Anterior cingulate gyrus epilepsy: the role of ictal rCBF SPECT in seizure localization

PURPOSE: The goal of this report is to demonstrate the utility of ictal brain single photon emission tomography (SPECT) in a 39-year-old man with complex partial seizures arising from the anterior cingulate gyrus. Seizures originating from the anterior cingulate gyrus are difficult to localize because they have variable ictal semiology, are usually brief, and have rapid cortical propagation. METHODS: Clinical neurologic examination, electroencephalography, extended video-electroencephalography with scalp and sphenoidal electrodes, magnetic resonance imaging, computed tomography, and ictal brain SPECT with Tc-99m HMPAO were performed to identify the seizure focus. The patient's regional cerebral blood flow (rCBF) findings were compared with those of eight normal controls, and changes in rCBF were assessed by comparing the patient's ictal scan with those of normal controls at rest by using statistical parametric mapping (SPM). RESULTS: Clinical and neurologic evaluations failed to demonstrate the epileptogenic focus. Ictal rCBF brain SPECT showed a focal region of hyperperfusion in the anterior cingulate gyrus. By using SPM, the ictal blood flow increase in the right anterior cingulate gyrus (x, y, z, -6, 42, 24 mm) was found to be statistically significant when compared with normal controls (z score, 4.88, p < 0.001). Subdural EEG recordings with intracranial electrodes positioned over this location confirmed that the cingulate gyrus was the origin of the seizures, and surgical resection resulted in >90% seizure reduction. CONCLUSIONS: We concluded that ictal brain SPECT localization in conjunction with subdural electrode confirmation is a useful test in the presurgical evaluation of difficult to localize cingulate epilepsy.     

Nonconscious attention bias to threat is correlated with anterior cingulate cortex gray matter volume: a voxel-based morphometry result and replication

An important aspect of the fear response is the allocation of spatial attention toward threatening stimuli. This response is so powerful that modulations in spatial attention can occur automatically without conscious awareness. Functional neuroimaging research suggests that the amygdala and anterior cingulate cortex (ACC) form a network involved in the rapid orienting of attention to threat. A hyper-responsive attention bias to threat is a common component of anxiety disorders. Yet, little is known of how individual differences in underlying brain morphometry relate to variability in attention bias to threat. Here, we performed two experiments using dot-probe tasks that measured individuals' attention bias to backward masked fearful faces. We collected whole-brain structural magnetic resonance images and used voxel-based morphometry to measure brain morphometry. We tested the hypothesis that reduced gray matter within the amygdala and ACC would be associated with reduced attention bias to threat. In Experiment 1, we found that backward masked fearful faces captured spatial attention and that elevated attention bias to masked threat was associated with greater ACC gray matter volumes. In Experiment 2, this association was replicated in a separate sample. Thus, we provide initial and replicating evidence that ACC gray matter volume is correlated with biased attention to threat. Importantly, we demonstrate that variability in affective attention bias within the healthy population is associated with ACC morphometry. This result opens the door for future research into the underlying brain morphometry associated with attention bias in clinically anxious populations.     

Posterior cingulate and retrosplenial cortex connections of the caudal superior temporal region in the rhesus monkey

The rostral part of the superior temporal gyrus (STG) is known to project to ventral temporal cortex, but analogous paralimbic connections of the caudal STG have received comparatively less attention. The present study of the connections of the STG with medial paralimbic cortex showed that the caudal part of the STG (area Tpt and caudal area paAlt) and adjacent cortex of the upper bank of the superior temporal sulcus (caudal area TPO) have reciprocal connections with the caudal cingulate gyrus (areas 23a, b and c), retrosplenial cortex (area 30), and area 31. By contrast, cortex of the rostral-to-mid STG (areas Ts2, Ts3, and the rostral part of area paAlt) and adjacent upper bank of the STS (mid-area TPO) have few, if any, such interconnections. It is suggested that this connectional pattern of the caudal STG is consistent with its putative role of localizing sounds in space as proposed in recent studies.     

Newly observed anterior thalamocortical fiber of the thalamus using 7.0 T super-resolution magnetic resonance tractography and its implications for the classical Papez circuit

Here, we have employed recently developed super-resolution tractography using 7.0 T-MRI to analyze the fine structures involved in thalamocortical connections, something that has proved difficult using conventional techniques. We detail a newly observed thalamocortical pathway connecting the anterior nucleus of the thalamus and the cingulate cortex not via the internal capsule but via the septal area. The observed pathway is believed to be a classical pathway of the Papez circuit but had not been previously identified.     

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study.

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI).We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB.Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test.These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.     

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors

Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI > 40 kg/m²) and compared it to that in twelve non-obese controls. PET was used with [¹¹C]raclopride to assess D2 receptors and with [¹⁸F]FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food.     

Functional Imaging of Cognitive Control During Acute Alcohol Intoxication

Background: The anterior cingulate and several other prefrontal and parietal brain regions are implicated in error processing and cognitive control. The effects of different doses of alcohol on activity within these brain regions during a functional magnetic resonance imaging (fMRI) task where errors are frequently committed have not been fully explored. Methods: This study examined the impact of a placebo [breath alcohol concentration (BrAC) = 0.00%], moderate (BrAC = 0.05%), and high (BrAC = 0.10%) doses of alcohol on brain hemodynamic activity during a functional MRI (fMRI) Go/No‐Go task in 38 healthy volunteers. Results: Alcohol increased reaction time and false alarm errors in a dose‐dependent manner. fMRI analyses showed alcohol decreased activity in anterior cingulate, lateral prefrontal cortex, insula, and parietal lobe regions during false alarm responses to No‐Go stimuli. Conclusions: These findings indicate that brain regions implicated in error processing are affected by alcohol and might provide a neural basis for alcohol’s effects on behavioral performance.     

Chronic ethanol administration alters immunoreactivity for GABA(A) receptor subunits in rat cortex in a region-specific manner

BACKGROUND: Chronic ethanol administration has a plethora of physiological effects. Among the most consistently observed findings is a change in the expression pattern of gamma-aminobutyric acid type A (GABA(A)) receptor subunits in the rat brain cortex. These findings led to the hypothesis of "subunit substitution" to account for changes in receptor function without changes in receptor number. METHODS: We used subunit (alpha1 and alpha4) specific antibodies and a combination of immunohistochemistry and immunoblotting to examine subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for their response to 2 weeks of forced ethanol administration. RESULTS: Overall, cortical immunoreactivity for the alpha1 subunit was decreased and for the alpha4 subunit increased whether measured immunohistochemically or by immunoblotting. Piriform cortex exhibited a bidirectional change in GABA(A) receptor alpha1 and alpha4 immunoreactivity, similar to that previously observed in preparations of whole cortex. However, in parietal cortex, declines in alpha1 immunoreactivity (55 +/- 12% control value [CV] and 88.3 +/- 4.3% CV; immunohistochemistry and immunoblotting, respectively) were not accompanied by concomitant increases in alpha4 immunoreactivity (104 +/- 8% CV and 116 +/- 9.3% CV; immunohistochemistry and immunoblotting, respectively). Conversely, alpha4 immunoreactivity increased in cingulate cortex (210 +/- 30% CV and 134 +/- 9.5% CV; immunohistochemistry and immunoblotting, respectively) without a decline in alpha1 immunoreactivity (90 +/- 4% CV and 91.3 +/- 3.9% CV; immunohistochemistry and immunoblotting, respectively). Prefrontal and motor cortex exhibited GABA(A) receptor subunit peptide alterations, but these changes varied with the method of analysis. CONCLUSIONS: These findings demonstrate that ethanol dependence results in nonuniform changes in GABA(A) receptor subunit peptide levels across the rat brain cortex and suggest that mechanisms which subserve functional changes in receptor activity may vary in accordance with anatomic or cellular differences within the cortex.     

Metabolic mapping of the rat brain after subanesthetic doses of ketamine: potential relevance to schizophrenia

Subanesthetic doses of ketamine have been shown to exacerbate symptoms in schizophrenia and to induce positive, negative, and cognitive schizophrenic-like symptoms in normal subjects. The present investigation sought to define brain regions affected by subanesthetic doses of ketamine, using high resolution autoradiographic analysis of ¹⁴C-2-deoxyglucose (2-DG) uptake and immunocytochemical staining for Fos-like immunoreactivity (Fos-LI). Both functional mapping approaches were used because distinct and complementary information is often obtained with these two mapping methods. Ketamine, at a subanesthetic dose of 35 mg/kg, substantially increased 2-DG uptake in certain limbic cortical regions, including medial prefrontal, ventrolateral orbital, cingulate, and retrosplenial cortices. In the hippocampal formation, the subanesthetic dose of ketamine induced prominent increases in 2-DG uptake in the dentate gyrus, CA-3 stratum radiatum, stratum lacunosum moleculare, and presubiculum. Increased 2-DG uptake in response to 35 mg/kg ketamine was also observed in select thalamic nuclei and basolateral amygdala. Ketamine induced Fos-LI in the same limbic cortical regions that exhibited increased 2-DG uptake in response to the subanesthetic dose of the drug. However, no Fos was induced in some brain regions that showed increased 2-DG uptake, such as the hippocampal formation, anterioventral thalamic nucleus, and basolateral amygdala. Conversely, ketamine induced Fos in the paraventricular nucleus of the hypothalamus and central amygdala, although no effect of the drug on 2-DG uptake was apparent in these regions. In contrast to the increase in 2-DG uptake observed in select brain regions after the subanesthetic dose, an anesthetic dose of ketamine (100 mg/kg) produced a global suppression of 2-DG uptake. By contrast, a robust induction of Fos-LI was observed after the anesthetic dose of ketamine that was neuroanatomically identical to that produced by the subanesthetic dose. Results of the present investigation show that anesthetic and subanesthetic doses of ketamine have pronounced effects on regional brain 2-DG uptake and induction of Fos-LI. The alterations in regional brain metabolism induced by the subanesthetic dose may be relevant to effects of ketamine to induce schizophrenic-like symptoms.