Functional Brain Imaging Studies Research Articles

Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy

ObjectiveSchizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. MethodsWe conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. ResultsDuring the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. Conclusions. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function.

Cold pressor gel test: A safe alternative to the cold pressor test in fMRI.

This study describes a new methodology-the cold pressor gel test (CPGT)-for delivering an accessible experimental pain stimulus, which is reproducible and safe for functional MRI (fMRI). The cold pressor test was modified to put safety precautions into the CPGT. The material used is cool gelled water with a thickening product, which provides a stable temperature at 0.2 °C. Thirteen women with chronic pelvic pain were scanned using a 3 Tesla (T) MR scanner equipped with a 12-channel head coil. Changes in BOLD activation during cold-induced pain were estimated. The results have demonstrated that gel substances maintain a stable temperature during the experiment, resulting in an insignificant variation. Before the experiment, the mean temperature was 0.2 ± 0.11 °C, and at the end it was 0.7 ± 0.15 °C. The time taken by participants to reach the maximum level of pain during the CPGT was 56.92 ± 11.09 s. The pain intensity during the experiments was 6.92 ± 1.66 on the visual analog scale (VAS). The fMRI analysis showed significant BOLD activation in the main brain regions involved in chronic pain processing. The CPGT is an experimental tool to deliver pain that is easily reproducible, particularly in brain functional imaging studies. Moreover, it is cost-effective, safe, and compatible with fMRI. Magn Reson Med 78:1464-1468, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Cortical Plasticity and Olfactory Function in Early Blindness.

Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

Higher Dimensional Meta-State Analysis Reveals Reduced Resting fMRI Connectivity Dynamism in Schizophrenia Patients.

Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject’s trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the first demonstration that high-level dynamic properties of whole-brain connectivity, generic enough to be commensurable under many decompositions of time-varying connectivity data, exhibit robust and systematic differences between schizophrenia patients and healthy controls.

Brain Mediation of Obsessive-Compulsive Disorder Symptoms: Evidence From Functional Brain Imaging Studies in the Human and Nonhuman Primate.

Obsessive-compulsive disorder (OCD) has a long history of speculations concerning its cause. This article reviews human functional neuroimaging studies of OCD, then presents data from a study in the nonhuman primate that concerns the localization of brain systems that may mediate the expression of OCD symptoms. We use these lines of evidence to argue that increased "neural tone" through a section of the behaviorally disinhibiting "direct" basal ganglia pathway, relative to tone in the behaviorally inhibiting or moderating "indirect" basal ganglia system, may mediate the expression of OCD symptoms. The limbic orbital prefrontal cortex, the involvement of which is highly implicated in OCD, may have a greater influence on neural tone in the direct pathway than in the indirect, whereas more dorsal neocortical prefrontal regions may have the opposite effects on these two basal ganglia subsystems. Effective OCD treatments may obtain their results by preferentially decreasing neural tone through the direct relative to the indirect basal ganglia system.

Multi-Voxel Decoding and the Topography of Maintained Information During Visual Working Memory.

The ability to maintain representations in the absence of external sensory stimulation, such as in working memory, is critical for guiding human behavior. Human functional brain imaging studies suggest that visual working memory can recruit a network of brain regions from visual to parietal to prefrontal cortex. In this review, we focus on the maintenance of representations during visual working memory and discuss factors determining the topography of those representations. In particular, we review recent studies employing multi-voxel pattern analysis (MVPA) that demonstrate decoding of the maintained content in visual cortex, providing support for a “sensory recruitment” model of visual working memory. However, there is some evidence that maintained content can also be decoded in areas outside of visual cortex, including parietal and frontal cortex. We suggest that the ability to maintain representations during working memory is a general property of cortex, not restricted to specific areas, and argue that it is important to consider the nature of the information that must be maintained. Such information-content is critically determined by the task and the recruitment of specific regions during visual working memory will be both task- and stimulus-dependent. Thus, the common finding of maintained information in visual, but not parietal or prefrontal, cortex may be more of a reflection of the need to maintain specific types of visual information and not of a privileged role of visual cortex in maintenance.

Contribution of writing to reading: Dissociation between cognitive and motor process in the left dorsal premotor cortex

Functional brain imaging studies reported activation of the left dorsal premotor cortex (PMd), that is, a main area in the writing network, in reading tasks. However, it remains unclear whether this area is causally relevant for written stimulus recognition or its activation simply results from a passive coactivation of reading and writing networks. Here, we used chronometric paired-pulse transcranial magnetic stimulation (TMS) to address this issue by disrupting the activity of the PMd, the so-called Exner's area, while participants performed a lexical decision task. Both words and pseudowords were presented in printed and handwritten characters. The latter was assumed to be closely associated with motor representations of handwriting gestures. We found that TMS over the PMd in relatively early time-windows, i.e., between 60 and 160 ms after the stimulus onset, increased reaction times to pseudoword without affecting word recognition. Interestingly, this result pattern was found for both printed and handwritten characters, that is, regardless of whether the characters evoked motor representations of writing actions. Our result showed that under some circumstances the activation of the PMd does not simply result from passive association between reading and writing networks but has a functional role in the reading process. At least, at an early stage of written stimuli recognition, this role seems to depend on a common sublexical and serial process underlying writing and pseudoword reading rather than on an implicit evocation of writing actions during reading as typically assumed.

A debate on working memory and cognitive control: can we learn about the treatment of substance use disorders from the neural correlates of anorexia nervosa?

BackgroundAnorexia Nervosa (AN) is a debilitating, sometimes fatal eating disorder (ED) whereby restraint of appetite and emotion is concomitant with an inflexible, attention-to-detail perfectionist cognitive style and obsessive-compulsive behaviour. Intriguingly, people with AN are less likely to engage in substance use, whereas those who suffer from an ED with a bingeing component are more vulnerable to substance use disorder (SUD).DiscussionThis insight into a beneficial consequence of appetite control in those with AN, which is shrouded by the many other unhealthy, excessive and deficit symptoms, may provide some clues as to how the brain could be trained to exert better, sustained control over appetitive and impulsive processes. Structural and functional brain imaging studies implicate the executive control network (ECN) and the salience network (SN) in the neuropathology of AN and SUD. Additionally, excessive employment of working memory (WM), alongside more prominent cognitive deficits may be utilised to cope with the experience of negative emotions and may account for aberrant brain function.SummaryWM enables mental rehearsal of cognitive strategies while regulating, restricting or avoiding neural responses associated with the SN. Therefore, high versus low WM capacity may be one of the factors that unites common cognitive and behavioural symptoms in those suffering from AN and SUD respectively. Furthermore, emerging evidence suggests that by evoking neural plasticity in the ECN and SN with WM training, improvements in neurocognitive function and cognitive control can be achieved. Thus, considering the neurocognitive processes of excessive appetite control and how it links to WM in AN may aid the application of adjunctive treatment for SUD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-0714-z) contains supplementary material, which is available to authorized users.

An Automated Motion Detection and Reward System for Animal Training.

A variety of approaches has been used to minimize head movement during functional brain imaging studies in awake laboratory animals. Many laboratories expend substantial effort and time training animals to remain essentially motionless during such studies. We could not locate an “off-the-shelf” automated training system that suited our needs. We developed a time- and labor-saving automated system to train animals to hold still for extended periods of time. The system uses a personal computer and modest external hardware to provide stimulus cues, monitor movement using commercial video surveillance components, and dispense rewards. A custom computer program automatically increases the motionless duration required for rewards based on performance during the training session but allows changes during sessions. This system was used to train cynomolgus monkeys (Macaca fascicularis) for awake neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI).The automated system saved the trainer substantial time, presented stimuli and rewards in a highly consistent manner, and automatically documented training sessions. We have limited data to prove the training system's success, drawn from the automated records during training sessions, but we believe others may find it useful. The system can be adapted to a range of behavioral training/recording activities for research or commercial applications, and the software is freely available for non-commercial use.

Altered sensorimotor activation patterns in idiopathic dystonia-an activation likelihood estimation meta-analysis of functional brain imaging studies.

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements or postures. Functional neuroimaging studies have yielded abnormal task‐related sensorimotor activation in dystonia, but the results appear to be rather variable across studies. Further, study size was usually small including different types of dystonia. Here we performed an activation likelihood estimation (ALE) meta‐analysis of functional neuroimaging studies in patients with primary dystonia to test for convergence of dystonia‐related alterations in task‐related activity across studies. Activation likelihood estimates were based on previously reported regional maxima of task‐related increases or decreases in dystonia patients compared to healthy controls. The meta‐analyses encompassed data from 179 patients with dystonia reported in 18 functional neuroimaging studies using a range of sensorimotor tasks. Patients with dystonia showed bilateral increases in task‐related activation in the parietal operculum and ventral postcentral gyrus as well as right middle temporal gyrus. Decreases in task‐related activation converged in left supplementary motor area and left postcentral gyrus, right superior temporal gyrus and dorsal midbrain. Apart from the midbrain cluster, all between‐group differences in task‐related activity were retrieved in a sub‐analysis including only the 14 studies on patients with focal dystonia. For focal dystonia, an additional cluster of increased sensorimotor activation emerged in the caudal cingulate motor zone. The results show that dystonia is consistently associated with abnormal somatosensory processing in the primary and secondary somatosensory cortex along with abnormal sensorimotor activation of mesial premotor and right lateral temporal cortex. Hum Brain Mapp 37:547–557, 2016. © 2015 Wiley Periodicals, Inc.

Social Function and Frontopolar Activation during a Cognitive Task in Patients with Bipolar Disorder

Background: It is important to understand the neural basis of functional impairments in patients with bipolar disorder (BD) in order to be able to address the recovery. Recently, neurocognitive impairment emerged as a predictor of psychosocial function. A number of functional brain imaging studies have shown that social function is associated with activation of the prefrontal cortex during a cognitive task in healthy adults, and in patients with major depressive disorder and schizophrenia. However, few studies have been conducted in patients with BD. Methods: We performed multichannel near-infrared spectroscopy (NIRS) imaging to investigate the activation of the prefrontal cortex during a verbal fluency task (VFT). We also used the Social Adaptation Self-Evaluation Scale (SASS) to assess social functioning in patients with BD. Thirty-three depressed patients with BD and 65 age-, gender- and task performance-matched healthy controls (HCs) participated in this study. Results: Depressed patients with BD showed reduced activation in the broader bilateral prefrontal cortex during the VFT compared to HCs. Moreover, a significant positive correlation was observed between the total SASS scores and right prefrontal activation in patients with BD. In the SASS subscores, the interest and motivation factor was also positively correlated with frontopolar activation. Conclusions: These results suggest an association between social function and prefrontal activation in depressed patients with BD. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social function.

A dual K-space UNFOLD method for 3D functional brain imaging: A preliminary study

PurposeTo investigate a method of dual k-space unaliasing by Fourier‐encoding the overlaps using the temporal dimension (DUNFOLD), a novel technique for high temporal resolution 3D functional brain imaging. MethodsTwo different methods of unaliasing by Fourier‐encoding the overlaps using the temporal dimension (UNFOLD), excitation UNFOLD (XUNFOLD) and acquisition UNFOLD, were merged to obtain a DUNFOLD. The feasibility of the DUNFOLD technique was examined by using a phantom and comparing its result to that of the previous XUNFOLD method. A high temporal resolution 3D functional brain imaging study was also performed, focusing on the microvascular response. Three different temporal resolutions, 20s, 10s and 5s, were tested with a spatial resolution of 0.63mm3 to evaluate the method. The vascular regions of interest were selected for data analysis. ResultsThe DUNFOLD method achieved a temporal resolution approximately four times greater than those of the UNFOLD and XUNFOLD methods, without apparent signal degradation. The vascular responses in the visual cortex were obtained with high spatiotemporal resolution by using the DUNFOLD method during visual stimulation. For small vessels, the percentage change in the signal reached 18%. ConclusionThe proposed DUNFOLD method yields a temporal resolution higher than those of the previous UNFOLD and XUNFOLD methods. The conclusions are likely to be important for functional imaging studies, especially those targeting cerebral vascular responsiveness.

Using oscillations to understand recovery after stroke.

This scientific commentary refers to ‘Coherent neural oscillations predict future motor and language improvement after stroke’, by Nicolo et al. (doi:10.1093/brain/awv200). The global impact of stroke remains high and improving long-term outcomes for stroke survivors is a crucially important clinical and scientific goal. Dramatic improvements will only come about through understanding the mechanisms of recovery and identifying novel therapeutic targets. Functional brain imaging studies of recovering human stroke survivors have been used for a number of years in an attempt to uncover these mechanisms. In general, such studies show that recovery of both movement and language after stroke is supported by functionally relevant reorganization within task-relevant brain networks. However, the exact pattern of reorganization, and therefore the exact role played by each brain region, appears to depend on factors such as the configuration of the residual structural architecture. While these studies have established that post-stroke brain network reorganization is functionally relevant, it is difficult as yet to see how they have influenced clinical practice (Ward, 2015). The questions that concern most clinicians are how to predict outcome, identify suitable patients for specific treatments, and develop new therapeutic approaches. In this issue of Brain , Nicolo et al. (2015) attempt the first of these by using electroencephalography (EEG) to identify regional and modality specific alterations in early post-stroke brain function that account for differences in subsequent clinical improvement over the next 3 months. EEG is a non-invasive method of measuring electrical currents generated by populations of neurons and, along with magnetoencephalography (MEG), which measures corresponding changes in magnetic field, is increasingly used to investigate properties of the pathological brain. Researchers will often examine synchronous activity (or oscillations) of large numbers of neurons in specific frequency bands. Brain regions can use this synchronous activity …

Headache. Current status of research and treatment

The starting point for German headache research and clinical education was the engagement of D. Soyka in the 1970s, which enabled the foundation of the German Headache Society (DMKG) on 28 June 1979 and, some years later, the founding congress of the International Headache Society (IHS) in Munich 1982. As a result of these activities, in 1988 the first international classification of headache disorders was published. This classification was one of the major milestones in the development of basic as well as clinical headache research. In the following years, epidemiological studies all over the world showed a 1-year prevalence for headache of approximately 60%, making headaches one of the most frequent medical complaints. Basic research showed an involvement of serotonergic mechanisms in migraine pain and triptans were one of the first drugs designed to influence these mechanisms. Functional brain imaging studies in migraine patients further showed a cyclic modulation of the activity of brainstem areas independent of the current pain state. Various research groups were involved in the clarification of the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache. A specific development in the German headache scene is the establishment of integrated headache centers and reflects the primarily multimodal treatment approach in Germany which contrasts with the settings in other countries. These successful developments are increasingly being undermined by the fact that the low financial support of headache research, for example, by the German science council is causing a decreasing interest in headache research, with the consequence that the clinical education of students as well as young medical doctors shows increasing deficits. The consequence for the future will be a deficit in the clinical care of the population.

Right parietal cortex mediates recognition memory for melodies.

Functional brain imaging studies have highlighted the significance of right‐lateralized temporal, frontal and parietal brain areas for memory for melodies. The present study investigated the involvement of bilateral posterior parietal cortices (PPCs) for the recognition memory of melodies using transcranial direct current stimulation (tDCS). Participants performed a recognition task before and after tDCS. The task included an encoding phase (12 melodies), a retention period, as well as a recognition phase (24 melodies). Experiment 1 revealed that anodal tDCS over the right PPC led to a deterioration of overall memory performance compared with sham. Experiment 2 confirmed the results of Experiment 1 and further showed that anodal tDCS over the left PPC did not show a modulatory effect on memory task performance, indicating a right lateralization for musical memory. Furthermore, both experiments revealed that the decline in memory for melodies can be traced back to an interference of anodal stimulation on the recollection process (remember judgements) rather than to familiarity judgements. Taken together, this study revealed a causal involvement of the right PPC for memory for melodies and demonstrated a key role for this brain region in the recollection process of the memory task.

Itch and brain.

Itch is an unpleasant somatic sensation that evokes the urge to scratch. Chronic itch is a severe problem that diminishes quality of life. There are many patients suffering from chronic itch across the world. The brain is the final terminal to receive itch-related signals from the body and plays an important role in perceiving the itch sensation. Thus, to understand the cerebral mechanism of itch perception and how this mechanism differs between healthy subjects and chronic itch patients is important for advancing our understanding on the pathophysiology of chronic itch. Itch is suppressed by scratching or applying painful stimuli. The pleasurable sensation evoked by scratching an itch increases the urge to scratch. Viewing others in itch or imagining the itch sensation may evoke real itch sensations and the scratching response. To understand the mechanisms responsible for these phenomena may provide useful information for the development of treatment of itch and advance our understanding of the cerebral mechanism of itch and scratch. Several functional brain imaging studies have addressed these issues and reported interesting findings. In this review article, the authors discussed the findings of previous studies and how they have advanced our understanding of the central mechanisms of itch, scratch and chronic itch.

Human Brain Representations of Haptic and Visual Textures

We present a literature review of functional brain imaging studies of haptic and visual texture perception, and highlight our ongoing functional magnetic resonance imaging (fMRI) experiment of the crossmodal links between vision and touch. In the fMRI experiment, the subjects viewed or touched a piece of wool or denim cloth. A multivoxel pattern analysis of whole-brain fMRI activity revealed the crossmodal nature of natural texture perception. Visual texture representations were found in the somatosensory and association cortices as well as the visual cortex, while haptic texture representations were found in the visual cortex and association cortices as well as the somatosensory cortex. Furthermore, shared visuo-haptic representations were found in the parietal association, somatosensory, and visual cortices. These results that suggested the crossmodal transfer of texture information across functionally segregated sensory and associative brain regions are discussed in relation to previous findings on texture perception and aesthetic texture or shitsukan.

Functional imaging and migraine

Over the last several years, a growing number of brain functional imaging studies have provided insights into mechanisms underlying migraine. This article reviews the recent migraine functional neuroimaging literature and provides recommendations for future studies that will help fill knowledge gaps. PET and functional MRI studies have identified brain regions that might be responsible for mediating the onset of a migraine attack and those associated with migraine symptoms. Enhanced activation of brain regions that facilitate processing of sensory stimuli suggests a mechanism by which migraineurs are hypersensitive to visual, olfactory, and cutaneous stimuli. Resting state functional connectivity MRI studies have identified numerous brain regions and functional networks with atypical functional connectivity in migraineurs, suggesting that migraine is associated with aberrant brain functional organization. Functional MRI and PET studies that have identified brain regions and brain networks that are atypical in migraine have helped to describe the neurofunctional basis for migraine symptoms. Future studies should compare functional imaging findings in migraine to other headache and pain disorders and should explore the utility of functional imaging data as biomarkers for diagnostic and treatment purposes.

Where smart brains are different: A quantitative meta-analysis of functional and structural brain imaging studies on intelligence

Individual differences in general intelligence have been associated with differences in brain structure and function. The currently most popular theory of the neural bases of intelligence – the Parieto-Frontal Integration Theory of Intelligence (P-FIT) – describes a network of frontal and parietal brain regions as the main neural basis of intelligence. Here, we put the theory to an empirical test by conducting voxel-based quantitative meta-analyses of 12 structural and 16 functional human brain imaging studies, testing for statistically significant spatial convergence across studies. We focused our analyses on studies reporting associations between individual differences in intelligence (as assessed by established tests of psychometric intelligence) and either (a) brain activation during a cognitive task (functional meta-analysis) or (b) amount of grey matter as assessed by voxel-based morphometry (structural meta-analysis). The functional meta-analysis resulted in eight clusters distributed across both hemispheres, located in lateral frontal, medial frontal, parietal, and temporal cortices. The structural meta-analysis of VBM studies resulted in 12 clusters distributed in lateral and medial frontal, temporal, and occipital cortices, as well as in subcortical structures. Results of the functional and structural meta-analyses did not show any overlap — although both independently showed good match with the P-FIT. Based on the meta-analyses, we present an updated model for the brain bases of intelligence that extends previous models in also considering the posterior cingulate cortex and subcortical structures as relevant for intelligence, and in differentiating between positive and negative associations of intelligence and brain activation. From a critical review of original studies and methods, we derive important suggestions for future research on brain correlates of intelligence.

NTRK2 expression levels are reduced in laser captured pyramidal neurons from the anterior cingulate cortex in males with autism spectrum disorder.

BackgroundThe anterior cingulate cortex (ACC) is a brain area involved in modulating behavior associated with social interaction, disruption of which is a core feature of autism spectrum disorder (ASD). Functional brain imaging studies demonstrate abnormalities of the ACC in ASD as compared to typically developing control patients. However, little is known regarding the cellular basis of these functional deficits in ASD. Pyramidal neurons in the ACC are excitatory glutamatergic neurons and key cellular mediators of the neural output of the ACC. This study was designed to investigate the potential role of ACC pyramidal neurons in ASD brain pathology.MethodsPostmortem ACC tissue from carefully matched ASD and typically developing control donors was obtained from two national brain collections. Pyramidal neurons and surrounding astrocytes were separately collected from layer III of the ACC by laser capture microdissection. Isolated RNA was subjected to reverse transcription and endpoint PCR to determine gene expression levels for 16 synaptic genes relevant to glutamatergic neurotransmission. Cells were also collected from the prefrontal cortex (Brodmann area 10) to examine those genes demonstrating differences in expression in the ACC comparing typically developing and ASD donors.ResultsThe level of NTRK2 expression was robustly and significantly lower in pyramidal neurons from ASD donors as compared to typically developing donors. Levels of expression of GRIN1, GRM8, SLC1A1, and GRIP1 were modestly lower in pyramidal neurons from ASD donors, but statistical significance for these latter genes did not survive correction for multiple comparisons. No significant expression differences of any genes were found in astrocytes laser captured from the same neocortical area. In addition, expression levels of NTRK2 and other synaptic genes were normal in pyramidal neurons laser captured from the prefrontal cortex.ConclusionsThese studies demonstrate a unique pathology of neocortical pyramidal neurons of the ACC in ASD. NTRK2 encodes the tropomyosin receptor kinase B (TrkB), transmission through which neurotrophic factors modify differentiation, plasticity, and synaptic transmission. Reduced pyramidal neuron NTRK2 expression in the ACC could thereby contribute to abnormal neuronal activity and disrupt social behavior mediated by this brain region.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0023-2) contains supplementary material, which is available to authorized users.