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1.  Output order and variability in free recall are linked to cognitive ability and hippocampal volume in elderly individuals 
Neuropsychologia  2015;80:126-132.
Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of order of recall in neuropsychological free recall tests. These are the position on the study list of the first recalled item, and the degree of variability in the order in which items are reported at test (i.e., the temporal distance across the first four recalled items). We tested two hypotheses in separate experiments: 1) whether these measures predicted generalized cognitive ability, and 2) whether they predicted gray matter hippocampal volume. To test hypothesis 1, we conducted ordinal regression analyses on data from a group of 452 participants, aged 60 or above. Memory performance was measured with Rey's AVLT and generalized cognitive ability was measured with the MMSE test. To test hypothesis 2, we conducted a linear regression analysis on data from a sample of 79 cognitively intact individuals aged 60 or over. Memory was measured with the BSRT and hippocampal volume was extracted from MRI images. Results of Experiment 1 showed that the position of the first item recalled and the degree of output order variability correlated with MMSE scores only in the delayed test, but not in the immediate test. In Experiment 2, the degree of variability in the recall sequence of the delayed trial correlated (negatively) with hippocampal size. These findings confirm the importance of delayed primacy as a marker of cognitive ability, and are consistent with the idea that the hippocampus is involved in coding the temporal context of learned episodes.
PMCID: PMC4698176  PMID: 26593881
Free recall; Output order; MMSE; Hippocampus
2.  From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes 
Neuropsychologia  2015;80:142-156.
The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes.
PMCID: PMC4698179  PMID: 26617263
Aging; spontaneous cognition; mind-wandering; involuntary autobiographical retrieval; intrusive thoughts; prospective memory
3.  Trans-Saccadic Repetition Priming: ERPs Reveal On-line Integration of Information across Words 
Neuropsychologia  2015;80:201-211.
We used a trans-saccadic priming paradigm combined with ERP recordings to track the time-course of integration of information across a prime word briefly presented at fixation and a subsequent target word presented 4 degrees to the right of fixation. Trans-saccadic repetition priming effects (Experiments 1 & 2) were compared with priming effects obtained with centrally located targets (Experiment 3). In Experiment 2, target stimuli were preceded by a 100 ms forward mask at the target location, hence allowing an attention shift to the target location prior to target onset. Compared with centrally located targets, repetition priming effects were found to onset later in Experiment 2 and even later in Experiment 1, and the growth of priming effects was slower in both Experiments 1 and 2 compared with Experiment 3. The results demonstrate integration of information across spatially distinct primes and targets, with the time-course of trans-saccadic priming being determined by the speed with which attention can be allocated to peripheral targets plus the quality of information available in peripheral vision prior to fixation of target stimuli.
PMCID: PMC4698207  PMID: 26656872
reading; repetition priming; ERPs; eye-movements; trans-saccadic priming
4.  Impairments in Precision, Rather than Spatial Strategy, Characterize Performance on the Virtual Morris Water Maze: A Case Study 
Neuropsychologia  2015;80:90-101.
Damage to the medial temporal lobes produces profound amnesia, greatly impairing the ability of patients to learn about new associations and events. While studies in rodents suggest a strong link between damage to the hippocampus and the ability to navigate using distal landmarks in a spatial environment, the connection between navigation and memory in humans remains less clear. Past studies on human navigation have provided mixed findings about whether patients with damage to the medial temporal lobes can successfully acquire and navigate new spatial environments, possibly due, in part, to issues related to patient demographics and characterization of medial temporal lobe damage. Here, we report findings from a young, high functioning patient who suffered severe medial temporal lobe damage. Although the patient is densely amnestic, her ability to acquire and utilize new, but coarse, spatial “maps” appears largely intact. Specifically, a novel computational analysis focused on the precision of her spatial search revealed a significant deficit in spatial precision rather than spatial search strategy. These findings argue that an intact hippocampus in humans is not necessary for representing multiple external landmarks during spatial navigation of new environments. We suggest instead that the human hippocampus may store and represent complex high-resolution bindings of features in the environment as part of a larger role in perception, memory, and navigation.
PMCID: PMC4698252  PMID: 26593960
Memory; spatial memory; allocentric; cognitive map; MTL lesion; hippocampus; Morris Water Maze
5.  Understanding the influence of personality on dynamic social gesture processing: an fMRI study 
Neuropsychologia  2015;80:71-78.
This fMRI study aimed at investigating how differences in personality traits affect the processing of dynamic and natural gestures containing social versus nonsocial intent. We predicted that while processing gestures with social intent extraversion would be associated with increased activity within the reticulothalamic–cortical arousal system (RTCS), while neuroticism would be associated with increased activity in emotion processing circuits. The obtained findings partly support our hypotheses. We found a positive correlation between bilateral thalamic activity and extraversion scores while participants viewed social (versus nonsocial) gestures. For neuroticism, the data revealed a more complex activation pattern. Activity in the bilateral frontal operculum and anterior insula, extending into bilateral putamen and right amygdala, was moderated as a function of actor-orientation (i.e., first versus third-person engagement) and face-visibility (actor faces visible versus blurred). Our findings point to the existence of factors other than emotional valence that can influence social gesture processing in particular, and social cognitive affective processing in general, as a function of personality.
PMCID: PMC4698311  PMID: 26541443
Personality; Extraversion; Neuroticism; fMRI; Social Cognition
6.  Impaired acquisition of new words after left temporal lobectomy despite normal fast-mapping behavior 
Neuropsychologia  2015;80:165-175.
Word learning under different conditions has been proposed to rely on different brain regions including the temporal lobes, and the left temporal lobe appears to be especially important. In order to investigate the role of the left temporal lobe in word learning under different conditions, we tested whether patients with left temporal lobectomies (N=6) could learn novel words using two distinct learning formats. Previous research has shown that word learning in contrastive fast mapping conditions may rely on different neural substrates than explicit encoding conditions (Sharon, Moscovitch, & Gilboa, 2011). In the current investigation, we used a previously reported word learning task that implemented two distinct study formats (Warren & Duff, 2014): a contrastive fast mapping condition in which a picture of a novel item was displayed beside a picture of a familiar item while the novel item's name was presented aurally (“Click on the numbat.”); and an explicit encoding (i.e., control) condition in which a picture of a novel item was displayed while its name was presented aurally (“This is a numbat.”). After a delay, learning of the novel words was evaluated with memory tests including three-alternative forced-choice recognition, free recall, cued recall, and familiarity ratings. During the fast-mapping study condition both the left temporal lobectomy and healthy comparison groups performed well, but at test only the comparison group showed evidence of novel word learning. Our findings indicate that unilateral resection of the left temporal lobe including the hippocampus and temporal pole can severely impair word learning, and that fast mapping study conditions do not promote subsequent word learning in temporal lobectomy populations.
PMCID: PMC4698347  PMID: 26617264
memory; language; word learning; hippocampus; unilateral temporal lobectomy; left temporal lobe
7.  Sex differences in the relationship between planum temporale asymmetry and corpus callosum morphology in chimpanzees (Pan troglodytes): A combined MRI and DTI analysis 
Neuropsychologia  2016;93(Pt B):325-334.
Increases brain size has been hypothesized to be inversely associated with the expression of behavioral and brain asymmetries within and between species. We tested this hypothesis by analyzing the relation between asymmetries in the planum temporale (PT) and different measures of the corpus callosum (CC) including surface area, streamline count as measured from diffusion tensor imaging, fractional anisotropy values and the ratio in the number of fibers to surface area in a sample of chimpanzees. We found that chimpanzees with larger PT asymmetries in absolute terms had smaller CC surface areas, fewer streamlines and a smaller ratio of fibers to surface area. These results were largely specific to male but not female chimpanzees. Our results partially support the hypothesis that brain asymmetries are linked to variation in corpus callosum morphology, although these associations may be sex-dependent.
PMCID: PMC5050170  PMID: 27055947
Corpus callosum; Planum temporale; Brain asymmetry; Primates
8.  Common Coding and Dynamic Interactions Between Observed, Imagined, and Experienced Motor and Somatosensory Activity 
Neuropsychologia  2015;79(0 0):233-245.
Motor imagery and perception- considered generally as forms of motor simulation- share overlapping neural representations with motor production. While much research has focused on the extent of this “common coding,” less attention has been paid to how these overlapping representations interact. How do imagined, observed, or produced actions influence one another, and how do we maintain control over our perception and behavior? In the first part of this review we describe interactions between motor production and motor simulation, and explore apparent regulatory mechanisms that balance these processes. Next, we consider the somatosensory system. Numerous studies now support a “sensory mirror system” comprised of neural representations activated by either afferent sensation or vicarious sensation. In the second part of this review we summarize evidence for shared representations of sensation and sensory simulation (including imagery and observed sensation), and suggest that similar interactions and regulation of simulation occur in the somatosensory domain as in the motor domain. We suggest that both motor and somatosensory simulations are flexibly regulated to support simulations congruent with our sensorimotor experience and goals and suppress or separate the influence of those that are not. These regulatory mechanisms are frequently revealed by cases of brain injury but can also be employed to facilitate sensorimotor rehabilitation.
PMCID: PMC4600026  PMID: 25863237
Simulation; Mirror neuron system; Sensory referral; Motor referral; Somatosensation; Imagery
9.  Ventromedial prefrontal cortex damage alters relative risk tolerance for prospective gains and losses 
Neuropsychologia  2015;79(0 0):70-75.
One paradigmatic example of "irrational" bias in human economic decision-making—known as the “reflection effect”—is a tendency to prefer sure amounts over risky gambles in situations involving potential gain, but to prefer risky gambles over sure amounts in situations involving potential loss. To date, there is no causal evidence regarding the neural basis of the reflection effect. The ventromedial prefrontal cortex (vmPFC) is believed to play a critical role in mediating value-based decision-making. In this study, we administered a behavioral test of the reflection effect to three groups of subjects: neurosurgical patients with focal bilateral vmPFC lesions, neurosurgical patients with lesions outside vmPFC, and neurologically healthy adults. Subjects made a series of choices between a sure amount (e.g., gain of $50) and a gamble (e.g., 50% chance of gaining $100, 50% chance of gaining $0). Half the trials featured potential gains while the other half featured potential losses. The sure amounts varied across trials. Relative to the two comparison groups, the vmPFC lesion patients exhibited a significantly greater reflection effect; more gambles selected in the loss condition and fewer gambles selected in the gain condition. This finding demonstrates a critical role for vmPFC in governing susceptibility to bias in decision-making.
PMCID: PMC4679627  PMID: 26597003
Neuroeconomics; Prefrontal Cortex; Decision-making; Lesion
10.  Amygdala responses to salient social cues vary with oxytocin receptor genotype in youth 
Neuropsychologia  2015;79(0 0):1-9.
Depression, anxiety, and posttraumatic stress disorder are linked to altered limbic morphology, dysregulated neuroendocrine function, and heightened amygdala responses to salient social cues. Oxytocin appears to be a potent modulator of amygdala reactivity and neuroendocrine responses to psychosocial stress. Given these stress regulatory effects, there is increasing interest in understanding the role of oxytocin in vulnerability to stress-related clinical disorders. The present study examines the impact of a common functional variant within the oxytocin receptor (OXTR) gene (rs2254298) on structure and function of the amygdala in a high-risk sample of urban, low-income, minority youth with a high incidence of early life stress (ELS). Compared to G/G homozygotes, youth carrying the OXTR A-allele showed increased amygdala volume, reduced behavioral performance, and heightened amygdala response during two functional magnetic resonance imaging (fMRI) tasks that involved viewing socially-relevant face stimuli. Higher amygdala response was related to ELS in A-alleles carriers but not G/G homozygotes. These findings underscore a series of relationships among a common oxytocin system gene variant, ELS exposure, and structure and function of the amygdala in early life. Heightened amygdala response to salient social cues in OXTR A-allele carriers may elevate risk for emotional psychopathology by increasing amygdala involvement in disambiguating environmental cues, particularly for individuals with ELS.
PMCID: PMC4679629  PMID: 26477647
Limbic; genetics; early stress; depression; Stroop
11.  Remote semantic memory is impoverished in hippocampal amnesia 
Neuropsychologia  2015;79(0 0):42-52.
The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition.
PMCID: PMC4679630  PMID: 26474741
semantic memory; semantic richness; hippocampus; consolidation; remote memory
12.  Remapping residual coordination for controlling assistive devices and recovering motor functions 
Neuropsychologia  2015;79(0 0):364-376.
The concept of human motor redundancy attracted much attention since the early studies of motor control, as it highlights the ability of the motor system to generate a great variety of movements to achieve any single well-defined goal. The abundance of degrees of freedom in the human body may be a fundamental resource in the learning and remapping problems that are encountered in human–machine interfaces (HMIs) developments. The HMI can act at different levels decoding brain signals or body signals to control an external device. The transformation from neural signals to device commands is the core of research on brain-machine interfaces (BMIs). However, while BMIs bypass completely the final path of the motor system, body-machine interfaces (BoMIs) take advantage of motor skills that are still available to the user and have the potential to enhance these skills through their consistent use. BoMIs empower people with severe motor disabilities with the possibility to control external devices, and they concurrently offer the opportunity to focus on achieving rehabilitative goals. In this study we describe a theoretical paradigm for the use of a BoMI in rehabilitation. The proposed BoMI remaps the user’s residual upper body mobility to the two coordinates of a cursor on a computer screen. This mapping is obtained by principal component analysis (PCA). We hypothesize that the BoMI can be specifically programmed to engage the users in functional exercises aimed at partial recovery of motor skills, while simultaneously controlling the cursor and carrying out functional tasks, e.g. playing games. Specifically, PCA allows us to select not only the subspace that is most comfortable for the user to act upon, but also the degrees of freedom and coordination patterns that the user has more difficulty engaging. In this article, we describe a family of map modifications that can be made to change the motor behavior of the user. Depending on the characteristics of the impairment of each high-level spinal cord injury (SCI) survivor, we can make modifications to restore a higher level of symmetric mobility (left versus right), or to increase the strength and range of motion of the upper body that was spared by the injury. Results showed that this approach restored symmetry between left and right side of the body, with an increase of mobility and strength of all the degrees of freedom in the participants involved in the control of the interface. This is a proof of concept that our BoMI may be used concurrently to control assistive devices and reach specific rehabilitative goals. Engaging the users in functional and entertaining tasks while practicing the interface and changing the map in the proposed ways is a novel approach to rehabilitation treatments facilitated by portable and low-cost technologies.
PMCID: PMC4679682  PMID: 26341935
motor learning; human-machine interface; rehabilitation; dimensionality reduction; movement reorganization; spinal cord injury
13.  Neural Substrates of Spontaneous Narrative Production in Focal Neurodegenerative Disease 
Neuropsychologia  2015;79(Pt A):158-171.
Conversational storytelling integrates diverse cognitive and socio-emotional abilities that critically differ across neurodegenerative disease groups and may have diagnostic relevance and predict anatomic changes. The present study employed mixed methods discourse and quantitative analyses to delineate patterns of storytelling across focal neurodegenerative disease groups, and to clarify the neuroanatomical contributions to common storytelling characteristics in these patients. Transcripts of spontaneous social interactions of 46 participants (15 behavioral variant frontotemporal dementia (bvFTD), 7 semantic variant primary progressive aphasia (svPPA), 12 Alzheimer's disease (AD), and 12 healthy older normal controls) were analysed for storytelling characteristics and frequency, and videos of the interactions were rated for patients' social attentiveness. Compared to controls, svPPAs also told more stories and autobiographical stories, and perseverated on aspects of self during storytelling. ADs told fewer autobiographical stories than NCs, and svPPAs and bvFTDs failed to attend to social cues. Storytelling characteristics were associated with a processing speed and mental flexibility, and voxel-based anatomic analysis of structural magnetic resonance imaging revealed that temporal organization, evaluations, and social attention correlated with atrophy corresponding to known intrinsic connectivity networks, including the default mode, limbic, salience, and stable task control networks. Differences in spontaneous storytelling among neurodegenerative groups elucidated diverse cognitive, socio-emotional, and neural contributions to narrative production, with implications for diagnostic screening and therapeutic intervention.
PMCID: PMC4809527  PMID: 26485159
Narrative; Autobiographical memory; Social functioning; Focal neurodegenerative disease; Neural Networks
14.  Understanding the role of the primary somatosensory cortex: Opportunities for rehabilitation 
Neuropsychologia  2015;79(Pt B):246-255.
Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes.
PMCID: PMC4904790  PMID: 26164474
Primary somatosensory cortex; Rehabilitation; Motor control; Motor learning; Neuroimaging; Noninvasive brain stimulation; Stroke
15.  Charting the effects of TMS with fMRI: Modulation of cortical recruitment within the distributed network supporting semantic control 
Neuropsychologia  2016;93(Pt A):40-52.
Semantic memory comprises our knowledge of the meanings of words and objects but only some of this knowledge is relevant at any given time. Thus, semantic control processes are needed to focus retrieval on relevant information. Research on the neural basis of semantic control has strongly implicated left inferior frontal gyrus (LIFG) but recent work suggests that a wider network supports semantic control, including left posterior middle temporal gyrus (pMTG), right inferior frontal gyrus (RIFG) and pre-supplementary motor area (pre-SMA). In the current study, we used repetitive transcranial magnetic stimulation (1 Hz offline TMS) over LIFG, immediately followed by fMRI, to examine modulation of the semantic network. We compared the effect of stimulation on judgements about strongly-associated words (dog-bone) and weaker associations (dog-beach), since previous studies have found that dominant links can be recovered largely automatically with little engagement of LIFG, while more distant connections require greater control. Even though behavioural performance was maintained in response to TMS, LIFG stimulation increased the effect of semantic control demands in pMTG and pre-SMA, relative to stimulation of a control site (occipital pole). These changes were accompanied by reduced recruitment of both the stimulated region (LIFG) and its right hemisphere homologue (RIFG), particularly for strong associations with low control requirements. Thus repetitive TMS to LIFG modulated the contribution of distributed regions to semantic judgements in two distinct ways.
•Offline rTMS was used to modulate the semantic control system.•fMRI revealed post-stimulation changes in other areas of the semantic control system.•Semantic retrieval requires the flexible activation of representations shaped by control processes.
PMCID: PMC5155664  PMID: 27650816
Semantic cognition; Inferior frontal gyrus; Posterior middle temporal gyrus; Transcranial magnetic stimulation; Executive function
16.  Elements of person knowledge: Episodic recollection helps us to identify people but not to recognize their faces 
Neuropsychologia  2016;93(Pt A):218-228.
Faces automatically draw attention, allowing rapid assessments of personality and likely behaviour. How we respond to people is, however, highly dependent on whether we know who they are. According to face processing models person knowledge comes from an extended neural system that includes structures linked to episodic memory. Here we use scalp recorded brain signals to demonstrate the specific role of episodic memory processes during face processing. In two experiments we recorded Event-Related Potentials (ERPs) while participants made identify, familiar or unknown responses to famous faces. ERPs revealed neural signals previously associated with episodic recollection for identify but not familiar faces. These findings provide novel evidence suggesting that recollection is central to face processing, providing one source of person knowledge that can be used to moderate the initial impressions gleaned from the core neural system that supports face recognition.
•Face recognition and person identification produce dissociable neural signals.•Person identification is associated with a recollection Event-Related Potential.•Episodic memory contributes to person knowledge via recollection.
PMCID: PMC5155667  PMID: 27816385
Person identification; Face recognition; Episodic memory; Recollection
17.  Levodopa medication improves incidental sequence learning in Parkinson's disease 
Neuropsychologia  2016;93(Pt A):53-60.
Empirical evidence suggests that levodopa medication used to treat the motor symptoms of Parkinson's disease (PD) may either improve, impair or not affect specific cognitive processes. This evidence led to the ‘dopamine overdose’ hypothesis that levodopa medication impairs performance on cognitive tasks if they recruit fronto-striatal circuits which are not yet dopamine-depleted in early PD and as a result the medication leads to an excess of dopamine. This hypothesis has been supported for various learning tasks including conditional associative learning, reversal learning, classification learning and intentional deterministic sequence learning, on all of which PD patients demonstrated significantly worse performance when tested on relative to off dopamine medication. Incidental sequence learning is impaired in PD, but how such learning is affected by dopaminergic therapy remains undetermined. The aim of the current study was to investigate the effect of dopaminergic medication on incidental sequence learning in PD. We used a probabilistic serial reaction time task (SRTT), a sequence learning paradigm considered to make the sequence less apparent and more likely to be learned incidentally rather than intentionally. We compared learning by the same group of PD patients (n=15) on two separate occasions following oral administration of levodopa medication (on state) and after overnight withdrawal of medication (off state). Our results demonstrate for the first time that levodopa medication enhances incidental learning of a probabilistic sequence on the serial reaction time task in PD. However, neither group significantly differed from performance of a control group without a neurological disease, which indicates the importance of within group comparisons for identifying deficits. Levodopa medication enhanced incidental learning by patients with PD on a probabilistic sequence learning paradigm even though the patients were not aware of the existence of the sequence or their acquired knowledge. The results suggest a role in acquiring incidental motor sequence learning for dorsal striatal areas strongly affected by dopamine depletion in early PD.
•Implicit sequence learning is impaired in non-medicated Parkinson's Patients.•l-Dopa medication ameliorates implicit sequence learning deficits.•Patients showed no indications of awareness of sequence structure.•Such deficits can be identified with greater sensitivity using a within groups comparison.
PMCID: PMC5155668  PMID: 27686948
Parkinson's disease; Incidental sequence learning; Serial reaction time; Levodopa medication; Striatum; Basal ganglia
18.  Altered striatal intrinsic functional connectivity in pediatric anxiety 
Neuropsychologia  2016;85:159-168.
Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders.
The current study examines striatal intrinsic functional connectivity (iFC), using six bilateral striatal seeds, among 35 adolescents with anxiety disorders and 36 healthy comparisons.
Anxiety is associated with abnormally low iFC within the striatum (e.g., between nucleus accumbens and caudate nucleus), and between the striatum and prefrontal regions, including subgenual anterior cingulate cortex, posterior insula and supplementary motor area.
The current findings extend prior behavioral and task-based imaging research, and provide novel data implicating decreased striatal iFC in adolescent anxiety. Alterations of striatal neurocircuitry identified in this study may contribute to the perturbations in the processing of motivational, emotional, interoceptive, and motor information seen in pediatric anxiety disorders. This pattern of the striatal iFC perturbations can guide future research on specific mechanisms underlying anxiety.
PMCID: PMC5107006  PMID: 27004799
Anxiety; Adolescence; Neuroimaging; Resting state fMRI; Reward; Striatum
19.  Development of space perception in relation to the maturation of the motor system in infant rhesus macaques (Macaca mulatta) 
Neuropsychologia  2014;70:429-441.
To act on the environment, organisms must perceive object locations in relation to their body. Several neuroscientific studies provide evidence of neural circuits that selectively represent space within reach (i.e., peripersonal) and space outside of reach (i.e., extrapersonal). However, the developmental emergence of these space representations remains largely unexplored. We investigated the development of space coding in infant macaques and found that they exhibit different motor strategies and hand configurations depending on the objects’ size and location. Reaching-grasping improved from 2 to 4 weeks of age, suggesting a broadly defined perceptual body schema at birth, modified by the acquisition and refinement of motor skills through early sensorimotor experience, enabling the development of a mature capacity for coding space.
PMCID: PMC5100747  PMID: 25486636
premotor cortex; space representation; peripersonal space; body schema; motor development
20.  Jumping to conclusions in untreated patients with Parkinson's disease 
Neuropsychologia  2016;85:19-23.
Jumping to conclusions due to impulsivity has been shown to be a sensitive marker for dopamine dysregulation and addictive behaviour patterns in treated patients with Parkinson's disease (PD). It is unknown whether drug naïve PD patients, who have never received dopaminergic therapy also have deficits in information sampling.
Twenty five de novo PD patients and twenty matched healthy controls were recruited and tested on the beads task, which is a validated information sampling task to assess reflection impulsivity and a temporal discounting questionnaire.
Patients gathered significantly less information and made more irrational choices than matched controls. There was, however, no group difference on the temporal discounting questionnaire.
Poor information sampling and irrational decision making may be an inherent component of the neuropsychological deficit in Parkinson's disease. These findings suggest that underlying impulsivity detected by a metric task is common in de novo PD.
PMCID: PMC5100739  PMID: 26956927
21.  Autonomic response to approachability characteristics, approach behavior, and social functioning in Williams syndrome 
Neuropsychologia  2015;78:159-170.
Williams syndrome (WS) is a neurogenetic disorder that is saliently characterized by a unique social phenotype, most notably associated with a dramatically increased affinity and approachability toward unfamiliar people. Despite a recent proliferation of studies into the social profile of WS, the underpinnings of the pro-social predisposition are poorly understood. To this end, the present study was aimed at elucidating approach behavior of individuals with WS contrasted with typical development (TD) by employing a multidimensional design combining measures of autonomic arousal, social functioning, and two levels of approach evaluations. Given previous evidence suggesting that approach behaviors of individuals with WS are driven by a desire for social closeness, approachability tendencies were probed across two levels of social interaction: talking versus befriending. The main results indicated that while overall level of approachability did not differ between groups, an important qualitative between-group difference emerged across the two social interaction contexts: whereas individuals with WS demonstrated a similar willingness to approach strangers across both experimental conditions, TD individuals were significantly more willing to talk to than to befriend strangers. In WS, high approachability to positive faces across both social interaction levels was further associated with more normal social functioning. A novel finding linked autonomic responses with willingness to befriend negative faces in the WS group: elevated autonomic responsivity was associated with increased affiliation to negative face stimuli, which may represent an autonomic correlate of approach behavior in WS. Implications for underlying organization of the social brain are discussed.
PMCID: PMC4630080  PMID: 26459097
Williams syndrome; Social behavior; Social functioning; Autonomic nervous system; Social interaction; Approachability task
22.  An Investigation of Care-Based vs. Rule-Based Morality in Frontotemporal Dementia, Alzheimer’s Disease, and Healthy Controls 
Neuropsychologia  2015;78:73-79.
Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer’s disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules.
PMCID: PMC4630103  PMID: 26432341
morality; dementia; brain; neuropsychology; neuroimaging; frontotemporal
23.  Effect of emotional valence on retrieval-related recapitulation of encoding activity in the ventral visual stream 
Neuropsychologia  2015;78:221-230.
While prior work has shown greater retrieval-related reactivation in the ventral visual stream for emotional stimuli compared to neutral stimuli, the effects of valence on retrieval-related recapitulation of successful encoding processes (Dm effects) have yet to be investigated. Here, seventeen participants (aged 19–35) studied line drawings of negative, positive, or neutral images followed immediately by the complete photo. After a 20-minute delay, participants performed a challenging recognition memory test, distinguishing the studied line drawing outlines from novel ones. First, results replicated earlier work by demonstrating that negative and positive hits elicited greater ventral occipito-temporal cortex (VOTC) activity than neutral hits during both encoding and retrieval. Moreover, the amount of activation in portions of the VOTC correlated with the magnitude of participants’ emotional memory enhancement. Second, results revealed significant retrieval-related recapitulation of Dm effects (Hits > Misses) in VOTC (anterior inferior temporal gyri) only for negative stimuli. Third, connectivity between the amygdala and fusiform gyrus during the encoding of negative stimuli increased the likelihood of fusiform activation during successful retrieval. Together, these results suggest that recapitulation in posterior VOTC reflects memory for the affective dimension of the stimuli (Emotional Hits > Neutral Hits) and the magnitude of activation in some of these regions is related to superior emotional memory. Moreover, for negative stimuli, recapitulation in more anterior portions of the VOTC is greater for remembered than forgotten items. The current study offers new evidence for effects of emotion on recapitulation of activity and functional connectivity in support of memory.
PMCID: PMC4630131  PMID: 26459096
emotion; memory; recapitulation; ventral visual stream; amygdala; fMRI
24.  Relationship between Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease and Cognition in Cognitively Normal Older Adults 
Neuropsychologia  2015;78:63-72.
The pathophysiological processes underlying Alzheimer’s disease (AD) are hypothesized to begin years to decades before clinical symptom onset, while individuals are still cognitively normal. Although many studies have examined the effect of biomarkers of amyloid pathology on measures of cognitive performance, less is known about the effect of tau pathology on cognitive performance. The present study examined the association between cerebrospinal fluid (CSF) biomarkers of AD pathology (amyloid, total tau (t-tau), and phosphorylated tau (p-tau)) and cognition in a large sample of cognitively normal middle-aged and older adults. Associations were examined with multivariate regressions, in which either amyloid and t-tau or amyloid and p-tau were included as simultaneous predictors of cognitive performance. Cognitive performance was measured with three composite scores assessing working memory, verbal episodic memory, and visuospatial episodic memory. In their respective models, CSF measures of both t-tau and p-tau were associated with the visuospatial episodic memory composite score (p < .001 and p = .02, respectively), but not with the other measures of cognition. In contrast, CSF amyloid was not significantly associated with cognitive performance, raising the possibility that measures of tau pathology have a more direct relationship with cognition in cognitively normal individuals. These results also suggest that tau pathology may have effects on visuospatial episodic memory during preclinical AD that precede alterations in other cognitive domains.
PMCID: PMC4630154  PMID: 26394023
preclinical Alzheimer’s disease; cerebrospinal fluid; amyloid; tau; cognition; biomarkers
25.  Compositionality and the angular gyrus: a multi-voxel similarity analysis of the semantic composition of nouns and verbs 
Neuropsychologia  2015;78:130-141.
The cognitive and neural systems that enable conceptual processing must support the ability to combine (and recombine) concepts to form an infinite number of ideas. Two candidate neural systems for conceptual combination—the left anterior temporal lobe (ATL) and the left angular gyrus (AG)—have been characterized as “semantic hubs” due to both functional and anatomical properties; however, these two regions likely support different aspects of composition. Here we consider two hypotheses for the role of AG in conceptual combination, both of which differ from a putative role for the ATL in “feature-based” combinatorics (i.e., meaning derived by combining concepts’ features). Firstly, we examine whether AG is more sensitive to function-argument relations of the sort that arise when a predicate is combined with its arguments. Secondly, we examine the non-mutually exclusive possibility that AG represents information carried on a verb in particular, whether this be information about event composition or about thematic relations denoted uniquely by verbs. We identified voxels that respond differentially to two-word versus one-word stimuli, and we measured the similarity of the patterns in these voxels evoked by (1) pairs of two-word phrases that shared a noun that was an argument, thus sharing function-argument composition (e.g. eats meat and with meat), in comparison with two-word phrases that shared only a noun, not an argument (e.g., eats meat and tasty meat); and (2) stimulus pairs that shared only an event (operationalized here as sharing a verb; e.g. eats meat and eats quickly), in comparison to both of the above. We found that activity patterns in left AG tracked information relating to the presence of an event-denoting verb in a pair of two-word phrases. We also found that the neural similarity in AG voxel patterns between two phrases sharing a verb correlated with subjects’ ratings of how similar the meanings of those two verb phrases were. These findings indicate that AG represents information specific to verbs, perhaps event structure or thematic relations mediated by verbs, as opposed to argument structure in general.
PMCID: PMC4633412  PMID: 26454087
pattern similarity analysis; angular gyrus; anterior temporal lobe; conceptual combination; semantic composition

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