Transcranial Magnetic Stimulation and the Understanding of Behavior.

The development of the use of transcranial magnetic stimulation (TMS) in the study of psychological functions has entered a new phase of sophistication. This is largely due to an increasing physiological knowledge of its effects and to its being used in combination with other experimental techniques. This review presents the current state of our understanding of the mechanisms of TMS in the context of designing and interpreting psychological experiments. We discuss the major conceptual advances in behavioral studies using TMS. There are meaningful physiological and technical achievements to review, as well as a wealth of new perceptual and cognitive experiments. In doing so we summarize the different uses and challenges of TMS in mental chronometry, perception, awareness, learning, and memory.

Decoding individual identity from brain activity elicited in imagining common experiences.

Everyone experiences common events differently. This leads to personal memories that presumably provide neural signatures of individual identity when events are reimagined. We present initial evidence that these signatures can be read from brain activity. To do this, we progress beyond previous work that has deployed generic group-level computational semantic models to distinguish between neural representations of different events, but not revealed interpersonal differences in event representations. We scanned 26 participants' brain activity using functional Magnetic Resonance Imaging as they vividly imagined themselves personally experiencing 20 common scenarios (e.g., dancing, shopping, wedding). Rather than adopting a one-size-fits-all approach to generically model scenarios, we constructed personal models from participants' verbal descriptions and self-ratings of sensory/motor/cognitive/spatiotemporal and emotional characteristics of the imagined experiences. We demonstrate that participants' neural representations are better predicted by their own models than other peoples'. This showcases how neuroimaging and personalized models can quantify individual-differences in imagined experiences.

Awake Craniotomy in a Patient with Previously Diagnosed Post-Traumatic Stress Disorder.

BACKGROUND: Awake craniotomy (AC) with brain mapping has been successfully used for the resection of lesions located in or near eloquent areas of the brain. The selection process includes a thorough presurgical evaluation to determine candidates suitable for the procedure. Psychiatric disorders including post-traumatic stress disorder (PTSD) are considered potential contraindications for this type of surgery because these patients may be less cooperative to tolerate AC. Here we present the management of a patient with PTSD who underwent an AC using a multidisciplinary team for removal of a dominant hemisphere low-grade insular glioma with speech, motor, and cognitive mapping. CASE DESCRIPTION: A 34-year-old right-handed male military veteran with a previous history of PTSD was scheduled for a left AC for resection of a low-grade insular glioma. He underwent preoperative neurocognitive assessment with a neuropsychologist and clinic visit with a neurosurgeon to characterize his PTSD and potential triggers, explain the procedure in a stepwise fashion, and address any concerns. The intraoperative environment was modified to minimize triggering stimuli, and an asleep-awake-asleep anesthetic protocol was followed. The patient tolerated the procedure well without any postoperative neurologic deficits including cognitive deficits. At 1-month follow-up, he denied any worsening of his PTSD symptoms and recalls the AC as a positive experience. CONCLUSIONS: With a multidisciplinary team, adequate preoperative education, detailed clinical interview to identify triggers, and a controlled intraoperative environment, awake surgery can be carried out safely in a patient with PTSD.

Characterization of the dynamic behavior of neural activity in Alzheimer's disease: exploring the non-stationarity and recurrence structure of EEG resting-state activity.

OBJECTIVE: Mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) have been shown to induce perturbations to normal neuronal behavior and disrupt neuronal networks. Recent work suggests that the dynamic properties of resting-state neuronal activity could be affected by MCI and AD-induced neurodegeneration. The aim of the study was to characterize these properties from different perspectives: (i) using the Kullback-Leibler divergence (KLD), a measure of non-stationarity derived from the continuous wavelet transform; and (ii) using the entropy of the recurrence point density ([Formula: see text]) and the median of the recurrence point density ([Formula: see text]), two novel metrics based on recurrence quantification analysis. APPROACH: KLD, [Formula: see text] and [Formula: see text] were computed for 49 patients with dementia due to AD, 66 patients with MCI due to AD and 43 cognitively healthy controls from 60 s electroencephalographic (EEG) recordings with a 10 s sliding window with no overlap. Afterwards, we tested whether the measures reflected alterations to normal neuronal activity induced by MCI and AD. MAIN RESULTS: Our results showed that frequency-dependent alterations to normal dynamic behavior can be found in patients with MCI and AD, both in non-stationarity and recurrence structure. Patients with MCI showed signs of patterns of abnormal state recurrence in the theta (4-8 Hz) and beta (13-30 Hz) frequency bands that became more marked in AD. Moreover, abnormal non-stationarity patterns were found in MCI patients, but not in patients with AD in delta (1-4 Hz), alpha (8-13 Hz), and gamma (30-70 Hz). SIGNIFICANCE: The alterations in normal levels of non-stationarity in patients with MCI suggest an initial increase in cortical activity during the development of AD. This increase could possibly be due to an impairment in neuronal inhibition that is not present during later stages. MCI and AD induce alterations to the recurrence structure of cortical activity, suggesting that normal state switching during rest may be affected by these pathologies.

Simultaneous EEG and fMRI reveals stronger sensitivity to orthographic strings in the left occipito-temporal cortex of typical versus poor beginning readers.

The level of reading skills in children and adults is reflected in the strength of preferential neural activation to print. Such preferential activation appears in the N1 event-related potential (ERP) over the occipitotemporal scalp after around 150-250 ms and the corresponding blood oxygen level dependent (BOLD) signal in the ventral occipitotemporal (vOT) cortex. Here, orthography-sensitive (print vs. false font) processing was examined using simultaneous EEG-fMRI in 38 first grade children with poor and typical reading skills, and at varying familial risk for developmental dyslexia. Coarse orthographic sensitivity was observed as an increased activation to print in the N1 ERP and in the BOLD signal of individually varying vOT regions in 57% of beginning readers. Finer differentiation in processing orthographic strings (words vs. nonwords) further occurred in specific vOT clusters. Neither method alone showed robust differences in orthography-sensitive processing between typical and poor reading children. Importantly, using single-trial N1 ERP-informed fMRI analysis, we found differential modulation of the orthography-sensitive BOLD response in the left vOT for typical readers only. This result, thus, confirms subtle functional alterations in a brain structure known to be critical for fluent reading at the very beginning of reading instruction.

Apples to apples? Neural correlates of emotion regulation differences between high- and low-risk adolescents.

Adolescence has been noted as a period of increased risk taking. The literature on normative neurodevelopment implicates aberrant activation of affective and regulatory regions as key to inhibitory failures. However, many of these studies have not included adolescents engaging in high rates of risky behavior, making generalizations to the most at-risk populations potentially problematic. We conducted a comparative study of nondelinquent community (n = 24, mean age = 15.8 years, 12 female) and delinquent adolescents (n = 24, mean age = 16.2 years, 12 female) who completed a cognitive control task during functional magnetic resonance imaging, where behavioral inhibition was assessed in the presence of appetitive and aversive socioaffective cues. Community adolescents showed poorer behavioral regulation to appetitive relative to aversive cues, whereas the delinquent sample showed the opposite pattern. Recruitment of the inferior frontal gyrus, medial prefrontal cortex, and tempoparietal junction differentiated community and high-risk adolescents, as delinquent adolescents showed significantly greater recruitment when inhibiting their responses in the presence of aversive cues, while the community sample showed greater recruitment when inhibiting their responses in the presence of appetitive cues. Accounting for behavioral history may be key in understanding when adolescents will have regulatory difficulties, highlighting a need for comparative research into normative and nonnormative risk-taking trajectories.

Laughter is in the air: involvement of key nodes of the emotional motor system in the anticipation of tickling.

In analogy to the appreciation of humor, that of tickling is based upon the re-interpretation of an anticipated emotional situation. Hence, the anticipation of tickling contributes to the final outburst of ticklish laughter. To localize the neuronal substrates of this process, functional magnetic resonance imaging (fMRI) was conducted on 31 healthy volunteers. The state of anticipation was simulated by generating an uncertainty respecting the onset of manual foot tickling. Anticipation was characterized by an augmented fMRI signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area, as well as by an attenuated one in the internal globus pallidus. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling. These findings are consistent with an encoding of the expected emotional consequences of tickling and suggest that early regulatory mechanisms influence, automatically, the laughter circuitry at the level of affective and sensory processing. Tickling activated not only those regions of the brain that were involved during anticipation, but also the posterior insula, the anterior cingulate cortex and the periaqueductal gray matter. Sequential or combined anticipatory and tickling-related neuronal activities may adjust emotional and sensorimotor pathways in preparation for the impending laughter response.

A meta-analysis of neuroimaging studies on pain empathy: investigating the role of visual information and observers' perspective.

Empathy relies on brain systems that support the interaction between an observer's mental state and cues about the others' experience. Beyond the core brain areas typically activated in pain empathy studies (insular and anterior cingulate cortices), the diversity of paradigms used may reveal secondary networks that subserve other more specific processes. A coordinate-based meta-analysis of fMRI experiments on pain empathy was conducted to obtain activation likelihood estimates along three factors and seven conditions: visual cues (body parts, facial expressions), visuospatial (first-person, thirdperson), and cognitive (self-, stimuli-, other-oriented tasks) perspectives. The core network was found across cues and perspectives, and common activation was observed in higher-order visual areas. Body-parts distinctly activated areas related with sensorimotor processing (superior and inferior parietal lobules, anterior insula) while facial expression distinctly involved the inferior frontal gyrus. Self- compared to other-perspective produced distinct activations in the left insula while stimulus- versus other-perspective produced distinctive responses in the inferior frontal and parietal lobules, precentral gyrus, and cerebellum. Pain empathy relies on a core network which is modulated by several secondary networks. The involvement of the latter seems to depend on the visual cues available and the observer's mental state that can be influenced by specific instructions.

When do we fall in neural synchrony with others?

This study aimed to investigate the situation in which interpersonal brain synchronization (IBS) occurs during a collaborative task and examined its trajectory over time by developing a novel functional near-infrared spectroscopy (fNIRS)-based hyperscanning paradigm. Participants were asked to perform a collaborative task in three-person groups where two of the members are real participants and one is a confederate. Compared to dyads between real participants and confederates, real-participant pairings showed greater cooperation behavior and IBS between bilateral dorsolateral prefrontal cortex. And, IBS and cooperation increased over time in real-participant pairings, whereas they remained low and constant in dyads with the confederate. These findings indicate that IBS occurs between individuals engaging in interpersonal interaction during a collaborative task, during which both IBS and cooperatively interpersonal interaction tend to increase over time.

Reading Acquisition in Children: Developmental Processes and Dyslexia-Specific Effects.

OBJECTIVE: Decreased activation to print in the left ventral, dorsal, and anterior pathways has been implicated in readers with dyslexia (DRs) but also is characteristic for typical beginning readers. Because most studies have compared DRs with their age-matched peers, the observed results could represent a dyslexia phenotype or a developmental delay. This study aimed to disentangle reading and dyslexia effects using 2 control groups matched for age and skill and a longitudinal design. METHOD: Brain response for print was compared in DRs and typical readers (TRs) who, at the beginning of schooling (time point 1 [TP]; 6-7 years old), read on average 3 words per minute, as did DRs at TP1, but improved their reading to an average level, and advanced readers (ARs) who at TP1 read as well as DRs 2 years later (TP3; 8-9 years old). The TR and DR groups were tracked longitudinally to observe neurodevelopmental changes. RESULTS: At TP1, DRs did not differ from TRs. Over time, only TRs developed a neural circuit for reading in the left inferior frontal and fusiform gyri. At TP3, DRs exhibited hypo-activation in these areas compared with age-matched (TRs at TP3) and reading-matched (ARs at TP1) controls. At TP3, TRs showed hypo-activation in the left frontal and bilateral ventral occipital regions compared with ARs, but these effects were nonoverlapping with DR hypo-activations and are partly explained by IQ. CONCLUSION: Decreased activation of the left fusiform and inferior frontal gyri to print in DRs results from an atypical developmental trajectory of reading and cannot be explained solely by lower reading skills.

The neural development of prosocial behavior from childhood to adolescence.

The transition from childhood to adolescence is marked by increasingly sophisticated social cognitive abilities that are paralleled by significant functional maturation of the brain. However, the role of social and neurobiological development in facilitating age differences in prosocial behavior remains unclear. Using a cross-sectional sample of children and adolescents (n = 51; 8-16 years), we examined the age-related correlates of prosocial behavior. Youth made costly and non-costly prosocial decisions to anonymous peers during a functional magnetic resonance imaging scan. Among a subsample of youth who made prosocial decisions (n = 35), we found quadratic age differences in neural activation that peaked in early adolescence relative to childhood and older adolescence. In particular, early adolescents showed heightened recruitment of the posterior superior temporal sulcus (pSTS), temporal pole and inferior frontal gyrus (IFG) when engaging in costly prosocial behavior at the expense of gaining a reward, whereas they evoked heightened pSTS and dorsolateral prefrontal cortex/IFG activation when engaging in costly vs non-costly forms of prosocial behavior. Given that we did not find age differences in prosocial behavior, this suggests that early adolescents show unique patterns of brain activation to inform similar levels of prosocial behavior.

Being a leader in a rhythmic interaction activates reward-related brain regions.

Interpersonal rhythmic interaction is one of the fundamental behaviors that allow humans to socially interact with others. In this study, we provide novel neuroimaging evidence that being followed by other agents in such an interaction is pleasant for humans. Using functional magnetic resonance imaging, we measured the brain activity of 17 participants while they performed a virtual drum-hitting task, in one of the following conditions: a) alternating with a virtual agent that would always copy their hitting pace, or b) alternating with a virtual agent that would randomly hit the drum. The participants reported a significantly higher subjective feeling of being followed by the agent in the first condition. Moreover, almost all participants preferred the agent that followed their drum-hitting rhythm. The activity of the caudate nucleus, which is one of the reward-related brain structures, was found to be associated with the subjective feeling of being followed, suggesting that the sense of being the leader, in an interpersonal rhythmic interaction, creates a pleasant feeling.

Exploring lateralization during memory through hemispheric pre-activation: Differences based on the stimulus type.

The original approach of the Hemispheric Encoding/Retrieval Asymmetry model (HERA) was aimed at the operations of encoding and retrieving episodic memories. However, whether HERA presumptions can apply to different types of stimuli (e.g., words and pictures) continues to be a matter of debate. Therefore, in order to analyse the effects of brain pre-activation on subsequent memory, HERA was tested through a hand-clenching paradigm using four types of stimuli: words, fractal images, silhouettes of common objects, and pseudowords. Results revealed that only the memory of words and pseudowords was enhanced by hand-clenching pre-activation, according to HERA predictions. Since the cognitive processes underlying recognition of verbal stimuli are considered to follow a cognitive route involving grapheme-morpheme conversion, it could be hypothesized that hand-clenching pre-activation might be associated with a selective pre-activation of the brain circuits participating in that pathway. Hence, the present work broadens possible interpretations behind the effects of hand-clenching on memory, based on the process engaged and the type of stimulus to be remembered.

Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.

A drama movie activates brains of holistic and analytical thinkers differentially.

People socialized in different cultures differ in their thinking styles. Eastern-culture people view objects more holistically by taking context into account, whereas Western-culture people view objects more analytically by focusing on them at the expense of context. Here we studied whether participants, who have different thinking styles but live within the same culture, exhibit differential brain activity when viewing a drama movie. A total of 26 Finnish participants, who were divided into holistic and analytical thinkers based on self-report questionnaire scores, watched a shortened drama movie during functional magnetic resonance imaging. We compared intersubject correlation (ISC) of brain hemodynamic activity of holistic vs analytical participants across the movie viewings. Holistic thinkers showed significant ISC in more extensive cortical areas than analytical thinkers, suggesting that they perceived the movie in a more similar fashion. Significantly higher ISC was observed in holistic thinkers in occipital, prefrontal and temporal cortices. In analytical thinkers, significant ISC was observed in right-hemisphere fusiform gyrus, temporoparietal junction and frontal cortex. Since these results were obtained in participants with similar cultural background, they are less prone to confounds by other possible cultural differences. Overall, our results show how brain activity in holistic vs analytical participants differs when viewing the same drama movie.

Two-Stage Processing of Aesthetic Information in the Human Brain Revealed by Neural Adaptation Paradigm.

Some researchers in aesthetics assume visual features related to aesthetic perception (e.g. golden ratio and symmetry) commonly embedded in masterpieces. If this is true, an intriguing hypothesis is that the human brain has neural circuitry specialized for the processing of visual beauty. We presently tested this hypothesis by combining a neuroimaging technique with the repetition suppression (RS) paradigm. Subjects (non-experts in art) viewed two images of sculptures sequentially presented. Some sculptures obeyed the golden ratio (canonical images), while the golden proportion were impaired in other sculptures (deformed images). We found that the occipito-temporal cortex in the right hemisphere showed the RS when a canonical sculpture (e.g. Venus de Milo) was repeatedly presented, but not when its deformed version was repeated. Furthermore, the right parietal cortex showed the RS to the canonical proportion even when two sculptures had different identities (e.g. Venus de Milo as the first stimulus and David di Michelangelo as the second), indicating that this region encodes the golden ratio as an abstract rule shared by different sculptures. Those results suggest two separate stages of neural processing for aesthetic information (one in the occipito-temporal and another in the parietal regions) that are hierarchically arranged in the human brain.

Differentiating emotional processing and attention in psychopathy with functional neuroimaging.

Individuals with psychopathy are often characterized by emotional processing deficits, and recent research has examined the specific contexts and cognitive mechanisms that underlie these abnormalities. Some evidence suggests that abnormal features of attention are fundamental to emotional deficits in persons with psychopathy, but few studies have demonstrated the neural underpinnings responsible for such effects. Here, we use functional neuroimaging to examine attention-emotion interactions among incarcerated individuals (n = 120) evaluated for psychopathic traits using the Hare Psychopathy Checklist-Revised (PCL-R). Using a task designed to manipulate attention to emotional features of visual stimuli, we demonstrate effects representing implicit emotional processing, explicit emotional processing, attention-facilitated emotional processing, and vigilance for emotional content. Results confirm the importance of considering mechanisms of attention when evaluating emotional processing differences related to psychopathic traits. The affective-interpersonal features of psychopathy (PCL-R Factor 1) were associated with relatively lower emotion-dependent augmentation of activity in visual processing areas during implicit emotional processing, while antisocial-lifestyle features (PCL-R Factor 2) were associated with elevated activity in the amygdala and related salience network regions. During explicit emotional processing, psychopathic traits were associated with upregulation in the medial prefrontal cortex, insula, and superior frontal regions. Isolating the impact of explicit attention to emotional content, only Factor 1 was related to upregulation of activity in the visual processing stream, which was accompanied by increased activity in the angular gyrus. These effects highlight some important mechanisms underlying abnormal features of attention and emotional processing that accompany psychopathic traits.

Distributed and Mixed Information in Monosynaptic Inputs to Dopamine Neurons.

Dopamine neurons encode the difference between actual and predicted reward, or reward prediction error (RPE). Although many models have been proposed to account for this computation, it has been difficult to test these models experimentally. Here we established an awake electrophysiological recording system, combined with rabies virus and optogenetic cell-type identification, to characterize the firing patterns of monosynaptic inputs to dopamine neurons while mice performed classical conditioning tasks. We found that each variable required to compute RPE, including actual and predicted reward, was distributed in input neurons in multiple brain areas. Further, many input neurons across brain areas signaled combinations of these variables. These results demonstrate that even simple arithmetic computations such as RPE are not localized in specific brain areas but, rather, distributed across multiple nodes in a brain-wide network. Our systematic method to examine both activity and connectivity revealed unexpected redundancy for a simple computation in the brain.

Behavioral evidence of heterospecific bonding between the lamb and the human caregiver and mapping of associated brain network.

While behavioral mechanisms of bonding between young mammals and humans have been explored, brain structures involved in the establishment of such processes are still unknown. The aim of the study was to identify brain regions activated by the presence of the caregiver. Since human positive interaction plays an important role in the bonding process, activation of specific brain structures by stroking was also examined. Twenty-four female lambs reared in groups of three were fed and stroked daily by a female caregiver between birth and 5-7 weeks of age. At 4 weeks, an isolation-reunion-separation test and a choice test revealed that lambs developed a strong bond with their caregiver. At 5-7 weeks of age, lambs were socially isolated for 90min. They either remained isolated or met their caregiver who stroked them, or not, at regular intervals over a 90-min period. Neuronal activation was investigated at the end of the period for maximum c-Fos expression. Reunion with the caregiver appeased similarly the lambs whether stroking was provided or not. Stroking did not activate a specific brain network compared to no stroking. In both cases, brain regions associated with olfactory, visual and tactile cue processing were activated in the presence of the caregiver, suggesting a multisensory process involved. In addition, activation of the oxytocinergic system in the hypothalamic paraventricular nucleus induced by the presence of the caregiver suggests similar neuroendocrine mechanisms involved in inter-conspecific and animal-human bonding.

Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression.

Depression is associated with alterations in corticostriatal reward circuitry. One pathophysiological pathway that may drive these changes is inflammation. Biomarkers of inflammation (for example, cytokines and C-reactive protein (CRP)) are reliably elevated in depressed patients. Moreover, administration of inflammatory stimuli reduces neural activity and dopamine release in reward-related brain regions in association with reduced motivation and anhedonia. Accordingly, we examined whether increased inflammation in depression affects corticostriatal reward circuitry to lead to deficits in motivation and goal-directed motor behavior. Resting-state functional magnetic resonance imaging was conducted on 48 medically stable, unmedicated outpatients with major depression. Whole-brain, voxel-wise functional connectivity was examined as a function of CRP using seeds for subdivisions of the ventral and dorsal striatum associated with motivation and motor control. Increased CRP was associated with decreased connectivity between ventral striatum and ventromedial prefrontal cortex (vmPFC) (corrected P<0.05), which in turn correlated with increased anhedonia (R=-0.47, P=0.001). Increased CRP similarly predicted decreased dorsal striatal to vmPFC and presupplementary motor area connectivity, which correlated with decreased motor speed (R=0.31 to 0.45, P<0.05) and increased psychomotor slowing (R=-0.35, P=0.015). Of note, mediation analyses revealed that these effects of CRP on connectivity mediated significant relationships between CRP and anhedonia and motor slowing. Finally, connectivity between striatum and vmPFC was associated with increased plasma interleukin (IL)-6, IL-1beta and IL-1 receptor antagonist (R=-0.33 to -0.36, P<0.05). These findings suggest that decreased corticostriatal connectivity may serve as a target for anti-inflammatory or pro-dopaminergic treatment strategies to improve motivational and motor deficits in patients with increased inflammation, including depression.