Left Hemisphere Regions Research Articles

Priming the Secure Attachment Schema Affects the Emotional Face Processing Bias in Attachment Anxiety: An fMRI Research.

Our study explored how priming with a secure base schema affects the processing of emotional facial stimuli in individuals with attachment anxiety. We enrolled 42 undergraduate students between 18 and 27 years of age, and divided them into two groups: attachment anxiety and attachment secure. All participants were primed under two conditions, the secure priming using references to the partner, and neutral priming using neutral references. We performed repeated attachment security priming combined with a dual-task paradigm and functional magnetic resonance imaging. Participants’ reaction times in terms of responding to the facial stimuli were also measured. Attachment security priming can facilitate an individual’s processing of positive emotional faces; for instance, the presentation of the partner’s name was associated with stronger activities in a wide range of brain regions and faster reaction times for positive facial expressions in the subjects. The current finding of higher activity in the left-hemisphere regions for secure priming rather than neutral priming is consistent with the prediction that attachment security priming triggers the spread of the activation of a positive emotional state. However, the difference in brain activity during processing of both, positive and negative emotional facial stimuli between the two priming conditions appeared in the attachment anxiety group alone. This study indicates that the effect of attachment secure priming on the processing of emotional facial stimuli could be mediated by chronic attachment anxiety. In addition, it highlights the association between higher-order processes of the attachment system (secure attachment schema priming) and early-stage information processing system (attention), given the increased attention toward the effects of secure base schema on the processing of emotion- and attachment-related information among the insecure population. Thus, the following study has applications in providing directions for clinical treatment of mood disorders in attachment anxiety.

Rethinking the function of brain regions for reading Chinese characters in a meta-analysis of fMRI studies

Abstract Neuroimaging studies have proposed specific brain regions for reading Chinese characters. For example, compared to alphabetic languages, Chinese reading has revealed more activation of the left Middle Frontal Gyrus (MFG) and null or deactivation at left posterior Superior Temporal Gyrus (pSTG). However, the model of specific regions for Chinese was contested by recent findings showing similar activities across languages under the same task demand. Thus, whether the engagement of the Chinese-specific regions was due to stimulus selectivity or to task demand was called into question. The current meta-analysis, using Activation Likelihood Estimation (ALE), summarized brain regions in previous fMRI studies from two types of contrast, stimulus contrasts (SC), in which more regions were activated for Chinese characters than for other visual stimuli (e.g., Korean words, faces) or for other types of characters (e.g., real > artificial characters), and task contrasts (TC), in which more regions were activated for one task than for another (e.g., lexical decision > symbol detection) in processing Chinese characters. ALE activation maps revealed a shared network for the two types of contrast, including the right Inferior Frontal Gyrus (IFG, BA47) and four clusters in the left hemisphere, the IFG (BA45/46), Superior Parietal Lobule, Superior Frontal Gyrus, and posterior Middle Temporal Gyrus (pMTG). The SC > TC comparison demonstrated the greater involvement of the left Angular Gyrus and left Fusiform Gyrus. The TC > SC comparison, in contrast, revealed the engagement of left-hemisphere regions in the IFG, MFG, pSTG, pMTG, and Medial Frontal Gyrus. These results suggest that the previously identified Chinese-specific areas (e.g., MFG, pSTG) might be task dependent rather than stimulus selective. This work shed light on the language-general neural network of visual word reading.

Activity associated with speech articulation measured through direct cortical recordings

The insula has been credited with a role in a number of functions, including speech production. Here, we recorded electrocorticography (ECoG) signals from the left insula during pseudoword articulation in two patients undergoing pre-surgical monitoring for the management of medically-intractable epilepsy. Event-related band power (ERBP) activity from electrodes implanted in the superior precentral gyrus of the insula (SPGI) was compared to that of other left hemisphere regions implicated in speech production. Results showed that SPGI contacts demonstrated significantly greater ERBP within the high-gamma frequency range (75–150Hz) during articulation compared to a listening condition. However, frontal and post-central regions demonstrated significantly greater responses to the articulation task compared to the SPGI. Results suggest the SPGI is active during articulation, but frontal and post-central regions demonstrate significantly more robust responses. Given the small sample size, and number of electrodes implanted in the SPGI, further study is warranted to confirm these findings.

Mapping visual dominance in human sleep

Sleep is a universal behavior, essential for humans and animals alike to survive. Its importance to a person’s physical and mental health cannot be overstated. Although lateralization of function is well established in the lesion, split-brain and task based neuroimaging literature, and more recently in functional imaging studies of spontaneous fluctuations of the fMRI BOLD signal during wakeful rest, it is unknown if these asymmetries are present during sleep. We investigated hemispheric asymmetries in the global brain signal during non-REM sleep. Here we show that increasing sleep depth is accompanied by an increasing rightward asymmetry of regions in visual cortex including primary bilaterally and in the right hemisphere along the lingual gyrus and middle temporal cortex. In addition, left hemisphere language regions largely maintained their leftward asymmetry during sleep. Right hemisphere attention related regions expressed a more complicated relation with some regions maintaining a rightward asymmetry while this was lost in others. These results suggest that asymmetries in the human brain are state dependent.

Activation of dominant hemisphere association cortex during naming as a function of cognitive performance in mild traumatic brain injury: Insights into mechanisms of lexical access.

Patients with a history of mild traumatic brain injury (mTBI) and objective cognitive deficits frequently experience word finding difficulties in normal conversation. We sought to improve our understanding of this phenomenon by determining if the scores on standardized cognitive testing are correlated with measures of brain activity evoked in a word retrieval task (confrontational picture naming). The study participants (n = 57) were military service members with a history of mTBI. The General Memory Index (GMI) determined after administration of the Rivermead Behavioral Memory Test, Third Edition, was used to assign subjects to three groups: low cognitive performance (Group 1: GMI ≤ 87, n = 18), intermediate cognitive performance (Group 2: 88 ≤ GMI ≤ 99, n = 18), and high cognitive performance (Group 3: GMI ≥ 100, n = 21). Magnetoencephalography data were recorded while participants named eighty pictures of common objects. Group differences in evoked cortical activity were observed relatively early (within 200 ms from picture onset) over a distributed network of left hemisphere cortical regions including the fusiform gyrus, the entorhinal and parahippocampal cortex, the supramarginal gyrus and posterior part of the superior temporal gyrus, and the inferior frontal and rostral middle frontal gyri. Differences were also present in bilateral cingulate cortex and paracentral lobule, and in the right fusiform gyrus. All differences reflected a lower amplitude of the evoked responses for Group 1 relative to Groups 2 and 3. These findings may indicate weak afferent inputs to and within an extended cortical network including association cortex of the dominant hemisphere in patients with low cognitive performance. The association between word finding difficulties and low cognitive performance may therefore be the result of a diffuse pathophysiological process affecting distributed neuronal networks serving a wide range of cognitive processes. These findings also provide support for a parallel processing model of lexical access.

Left Ventral Stream White Matter Connectivity Predicts Response to Semantic Feature Analysis Treatment in Chronic Aphasia

Left Ventral Stream White Matter Connectivity Predicts Response to Semantic Feature Analysis Treatment in Chronic Aphasia

Age-related differences in resolving semantic and phonological competition during receptive language tasks

Receptive language (e.g., reading) is largely preserved in the aging brain, and semantic processes in particular may continue to develop throughout the lifespan. We investigated the neural underpinnings of phonological and semantic retrieval in older and younger adults during receptive language tasks (rhyme and semantic similarity judgments). In particular, we were interested in the role of competition on language retrieval and varied the similarities between a cue, target, and distractor that were hypothesized to affect the mental process of competition. Behaviorally, all participants responded faster and more accurately during the rhyme task compared to the semantic task. Moreover, older adults demonstrated higher response accuracy than younger adults during the semantic task. Although there were no overall age-related differences in the neuroimaging results, an Age×Task interaction was found in left inferior frontal gyrus (IFG), with older adults producing greater activation than younger adults during the semantic condition. These results suggest that at lower levels of task difficulty, older and younger adults engaged similar neural networks that benefited behavioral performance. As task difficulty increased during the semantic task, older adults relied more heavily on largely left hemisphere language regions, as well as regions involved in perception and internal monitoring. Our results are consistent with the stability of language comprehension across the adult lifespan and illustrate how the preservation of semantic representations with aging may influence performance under conditions of increased task difficulty.

Multi-parameter machine learning approach to the neuroanatomical basis of developmental dyslexia.

Despite decades of research, the anatomical abnormalities associated with developmental dyslexia are still not fully described. Studies have focused on between-group comparisons in which different neuroanatomical measures were generally explored in isolation, disregarding potential interactions between regions and measures. Here, for the first time a multivariate classification approach was used to investigate grey matter disruptions in children with dyslexia in a large (N = 236) multisite sample. A variety of cortical morphological features, including volumetric (volume, thickness and area) and geometric (folding index and mean curvature) measures were taken into account and generalizability of classification was assessed with both 10-fold and leave-one-out cross validation (LOOCV) techniques. Classification into control vs. dyslexic subjects achieved above chance accuracy (AUC = 0.66 and ACC = 0.65 in the case of 10-fold CV, and AUC = 0.65 and ACC = 0.64 using LOOCV) after principled feature selection. Features that discriminated between dyslexic and control children were exclusively situated in the left hemisphere including superior and middle temporal gyri, subparietal sulcus and prefrontal areas. They were related to geometric properties of the cortex, with generally higher mean curvature and a greater folding index characterizing the dyslexic group. Our results support the hypothesis that an atypical curvature pattern with extra folds in left hemispheric perisylvian regions characterizes dyslexia. Hum Brain Mapp 38:900-908, 2017. © 2016 Wiley Periodicals, Inc.

An event-related potential study of the relationship between N170 lateralization and phonological awareness in developing readers

As reading development progresses, the visual processing of word forms becomes increasingly left-lateralized. This is visible, among other ways, as increased left-lateralization of the N170 ERP component. A primary explanation of this effect, the phonological mapping hypothesis, proposes that the left-lateralization of visual word form processing that accompanies reading development is the result of calling upon left hemisphere auditory language regions to perform the linking of orthography with phonology (phonological mapping). A key, but untested, prediction of the phonological mapping hypothesis is thus that individuals with greater phonological awareness should exhibit more left lateralized visual processing of word forms than individuals with poorer phonological awareness. We set out to test this hypothesis here. We accomplished this by collecting ERPs while children grades 5–6 viewed words, objects, and word/object ambiguous items (e.g., “SMILE” shaped like a smile - hereafter referred to as wobjects). Results revealed that, consistent with the phonological mapping hypothesis, individual phonological awareness (but not other measures of reading development) predicted left-lateralization of the N170 component elicited in response to words (but not item types that were not word-like).

Greater Repertoire and Temporal Variability of Cross-Frequency Coupling (CFC) Modes in Resting-State Neuromagnetic Recordings among Children with Reading Difficulties.

Cross-frequency, phase-to-amplitude coupling (PAC) between neuronal oscillations at rest may serve as the substrate that supports information exchange between functionally specialized neuronal populations both within and between cortical regions. The study utilizes novel algorithms to identify prominent instantaneous modes of cross-frequency coupling and their temporal stability in resting state magnetoencephalography (MEG) data from 25 students experiencing severe reading difficulties (RD) and 27 age-matched non-impaired readers (NI). Phase coherence estimates were computed in order to identify the prominent mode of PAC interaction for each sensor, sensor pair, and pair of frequency bands (from δ to γ) at successive time windows of the continuous MEG record. The degree of variability in the characteristic frequency-pair PACf1−f2 modes over time was also estimated. Results revealed a wider repertoire of prominent PAC interactions in RD as compared to NI students, suggesting an altered functional substrate for information exchange between neuronal assemblies in the former group. Moreover, RD students showed significant variability in PAC modes over time. This temporal instability of PAC values was particularly prominent: (a) within and between right hemisphere temporo-parietal and occipito-temporal sensors and, (b) between left hemisphere frontal, temporal, and occipito-temporal sensors and corresponding right hemisphere sites. Altered modes of neuronal population coupling may help account for extant data revealing reduced, task-related neurophysiological and hemodynamic activation in left hemisphere regions involved in the reading network in RD. Moreover, the spatial distribution of pronounced instability of cross-frequency coupling modes in this group may provide an explanation for previous reports suggesting the presence of inefficient compensatory mechanisms to support reading.

Functional reorganization of language networks for semantics and syntax in chronic stroke: Evidence from MEG.

Using magnetoencephalography, we investigated the potential of perilesional and contralesional activity to support language recovery in patients with poststroke aphasia. In healthy young controls, left-lateralized ventral frontotemporal regions responded to semantic anomalies during sentence comprehension and bilateral dorsal frontoparietal regions responded to syntactic anomalies. Older adults showed more extensive bilateral responses to the syntactic anomalies and less lateralized responses to the semantic anomalies, with decreased activation in the left occipital and parietal regions for both semantic and syntactic anomalies. In aphasic participants, we observed compensatory recruitment in the right hemisphere (RH), which varied depending on the type of linguistic information that was processed. For semantic anomalies, aphasic patients activated some preserved left hemisphere regions adjacent to the lesion, as well as homologous parietal and temporal RH areas. Patients also recruited right inferior and dorsolateral frontal cortex that was not activated in the healthy participants. Responses for syntactic anomalies did not reach significance in patients. Correlation analyses indicated that recruitment of homologous temporoparietal RH areas is associated with better semantic performance, whereas higher accuracy on the syntactic task was related to bilateral superior temporoparietal and right frontal activity. The results suggest that better recovery of semantic processing is associated with a shift to ventral brain regions in the RH. In contrast, preservation of syntactic processing is mediated by dorsal areas, bilaterally, although recovery of syntactic processing tends to be poorer than semantic. Hum Brain Mapp 37:2869-2893, 2016. © 2016 Wiley Periodicals, Inc.

Brain Activation Patterns Characterizing Different Phases of Motor Action: Execution, Choice and Ideation.

Motor behaviour is controlled by a large set of interacting neural structures, subserving the different components involved in hierarchical motor processes. Few studies have investigated the neural substrate of higher-order motor ideation, i.e. the mental operation of conceiving a movement. The aim of this functional magnetic resonance imaging study was to segregate the neural structures involved in motor ideation from those involved in movement choice and execution. An index finger movement paradigm was adopted, including three different conditions: performing a pre-specified movement, choosing and executing a movement and ideating a movement of choice. The tasks involved either the right or left hand, in separate runs. Neuroimaging results were obtained by comparing the different experimental conditions and computing conjunction maps of the right and left hands for each contrast. Pre-specified movement execution was supported by bilateral fronto-parietal motor regions, the cerebellum and putamen. Choosing and executing finger movement involved mainly left fronto-temporal areas and the anterior cingulate. Motor ideation activated almost exclusively left hemisphere regions, including the inferior, middle and superior frontal regions, middle temporal and middle occipital gyri. These findings show that motor ideation is controlled by a cortical network mainly involved in abstract thinking, cognitive and motor control, semantic and visual imagery processes.

Hemispheric contributions to language reorganisation: An MEG study of neuroplasticity in chronic post stroke aphasia

Previous studies have demonstrated that efficient neurorehabilitation in post stroke aphasia leads to clinical language improvements and promotes neuroplasticity. Brain areas frequently implicated in functional restitution of language after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying therapy-induced language restitution are still largely unclear. In this study, magnetoencephalography was used to investigate neurophysiological changes in a group of chronic aphasia patients who underwent intensive language action therapy (ILAT), also known as constraint-induced aphasia therapy (CIAT). Before and immediately after ILAT, patients’ language and communication skills were assessed and their brain responses were recorded during a lexical magnetic mismatch negativity (MMNm) paradigm, presenting familiar spoken words and meaningless pseudowords. After the two-week therapy interval, patients showed significant clinical improvements of language and communication skills. Spatio-temporal dynamics of neuronal changes revealed a significant increase in word-specific neuro-magnetic MMNm activation around 200ms after stimulus identification points. This enhanced brain response occurred specifically for words and was most pronounced over perilesional areas in the left hemisphere. Therapy-related changes in neuromagnetic activation for words in both hemispheres significantly correlated with performance on a clinical language test. The findings indicate that functional recovery of language in chronic post stroke aphasia is associated with neuroplastic changes in both cerebral hemispheres, with stronger left-hemispheric contribution during automatic stages of language processing.

Brain activity underlying tool-related and imitative skills after major left hemisphere stroke.

Apraxia is a debilitating cognitive motor disorder that frequently occurs after left hemisphere stroke and affects tool-associated and imitative skills. However, the severity of the apraxic deficits varies even across patients with similar lesions. This variability raises the question whether regions outside the left hemisphere network typically associated with cognitive motor tasks in healthy subjects are of additional functional relevance. To investigate this hypothesis, we explored regions where functional magnetic resonance imaging activity is associated with better cognitive motor performance in patients with left hemisphere ischaemic stroke. Thirty-six patients with chronic (>6 months) large left hemisphere infarcts (age ± standard deviation, 60 ± 12 years, 29 male) and 29 control subjects (age ± standard deviation, 72 ± 7, 15 male) were first assessed behaviourally outside the scanner with tests for actual tool use, pantomime and imitation of tool-use gestures, as well as for meaningless gesture imitation. Second, functional magnetic resonance imaging activity was registered during the passive observation of videos showing tool-associated actions. Voxel-wise linear regression analyses were used to identify areas where behavioural performance was correlated with functional magnetic resonance imaging activity. Furthermore, lesions were delineated on the magnetic resonance imaging scans for voxel-based lesion-symptom mapping. The analyses revealed two sets of regions where functional magnetic resonance imaging activity was associated with better performance in the clinical tasks. First, activity in left hemisphere areas thought to mediate cognitive motor functions in healthy individuals (i.e. activity within the putative 'healthy' network) was correlated with better scores. Within this network, tool-associated tasks were mainly related to activity in supramarginal gyrus and ventral premotor cortex, while meaningless gesture imitation depended more on the anterior intraparietal sulcus and superior parietal lobule. Second, repeating the regression analyses with total left hemisphere lesion volume as additional covariate demonstrated that tool-related skills were further supported by right premotor, right inferior frontal and left anterior temporal areas, while meaningless gesture imitation was also driven by the left dorso-lateral prefrontal cortex. In summary, tool-related and imitative skills in left hemisphere stroke patients depend on the activation of spared left hemisphere regions that support these abilities in healthy individuals. In addition, cognitive motor functions rely on the activation of ipsi- and contralesional areas that are situated outside this 'healthy' network. This activity may explain why some patients perform surprisingly well despite large left brain lesions, while others are severely impaired.

Preliminary Findings Show Maternal Hypothyroidism May Contribute to Abnormal Cortical Morphology in Offspring.

In rodents, insufficient thyroid hormone (TH) gestationally has adverse effects on cerebral cortex development. Comparable studies of humans examining how TH insufficiency affects cortical morphology are limited to children with congenital hypothyroidism or offspring of hypothyroxinemic women; effects on cortex of children born to women with clinically diagnosed hypothyroidism are not known. We studied archived MRI scans from 22 children aged 10–12 years born to women treated for preexisting or de novo hypothyroidism in pregnancy (HYPO) and 24 similar age and sex controls from euthyroid women. FreeSurfer Image Analysis Suite software was used to measure cortical thickness (CT) and a vertex-based approach served to compare HYPO versus control groups and Severe versus Mild HYPO subgroups as well as to perform regression analyses examining effects of trimester-specific maternal TSH on CT. Results showed that relative to controls, HYPO had multiple regions of both cortical thinning and thickening, which differed for left and right hemispheres. In HYPO, thinning was confined to medial and mid-lateral regions of each hemisphere and thickening to superior regions (primarily frontal) of the left hemisphere and inferior regions (particularly occipital and temporal) of the right. The Severe HYPO subgroup showed more thinning than Mild in frontal and temporal regions and more thickening in bilateral posterior and frontal regions. Maternal TSH values predicted degree of thinning and thickening within multiple brain regions, with the pattern and direction of correlations differing by trimester. Notably, some correlations remained when cases born to women with severe hypothyroidism were removed from the analyses, suggesting that mild variations of maternal TH may permanently affect offspring cortex. We conclude that maternal hypothyroidism during pregnancy has long-lasting manifestations on the cortical morphology of their offspring with specific effects reflecting both severity and timing of maternal TH insufficiency.

The relationships between the amount of spared tissue, percent signal change, and accuracy in semantic processing in aphasia

Recovery from aphasia, loss of language following a cerebrovascular incident (stroke), is a complex process involving both left and right hemispheric regions. In our study, we analyzed the relationships between semantic processing behavioral data, lesion size and location, and percent signal change from functional magnetic resonance imaging (fMRI) data. This study included 14 persons with aphasia in the chronic stage of recovery (six or more months post stroke), along with normal controls, who performed semantic processing tasks of determining whether a written semantic feature matched a picture or whether two written words were related. Using region of interest (ROI) analysis, we found that left inferior frontal gyrus pars opercularis and pars triangularis, despite significant damage, were the only regions to correlate with behavioral accuracy. Additionally, bilateral frontal regions including superior frontal gyrus, middle frontal gyrus, and anterior cingulate appear to serve as an assistive network in the case of damage to traditional language regions that include inferior frontal gyrus, middle temporal gyrus, supramarginal gyrus, and angular gyrus. Right hemisphere posterior regions including right middle temporal gyrus, right supramarginal gyrus, and right angular gyrus are engaged in the case of extensive damage to left hemisphere language regions. Additionally, right inferior frontal gyrus pars orbitalis is presumed to serve a monitoring function. These results reinforce the importance of the left hemisphere in language processing in aphasia, and provide a framework for the relative importance of left and right language regions in the brain.

An fMRI Study of Concreteness Effects during Spoken Word Recognition in Aging. Preservation or Attenuation?

It is unclear whether healthy aging influences concreteness effects (i.e., the processing advantage seen for concrete over abstract words) and its associated neural mechanisms. We conducted an fMRI study on young and older healthy adults performing auditory lexical decisions on concrete vs. abstract words. We found that spoken comprehension of concrete and abstract words appears relatively preserved for healthy older individuals, including the concreteness effect. This preserved performance was supported by altered activity in left hemisphere regions including the inferior and middle frontal gyri, angular gyrus, and fusiform gyrus. This pattern is consistent with age-related compensatory mechanisms supporting spoken word processing.

Brain Activation during Memory Encoding in Type 2 Diabetes Mellitus: A Discordant Twin Pair Study.

Type 2 diabetes mellitus increases the risk of dementia and neuronal dysfunction may occur years before perceptible cognitive decline. We aimed to study the impact of type 2 diabetes on brain activation during memory encoding in middle-aged people, controlling for age, sex, genes, and early-shared environment. Twenty-two twin pairs discordant for type 2 diabetes mellitus (mean age 60.9 years) without neurological disease were recruited from the Australian Twin Registry (ATR) and underwent functional magnetic resonance imaging (fMRI) during a memory encoding task, cognitive tests, and structural MRI. Type 2 diabetes was associated with significantly reduced activation in left hemisphere temporoparietal regions including angular gyrus, supramarginal gyrus, and middle temporal gyrus and significantly increased activation in bilateral posteriorly distributed regions. These findings were present in the absence of within-pair differences in standard cognitive test scores, brain volumes, or vascular lesion load. Differences in activation were more pronounced among monozygotic (MZ) pairs, with MZ individuals with diabetes also displaying greater frontal activation. These results provide evidence for preclinical memory-related neuronal dysfunction in type 2 diabetes. They support the search for modifiable later-life environmental factors or epigenetic mechanisms linking type 2 diabetes and cognitive decline.

White Matter Alterations in Infants at Risk for Developmental Dyslexia.

Developmental dyslexia (DD) is a heritable condition characterized by persistent difficulties in learning to read. White matter alterations in left-lateralized language areas, particularly in the arcuate fasciculus (AF), have been observed in DD, and diffusion properties within the AF correlate with (pre-)reading skills as early as kindergarten. However, it is unclear how early these alterations can be observed. We investigated white matter structure in 14 infants with (FHD+; ages 6.6-17.6 months) and 18 without (FHD-; ages 5.1-17.6 months) familial risk for DD. Diffusion scans were acquired during natural sleep, and early language skills were assessed. Tractography for bilateral AF was reconstructed using manual and automated methods, allowing for independent validation of results. Fractional anisotropy (FA) was calculated at multiple nodes along the tracts for more precise localization of group differences. The analyses revealed significantly lower FA in the left AF for FHD+ compared with FHD- infants, particularly in the central portion of the tract. Moreover, expressive language positively correlated with FA across groups. Our results demonstrate that atypical brain development associated with DD is already present within the first 18 months of life, suggesting that the deficits associated with DD may result from altered structural connectivity in left-hemispheric regions.

Hemispheric activation differences in novice and expert clinicians during clinical decision making.

Clinical decision making requires knowledge, experience and analytical/non-analytical types of decision processes. As clinicians progress from novice to expert, research indicates decision-making becomes less reliant on foundational biomedical knowledge and more on previous experience. In this study, we investigated how knowledge and experience were reflected in terms of differences in neural areas of activation. Novice and expert clinicians diagnosed simple or complex (easy, hard) cases while functional magnetic resonance imaging (fMRI) data were collected. Our results highlight key differences in the neural areas activated in novices and experts during the clinical decision-making process. fMRI data were collected from ten second year medical students (novices) and ten practicing gastroenterologists (experts) while they diagnosed sixteen (eight easy and eight hard) clinical cases via multiple-choice questions. Behavioral data were collected for diagnostic accuracy (correct/incorrect diagnosis) and time taken to assign a clinical diagnosis. Two analyses were performed with the fMRI data. First, data from easy and hard cases were compared within respective groups (easy>hard, hard>easy). Second, neural differences between novices and experts (novice>expert, expert>novice) were assessed. Experts correctly diagnosed more cases than novices and made their diagnoses faster than novices on both easy and hard cases (all p's<0.05). Time taken to diagnose hard cases took significantly longer for both novices and experts. While similar neural areas were activated in both novices and experts during the decision making process, we identified significant hemispheric activation differences between novice and expert clinicians when diagnosing hard clinical cases. Specifically, novice clinicians had greater activations in the left anterior temporal cortex and left ventral lateral prefrontal cortex whereas expert clinicians had greater activations in the right dorsal lateral, right ventral lateral, and right parietal cortex. Hemispheric differences in activation were not observed between novices and experts while diagnosing easy clinical cases. While clinical decision-making engaged the prefrontal cortex (PFC) in both novices and experts, interestingly we observed expertise related differences in the regions and hemispheres of PFC activation between these groups for hard clinical cases. Specifically, in novices we observed activations in left hemisphere neural regions associated with factual rule-based knowledge, whereas in experts we observed right hemisphere activation in neural regions associated with experiential knowledge. Importantly, at the neural level, our data highlight differences in so called type 2 clinical decision-making processes related to prior knowledge and experience.