R.D. Hichwa

Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a "cognitive dysmetria" due to dysfunctional prefrontal-thalamic-cerebellar circuitry.

OBJECTIVE: This study used positron emission tomography to examine two kinds of personal memory that are used in psychiatric evaluation: focused episodic memory (recall of past experience, employed in "taking a history") and random episodic memory (uncensored thinking about experience, examined during analytic therapy using free association). For comparison, a third memory task was used to tap impersonal memory that represents general information about the world ("semantic memory"). METHOD: Thirteen subjects were studied using the [15O]H2O method to obtain quantitative measurements of cerebral blood flow. The three conditions were subtracted and their relative relationships examined. RESULTS: The random episodic condition produced activations in widely distributed association cortex (right and left frontal, parietal, angular/supramarginal, and posterior inferior temporal regions). Focused episodic memory engaged a network that included the medial inferior frontal regions, precuneus/retrosplenial cingulate, anterior cingulate, thalamus, and cerebellum. The use of medial frontal regions and the precuneus/retrosplenial cingulate was common to both focused and random episodic memory. The major difference between semantic and episodic memory was activation of Broca's area and the left frontal operculum by semantic memory. CONCLUSIONS: These results indicate that free-ranging mental activity (random episodic memory) produces large activations in association cortex and may reflect both active retrieval of past experiences and planning of future experiences. Focused episodic memory shares some components of this circuit (inferior frontal and precuneus), which may reflect the time-linked components of both aspects of episodic memory, and which permit human beings to experience personal identity, consciousness, and self-awareness.

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.

OBJECTIVE: This study was undertaken to identify brain structures associated with emotion in normal elderly subjects. METHOD: Eight normal subjects aged 55-78 years were shown film clips intended to provoke the emotions of happiness, fear, or disgust as well as a neutral state. During emotional activation, regional cerebral blood flow was measured with the use of [15O]H2O positron emission tomography imaging, and subjective emotional responses were recorded. Data were analyzed by subtracting the values during the neutral condition from the values in the various emotional activations. RESULTS: The stimuli produced a general activation in visual pathways that included the primary and secondary visual cortex, involving regions associated with object and spatial recognition. In addition, the specific emotions produced different regional limbic activations, which suggests that different pathways may be used for different types of emotional stimuli. CONCLUSIONS: Emotional activation in normal elderly subjects was associated with increases in blood flow in limbic and paralimbic brain structures. Brain activation may be specific to the emotion being elicited but probably involves complex sensory, association, and memory circuitry. Further studies are needed to identify activations that are specific for emotion.

We performed interictal [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in 17 patients with well-defined unilateral anterior mesial temporal epileptogenic foci as determined by EEG procedures. Sixteen of these patients subsequently underwent surgical resection of the epileptogenic focus. We measured local cerebral metabolic rates for glucose in mesial and lateral temporal structures and compared them with metabolic rates for analogous regions in 16 healthy normal volunteers and the contralateral hemisphere of the epileptic patients. We found relative hypometabolism ipsilateral to the seizure focus more frequently and to a greater degree in the lateral than in the mesial temporal cortex. Since the physiologic abnormalities involved mesial temporal structures, this observation suggests that functional pathways exist between mesial and lateral temporal cortex normally and that these pathways are altered in epilepsy of mesial temporal origin. Hypometabolism did not correlate well with histologic abnormalities in the surgical specimens.