Erbil Akbudak

Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function

Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an organized mode of default brain function, elements of which may be either attenuated or enhanced. Extant data suggest that these MPFC regions may contribute to the neural instantiation of aspects of the multifaceted “self.” We explore this important concept by targeting and manipulating elements of MPFC default state activity. In this functional magnetic resonance imaging (fMRI) study, subjects made two judgments, one self-referential, the other not, in response to affectively normed pictures: pleasant vs. unpleasant (an internally cued condition, ICC) and indoors vs. outdoors (an externally cued condition, ECC). The ICC was preferentially associated with activity increases along the dorsal MPFC. These increases were accompanied by decreases in both active task conditions in ventral MPFC. These results support the view that dorsal and ventral MPFC are differentially influenced by attentiondemanding tasks and explicitly self-referential tasks. The presence of self-referential mental activity appears to be associated with increases from the baseline in dorsal MPFC. Reductions in ventral MPFC occurred consistent with the fact that attention-demanding tasks attenuate emotional processing. We posit that both self-referential mental activity and emotional processing represent elements of the default state as represented by activity in MPFC. We suggest that a useful way to explore the neurobiology of the self is to explore the nature of default state activity.

A Common Network of Functional Areas for Attention and Eye Movements

Functional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level.

Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding

The involvement of dorsal frontal and medial temporal regions during the encoding of words, namable line-drawn objects, and unfamiliar faces was examined using functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations were observed in each instance, but lateralization was strongly dependent on the materials being encoded. Encoding of words produced left-lateralized dorsal frontal activation, whereas encoding of unfamiliar faces produced homologous right-lateralized activation. Encoding of namable objects, which are amenable to both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation. A similar pattern of results was observed in the medial temporal lobe. These results indicate that regions in both hemispheres underlie human long-term memory encoding, and these regions can be engaged differentially according to the nature of the material being encoded.

Direct Comparison of Prefrontal Cortex Regions Engaged by Working and Long-Term Memory Tasks

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

The Emotional Modulation of Cognitive Processing: An fMRI Study

The functional neuroanatomy of visual processing of surface features of emotionally valenced pictorial stimuli was examined in normal human subjects using functional magnetic resonance imaging (fMRI). Pictorial stimuli were of two types: emotionally negative and neutral pictures. Task performance was slower for the negatively valenced than for the neutral pictures. Significant blood oxygen level dependent (BOLD) increases occurred in the medial and dorsolateral prefrontal cortex, midbrain, substantia innominata, and/or amygdala, and in the posterior cortical visual areas for both stimulus types. Increases were greater for the negatively valenced stimuli. While there was a small but significant BOLD decrease in the subgenual prefrontal cortex, which was larger in response to the negatively valenced pictures, there was an almost complete absence of other decreases prominently seen during the performance of demanding cognitive tasks [Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. Journal of Cognitive Neuroscience, 9, 648-663]. These results provide evidence that the emotional valence and arousing nature of stimuli used during the performance of an attention-demanding cognitive task are reflected in discernable, quantitative changes in the functional anatomy associated with task performance.

Functional MRI Studies of Word-Stem Completion: Reliability Across Laboratories and Comparison to Blood Flow Imaging With PET

Functional magnetic resonance imaging (fMRI) based on blood oxygen level‐dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD‐fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word‐stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient‐refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated. Hum. Brain Mapping 6:203–215, 1998.

Anterior thalamic radiation integrity in schizophrenia: A diffusion-tensor imaging study

The anterior limb of the internal capsule (ALIC) is a white matter structure, the medial portion of which includes the anterior thalamic radiation (ATR) carrying nerve fibers between thalamus and prefrontal cortex. ATR abnormalities have a possible link with cognitive abnormalities and negative symptoms in schizophrenia. We aimed to study the fiber integrity of the ATR more selectively by isolating the medial portion of the ALIC using region-of-interest based methodology. Diffusion-tensor imaging was used to measure the anisotropy of total ALIC (tALIC) and medial ALIC (mALIC) in 39 schizophrenia and 33 control participants, matched for age/gender/handedness. Relationships between anisotropy, psychopathology, and cognitive performance were analyzed. Compared with controls, schizophrenia participants had 4.55% lower anisotropy in right tALIC, and 5.38% lower anisotropy in right mALIC. There were no significant group anisotropy differences on the left. Significant correlations were observed between right ALIC integrity and relevant domains of cognitive function (e.g., executive function, working memory). Our study suggests an asymmetric microstructural change in ALIC in schizophrenia involving the right side, which is only minimally stronger in mALIC, and which correlates with cognitive impairment. Microstructural changes in the ALIC may be linked to cognitive dysfunction in schizophrenia.

Neuronal fiber pathway abnormalities in autism: An initial MRI diffusion tensor tracking study of hippocampo-fusiform and amygdalo-fusiform pathways

MRI diffusion-tensor tracking (DTT) was performed in 17 high-functioning adolescents/adults with autism and 17 pairwise-matched controls. White matter pathways involved in face processing were examined due to the relevance of face perception to the social symptoms of autism, and due to known behavioral and functional imaging findings in autism. The hippocampo-fusiform (HF) and amygdalo-fusiform (AF) pathways had normal size and shape but abnormal microstructure in the autism group. The right HF had reduced across-fiber diffusivity (D-min) compared with controls, opposite to the whole-brain effect of increased D-min. In contrast, left HF, right AF, and left AF had increased D-min and increased along-fiber diffusivity (D-max), more consistent with the whole-brain effect. There was a general loss of lateralization compared with controls. The right HF D-min was markedly low in the autism subgroup with lower Benton face recognition scores, compared with the lower-Benton control subgroup, and compared with the higher-Benton autism subgroup. Similar behavioral relationships were found for performance IQ. Such results suggest an early functionally-significant pathological process in right HF consistent with small-diameter axons (with correspondingly slower neural transmission) and/or higher packing density. In left AF and HF, changes were interpreted as secondary, possibly reflecting axonal loss and/or decreased myelination.

Direct Comparison of Episodic Encoding and Retrieval of Words: An Event-related fMRI Study

Functional magnetic resonance imaging (fMRI) was used to compare directly episodic encoding and retrieval. During encoding, subjects studied visually presented words and reported via keypress whether each word represented a pleasant or unpleasant concept (intentional, deep encoding). During the retrieval phase, subjects indicated (via keypress) whether visually presented words had previously been studied. No reliable differences were found during the recognition phase for words that had been previously studied and those that had not been studied. Areas preferentially active during encoding (relative to retrieval) included left superior frontal cortex, medial frontal cortex, left superior temporal cortex, posterior cingulate, left parahippocampal gyrus, and left inferior frontal gyrus. Regions more active in retrieval than encoding included bilateral inferior parietal cortex, bilateral precuneus, right frontal polar cortex, right dorsolateral prefrontal cortex, and right inferior frontal/insular cortex.

Functional reorganization and stability of somatosensory-motor cortical topography in a tetraplegic subject with late recovery

The functional organization of somatosensory and motor cortex was investigated in an individual with a high cervical spinal cord injury, a 5-year absence of nearly all sensory/motor function at and below the shoulders, and rare recovery of some function in years 6–8 after intense and sustained rehabilitation therapies. We used functional magnetic resonance imaging to study brain activity to vibratory stimulation and voluntary movements of body parts above and below the lesion. No response to vibratory stimulation of the hand was observed in the primary somatosensory cortex (SI) hand area, which was conversely recruited during tongue movements that normally evoke responses only in the more lateral face area. This result suggests SI reorganization analogous to previously reported neuroplasticity changes after peripheral lesions in animals and humans. In striking contradistinction, vibratory stimulation of the foot evoked topographically appropriate responses in SI and second somatosensory cortex (SII). Motor cortex responses, tied to a visuomotor tracking task, displayed a near-typical topography, although they were more widespread in premotor regions. These findings suggest possible preservation of motor and some somatosensory cortical representations in the absence of overt movements or conscious sensations for several years after spinal cord injury and have implications for future rehabilitation and neural-repair therapies.