The late positive potential, emotion and apathy in Parkinson's disease.

Parkinson's disease is associated with emotional changes including depression, apathy, and anxiety. The current study investigated emotional processing in non-demented individuals with Parkinson disease (PD) using an electrophysiological measure, the centro-parietal late positive potential (LPP). Non-demented patients with Parkinson's disease (n=17) and healthy control participants (n=16) viewed pleasant, neutral, and unpleasant pictures while EEG was recorded from a 64-channel geodesic net. The Parkinson patients did not differ from controls in terms of early electrophysiological components that index perceptual processing (occipital P100, N150, P250). Parkinson patients, however, showed reduced LPP amplitude specifically when viewing unpleasant, compared to pleasant, pictures as well as when compared to controls, consistent with previous studies suggesting a specific difference in aversive processing between PD patients and healthy controls. Importantly, LPP amplitude during unpleasant picture viewing was most attenuated for patients reporting high apathy. The data suggest that apathy in PD may be related to a deficit in defensive activation, and may be indexed cortically using event-related potentials.

Individualized piano instruction enhances executive functioning and working memory in older adults.

This study evaluates transfer from domain-specific, sensorimotor training to cognitive abilities associated with executive function. We examined Individualized Piano Instruction (IPI) as a potential cognitive intervention to mitigate normal age-related cognitive decline in older adults. Thirty-one musically naïve community-dwelling older adults (ages 60-85) were randomly assigned to either the experimental group (n = 16) or control group (n = 15). Neuropsychological assessments were administered at three time points: pre-training, following six months of intervention, and following a three-month delay. The experimental group significantly improved performance on the Trail Making Test and Digit Symbol measures as compared to healthy controls. Results of this study suggest that IPI may serve as an effective cognitive intervention for age-related cognitive decline.

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.

Prepulse effects as a function of cortical projection system.

A putative gating mechanism reduces startle blink, midline scalp potentials beginning with P50, and perceived loudness of startling stimuli. Tactile prestimuli were paired with auditory startle stimuli to determine if: (1) P50 inhibition is due to an extrinsic mechanism, (2) pairing differentially affects potentials reflecting modality specific and nonspecific system activity, and (3) crossmodal pairing modifies perceptual magnitudes of both pair members. Stimuli were presented alone and in pairs separated by 60 or 360 ms. Event-related potentials (ERPs) were recorded from midline and lateral sites; EMG was recorded from several facial and scalp muscles. Pairing reduced blink, and midline P50, N100 and P200 amplitudes; reductions were greater at the longer interval. P30 was largely unaffected by pairing. Pairing also differentially affected lateral N100 components reflecting later activity in specific and nonspecific systems. Results show that prestimulus inhibition of ERPs is not due to intrinsic refractoriness and that pairing differentially affects ERPs associated with modality specific and nonspecific projection systems.

The Stroop task and attention deficits in schizophrenia: a critical evaluation of card and single-trial Stroop methodologies.

The Stroop task, considered by many to be a paradigmatic measure of selective attention, has often been employed to investigate attention deficits in schizophrenia. Card and single-trial versions of this task have yielded different results. In this study both card and single-trial versions were administered to healthy controls (n = 24) and patients with schizophrenia (n = 55). No differences in reaction time (RT) interference were found on either version. On the single-trial version, patients showed greater RT facilitation and error rate interference, evidence for a deficit in selective attention. Methodologic and analytic issues that account for the mixed results from earlier card Stroop studies are addressed. It is concluded that single-trial versions provide greater sensitivity to selective attention pathology in schizophrenia.

Selective pharmacological activation of limbic structures in human volunteers: a positron emission tomography study.

Using a pharmacological probe, procaine hydrochloride, the authors elicited consistent and selective activation of anterior limbic and paralimbic structures in normal human volunteers as documented by H215O positron emission tomography. This activation was associated with a range of emotional, somatic, and visceral experiences, often similar to those experienced during the aura of temporal lobe epilepsy. Several subjects also experienced panic attacks. This study confirms that selective anterior limbic/paralimbic activity in normal human volunteers evokes many emotional phenomena as well as common "ill-defined" symptoms observed in clinical conditions. The present combination of procaine challenge and neuroimaging provides a noninvasive procedure to probe the contribution of different anterior limbic and paralimbic structures to normal human emotions and to neuropsychiatric disorders.

Temporal dynamics of brain activation during a working memory task.

Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.

Anxiety disorders and the syndrome of chest pain with normal coronary arteries: prevalence and pathophysiology.

Recurrent chest pain in the presence of normal coronary arteries is a common and perplexing problem in primary care medicine and cardiology and is associated with significant morbidity and health care utilization. A series of carefully controlled prospective studies conducted over the past decade have suggested a strong association between this syndrome and the presence of anxiety disorders. Thirty percent to 50% of patients with recurrent chest pain and normal coronary arteries meet criteria for panic disorder. Generalized anxiety disorder may also be associated with this syndrome. In contrast, major depression seems strongly associated with the syndrome only when it presents as a comorbidity with panic disorder. Reluctance of nonpsychiatric physicians to diagnose and treat anxiety disorders in this population may reflect a lack of knowledge of the well-established pathophysiologic mechanisms that can mediate the association of anxiety disorders and cardiac symptoms. We propose a conceptual framework, derived from the neurologic literature and from recent studies using positron emission tomography and intravenous procaine challenge, which links anxiety and subjective cardiovascular symptoms to abnormal activity in neural circuits involving the anterior limbic system of the brain. This neuropsychiatric model of the role of anxiety disorders in the pathophysiology of chest pain in patients with normal coronary arteries is proposed to strengthen the rationale for the identification and treatment of anxiety disorders in this population by nonpsychiatric physicians.

Pharmacologic activation of limbic structures and neuroimaging studies of emotions.

Two primary paradigms have been employed to study the neurobiological basis of human emotions. These are induced emotions in normal subjects and the comparison of patients suffering from emotional disorders with normal control subjects. These traditional methods, which have limitations, may be complemented by a third approach: the experimental elicitation of affect through pharmacologic limbic stimulation with intravenous procaine hydrochloride. In this paper, the authors review their research using the direct stimulation approach. To determine whether procaine produces affectively laden experiences accompanied by a reliable change in brain activity, 10 normal subjects received two injections each of placebo (A) and procaine (B)-in ABBA order-while in a positron emission tomography (PET) scanner. In a further study, emotional responses were observed among 24 subjects (including the 10 subjects in the PET study) for a total of 80 procaine injections. Procaine was shown to induce bilateral activation of an anterior limbic network concomitant with powerful, transient emotional and other subjective phenomena as well as autonomic and endocrine responses. Considerable between-subject variability in responses was noted, suggesting that this method can be used to explore individual differences in the neurobiological basis of emotion and affective disposition. Experimental elicitation of affect through limbic stimulation with procaine, when used as part of a triangulation strategy with traditional imaging paradigms, can contribute to our understanding of emotion and its disorders, of the different components of emotion-response systems (e.g., subjective, autonomic, and endocrine), and of individual differences in affective disposition.

Lead stimulation effects on reflex blink, exogenous brain potentials, and loudness judgments.

Prepulse inhibition of the reflex blink by a weak stimulus shortly preceding a blink-eliciting stimulus has been described as a sensorimotor gating phenomenon that may protect processing of the first stimulus. To determine how a stimulus configuration that elicits prepulse inhibition also affects exogenous evoked potentials and perceived loudness of the paired stimuli, the three types of response were recorded simultaneously under four conditions: tone pairs of 75-110 dB and 75-75 dB and single control tones of each intensity. Two studies using different intrapair intervals found that blinks and exogenous potentials peaking after 50 ms were smaller for the second tone of pairs than for equal-intensity single tones. Pairing also reduced the loudness of 110-dB second tones, but the loudness of 75-dB first and second tones was unaffected or increased. These effects are discussed in terms of parallel processing of transient, unmodulated information in specific paths, steady-state modulated information in nonspecific paths, and a context-dependent effect on loudness judgments.