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OBJECT Predicting cognitive function following resective surgery remains an important clinical goal. Each MRI neuroimaging technique can potentially provide unique and distinct insight into changes that occur in the structural or functional organization of “at-risk” cognitive functions. The authors tested for the singular and combined power of 3 imaging techniques (functional MRI [fMRI], resting state fMRI, diffusion tensor imaging) to predict cognitive outcome following left (dominant) anterior temporal lobectomy for intractable epilepsy. METHODS The authors calculated the degree of deviation from normal, determined the rate of change in this measure across the pre- and postsurgical imaging sessions, and then compared these measures for their ability to predict verbal fluency changes following surgery. RESULTS The data show that the 3 neuroimaging techniques, in a combined model, can reliably predict cognitive outcome following anterior temporal lobectomy for medically intractable temporal lobe epilepsy. CONCLUSIONS These findings suggest that these 3 imaging modalities can be used effectively, in an additive fashion, to predict functional reorganization and cognitive outcome following anterior temporal lobectomy.

Objectives:As surprisingly little is known about the developing brain studiedin vivoin youth with Down syndrome (DS), the current review summarizes the small DS pediatric structural neuroimaging literature and begins to contextualize existing research within a developmental framework.Methods:A systematic review of the literature was completed, effect sizes from published studies were reviewed, and results are presented with respect to the DS cognitive behavioral phenotype and typical brain development.Results:The majority of DS structural neuroimaging studies describe gross differences in brain morphometry and do not use advanced neuroimaging methods to provide nuanced descriptions of the brain. There is evidence for smaller total brain volume (TBV), total gray matter (GM) and white matter, cortical lobar, hippocampal, and cerebellar volumes. When reductions in TBV are accounted for, specific reductions are noted in subregions of the frontal lobe, temporal lobe, cerebellum, and hippocampus. A review of cortical lobar effect sizes reveals mostly large effect sizes from early childhood through adolescence. However, deviance is smaller in adolescence. Despite these smaller effects, frontal GM continues to be largely deviant in adolescence. An examination of age-frontal GM relations using effect sizes from published studies and data from Lee et al. (2016) reveals that while there is a strong inverse relationship between age and frontal GM volume in controls across childhood and adolescence, this is not observed in DS.Conclusions:Further developmentally focused research, ideally using longitudinal neuroimaging, is needed to elucidate the nature of the DS neuroanatomic phenotype during childhood and adolescence. (JINS, 2018,24, 966–976)

Background: Both an elevated brain-reward-region response to palatable food and elevated weight variability have been shown to predict future weight gain.Objective: We examined whether the brain-reward response to food is related to future weight variability.Design: A total of 162 healthy-weight adolescents, who were aged 14-18 y at baseline, were enrolled in the study and were assessed annually over a 3-y follow-up period with 127 participants completing the final 3-y follow-up assessment. With the use of functional magnetic resonance imaging, we tested whether the neural responses to a cue that signaled an impending milkshake receipt and the receipt of the milkshake predicted weight variability over the follow-up period. Weight variability was modeled with a root mean squared error method to reflect fluctuations in weight independent of the net weight change.Results: Elevated activation in the medial prefrontal cortex and supplementary motor area, cingulate gyrus, cuneus and occipital gyrus, and insula in response to milkshake receipt predicted greater weight variability. Greater activation in the precuneus and middle temporal gyrus predicted lower weight variability.Conclusions: From our study data, we suggest that the elevated activation of reward and emotional-regulation brain regions (medial prefrontal cortex, cingulate cortex, and insula) and lower activation in self-reference regions (precuneus) in response to milkshake receipt predict weight variability over 3 y of follow-up. The fact that the reward response in the current study emerged in response to high-calorie palatable food receipt suggests that weight variability may be a measure of propensity periods of a positive energy balance and should be examined in addition to measures of the net weight change. With our collective results, we suggest that weight variability and its brain correlates should be added to other variables that are predictive of weight gain to inform the design of obesity-preventive programs in adolescents. This trial was registered at clinicaltrials.gov as NCT01807572.

Epileptic seizures can initiate a neural circuit and lead to aberrant neural communication with brain areas outside the epileptogenic region. We focus on interictal activity in focal temporal lobe epilepsy and evaluate functional connectivity (FC) differences that emerge as function of bilateral versus strictly unilateral epileptiform activity. We assess the strength of FC at rest between the ictal and non-ictal temporal lobes, in addition to whole brain connectivity with the ictal temporal lobe. Results revealed strong connectivity between the temporal lobes for both patient groups, but this did not vary as a function of unilateral versus bilateral interictal status. Both the left and right unilateral temporal lobe groups showed significant anti-correlated activity in regions outside the epileptogenic temporal lobe, primarily involving the contralateral (non-ictal/non-pathologic) hemisphere, with precuneus involvement prominent. The bilateral groups did not show this contralateral anti-correlated activity. This anti-correlated connectivity may represent a form of protective and adaptive inhibition, helping to constrain epileptiform activity to the pathologic temporal lobe. The absence of this activity in the bilateral groups may be indicative of flawed inhibitory mechanisms, helping to explain their more widespread epileptiform activity. Our data suggest that the location and build up of epilepsy networks in the brain are not truly random, and are not limited to the formation of strictly epileptogenic networks. Functional networks may develop to take advantage of the regulatory function of structures such as the precuneus to instantiate an anti-correlated network, generating protective cortico-cortico inhibition for the purpose of limiting seizure spread or epileptogenesis.

Functional neuroimaging technologies are increasingly being used to predict cognitive/behavioral outcomes after the initiation of clinical interventions such as resective surgery or cognitive rehabilitation. We provide a conceptual model and a case example to explain how the results from various neuroimaging techniques can be integrated to answer important questions about clinical recovery such as whether neural reorganization has occurred and, if so, the type of adaptive cognitive mechanism driving this reorganization. This proposed framework and its use in interpreting neuroimaging outcomes studies should help uncover the principles that govern neural reorganization, and be of use to any patient for whom the risk, or potential benefit, of brain-based interventions is unknown.

There are a number of prefrontal/sub-cortical networks in the brain (e.g., cerebellar-thalamic-prefrontal or basal ganglia/supplementary motor cortex circuits) that despite having a clear role in motor function have been shown to be involved in non-motor tasks. In this project we test for the involvement of these networks in a dimensional judgment task that utilizes visual perceptual, visual spatial processing and requires the ordering of dimensional (height) information. Unlike previous studies examining non-motor sequencing, we directly compare both non-motor and motor versions of our dimensional judgment task. In addition, we examine activation uniquely associated with correct task responses. The findings provide evidence for the role of cortical not subcortical structures in the sequencing of visuo-spatial material apart from any motor output requirements. Our results suggest that the inferior parietal cortex (BA 7, 40) and medial frontal regions (BA 6, 8, 9 including the SMA) are instrumental to the task. Based on these results, we propose a prefrontal/parietal network plays a role in the implementation of a comparator mechanism that makes accurate comparisons along the dimension of interest, holds the information in working memory, and then (regardless of whether the information is correct or incorrect) generates a tag or abstract code that assigns the information a place in an ordered sequence. Most important, the information involved can be visual/symbolic and non-motor (not just motor) in nature.

Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region.

An fMRI pitch memory task was administered to left and right anterior temporal lobectomy (ATL) patients. The goal was to verify the neuroanatomical correlates of non-verbal memory, and to determine if pitch memory tasks can identify cognitive risk prior to ATL. The data showed that the bilateral posterior superior temporal lobes implement pitch memory in both ATL patients and NCs (normal controls), indicating that the task can be accomplished with either anterior temporal lobe resected. NCs activate the posterior temporal lobes more strongly than ATL patients during highly accurate performance. In contrast, both ATL groups activate the anterior cingulate in association with accuracy. While our data clarifies the functional neuroanatomy of pitch memory, it also indicates that such tasks do not serve well to lateralize and functionally map potentially “at risk” non-verbal memory skills prior to ATL.

While occupying a relatively brief space in the history of scientific inquiry, many social psychologists have nonetheless recognized the need to integrate the field’s myriad findings into a coherent, meta-theoretical framework. Chester et al. (2012), consistent with the spirit of this movement, have answered this call by utilizing a Life History Theory (LHT) framework to understand the relationship between attachment bonds formed during early critical developmental periods and later reactions to social rejection experiences in adulthood. While attachment theory and social exclusion research are well-developed phenomena in their own right, the utilization of LHT clarifies how these areas of inquiry are interrelated. As the authors note, LHT has been successfully used across the biological sciences to explain how specific developmental periods require organisms to differentially allocate limited resources to navigate various aspects of survival and reproduction. At its core, LHT is a motivational framework, whereby motivational “states” are determined by the specific problems and opportunities associated with an organism’s current developmental stage and local ecology. In the current paper, Chester and colleagues provide a theoretical framework and supporting evidence indicating early life stages can critically influence, via calibration processes, responses in subsequent developmental periods. Consistent with the notion that evolution is incapable of forward-thinking, the authors argue that early social experiences provide the data that calibrates organisms’ systems for responding to their future social environments (see Figure ​Figure1).1). Specifically, children’s early attachment experiences calibrate their social pain system response, which partially determines the intensity of reactions to rejection experiences in adulthood. Although intense reactions to social rejection can be adaptive, specifically by helping an organism secure subsequent social belonging, the intensity of these responses is only beneficial provided social opportunity is actually available; otherwise, such chronic and intense responses to social rejection can negatively impact other vital systems (e.g., biological immune system). Whereas consistently unavailable attachment in childhood (avoidant attachment) communicates an environment in which social exclusion is likely to be normative, variable attachment opportunity in childhood (anxious attachment) indicates that social belonging opportunities will be unpredictable. Based on these early experiences, the authors provide evidence that avoidantly attached individuals show a blunted response to social rejection (reduced activation of dACC and insula), whereas anxiously attached individuals show a heightened response to social rejection. For avoidantly attached individuals, social resources have been consistently unavailable and calibration of the social pain system to respond intensely to social rejection would have numerous costs (e.g., suppression of immune system), with very few opportunities (social inclusion). Conversely, anxiously attached individuals, because social inclusion opportunities have been unpredictable, have a social pain system calibrated to be especially sensitive to cues signaling social rejection. Collectively, the current article effectively explains how early attachment bonds calibrate reactions to social rejection. Figure 1 Depicts the optimal calibration and response of the social pain system in relation to different life histories. Early S.E. refers to the social environment in which the social pain system is calibrated, Attachment Orientation refers to the resultant attachment ... Interestingly, the optimal calibration hypothesis is not only a powerful explanatory framework for research on social attachment and social rejection; it may have clinical significance as well, with implications beyond social psychology. For example, an understanding of how the dACC and anterior insula are implicated in social pain system calibration may inform the understanding and treatment of individuals with damage to these areas, who are being treated primarily for symptoms unrelated to the social pain system. For example, patients with left middle cerebral artery (MCA) strokes often suffer injury to the anterior insula and the frontal opercula, producing pronounced expressive dysphasias. Some patients respond to therapy and recover expressive language function to almost basal levels, while other patients are completely intractable to therapy. While current treatments focus specifically on the recovery of language function, such injuries may also disrupt social pain responses, producing heightened levels of anxiety that can interfere with treatment adherence. If considered from a LHT perspective, this therapeutic approach should also address the patient’s attachment orientation and concomitant social pain system calibration to achieve optimal therapeutic outcomes. Understanding how specific brain injuries may disrupt social pain system responses could help catalyze the development of therapeutic interventions that address both primary (language deficits) and secondary symptoms (disruption of social pain system), which may improve overall patient outcomes. Thus, this theoretical framework has the potential to inform the study and treatment of neurologically impaired individuals. Chester and colleagues also identify critical periods for the calibration of the social rejection system: (1) early on during development when parental rejection would be devastating to survival, and (2) during adolescence, when rejection of a possible mate would reduce reproductive fitness. Interestingly, these two critical periods are well aligned with critical periods in language development (e.g., Johnson and Newport, 1989; Hurford, 1991), suggesting that language and socio-affective development are inextricably linked – a postulation supported by the evolutionary evidence of con-committal language ability and societal size increases in hominids (Holloway, 1981). This allows for the extension of this hypothesis to not only include responses to social pain, but also linguistic function/ability as a calibratable system responsive to early life history. Interestingly, one of the major nodes of the social pain network (insula) is close in proximity and highly connected to a major node in the language network (Broca’s area), suggesting that the calibration of the social pain system and language system may be related. The development of these ideas could lead to interesting research that takes advantage of both neuropsychological and neuroimaging techniques. Chester and colleagues have begun an exciting dialog that combines findings from a number of fields and unites them through one common theoretical perspective. Indeed, the current research program is one of a growing number in social psychology to use LHT to not only organize a variety of social psychological phenomena, but integrate them within the larger scientific community (e.g., Brown et al., 2009; Buss, 2009; Wang et al., 2009; Figueredo et al., 2011; Griskevicius et al., 2011; Sundie et al., 2011). Based on this expanding body of evidence, it seems as though a LHT framework will continue to be a powerful tool for organizing and generating rigorous research in the study of human behavior.

Temporal lobe epilepsy patients have demonstrated a relative preservation in the integrity of implicit memory procedures. We examined performance in a verbal implicit and explicit memory task in left anterior temporal lobectomy patients (LATL) and healthy normal controls (NCs) while undergoing fMRI. We hypothesized that despite the relative integrity of implicit memory in both the LATL patients and normal controls, the two groups would show distinct functional neuroanatomic profiles during implicit memory. LATLs and NCs performed Jacoby’s Process Dissociation Process (PDP) procedure during fMRI, requiring completion of word stems based on the previously studied words or new/unseen words. Measures of automaticity and recollection provided uncontaminated indices of implicit and explicit memory, respectively. The behavioral data showed that in the face of temporal lobe pathology implicit memory can be carried out, suggesting implicit verbal memory retrieval is non-mesial temporal in nature. Compared to NCs, the LATL patients showed reliable activation, not deactivation, during implicit (automatic) responding. The regions mediating this response were cortical (left medial frontal and precuneus) and striatal. The active regions in LATL patients have the capacity to implement associative, conditioned responses that might otherwise be carried out by a healthy temporal lobe, suggesting this represented a compensatory activity. Because the precuneus has also been implicated in explicit memory, the data suggests this structure may have a highly flexible functionality, capable of supporting implementation of either explicit memory, or automatic processes such as implicit memory retrieval. Our data suggest that a healthy mesial/anterior temporal lobe may be needed for generating the posterior deactivation perceptual priming response seen in normals.

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non-pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non-verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra-temporal FC may vary as a function of episodic memory material and each hemisphere’s capacity for cognitive reorganization.

Epilepsy provided neuropsychology with the canonical cases of amnesia and episodic memory disorders. These cases strongly encouraged the development of modular conceptions of memory. As neuropsychology moves to develop non-modular, network approaches to cognition, it is ironic that epilepsy can be seen as providing clear, illustrative examples of a network disturbance in cognition. The key to understanding this shift in thinking is to grasp that the neural mechanism underlying network development (i.e., neuroplasticity) and the neuropathology of seizures are separated by little. Many of the neural mechanisms of learning are key factors in the regulation of seizures, and the highly plastic regions specialized for learning and memory are also prone to seizures. More than characterizing the effects of seizures, and determining the risks and outcomes of brain surgery, there are fundamental cognitive neuroscience reasons for the neuropsychologist to study epilepsy.