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Background Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. Results SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function−structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function−structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function−structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function−structure relationships in SZ.

Diagnosis of neurobehavioral syndromes associated with HIV infection requires the determination that neuropsychological (NP) deficits are present, are not caused by any comorbid (e.g., psychiatric) condition, and significantly affect everyday functioning. Methamphetamine (Meth) dependence and depression are common comorbid conditions with HIV and may complicate diagnosis of HIV-associated neurobehavioral syndromes. The current study examined the complex relationships between depression and NP impairment, and self-report of problems with everyday functioning, in 362 adults with HIV infection or Meth dependence, or both. Everyday functioning was measured with questionnaires of instrumental activities of daily living (IADLs) and reported cognitive difficulties. Results indicate that comorbid HIV and Meth did not increase the likelihood of complaints regarding everyday functioning, beyond what was seen with either single risk factor. Across all groups, depressive symptoms predicted greater IADL decline and cognitive complaints, while NP impairment predicted cognitive complaints more than IADL decline. Both IADL decline and cognitive complaints were associated with higher rates of unemployment and worse clinician ratings of overall functioning (Karnofsky ratings), even when depressive symptoms were controlled. These results suggest that depressive symptoms should not be used to dismiss subjective complaints related to everyday functioning even though depressive symptoms account for significant variance in self-reported complaints. Additional research is needed to clarify the potentially reciprocal causal relationships between depressive symptoms and impairment in everyday functioning.

Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca's area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p < .001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca's area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca's area, Goldberg's hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.

Previous studies showed that cortex in the anterior portions of the left frontal and temporal lobes participates in generating words with emotional connotations and processing pictures with emotional content. If these cortices process the semantic attribute of emotional connotation, they should be active whenever processing emotional connotation, without respect to modality of input or mode of output. Thus, we hypothesized that they would activate during monitoring of words with emotional connotations. Sixteen normal subjects performed semantic monitoring of words with emotional connotations, animal names, and implement names during fMRI. Cortex in the anterior left frontal lobe demonstrated significant activity for monitoring words with emotional connotations compared to monitoring tone sequences, animal names, or implement names. Together, the current and previous results implicate cortex in the anterior left frontal lobe in semantic processing of emotional connotation, consistent with connections of this cortex to paralimbic association areas. Current findings also indicate that neural substrates for processing emotional connotation are independent of substrates for processing the categories of living and nonliving things.

Areas of the brain's left hemisphere involved in retrieving words with emotional connotations were studied with fMRI. Participants silently generated words from different semantic categories which evoked either words with emotional connotations or emotionally neutral words. Participants repeated emotionally neutral words as a control task. Compared with generation of emotionally neutral words, generation of words with emotional connotations engaged cortices near the left frontal and temporal poles which are connected to the limbic system. Thus, emotional connotations of words are processed in or near cortices with access to emotional experience.