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PubMed2007

Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy.

BACKGROUND: Previous studies have shown cognitive impairment in breast cancer survivors who were exposed to adjuvant chemotherapy. Neural damage by chemotherapy might have played some part in these findings. The current study explored the regional brain volume difference between breast cancer survivors exposed to adjuvant chemotherapy (C+) and those unexposed (C-). METHODS: High-resolution 1.5-tesla brain magnetic resonance imaging (MRI) databases of breast cancer survivors and healthy controls were used. Brain images were preprocessed for optimal voxel-based morphometry. Comparisons of gray matter and white matter were performed between the C+ and the C- groups, by using MRI scans from within 1 year (the 1-year study, n = 51 and n = 55, respectively) or 3 years after their cancer surgery (the 3-year study, n = 73 and n = 59, respectively). As exploratory analyses, correlation analyses were performed between indices of the Wechsler Memory Scale-Revised and regional brain volume where the volume were significantly smaller. As a reference, MRI scans of cancer survivors were compared with those of healthy controls (n = 55 for the 1-year study and n = 37 for the 3-year study). RESULTS: The C+ patients had smaller gray matter and white matter including prefrontal, parahippocampal, and cingulate gyrus, and precuneus in the 1-year study. However, no difference was observed in the 3-year study. The volumes of the prefrontal, parahippocampal gyrus, and precuneus were significantly correlated with indices of attention/concentration and/or visual memory. Comparisons with healthy controls did not show any significant differences. CONCLUSIONS: Adjuvant chemotherapy might have an influence on brain structure, which may account for previously observed cognitive impairments.

Adolescent↗
PubMed2003

Topography, cytoarchitecture, and cellular phenotypes of cortical areas that form the cingulo-parahippocampal isthmus and adjoining retrocalcarine areas in the monkey.

The monkey cingulo-parahippocampal isthmus was identified recently in the depths and lateral bank of the anterior calcarine fissure but was not characterized fully. Cytoarchitectonic and immunohistochemical results presented here reveal that the isthmus is composed of four cortical areas. These include the presubiculum of the isthmus (PrSi), parasubiculum of the isthmus (PaSi), area 29 of the isthmus (area 29i) and area prostriata (Pro), which has anterior (Pro-a) and posterior (Pro-p) divisions. The PrSi, characterized by dense calbindin+ (CB+) neuropil in layer III, merges with area 29i at approximately the middle portion of the isthmus; the latter lacking the CB+ neuropil. The PaSi, characterized by a cell-free lamina dissecans and light parvalbumin+ labeling, is observed in the ventral isthmus. The Pro, located posterior to area 29i and PaSi, and anterior to area 17, has an incipient layer IV, but the density of granule cells gradually increase toward area 17. Pro-a has an incipient layer IV, contains few SMI-32+ neurons, and adjoins area 30 dorsally. The latter also has an incipient layer IV but contains, in contrast, more SMI-32+ neurons. Pro-p has a clear but thin layer IV, contains a small number of SMI-32+ neurons, and adjoins both area 23 and area 18 dorsally and area 18 ventrally. Compared with Pro-p, area 23 contains many more SMI-32+ neurons, whereas area 18 contains far more SMI-32+ neurons. These findings reveal that the isthmus is a key cortical zone connecting both the cingulate and parahippocampal gyri, but also the limbic and visual cortices. Emphasizing the former only, which has been the tendency historically, underestimates the anatomic complexity of the isthmus, and likely, its functional correlates.

Animals↗
PubMed2003

Macaque monkey retrosplenial cortex: II. Cortical afferents.

We investigated the cortical afferents of the retrosplenial cortex and the adjacent posterior cingulate cortex (area 23) in the macaque monkey by using the retrograde tracers Fast blue and Diamidino yellow. We quantitatively analyzed the distribution of labeled neurons throughout the cortical mantle. Injections involving the retrosplenial cortex resulted in labeled neurons within the retrosplenial cortex and in areas 23 and 31 (approximately 78% of the total labeled cells). In the remainder of the cortex, the heaviest projections originated in the hippocampal formation, including the entorhinal cortex, subiculum, presubiculum, and parasubiculum. The parahippocampal and perirhinal cortices also contained many labeled neurons, as did the prefrontal cortex, mainly in areas 46, 9, 10, and 11, and the occipital cortex, mainly area V2. Injections in area 23 also resulted in numerous labeled cells in the posterior cingulate and retrosplenial regions (approximately 67% of total labeled cells). As in the retrosplenial cortex, injections of area 23 led to many labeled neurons in the frontal cortex, although most of these cells were in areas 9 and 46. Larger numbers of retrogradely labeled cells were also distributed more widely in the posterior parietal cortex, including areas 7a, 7m, LIP, and DP. There were some labeled cells in the parahippocampal cortex. These connections are consistent with the retrosplenial cortex acting as an interface between the working memory functions in the prefrontal areas and the long-term memory encoding in the medial temporal lobe. The posterior cingulate cortex, in contrast, may be more highly associated with visuospatial functions.

Afferent Pathways↗
PubMed2003

Brain regions showing increased activation by threat-related words in panic disorder.

Threat-related stimuli consistently activate the posterior cingulate cortex in normal subjects and have exaggerated effects on memory in patients with panic disorder. We hypothesized that panic patients would show increased response to threat-related stimuli in the posterior cingulate cortex. While undergoing fMRI, six panic patients and eight healthy volunteers made valence judgements of threat-related and neutral words. Both groups showed threat-related activation in the left posterior cingulate and left middle frontal cortices, but the activation was significantly greater in panic patients. Panic patients also had more right>left asymmetry of activation in the mid-parahippocampal region. The increased responsivity observed in the posterior cingulate and dorsolateral prefrontal cortices is consistent with the hypothesis that panic disorder patients engage in more extensive memory processing of threat-related stimuli.

Adult↗
PubMed2000

A fronto-posterior network involved in visual dimension changes.

Objects characterized by a unique visual feature may pop out of their environment. When participants have to search for such "odd-one-out" targets, detection is facilitated when targets are consistently defined within the same feature dimension (e.g., color) compared with when the target dimension is uncertain (e.g., color or motion). Further, with dimensional uncertainty, there is a cost when a given target is defined in a different dimension to the preceding target, relative to when the critical dimension remains the same. Behavioral evidence suggests that a target dimension change involves a shift of attention to the new dimension. The present fMRI study revealed increased activation in the left frontopolar cortex, as well as in posterior visual areas of the dorsal and ventral streams, specific to changes in the target dimension. In contrast, activation in the striate cortex was decreased. This pattern suggests control of cross-dimensional attention shifts by the frontopolar cortex, modulating visual cortical processing by increased activation in higher-tier visual areas and suppression of activation in lower-tier areas.

Adolescent↗
PubMed2001

Cytology of human caudomedial cingulate, retrosplenial, and caudal parahippocampal cortices.

Brodmann showed areas 26, 29, 30, 23, and 31 on the human posterior cingulate gyrus without marking sulcal areas. Histologic studies of retrosplenial areas 29 and 30 identify them on the ventral bank of the cingulate gyrus (CGv), whereas standardized atlases show area 30 on the surface of the caudomedial region. This study evaluates all areas on the CGv and caudomedial region with rigorous cytologic criteria in coronal and oblique sections Nissl stained or immunoreacted for neuron-specific nuclear binding protein and nonphosphorylated neurofilament proteins (NFP-ir). Ectosplenial area 26 has a granular layer with few large pyramidal neurons below. Lateral area 29 (29l) has a dense granular layer II-IV and undifferentiated layers V and VI. Medial area 29 (29m) has a layer III of medium and NFP-ir pyramids and a layer IV with some large, NFP-ir pyramidal neurons that distinguish it from areas 29l, 30, and 27. Although area 29m is primarily on the CGv, a terminal branch can extend onto the caudomedial lobule. Area 30 is dysgranular with a variable thickness layer IV that is interrupted by large NFP-ir neurons in layers IIIc and Va. Although area 30 does not appear on the surface of the caudomedial lobule, a terminal branch can form less that 1% of this gyrus. Area 23a is isocortex with a clear layer IV and large, NFP-ir neurons in layers IIIc and Va. Area 23b is similar to area 23a but with a thicker layer IV, more large neurons in layer Va, and a higher density of NFP-ir neurons in layer III. The caudomedial gyral surface is composed of areas 23a and 23b and a caudal extension of area 31. Although posterior area 27 and the parasubiculum are similar to rostral levels, posterior area 36' differs from rostral area 36. Subregional flat maps show that retrosplenial cortex is on the CGv, most of the surface of caudomedial cortex is areas 23a, 23b, and 31, and the retrosplenial/parahippocampal border is at the ventral edge of the splenium. Thus, Brodmann's map understates the rostral extent of retrosplenial cortex, overstates its caudoventral extent, and abridges the caudomedial extent of area 23.

Aged↗
PubMed2004

fMRI differences in encoding and retrieval of pictures due to encoding strategy in the elderly.

Functional MRI (fMRI) was used to examine the neural correlates of depth of processing during encoding and retrieval of photographs in older normal volunteers (n = 12). Separate scans were run during deep (natural vs. man-made decision) and shallow (color vs. black-and-white decision) encoding and during old/new recognition of pictures initially presented in one of the two encoding conditions. A baseline condition consisting of a scrambled, color photograph was used as a contrast in each scan. Recognition accuracy was greater for the pictures on which semantic decisions were made at encoding, consistent with the expected levels of processing effect. A mixed-effects model was used to compare fMRI differences between conditions (deep-baseline vs. shallow-baseline) in both encoding and retrieval. For encoding, this contrast revealed greater activation associated with deep encoding in several areas, including the left parahippocampal gyrus (PHG), left middle temporal gyrus, and left anterior thalamus. Increased left hippocampal, right dorsolateral, and inferior frontal activations were found for recognition of items that had been presented in the deep relative to the shallow encoding condition. We speculate that the modulation of activity in these regions by the depth of processing manipulation shows that these regions support effective encoding and successful retrieval. A direct comparison between encoding and retrieval revealed greater activation during retrieval in the medial temporal (right hippocampus and bilateral PHG), anterior cingulate, and bilateral prefrontal (inferior and dorsolateral). Most notably, greater right posterior PHG was found during encoding compared to recognition. Focusing on the medial temporal lobe (MTL) region, our results suggest a greater involvement of both anterior MTL and prefrontal regions in retrieval compared to encoding.

Aged↗
PubMed2004

Age and ApoE genotype interaction in Alzheimer's disease: an FDG-PET study.

Previous positron emission tomography (PET) studies with fluorodeoxglucose (FDG) as tracer in healthy elders showed that the epsilon4 allele of the apolipoprotein E (ApoE) gene is disruptive to cerebral glucose metabolism (rCMRglu), possibly through the interaction with the aging process. The present study was aimed at assessing whether this interaction occurs in patients with Alzheimer's disease (AD). Eight-six AD patients, including 40 ApoE4 carriers and 46 non-carriers, underwent (18)F-FDG PET scanning at rest. ApoE groups were comparable for age, gender, age at onset and disease duration. SPM'99 was used to assess rCMRGlu correlations with age, differences between ApoE groups and ApoE by age interaction, correcting for disease severity. Results were reported at P<0.001, uncorrected. Correlations between age and rCMRGlu confirmed the well-known negative relationship for both groups. Lower rCMRGlu was found within the frontal and cingulate areas for ApoE4 carriers as compared with the non-carriers. Additionally, a significant ApoE by age interaction was detected in the frontal and anterior cingulate cortex, with the ApoE4 carriers having a steeper regression slope with respect to the non-carriers. These results indicate that age-related regional rCMRglu decreases within the frontal and anterior cingulate areas may be more severe in AD patients carrying the ApoE4 allele.

Age Factors↗
PubMed2006

Interleaving brain systems for episodic and recognition memory.

Conflicting models persist over the nature of long-term memory. Crucial issues are whether episodic memory and recognition memory reflect the same underlying processes, and the extent to which various brain structures work as a single unit to support these processes. New findings that have resulted from improved resolution of functional brain imaging, together with recent studies of amnesia and developments in animal testing, reinforce the view that recognition memory comprises at least two independent processes: one recollective and the other using familiarity detection. Only recollective recognition appears to depend on episodic memory. Attempts to map brain areas supporting these two putative components of recognition memory indicate that they depend on separate, but interlinked, structures.

Amnesia, Anterograde↗
PubMed2001

A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events.

Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations in medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events.

Adult↗
PubMed2001

Mental calculation in a prodigy is sustained by right prefrontal and medial temporal areas.

Calculating prodigies are individuals who are exceptional at quickly and accurately solving complex mental calculations. With positron emission tomography (PET), we investigated the neural bases of the cognitive abilities of an expert calculator and a group of non-experts, contrasting complex mental calculation to memory retrieval of arithmetic facts. We demonstrated that calculation expertise was not due to increased activity of processes that exist in non-experts; rather, the expert and the non-experts used different brain areas for calculation. We found that the expert could switch between short-term effort-requiring storage strategies and highly efficient episodic memory encoding and retrieval, a process that was sustained by right prefrontal and medial temporal areas.

Adult↗
PubMed2006

Brain activity associated with expectancy-enhanced placebo analgesia as measured by functional magnetic resonance imaging.

In this study, a well established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle, to investigate the brain network involved in placebo analgesia. Sixteen subjects completed the experiment. We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo-treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the functional magnetic resonance imaging (fMRI) signal difference between post-treatment and pretreatment during pain application on placebo side from the same difference on control side [e.g., placebo (post - pre) - control (post - pre)], significant differences were observed in the bilateral rostral anterior cingulate cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal gyrus, and left inferior parietal lobule. The simple regression (correlation) analysis between each subject's fMRI signal difference of post-treatment and pretreatment difference on placebo and control side and the corresponding subjective pain rating difference showed that significant negative correlation was observed in the bilateral lateral/orbital prefrontal cortex, rACC, cerebellum, right fusiform, parahippocampus, and pons. These results are different from a previous study that found decreased activity in pain-sensitive regions such as the thalamus, insula, and ACC when comparing the response to noxious stimuli applied to control and placebo cream-treated areas of the skin. Our results suggest that placebo analgesia may be configured through multiple brain pathways and mechanisms.

Acupuncture Analgesia↗
PubMed2006

Reduced activation to implicit affect induction in euthymic bipolar patients: an fMRI study.

OBJECTIVE: To examine whether euthymic bipolar patients engage similar or contrasting brain regions as healthy subjects when responding to implicit affect induction. METHODS: The study examined 10 euthymic patients with bipolar I disorder, and 10 age- and gender-matched healthy subjects using event-related functional magnetic resonance imaging (fMRI) while subjects engaged in a modified word-based memory task designed to implicitly evoke negative, positive or no affective change. The activation paradigm involved nominating whether a target word was contained within a previously presented word list using specified response keys. RESULTS: The fMRI task produced significantly greater activation in healthy subjects as compared to patients in response to both negative and positive affect in the anterior and posterior cingulate, medial prefrontal cortex, middle frontal and right parahippocampal gyri. Only negative affect produced significantly greater activation in the postcentral gyrus, inferior parietal lobule, thalamus and putamen and only positive affect achieved the same in the precentral, superior temporal and lingual gyri, precuneus, cuneus, caudate, pons, midbrain and cerebellum. There were no brain regions in which responses were greater in patients as compared to healthy subjects. There were no statistically significant differences between the groups with respect to speed or accuracy. CONCLUSIONS: Diminished prefrontal, cingulate, limbic and subcortical neural activity in euthymic bipolar patients as compared to healthy subjects is suggestive of emotional compromise that is independent of cognitive and executive functioning. This finding is of clinical importance and has implications both for the diagnosis and treatment of bipolar disorder. Future studies should aim to replicate these findings and examine the development of bipolar disorder, investigating in particular the effects of medication.

Adult↗
PubMed2006

Processing of autobiographical memory retrieval cues in borderline personality disorder.

BACKGROUND: Affective dysregulation in borderline personality disorder (BPD) in response to both external stimuli and memories has been shown to be associated with functional alterations of limbic and prefrontal brain areas. This study aimed to examine neuronal networks involved in autobiographical memory retrieval using standardized stimuli that gain autobiographical significance by illustrating marked solitary and social situations of human life. METHODS: Using event-related functional Magnetic Resonance Imaging (fMRI), we examined the processing of pictures from the Thematic Apperception Test (TAT) in 14 BPD patients and 14 controls. RESULTS: In both groups, TAT stimuli activated brain areas known to be involved in autobiographical memory retrieval. BPD subjects lacked differential amygdala, orbitofrontal and cingulate activations for TAT versus neutral stimuli. In the TAT condition, compared to controls, BPD subjects displayed increased BOLD responses in the bilateral orbitofrontal and insular regions, in the left anterior cingulate and medial prefrontal cortex, as well as in the parietal and parahippocampal areas, consistent with a more aversive and arousing experience assessed by self-reports. CONCLUSIONS: Increased BOLD responses during TAT processing in BPD subjects were in line with previously reported changes in anterior cingulate and orbitofrontal cortices, which are known to be involved in memory retrieval. However, BPD subjects displayed hyperactivation in these areas for both TAT and neutral stimuli. The deficit of selective activation of areas involved in autobiographical memory retrieval suggests a general tendency towards a self-referential mode of information processing in BPD, or a failure to switch between emotionally salient and neutral stimuli.

Affect↗
PubMed2003

Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia.

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.

Acute Disease↗
PubMed2002

Changes in Fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei.

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial-arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, 'dorsal' hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.

Animals↗
PubMed2005

Global and regional gray matter reductions in ADHD: a voxel-based morphometric study.

Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior/middle/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.

Adolescent↗