 36 networks, strength of FC of 8 networks was modified under physiological noise correction. Connectivity between left and right anterior medial frontal regions increased strength of connectivity. These areas are located on the medial cerebral hemisphere, close to the sagittal sinus and arteries in the cerebral hemispheres, suggesting that medial frontal areas may be sensitive to cardiac rhythm close to arteries. The other networks observed temporal regions and showed a decrease in their connectivity strength by removing physiological noise, indicating that physiological noise, especially respiration, may be sensitive to BOLD signal in the temporal regions during resting state. Temporal lobe was highly correlated with anxiety-related respiration changes (Masaoka and Homma, 2000), speech processing, and respiratory sensation. These factors may affect the rs-fMRI signaling sensitivity.

Utility of FDG-PET in diagnosis of Alzheimer-related TDP-43 proteinopathy.

To evaluate FDG-PET as an antemortem diagnostic tool for Alzheimer-related TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy. We conducted a cross-sectional neuroimaging-histologic analysis of patients with antemortem FDG-PET and postmortem brain tissue from the Mayo Clinic Alzheimer's Disease Research Center and Study of Aging with Alzheimer spectrum pathology. TDP-43-positive status was assigned when TDP-43-immunoreactive inclusions were identified in the amygdala. Statistical parametric mapping (SPM) analyses compared TDP-43-positive (TDP-43[+]) with TDP-43-negative cases (TDP-43[-]), correcting for field strength, sex, Braak neurofibrillary tangle, and neuritic plaque stages. Cross-validated logistic regression analyses were used to determine whether regional FDG-PET values predict TDP-43 status. We also assessed the ratio of inferior temporal to medial temporal (IMT) metabolism as this was proposed as a biomarker of hippocampal sclerosis. Of 73 cases, 27 (37%) were TDP-43(+), of which 6 (8%) had hippocampal sclerosis. SPM analysis showed TDP-43(+) cases having greater hypometabolism of medial temporal, frontal superior medial, and frontal supraorbital (FSO) regions (p unc < 0.001). Logistic regression analysis showed only FSO and IMT to be associated with TDP-43(+) status, identifying up to 81% of TDP-43(+) cases (p < 0.001). An IMT/FSO ratio was superior to the IMT in discriminating TDP-43(+) cases: 78% vs 48%, respectively. Alzheimer-related TDP-43 proteinopathy is associated with hypometabolism in the medial temporal and frontal regions. Combining FDG-PET measures from these regions may be useful for antemortem prediction of Alzheimer-related TDP-43 proteinopathy. This study provides Class II evidence that hypometabolism in the medial temporal and frontal regions on FDG-PET is associated with Alzheimer-related TDP-43 proteinopathy.

Salience Network Atrophy Links Neuron Type-Specific Pathobiology to Loss of Empathy in Frontotemporal Dementia.

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

Brain activity reflects the predictability of word sequences in listened continuous speech

Natural speech builds on contextual relations that can prompt predictions of upcoming utterances. To study the neural underpinnings of such predictive processing we asked 10 healthy adults to listen to a 1-h-long audiobook while their magnetoencephalographic (MEG) brain activity was recorded. We correlated the MEG signals with acoustic speech envelope, as well as with estimates of Bayesian word probability with and without the contextual word sequence (N-gram and Unigram, respectively), with a focus on time-lags. The MEG signals of auditory and sensorimotor cortices were strongly coupled to the speech envelope at the rates of syllables (4–8 ​Hz) and of prosody and intonation (0.5–2 ​Hz). The probability structure of word sequences, independently of the acoustical features, affected the ≤ 2-Hz signals extensively in auditory and rolandic regions, in precuneus, occipital cortices, and lateral and medial frontal regions. Fine-grained temporal progression patterns occurred across brain regions 100–1000 ​ms after word onsets. Although the acoustic effects were observed in both hemispheres, the contextual influences were statistically significantly lateralized to the left hemisphere. These results serve as a brain signature of the predictability of word sequences in listened continuous speech, confirming and extending previous results to demonstrate that deeply-learned knowledge and recent contextual information are employed dynamically and in a left-hemisphere-dominant manner in predicting the forthcoming words in natural speech.

Changed functional connectivity at rest in functional illiterates after extensive literacy training

BackgroundAbout 6.2 million adults in Germany cannot read and write properly despite attending school for several years. They are considered to be functional illiterates (FI). Since the ability to read and write is crucial for being employed and socially accepted, we developed a special literacy training to overcome these deficits.MethodsIn this study, we investigate training-related changes in intrinsic functional connectivity (iFC) at rest in a group of 20 FI and 20 adult normal readers using resting state functional magnetic resonance imaging (rsfMRI). We used independent component analysis (ICA) to define different networks.ResultsBefore training, the between group analysis showed increased iFC in FI in a left-fronto-parietal network (LFPN; anterior insula, medial frontal cortex, lateral and frontal parietal regions) and in the Basal Ganglia network (BGN: thalamus, caudate, putamen, pallidum, amygdala, supplementary motor cortex and cingulate gyrus). Furthermore, the Visual Network-1 (VN1; temporal occipital fusiform gyrus, lateral occipital cortex, occipital pole, lingual gyrus, thalamus) showed decreased iFC in FI. After training the FI group showed reversal of the “hyperconnectivity” in middle frontal gyrus and in the frontal orbital cortex and between supramarginal gyrus and the BGN. Furthermore, functional connectivity increased in FI VN1 (lateral occipital cortex, insular cortex). These changes in connectivity correlated with gains in reading speed and spelling accuracy.ConclusionsThese findings show that poor reading and writing abilities are associated with abnormalities in iFC in several brain areas subserving cognitive processes important for reading. Intensive literacy training induces changes in the functional connectivity between and within neural networks important for literacy skills.

Task experience eliminates catecholaminergic effects on inhibitory control – A randomized, double-blind cross-over neurophysiological study

Catecholaminergic neural transmission plays an important role during the inhibition of prepotent responses. Methylphenidate (MPH) is an important drug that modulates the catecholaminergic system. However, theoretical considerations suggest that the effects of drugs (e.g. MPH) on cognitive control may depend on prior learning effects. Here we investigate this in a conflict-modulated Go/Nogo task and evaluate neurophysiological processes associated with this dynamic using EEG signal decomposition methods and source localization analysis. The behavioral data show that prior learning experiences eliminate effects of MPH on response inhibition processes. On a neurophysiological level, we show that MPH modulates specific processes in medial frontal brain regions. Although MPH seems to consistently modulate neurophysiological processes associated with response inhibition, this is no longer sufficient to modulate behavioral performance once learning or task familiarization processes have taken place. An important consequence of this study finding is that it may be important to adjust MPH dosage depending on learning effects in a specific setting to constantly increase cognitive control functions in that setting. This has important implications for clinical practice, since MPH is the first-line pharmacological therapy in attention-deficit hyperactivity disorder (ADHD). Cross-over study designs with constant doses of MPH can mask effects on cognitive functions. The impact of learning needs careful consideration in cross-over study designs examining catecholaminergic drug effects.

Pre-reading language abilities and the brain’s functional reading network in young children

Early childhood is an important period for language development that lays the foundation for future reading abilities. However, little research has focused on the functional brain systems supporting pre-reading language abilities in typically developing children. Here, we investigated functional connectivity using passive viewing functional magnetic resonance imaging (fMRI) in 50 healthy children aged 2.85–5.07 years (3.84 ​± ​0.60 years, 22 female/28 male). Children completed the NEPSY-II Phonological Processing and Speeded Naming subtests and underwent fMRI while watching a movie of their choice. Functional connectivity was measured between key brain reading areas (bilateral angular gyrus, superior temporal gyrus, and inferior frontal gyrus) and the rest of the brain. Age-adjusted pre-reading scores positively correlated with functional connectivity between (1) the right angular gyrus and superior temporal gyrus, (2) the bilateral angular gyri and right pars triangularis and motor areas, (3) the left superior temporal gyrus and bilateral medial frontal gyrus and right cerebellum, (4) the left pars triangularis and middle occipital gyrus and insula, and (5) the right pars triangularis and the bilateral thalamus. Higher pre-reading scores were associated with stronger negative functional connectivity between (1) the left angular gyrus and auditory cortex, (2) the left superior temporal gyrus and occipital vision areas, (3) the right pars triangularis and medial frontal region, and (4) the right superior temporal gyrus and the posterior cingulate/precuneus. These results suggest better integration of the reading network, as well as its connections with other brain areas that support language or reading, and more dissociation between reading areas and the default mode network, in young children with better pre-reading skills. Our findings show that relationships between functional connectivity and pre-reading language skills are evident in young children even before formal reading instruction.

Hypoplasia of cerebellar afferent networks in Down syndrome revealed by DTI-driven tensor based morphometry

Quantitative magnetic resonance imaging (MRI) investigations of brain anatomy in children and young adults with Down syndrome (DS) are limited, with no diffusion tensor imaging (DTI) studies covering that age range. We used DTI-driven tensor based morphometry (DTBM), a novel technique that extracts morphometric information from diffusion data, to investigate brain anatomy in 15 participants with DS and 15 age- and sex-matched typically developing (TD) controls, ages 6–24 years (mean age ~17 years). DTBM revealed marked hypoplasia of cerebellar afferent systems in DS, including fronto-pontine (middle cerebellar peduncle) and olivo-cerebellar (inferior cerebellar peduncle) connections. Prominent gray matter hypoplasia was observed in medial frontal regions, the inferior olives, and the cerebellum. Very few abnormalities were detected by classical diffusion MRI metrics, such as fractional anisotropy and mean diffusivity. Our results highlight the potential importance of cerebro-cerebellar networks in the clinical manifestations of DS and suggest a role for DTBM in the investigation of other brain disorders involving white matter hypoplasia or atrophy.

Functional near-infrared spectroscopy in toddlers: Neural differentiation of communicative cues and relation to future language abilities.

The toddler and preschool years are a time of significant development in both expressive and receptive communication abilities. However, little is known about the neurobiological underpinnings of language development during this period, likely due to difficulties acquiring functional neuroimaging data. Functional near‐infrared spectroscopy (fNIRS) is a motion‐tolerant neuroimaging technique that assesses cortical brain activity and can be used in very young children. Here, we use fNIRS during perception of communicative and noncommunicative speech and gestures in typically developing 2‐ and 3‐year‐olds (Study 1, n = 15, n = 12 respectively) and in a sample of 2‐year‐olds with both fNIRS data collected at age 2 and language outcome data at age 3 (Study 2, n = 18). In Study 1, 2‐ and 3‐year‐olds differentiated between communicative and noncommunicative stimuli as well as between speech and gestures in the left lateral frontal region. However, 2‐year‐olds showed different patterns of activation from 3‐year‐olds in right medial frontal regions. In Study 2, which included two toddlers identified with early language delays along with 16 typically developing toddlers, neural differentiation of communicative stimuli in the right medial frontal region at age 2 predicted receptive language at age 3. Specifically, after accounting for variance related to verbal ability at age 2, increased neural activation for communicative gestures (vs. both communicative speech and noncommunicative gestures) at age 2 predicted higher receptive language scores at age 3. These results are discussed in the context of the underlying mechanisms of toddler language development and use of fNIRS in prediction of language outcomes.

Longitudinal Changes in Whole-Brain Functional Connectivity Strength Patterns and the Relationship With the Global Cognitive Decline in Older Adults.

Aging is associated with changes in brain functional patterns as well as cognition. The present research sought to investigate longitudinal changes in whole brain functional connectivity strength (FCS) and cognitive performance scores in very old cognitively unimpaired individuals. We studied 34 cognitively normal elderly individuals at both baseline and 4-year follow-up (baseline age = 78 ± 3.14 years) with resting-state functional magnetic resonance imaging (r-fMRI), structural MRI scans, and neuropsychological assessments conducted. Voxel-based whole brain FCS was calculated and we found that bilateral superior parietal and medial frontal regions showed decreased FCS, while the supplementary motor area (SMA) and insula showed increased FCS with age, along with a decrease in bilateral prefrontal cortical thickness. The changes of FCS in left precuneus were associated with an aging-related decline in global cognition. Taken together, our results suggest changes in FCS with aging with the precuneus as a hub and this may underlie changes in global cognition that accompany aging. These findings help better understand the normal aging mechanism.

Spatially Distinct Beta-Band Activities Reflect Implicit Sensorimotor Adaptation and Explicit Re-aiming Strategy.

Previous research suggests that so-called implicit and explicit processes of motor adaptation are implemented by distinct neural structures. Here we tested whether implicit sensorimotor adaptation and strategic re-aiming used to reduce movement error are reflected by spatially distinct EEG oscillatory components. We analyzed beta-band oscillations (∼13-30 Hz), which have long been linked to sensorimotor functions, at the time when these adaptive processes intervene for movement planning. We hypothesized that beta-band activity within sensorimotor regions relates to implicit adaptive processes, whereas beta-band activity within medial motor areas reflects deliberate re-aiming. In female and male human volunteers, we recorded EEG in a motor adaptation task in which a visual rotation was introduced in short series of trials separated by unperturbed trials. Participants were instructed in advance about the nature of the visual perturbation and trained to counter it by strategically re-aiming at a neighboring target. Consistent with our hypothesis, we found that preparatory beta-band activities within the two regions exhibited different patterns of modulation. Beta power in lateral central regions was attenuated when a change in the visual condition rendered internal-model predictions uncertain. In contrast, beta power in medial frontal regions was selectively decreased when participants strategically re-aimed their reaches. We propose that the reduction in lateral central beta power reflects an increased weighting of peripheral sensory information implicitly triggered when an adaptive change in the sensorimotor mapping is required, whereas the reduction in medial frontal beta-band activity relates to the inhibition of automatic motor responses in favor of cognitively controlled movements.SIGNIFICANCE STATEMENT Behavioral and modeling studies have proposed that so-called implicit and explicit components of motor adaptation recruit different neural circuits. Here, we investigated whether these different processes are reflected by spatially distinct beta-band activities. Analyzing EEG signals at the time they influence movement planning, during the foreperiod, we found that beta power within lateral central regions was decreased when a change in visual conditions required implicit sensorimotor remapping, which may reflect enhanced sensory processing when internal-model predictions are rendered uncertain. In contrast, beta-band power within medial frontal areas was selectively attenuated when participants deliberately re-aimed their movements to improve task performance, which may be associated with the inhibition of automatic motor responses in favor of cognitively controlled movements.

P.215 Comparing antidepressant efficacy of fluoxetine and minocycline treatment in different environmental conditions

Catecholaminergic neural transmission plays an important role during the inhibition of prepotent responses. Methylphenidate (MPH) is an important drug that modulates the catecholaminergic system. However, theoretical considerations suggest that the effects of drugs (e.g. MPH) on cognitive control may depend on prior learning effects. Here we investigate this in a conflict-modulated Go/Nogo task and evaluate neurophysiological processes associated with this dynamic using EEG signal decomposition methods and source localization analysis. The behavioral data show that prior learning experiences eliminate effects of MPH on response inhibition processes. On a neurophysiological level, we show that MPH modulates specific processes in medial frontal brain regions. Although MPH seems to consistently modulate neurophysiological processes associated with response inhibition, this is no longer sufficient to modulate behavioral performance once learning or task familiarization processes have taken place. An important consequence of this study finding is that it may be important to adjust MPH dosage depending on learning effects in a specific setting to constantly increase cognitive control functions in that setting. This has important implications for clinical practice, since MPH is the first-line pharmacological therapy in attention-deficit hyperactivity disorder (ADHD). Cross-over study designs with constant doses of MPH can mask effects on cognitive functions. The impact of learning needs careful consideration in cross-over study designs examining catecholaminergic drug effects.

Reward and empathy in the treating clinician: the neural correlates of successful doctor\u2013patient interactions

The goal of this study was to determine the neural correlates of successful doctor–patient interactions. We performed an experimental neuroimaging study where medical doctors (MDs) performed a treatment task while their brain activation pattern was measured, using functional magnetic resonance imaging (fMRI). MDs (25–37 years old) first performed a standardized clinical exam of a “professional patient”. Unbeknownst to the doctors, the professional patient was a confederate that rated the doctors’ clinical examination using the Consultation And Relational Empathy (CARE) questionnaire, a standardized protocol assessing a clinician’s social interaction during a consultation. After the clinical exam, MDs were placed inside a brain scanner and the patient was placed on a chair next to the MD. MDs performed a treatment task where an analgesic device was used to alleviate the patient’s pain (experimentally induced), while the MD’s brain activity was measured with fMRI. MDs rated their own empathic concern (equivalent of compassion) and personal distress using the Interpersonal Reactivity Index questionnaire. The patient’s rating of CARE was robustly related to the MD’s own ratings of trait empathic concern and to compassion-related and reward-related activation of medial frontal brain regions during treatment. In contrast, there was no relation with MD’s personal distress, nor with activation in regions associated with the aversive component of experiencing empathy. We conclude that a patient’s positive experience of a medical examination is reflected in doctors’ empathic concern and reward-related brain activations during treatment, suggesting that compassion and pleasure are key factors for successful doctor–patient interactions.

Music evoked autobiographical memories in people with behavioural variant frontotemporal dementia

ABSTRACTMusic is highly efficient at evoking autobiographical memories in both healthy and neurological populations. Music evoked autobiographical memories (MEAMs) are preserved in people with Alzheimer’s Dementia (AD), and occur at the same frequency as in healthy people. To date there has been no investigation of the integrity of MEAMs in people with non-AD dementia. This study provides the first characterisation of the frequency and specificity of MEAMs and photo evoked autobiographical memories (PEAMs) in 6 people with Behavioural variant frontotemporal dementia (Bv-FTD). We found significantly reduced frequency and specificity of MEAMs and PEAMs in people with Bv-FTD compared with healthy elderly. This supports the known decline in autobiographical memory function in this population, and the integral role of medial frontal regions in the retrieval of MEAMs. Our findings highlight that the mnemonic effects of music vary between people with different types of dementia, which has implications for dementia care.